Having frequent, persistent, or intense feelings of guilt or shame
"I often feel guilty or ashamed."
Low Self-Esteem
Having feelings of low self-worth or low self-confidence; feeling inferior
"I often lack confidence or feel inferior to others."
Self-Harm
Having thoughts of deliberate self-harm or suicide OR showing severe
self-neglect
"I sometimes think of hurting or killing myself."
Distractibility
Difficulty concentrating on doing something for 10 minutes; easily
distracted; poor attention span
"I am easily distracted." "I can't focus on things for very long."
Fatigue
Tired; lack of energy
"Im tired all the time."
Abnormal Sleep
Under- or over-sleeping
"My sleep is a problem."
Abnormal Appetite
Under- or over-eating
"My eating is a problem."
Loss of Interest or Pleasure
Lacking interest or pleasure in doing one’s usual activities
"I rarely get enthusiastic about anything."
PSYCHOSIS (When Severely Ill)
Impaired Reasoning
Difficulty analyzing and finding solutions to problems in day-to-day life;
poor judgment
"My judgment or ability to solve problems isn't good."
Perceptual Dysregulation
Having odd or unusual perceptions e.g. feeling unreal, things looking
unreal, out-of-body feeling
"Things around me often feel unreal, or more real than usual."
Unusual Beliefs or Experiences
Firmly believing a false belief (delusion) or false perception
(hallucination) e.g. hearing “voices”
"I've had some really weird experiences that are very difficult to explain."
Disorganized Speech or Behavior
Speech is frequently derailed or incoherent; OR grossly disorganized or
catatonic behavior
"My thoughts or behaviors often don’t make sense to others."
Onset:
Major Depressive Disorder often starts slowly with a depressive episode
characterized by a period of almost daily depressed mood or diminished interest in
activities lasting at least two weeks accompanied by other symptoms such as difficulty
concentrating, feelings of worthlessness or excessive or inappropriate guilt, hopelessness,
recurrent thoughts of death or suicide, changes in appetite or sleep, psychomotor agitation
or retardation, and reduced energy or fatigue. There have never been any prior manic,
hypomanic, or mixed episodes, which would indicate the presence of a bipolar
disorder.
Depressive disorders account for 40.5% of the disabililty
caused by mental illness worldwide. Major Depressive Disorder causes significant impairment
in academic, occupational and/or social functioning. Yet only a minority are so chronically
disabled that they require a disability pension.
When facing adversity, many people develop depressive symptoms, but lack impairment
in their usual activites - hence would not be diagnosed as having Major Depressive Disorder.
The diagnosis of Major Depressive Disorder requires that the person not only has depressive
symptoms, but also has difficulties in day-to-day functioning due to these symptoms.
During psychosis, severe suspiciousness (paranoia) is much more prevalent in Bipolar
Disorder and Schizophrenia than in Major Depressive Disorder. Likewise, severe disorganized
speech or behavior is much more prevalent in Schizophrenia than in Bipolar Disorder or Major
Depressive Disorder.
During psychosis, individuals usually lack insight, hence actively resist any suggestion by
others that they are ill and need help. During a psychotic episode, many individuals become
very forgetful; hence can't recall being psychotic afterwards when they recover their
sanity. This makes it very difficult to convince them that they need treatment.
What Every Suicidal Person Should
Read:
Major Depressive Disorder is a time-limited disease.
Worldwide, the average duration of an episode of Major Depressive Disorder is
30 weeks
.
Individuals with moderate to severe Major Depressive Disorder usually respond to
antidepressant medication within 6 weeks, and one-third become symptom-free within 7 weeks.
Even if someone doesn't respond to their first antidepressant medication, by switching to
another antidepressant (sometimes up to 3 times), antidepressant medication eventually
brings about
full recovery for 70%
of patients. That is why suicide is so tragic.
Suicide is a
lethal over-reaction to a temporary problem
.
Treatment:
In Major Depressive Disorder (MDD) without treatment:
23%
recover within 3 months,
32%
within 6 months, and
53%
within one year. The chance of spontaneous recovery is much less for individuals having
severe depression - especially when it is recurrent or chronic.
Repetitive transcranial magnetic stimulation (rTMS) was found to be no better than sham (placebo) treatment for treatment-resistant
major depression. The overall remission rate was
39%
, with no significant difference between the active and sham groups.
An active placebo is an inert substance, given on frequent visits to a doctor,
which increases the patient's hope for recovery. In research, "response" to a
treatment is defined as "having at least a 50% reduction in symptoms". "Remission" is
defined as "becoming symptom-free".
The active placebo effect causes most of the treatment benefit in Major Depressive Disorder.
When compared to the 40% response rate for treatment of acute MDD on active placebo,
the response
rate after 8-weeks on the first antidepressant medication used is
45%
for mild depression,
52%
for moderate depression, and
56%
for severe depression.
The current expert consensus is, for mild depression, antidepressant medication is
no more effective than an "active placebo" therapy of frequent contact with a
competent, supportive clinician who instills hope of a recovery. The warmer and more
competent appearing the clinician, the greater the resulting active placebo effect.
Treatment by a cold, uncaring, incompetent appearing clinician dramatically decreases the
active placebo effect.
Research has shown that antidepressant medication is effective for the treatment of
moderate to severe Major Depressive Disorder.
The STAR*D study of individuals with chronic or recurrent
Major Depressive Disorder found:
It takes an average of
6
weeks of antidepressant medication treatment for patients to achieve a 50%
reduction in symptoms and nearly
7
weeks for them to become symptom-free.
At the end of
8
weeks of treatment (on the first antidepressant used), on average,
45%
respond (lose half of their symptoms), and
30%
enter remission (become symptom-free).
Of those initial nonresponders who try up to
3
different switches in their antidepressant treatment and do not withdraw
from treatment, almost
70%
become symptom-free.
Approximately
80%
of those with a history of two depressive episodes will have another depressive
episode. Once a first depressive episode has occurred, recurrent episodes will usually begin
within five years of the initial episode, and, on average, individuals with a history of
depression will have 5 to 9 separate depressive episodes in their lifetime. However,
maintenance treatment with antidepressant medication reduces the
relapse rate by
52%
when compared to placebo.
Since severe Major Depressive Disorder has up to a
15%
fatality rate due to suicide; it is vitally important to prevent suicide by quickly
starting treatment.
Unlike illicit drugs (e.g., heroin, cocaine), antidepressants and lithium take at least 2
weeks to start working, are not addictive, and do not produce elation.
Most individuals fully recover from their Major Depressive Disorder. However, some only
partially recover, and at least
50%
recover only to later relapse a few years later. These relapsing individuals
may require long-term treatment with medication or psychotherapy to treat their residual
depressive symptoms or to prevent their depressive relapses.
Why Do Blameless People Suffer From Severe Depression?
Job 2,500 Years Ago
Every religious tradition has tried to explain why people suffer from severe depression.
The oldest reference to severe depression was written 2,500 years ago in the Bible's
Book of Job. The Bible tells the story of Job, a very just and rich man, who suddenly
lost everything - his family, his possessions, and his health.
Psychiatrically, it is amazing how Job's resulting symptoms were identical to those of a
modern person having Major Depressive Disorder. This is how Job described his severe
depression 2,500 years ago:
Depressed mood most of the day
"My days are swifter than a weaver's shuttle and come to their end without hope.
Remember that my life is a breath; my eye will never again see good."
"My face is red with weeping, and on my eyelids is deep darkness."
".. when I hoped for good, evil came, and when I waited for light, darkness
came. My inward parts are in turmoil and never still; days of affliction come to
meet me. I go about darkened, but not by the sun."
"For the thing that I fear comes upon me, and what I dread befalls me. I am not
at ease, nor am I quiet; I have no rest, but trouble comes."
Markedly diminished interest or pleasure
"I am allotted months of emptiness, and nights of misery are apportioned to me."
Significant weight loss when not dieting
"And He (God) has shriveled me up, which is a witness against me, and my
leanness has risen up against me; it testifies to my face."
Insomnia
"When I lie down I say, 'When shall I arise?' But the night is long, and I am
full of tossing till the dawn."
"... when deep sleep falls on men, dread came upon me, and trembling, which made
all my bones shake."
Fatigue or loss of energy
"I ... have laid my strength in the dust." ... "God has worn me out."
Feelings of worthlessness
"My relatives have failed me, my close friends have forgotten me. The guests in
my house and my maidservants count me as a stranger; I have become a foreigner
in their eyes."
"Even young children despise me; when I rise they talk against me. All my
intimate friends abhor me, and those whom I loved have turned against me."
Recurrent thoughts of death
"My spirit is broken; my days are extinct; the graveyard is ready for me."
"Oh that I might have my request, and that God would fulfill my hope, that it
would please God to crush me, that he would let loose his hand and cut me off!"
"When I say, 'My bed will comfort me, my couch will ease my complaint,' then you
(God) scare me with dreams and terrify me with visions, so that I would choose
strangling and death rather than my bones."
Lessons To Be Learned From 2,500 Years Ago
Job correctly believed that "I am blameless" - thus he could not understand why
his suffering occurred.
The Bible states that, after a number of months, Job fully recovered and did
even better than before his severe depression.
There are a number of modern lessons that can be learned from this ancient
story:
People should not be blamed for their severe depression. Their depression is
an illness, and not a punishment for sinful behavior or a lack of religious
faith.
Even without treatment, severe depression is usually time-limited, and in a
few months totally recovers.
The symptoms of major depressive disorder haven't changed in the past 2,500
years.
Individuals with this
disorder would have a significant impairment in the behaviors that are displayed in
red
:
Most of the time and in most situations:
In general, do you have difficulty making and
keeping friends?
Would you normally describe yourself as a
loner?
In general, do you trust other people?
("No")
Do you normally lose your temper easily?
Are you normally an impulsive sort of
person?
Are you normally a worrier?
In general, do you depend on others a lot?
In general, are you a
perfectionist?
Answer "Yes" or "No" to each of these 8
questions.
7-Question Well-Being Screening Test (By P. W. Long MD, 2020
Individuals
with this disorder would have a significant impairment in the behaviors that are
displayed in
red
:
Agreeableness: I was kind and honest. Conscientiousness: I was diligent and self-disciplined. (Instead had distractibility [and hyperactivity in
an agitated depression]) Openness/Intellect:I showed good problem-solving and curiosity. (Instead had impaired
reasoning, and if psychotic had delusions, hallucinations, psychomotor slowing or
stupor) Sociality:
I was gregarious, enthusiastic, and assertive. (Instead had loss of
interest or pleasure) Emotional
Stability: I was emotionally stable and calm. (Instead had
depressed mood, guilt/shame, feeling worthless, thoughts of self-harm) Physical
Health: I was physically healthy. (Instead had fatigue,
weight gain/loss, increased/decreased sleep) Role Functioning: I functioned well socially and at school/work.
How often in the past
week did you do each of these 7 behaviors:
Self-diagnosis of this disorder is often inaccurate. Accurate diagnosis of this disorder
requires assessment by a qualified practitioner trained in psychiatric diagnosis and
evidence-based treatment.
However, if no such professional is available, our free computerized diagnosis is usually
accurate when completed by an informant who knows the patient well. Computerized
diagnosis is less accurate when done by patients (because they often lack insight).
Example Of Our Computer Generated Diagnostic Assessment
Major Depressive Disorder, Single Episode, Nonpsychotic 296.2X
This diagnosis is based on the following findings:
Never had psychotic symptoms in the absence of prominent mood disturbances
(when off drugs)
Depressive episode is not better accounted for by Schizoaffective Disorder
Depressive episode is not superimposed on Schizophrenia or Schizophreniform
Disorder
Depressive episode is not superimposed on Delusional Disorder or Psychotic
Disorder Not Otherwise Specified
Depressive episode was not due to a general medical condition
Depressive episode was not due to substance use or other treatment
Depressive episode caused clinically significant distress or disability for at
least 2 weeks (still present)
Depressive episode had abnormal depressed mood for at least 2 weeks (still
present)
Depressive episode had markedly diminished interest or pleasure for at least 2
weeks (still present)
Depressive episode had appetite or weight disturbance for at least 2 weeks
(still present)
Depressive episode had insomnia or hypersomnia for at least 2 weeks (still
present)
Depressive episode had psychomotor agitation or slowing for at least 2 weeks
(still present)
Depressive episode had fatigue or loss of energy for at least 2 weeks (still
present)
Depressive episode had self-reproach or inappropriate guilt for at least 2
weeks (still present)
Depressive episode had poor concentration or indecisiveness for at least 2
weeks (still present)
Depressive episode had recurrent thoughts of death or suicide for at least 2
weeks (still present)
Depressive episode was not due to normal bereavement
Depressive episode lacked psychotic symptoms (when off drugs)
Has had only one depressive episode lasting at least 2 weeks
Treatment Goals:
Goal: prevent depressed mood.
If this problem persists: She will feel sad, hopeless, discouraged, "down in the
dumps", or "blah". She may emphasize somatic complaints (e.g., bodily aches and
pains) rather than reporting feelings of sadness. She may exhibit increased
irritability (e.g.,
persistent anger, a tendency to respond to events with angry outbursts or
blaming others, or an exaggerated sense of frustration over minor matters).
Goal: prevent loss of interest or pleasure.
If this problem persists: She will feel less interested in hobbies, "not caring
anymore," or not feeling any enjoyment in activities that were previously
considered pleasurable. There may be a significant reduction in her sexual
interest or desire.
Goal: prevent appetite or weight disturbance.
If this problem persists: She will have either abnormally decreased or increased
appetite. This may progress to significant loss or gain in weight.
Goal: prevent insomnia or hypersomnia.
If this problem persists: She will sleep too little or too much. Typically she
will have middle insomnia (i.e., waking up during the night and having
difficulty returning to sleep) or terminal insomnia (i.e., waking too early and
being unable to sleep).
Initial insomnia (i.e., difficulty falling asleep) may also occur. Less
frequently, she may have oversleeping (hypersomnia).
Goal: prevent psychomotor agitation or slowing.
If this problem persists: She will have agitation (e.g., the inability to sit
still, pacing, hand-wringing; or pulling or rubbing of the skin, clothing, or
other objects) or psychomotor retardation (e.g., slowed speech, thinking, and
body movements; increased
pauses before answering; speech that is decreased in volume, inflection, amount,
or variety of content, or muteness).
Goal: prevent fatigue or loss of energy.
If this problem persists: She will experience decreased energy, tiredness, and
fatigue. Eventually, even the smallest tasks will seem to require substantial
effort. She may find that washing and dressing in the morning are exhausting and
take twice as long as
usual.
Goal: prevent inappropriate self-reproach or guilt.
If this problem persists: She will have unrealistic negative evaluations of her
worth or guilty preoccupations or ruminations over minor failings. She may often
misinterpret neutral or trivial day-to-day events as evidence of her defects and
have an
exaggerated sense of responsibility for untoward events. This may progress to
delusional proportions.
Goal: prevent poor concentration or indecisiveness.
If this problem persists: She will have an impaired ability to think,
concentrate, or make decisions.
Goal: prevent recurrent thoughts of death or suicide.
If this problem persists: She will be at risk of suicide. Many studies have
shown that it is not possible to predict accurately whether or when a particular
individual with depression will attempt suicide. Motivations for suicide may
include a desire to give up in the face of perceived insurmountable obstacles or
an intense wish to end an excruciatingly painful emotional state that is
perceived by the person to be without end.
Major Depressive Disorder is a condition characterized by one or more Major Depressive
Episodes without a history of Manic, Mixed, or Hypomanic Episodes.
These Major Depressive Episodes are not due to a medical condition, medication, abused
substance, or Psychosis. If Manic, Mixed, or Hypomanic Episodes develop, the diagnosis is
changed to Bipolar Disorder.
The Major Depressive Episode must have either depressed mood or loss of interest. A Major
Depressive Episode represents a decline from previous functioning which has at least 5 of
the following 9 symptoms: (1) depressed mood, (2) loss of interest or pleasure, (3)
significant
change in appetite/weight, (4) insomnia/hypersomnia, (5) psychomotor agitation/slowing, (6)
fatigue/loss of energy, (7) feelings of worthlessness/inappropriate guilt, (8) inability to
concentrate/indecisiveness, (9) recurrent thoughts of death/suicide. (Note: do not include
symptoms that are clearly attibutable to another medical condition.)
Completed suicide occurs in up to 15% of individuals with severe Major Depressive Disorder.
There is a fourfold increase in deaths in individuals with this disorder who are over age
55. Individuals with this disorder have more pain and physical illness and decreased
physical,
social,
and role functioning.
Comorbidity
Alcoholism and illicit drug abuse dramatically worsen the course of this illness, and are
frequently associated with it. Persistent Depressive Disorder often precedes the onset of
this disorder for 10%-25% of individuals. This disorder also increases risk of also having
Panic
Disorder, Obsessive-Compulsive Disorder, Anorexia Nervosa, Bulimia Nervosa, and Borderline
(Emotionally Unstable) Personality Disorder.
Associated Laboratory Findings
No laboratory test has been found to be diagnostic of this disorder.
Prevalence
Major Depressive Disorder affects approximately one in six
men and one in four women in their lifetimes. The US 12-month community prevalence
rate for this disorder is 7%. The prevalence in 18- to 29-year-old individuals is threefold
higher than the prevalence in those aged 60 or older. The prevalence rates for this disorder
appear to be unrelated to ethnicity, education,
income, or marital status. In childhood, boys and girls are equally affected. However, in
adolescence and adulthood, the prevalence is 1.5- to 3-fold higher in females compared to
males
Course
Major Depressive Disorder "is usually
highly recurrent, with at least 50% of those who recover from a first episode of
depression having one or more additional episodes in their lifetime, and approximately
80% of those with a history of two episodes having another recurrence. Once a first
episode has occurred, recurrent episodes will usually begin within five years of the
initial episode, and, on average, individuals with a history of depression will have 5
to 9 separate depressive episodes in their lifetime."
The first episode may occur at any age from childhood to old age, the onset may be either
acute or insidious, and the duration varies from a few weeks to many months. The average age
at onset is in the mid-20s. Some individuals have isolated episodes that are separated by
many years without any depressive symptoms, whereas others have clusters of episodes, and
still others have increasingly frequent episodes as they grow older.
After the first episode of this disorder, there is a 60% chance of having a second episode.
After the second episode, there is a 80% chance of having a third, and after the third
episode, there is a 90% chance of having a fourth. Chronicity of depressive symptoms
substantially increases the likelihood of underlying personality, anxiety, and substance use
disorders and decreases the likelihood that treatment will be followed by full symptom
resolution.
Outcome
In moderate to severe Major Depressive Disorder, one review study
found the remission rates after 16 weeks of therapy were
46%
for treatment with a single antidepressant medication (tricyclics or phenelzine),
46%
for psychotherapy (primarily cognitive behavior and interpersonal therapies), and
24%
for control conditions. Another study for moderate to severe depression found the remission
rates after 16 weeks of therapy were
46%
for medication and
40%
for cognitive therapy.
In the famous STAR*D study of individuals with chronic or recurrent
moderate to severe Major Depressive Disorder, after 8 weeks of treatment, the
remission rate to the first antidepressant medication used (citalopram, a SSRI
antidepressant) was
30%
. This closely resembled the results seen in most other 8-week antidepressant medication
efficacy trials. Repeatedly switching nonresponders to different antidepressant medication
+/- cognitive behavior therapy eventually doubled this remission rate.
In Major Depressive Disorder, lower recovery rates are associated with: longer duration,
psychotic features, prominent anxiety, personality disorders, and symptom severity.
There is a greater likelihood of developing additional depressive episodes if:
the preceding episode was severe
the individual is younger
the individual has had multiple episodes
there was pre-existing Persistent Depressive Disorder
the individual has made only a partial recovery
the individual has a chronic general medical condition
Among those with an
onset of depression in later life, there is evidence of subcortical white matter
hyperintensities associated with cerebrovascular disease. These vascular depressions are
associated with greater neuropsychological impairments and poorer responses to standard
therapies.
Many individuals with Bipolar Disorder begin with one or more depressive episodes. About
5%-10% of individuals with Major Depressive Disorder eventually convert into Bipolar
Disorder. The acute onset of severe depression, especially with psychotic features and
psychomotor
retardation, in a young person without prepubertal psychopathology is more likely to predict
a bipolar course.
A family history of Bipolar Disorder may also be suggestive of subsequent development of
Bipolar Disorder. The risk that recurrent Major Depressive Disorder will have a Manic
Episode never disappears completely, however many Major Depressive Episodes have been
experienced.
Major Depressive Disorder, particularly with psychotic features, may also convert into
Schizophrenia, a change that is much more frequent than the reverse.
Mood Disorder Recovery At 10-Year Follow-up Compared To
Schizophrenia
Precipitants
Stressors may play a more significant role in the precipitation of the first or second
episode of this disorder and play less of a role in the onset of subsequent episodes.
Chronic medical conditions and Substance Use Disorders (particularly Alcohol or Cocaine
Dependence) may
contribute to the onset or exacerbation of this disorder. The presence or absence of
stressful life events does not appear to provide a useful guide to prognosis or treatment
selection.
Familial Pattern
First-degree biological relatives of individuals with this disorder are 2-4 times more
likely to develop Major Depressive Disorder. They also have an increased risk of having
Alcohol Dependence, Anxiety Disorder (e.g., Panic Disorder, Social Anxiety Disorder), and
Attention Deficit - Hyperactivity Disorder compared with the general population.
Heritability is approximately 40%, and the personality trait neuroticism accounts for a
substantial portion of this genetic liability.
Controlled Clinical Trials Of Therapy
Click here for a list of all the controlled clinical trials of
therapy for this disorder.
Treatment As Usual
In research many controlled clinical trials use "treatment as usual" (TAU) as their control
group. For Major Depressive Disorder, meta-analysis of 38 such studies (having 2099 patients) showed that
in TAU
33% of the patients remitted
from depression and
12% of the patients deteriorated
. TAU varied considerably from study to study; thus TAU is a poor control group in
research. A fraudulent research design is one in which the experimental treatment is given
by expert therapists, and the TAU is given by inexpert therapists.
Psychotherapy
The major psychological treatments for depression [cognitive behavior therapy (CBT),
mindfulness-based cognitive therapy (MBCT), interpersonal therapy (IPT), short-term psychodynamic
psychotherapy
(STPP)] when compared to each other are equally
effective.
One large NIMH
study on major depressive disorder found that the remission rate (after 16 weeks of
treatment, at 18-month followup) did not differ statistically among four treatments:
30%
for cognitive behavior therapy, 26% for interpersonal therapy, 19% for imipramine plus
clinical management, and 20% for placebo plus clinical management. Among patients who had
recovered, rates of relapse back into depression (at 18-month followup) were 36% for
cognitive behavior therapy, 33% for interpersonal therapy, 50% for imipramine plus clinical
management, and 33% for placebo plus clinical management.
A second
study on moderate to severe major depressive disorder found (at 12-month
followup) a 31% relapse rate back into depression for cognitive behavioral therapy, and a
47% relapse rate
for patients who kept taking medication. A third study
on moderate to severe major depressive disorder found that (after 16 weeks of
therapy) there was a 46% remission rate for medication,
and a 40% remission rate for cognitive therapy.
The addition of psychological treatment (CBT, MBCT, IPT,
STTP) to
antidepressant medication results
in an improvement in outcome. St John's wort and regular exercise appear mildly effective in the
treatment of depression (but their effect size is small).
Pharmacotherapy
Research on antidepressant medication has made startling findings: (1) all second-generation
antidepressant medications are equally effective, (2) treatment with a combination of
antidepressant medications (especially TCA + SSRI) is more effective than treatment with a single antidepressant
medication, (3) only 60% of individuals with major depression respond to antidepressant
medication, (4) antidepressant medication (like psychotherapy) has relatively modest effects
when compared with an active placebo, and (5) more than 50% of the patients
fail to respond to the first antidepressant medication they receive; hence require a
switch to another antidepressant medication.
An active placebo is an inert substance,
given by a doctor, which increases the patient's hope for recovery. The warmer and more
competent appearing the doctor, the greater the resulting active placebo effect. Treatment
by a cold, uncaring, incompetent appearing physician dramatically decreases the active
placebo effect.
The active placebo effect causes most of the treatment benefit in major depressive disorder.
When compared to the 40% remission rate on active placebo,
the remission
rate on antidepressant medication is
45%
for mild depression,
52%
for moderate depression, and
56%
for severe depression.
Since antidepressant medication is no more effective than active placebo for the treatment
of mild Major
Depressive Disorder; antidepressant medication has proven benefit only in the
treatment of
moderate to severe Major Depressive Disorder. For those whose depression causes marked
distress or disability; antidepressant medication significantly reduces the risk of
suicide, and
returns the individual back to health, months sooner than would have been the case without
treatment.
It should be remembered that, even without treatment, the median duration of major
depressive disorder is 30 weeks.
In the famous STAR*D study of individuals with chronic or recurrent
major depression, the 8-week response rate to the first
antidepressant medication used (citalopram) was
47%
, and the remission rate was about
30%
. This closely resembled the results seen in most other 8-week antidepressant medication
efficacy trials. Participants not responding to citalopram were switched to a different
antidepressant or had another medication added to their existing antidepressant medication.
This change in medication happened up to 3 times if the participant didn't respond.
Eventually switching antidepressants brought the response rate up to
60%
(counting everyone in the study). This response rate is considerably higher than
the placebo response rate for chronic or recurrent MMD. If dropouts weren't
counted, the final remission (symptom-free) rate was
70%
. However, the rate at which participants withdrew from the STAR*D study was significant
-
21%
withdrew after citalopram,
30%
withdrew after the 1st switch, and
42%
withdrew after the 2nd switch.
If antidepressant medication/lithium is used, it should be started at a half of the
therapeutic dose for the first week before being increased to the full therapeutic dose.
Prematurely starting at the full therapeutic dose significantly increases adverse effects
and causes a high drop-out rate.
Optimal effectiveness of an antidepressant medication occurs within 4-8 weeks. If there has
been no response after the first 6 weeks, the dose should be increased. If there has been no
response after 8 weeks, the antidepressant should be changed or another medication added to it.
After successful treatment with an antidepressant medication, the effective dose is usually
continued for another 4-9 months. Stopping before that time often triggers a return of the
depression. The more severe or frequent the depressive episodes, the longer the
antidepressant medication/lithium therapy should be continued.
Stopping antidepressant medication/lithium should be done slowly over 1-2 months. Lithium
has no withdrawal symptoms, but two antidepressant medications (paroxetine and venlafaxine)
have significant withdrawal symptoms which limits their use.
Treatment
refractory depressions may respond to a combination of an antidepressant plus
lithium or electroconvulsive therapy (ECT). In terms of symptom reduction, some atypical
antipsychotic
medications added to antidepressant medications result in a small benefit [aripiprazole (NNT= 7), risperidone (NNT= 8)]; whereas
others are ineffective [quetiapine (NNT=
10), and olanzapine/fluoxetine combination (NNT= 19)]. (Note: A treatment with a Number
Needed To Treat (NNT) >8 is generally considered clinically insignificant.) The only
antidepressants approved for use in depressed children in the U.S. are fluoxetine and
escitalopram.
Electroconvulsive Therapy (ECT)
When given ECT, 55% of individuals with major depressive disorder will go into remission.
Unfortunately, there is a very high relapse rate 6 months after ECT. Of those going into
remission with ECT, at
6 months posttreatment: (1) on placebo 84% relapse, and (2) on antidepressant medication
plus lithium 39% relapse. Thus ECT is effective during the acute treatment phase in
hospital, but steadily loses its benefit after hospital discharge. The effectiveness of ECT
vs sham ECT
at one or more months
posttreatment is still controversial.
Ineffective Therapies
Vitamins, dietary supplements, and acupuncture are all ineffective
for depression.
Is The Active Placebo Effect The Key To Understanding Recovery?
Many cases of major depressive disorder occur after events which trigger hopelessness
(e.g., bereavement, divorce, job loss, academic failure). Also many activities that
foster hope serve to decrease depression (e.g., socializing with friends, supportive
counselling, religious involvement).
To get a significant active placebo effect, the placebo treatment must be given by a
warm, competent physician who instills hope for recovery. Thus it isn't the placebo that
causes the improvement. It is the active encouragement of hope done by a warm, competent
physician that makes the placebo work.
Antidepressant
medication is 5% more effective than active placebo in mild depression, 12% more
effective than active placebo in moderate depression, and 16% more effective than active
placebo in severe depression. Thus, for moderate to severe major depression, it is important
to have both antidepressant medication and active treatment with a warm,
competent physician who instills hope of recovery.
Most Antidepressants Ineffective for Kids With Depression -
Medscape (2016)
"'In adults, mainly in the elderly, depression is a lot about mood, while in young
people, it's a lot about irritability and difficulty with concentration,' said Dr
Cipriani. 'We tend to call it all depression and assume that the same drugs work for
young people.'
The analysis showed that in terms of efficacy, only fluoxetine was better than
placebo (standardized mean difference [SMD], - 0.51; 95% credible interval [CrI],
-0.99 to -0.03). However, the authors point out that 'the large credible interval
and its upper limit close
to the point of no difference raise the question of whether this estimate is robust
enough to inform clinical practice.'
Although the current study could not comprehensively assess the risk for suicidality
for all drugs, there was robust evidence suggesting a significantly increased risk
for suicidality for young people given venlafaxine. According to Dr Cipriani, 50% to
60% of patients
respond to an antidepressant, and about 40% respond to placebo, so the "added value"
is about 10% to 15%.
Dr Jureidini suggests taking a 'watchful waiting' approach, even in cases of
moderate and severe depression. It might be a matter of helping the child make sense
of what they are feeling. For example, he or she might still be grieving from the
loss of a beloved
grandmother. Dr Jureidini pointed out that (childhood) depression usually lasts
weeks, not months."
Lack Of Social Skills During Major Depressive Disorder
There are social skills that are essential for healthy social functioning. During major
depressive disorder, individuals lack the essential social skills of self-confidence,
optimism, belonging, and sociability. These are the same social skills
that are lacking in individuals with persistent depressive disorder, avoidant personality
disorder and social anxiety disorder.
SOCIAL SKILL
MAJOR DEPRESSION
NORMAL
Self-Confidence
Feeling inferior or shy
Having a good opinion of one's self and abilities; socially confident and
out-going
Optimism
Pessimism or expecting the worst
Having a positive outlook on life; expecting a good outcome; hopeful
Belonging
Fearing rejection by others
Feeling liked and accepted by friends, and included in their group; not
fearing rejection
Sociality
Social withdrawal
Friendly; interested in social contacts and activities
What Improves When You Recover From Depression?
Over 5 years (2005-2011) I studied my outpatient psychiatric patients that had a DSM-IV
diagnosis of Major Depressive Disorder. I recorded their progress on every office visit
using my Internet Mental Health Quality
of Life
Scale. At the
end
of this study, I compared 72 of them when they were moderately or severely depressed, to
another 30 of them when they had fully recovered or were only mildly depressed. In this
way, I could statistically determine which symptoms were elevated in major depressive
disorder.
Explanation Of Terms And Symbols
Fatigue, sleep disturbance, appetite disturbance, occupational impairment and social
impairment are all part of the diagnostic criteria for major depressive disorder. These
classical symptoms of major depression decreased as my patients recovered. The Quality
of Life
Scale
showed
additional symptoms which decreased as my patients recovered from their depression,
namely:
Overall physical health (i.e., less physical illness)
Friendship problems
Mistrust
Dependent behavior
Housing problems
Financial problems
Agoraphobia (fear of leaving home)
Explanation Of Terms And Symbols
Depressed mood, guilt, self-harm, agitation, distractibility, apathy, and impaired
executive functioning are all part of the diagnostic criteria for major depressive
disorder. As expected, these classical symptoms of major depression decreased as my
patients recovered.
However,
the Quality of Life Scale also showed that other important symptoms decreased as my
patients recovered from their depression, namely:
Generalized anxiety
Hostility
Forgetfulness
Personal neglect
It's important to note that, except for 2 patients that committed suicide, none of the
other depressed patients remained suicidal. The terrible pain of depression was
time-limited. Eighty percent of individuals with major depressive disorder recover
within one year. Some
even
recover after 3 months. Thus suicide is a tragic waste of life; especially when major
depressive disorder is so time-limited.
Explanation Of Terms And Symbols
The most striking finding was the extent to which depression had impaired my patients'
social functioning. The following behaviors were induced by depression, and disappeared
when my patients recovered from their depression:
Avoidant-Dependent Behaviors
Low self-esteem (previous chart)
Pessimism
Loneliness
Separation insecurity
Submissiveness
Difficulty handling conflict
Schizoid Behaviors
Intimacy avoidance
Social withdrawal
Lack of emotional expression
Obsessive-Compulsive Behaviors
Perfectionism
Inflexibility
Histrionic-Borderline Behaviors
Emotional instability
Unstable self-image
Paranoid Behavior
Feeling victimized
People Becoming Depressed After 4 Days Of Starvation
Studies on starvation have repeatedly shown that, after a few days of starvation, some
individuals can become clinically depressed. Recently there was a 10 day experiment in
which 10 individuals agreed to be cavemen and go into the Colorado wildness equipped only
with caveman clothing and tools.
Psychiatrically, the results were amazing.
The group was able to catch fish on the first day, then they ran out of food. By the fourth
day of starvation, the entire group suffered from severe fatigue, insomnia and apathy. Three
members of the group became dysfunctional and just spent the day lying down or sitting.
One
woman, a vegetarian, was very weak and inactive because she couldn't find nutritious
vegetarian food. Another female member became very tearful, pessimistic, and emotionally
unstable. This woman gave up on the fifth day of starvation, and exited the experiment.
On the sixth day of starvation, a male member of the group just gave up, and said that they
had no chance of getting any more food. He then exited the experiment.
Fortunately, on the seventh day of starvation, the four group members that still had the
energy and optimism to hunt, actually killed an elk using their caveman spears. To
everyone's surprise, the vegetarian woman refused to eat the meat, and - had the experiment
run
longer
than
10 days - would have starved to death.
When you watch the video of this caveman experiment, you can see practically all of the
symptoms of major depressive disorder appear. By the fourth day of starvation, all the group
had developed severe fatigue, insomnia, hunger, apathy, and half the group developed
crippling
pessimism. Those that exited the experiment had developed marked loneliness and social
withdrawal. In addition, the woman that exited the group had developed emotional
instability. The vegetarian's meat-refusal, even if it meant her starvation, could be
interpreted as
perfectionism and inflexibility. By the 7th day of starvation, 4 group members were still
functional (and saved the group by going hunting), and the other 4 remaining members were
dysfunctional and so fatigued and apathetic that all they could do is stay in the camp and
lie
down.
So What Causes Major Depressive Disorder?
This disorder can be triggered by exposure to any major physical, psychological, or social
adversity. So depression can be triggered by a physical illness or stress, an addiction to
alcohol or drugs, or a significant psychological or social stress. It appears that
depression
is
nature's way of shutting down the body (similar to hibernation).
Many animals hibernate during adversity (e.g., during foodless winter, frogs and bears
hibernate; during the foodless summer dry season of Madagascar, the dwarf lemur hibernates).
In terms of survival, hibernation or "shutting down" makes sense if there is nothing more
you can do in the face of adversity. However, if this ancient hibernation or "shutting down"
circuit in the brain becomes active at an inappropriate time, the resulting depression
could prove disastrous.
Medical
Differential Diagnosis (Medical Illnesses Similar To Major Depressive Disorder)
Single episode depressive disorder is characterized by the presence or history of one
depressive episode when there is no history of prior depressive episodes.
A depressive episode is characterized by a period of almost daily depressed mood
or diminished interest in activities lasting at least two weeks accompanied by other
symptoms such as difficulty concentrating, feelings of worthlessness or excessive or
inappropriate guilt, hopelessness, recurrent thoughts of death or suicide, changes in
appetite or sleep, psychomotor agitation or retardation, and reduced energy or
fatigue.
There have never been any prior manic, hypomanic, or mixed episodes, which would
indicate the presence of a bipolar disorder.
This is diagnosed when the definitional requirements of a depressive episode
are met and the episode is of mild severity. None of the symptoms of the
depressive episode should be present to an intense degree.
An individual with a mild depressive episode typically has some, but not
considerable, difficulty in continuing with ordinary work, social, or domestic
activities and there are no delusions or hallucinations.
This is diagnosed when the definitional requirements of a depressive episode
have been met, there is no history of prior depressive episodes, the episode
is of moderate severity, and there are no delusions or hallucinations during the
episode.
In a moderate depressive episode, several symptoms of a depressive
episode are present to a marked degree, or a large number of depressive
symptoms of lesser severity are present overall.
An individual with a moderate depressive episode typically has considerable
difficulty in continuing with work, social, or domestic activities, but is still
able to function in at least some areas.
This is diagnosed when the definitional requirements of a depressive episode
have been met, there is no history of prior depressive episodes, the episode
is of moderate severity, and there are delusions or hallucinations during the
episode.
In a moderate depressive episode, several symptoms of a depressive
episode are present to a marked degree, or a large number of depressive
symptoms of lesser severity are present overall.
An individual with a moderate depressive episode typically has considerable
difficulty in continuing with work, social, or domestic activities, but is still
able to function in at least some areas.
This is diagnosed when the definitional requirements of a depressive episode
have been met, the current episode is severe, and there are no delusions or
hallucinations during the episode.
In a severe depressive episode, many or most symptoms of a depressive episode are
present to a marked degree, or a smaller number of symptoms are present and manifest
to an intense degree and the individual is unable to function in personal, family,
social, educational, occupational, or other important domains, except to a very
limited degree.
This is diagnosed when the definitional requirements of a depressive episode
have been met, the current episode is severe, and there are delusions or
hallucinations during the episode.
In a severe depressive episode, many or most symptoms of a depressive episode are
present to a marked degree, or a smaller number of symptoms are present and manifest
to an intense degree and the individual is unable to function in personal, family,
social, educational, occupational, or other important domains, except to a very
limited degree.
This is diagnosed when the full definitional requirements for a depressive episode
have been met and there is no history of prior depressive episodes. The full
definitional requirements for a depressive episode are no longer met but some
significant mood symptoms remain.
This is diagnosed when the full definitional requirements for one depressive episode
have been met in the past and there are no longer any significant mood symptoms.
There is no history of depressive episodes preceding the episode under
consideration.
Recurrent depressive disorder is characterized by a history of at least two
depressive episodes separated by at least several months without significant mood
disturbance.
A depressive episode is characterized by a period of almost daily depressed mood
or diminished interest in activities lasting at least two weeks accompanied by other
symptoms such as difficulty concentrating, feelings of worthlessness or excessive or
inappropriate guilt, hopelessness, recurrent thoughts of death or suicide, changes in
appetite or sleep, psychomotor agitation or retardation, and reduced energy or
fatigue.
There have never been any prior manic, hypomanic, or mixed episodes, which would
indicate the presence of a bipolar disorder.
This is dignosed when the definitional requirements for recurrent depressive
disorder have been met and there is currently a depressive episode of mild
severity. None of the symptoms of the depressive episode should be present to
an intense degree.
An individual with a mild depressive episode typically has some, but not
considerable, difficulty in continuing with ordinary work, social, or domestic
activities and there are no delusions or hallucinations.
This is diagnosed the definitional requirements for recurrent depressive disorder
have been met and there is currently a depressive episode of moderate
severity, and there are no delusions or hallucinations during the episode.
In a moderate depressive episode, several symptoms of a depressive
episode are present to a marked degree, or a large number of depressive
symptoms of lesser severity are present overall.
An individual with a moderate depressive episode typically has considerable
difficulty in continuing with work, social, or domestic activities, but is still
able to function in at least some areas.
This is diagnosed when the definitional requirements of a recurrent depressive
disorder have been met, the episode is of moderate severity, and there are delusions
or hallucinations during the episode.
In a moderate depressive episode, several symptoms of a depressive
episode are present to a marked degree, or a large number of depressive
symptoms of lesser severity are present overall.
An individual with a moderate depressive episode typically has considerable
difficulty in continuing with work, social, or domestic activities, but is still
able to function in at least some areas.
This is diagnosed when the definitional requirements of a recurrent depressive
disorder have been met, the current episode is severe, and there are no
delusions or hallucinations during the episode.
In a severe depressive episode, many or most symptoms of a depressive episode
are present to a marked degree, or a smaller number of symptoms are present and
manifest to an intense degree and the individual is unable to function in personal,
family, social, educational, occupational, or other important domains, except to a
very limited degree.
This is diagnosed when the definitional requirements of a recurrent depressive
disorder have been met, the current episode is severe, and there are delusions or
hallucinations during the episode.
In a severe depressive episode, many or most symptoms of a depressive episode
are present to a marked degree, or a smaller number of symptoms are present and
manifest to an intense degree and the individual is unable to function in personal,
family, social, educational, occupational, or other important domains, except to a
very limited degree.
This is diagnosed when the definitional requirements for recurrent depressive
disorder have been met; the full definitional requirements for a depressive
episode are no longer met but some significant mood symptoms remain.
This is diagnosed when the definitional requirements for recurrent depressive
disorder have been met but currently there are no significant mood symptoms.
An individual diagnosed with major depressive disorder needs to meet all of the
following criteria:
Five (or more) of the following symptoms have been present during the same
2-week period and represent a change from previous functioning; at least one of
the symptoms is either (1) depressed mood or (2) loss of interest or
pleasure.
Note: Do not include symptoms that are clearly attibutable to another
medical condition.
Depressed mood most of the day, nearly every day, as indicated by either
subjective report (e.g., feels sad, empty, hopeless) or observation made by
others (e.g., appears tearful). (Note: In children and adolescents,
can be irritable mood.)
Markedly diminished interest or pleasure in all, or almost all, activities
most of the day, nearly every day (as indicated by either subjective account
or observation).
Significant weight loss when not dieting or weight gain (e.g., a change of
more than 5% of body weight in a month), or decrease or increase in appetite
nearly every day. (Note: In children, consider failure to make
expected weight gain.)
Insomnia or hypersomnia nearly every day.
Psychomotor agitation or retardation nearly every day (observable by others,
not merely subjective feelings of restlessness or being slowed down).
Fatigue or loss of energy nearly every day.
Feelings of worthlessness or excessive or inappropriate guilt (which may be
delusional) nearly every day (not merely self-reproach or guilt about being
sick).
Diminished ability to think or concentrate, or indecisiveness, nearly every
day (either by subjective account or as observed by others).
Recurrent thoughts of death (not just fear of dying), recurrent suicidal
ideation without a specific plan, or a suicide attempt or a specific plan
for committing suicide.
The symptoms cause clinically significant distress or impairment in social,
occupational, or other important areas of functioning.
The episode is not attributable to the physiological effects of a substance or
to another medical condition.
Note: The above criteria represent a major depressive episode.
Note: Responses to a significant loss (e.g., bereavement, financial ruin,
losses from a natural disaster, a serious medical illness or disability) may
include the feelings of intense sadness, rumination about the loss, insomnia,
poor appetite, and weight
loss
noted in the above criteria, which may resemble a depressive episode.
Although such symptoms may be understandable or considered appropriate to the
loss, the presence of a major depressive episode in addition to the normal
response to a significant loss should also be carefully considered.
This decision inevitably requires the exercise of clinical judgment based on the
individual's history and the cultural norms for the expression of distress in
the context of loss.
The occurrence of the major depressive episode is not better explained by
schizoaffective disorder, schizophrenia, schizophreniform disorder, delusional
disorder, or other specified and unspecified schizophrenia spectrum and other
psychotic disorders.
There has never been a manic episode or a hypomanic episode.
Note: This exclusion does not apply if all of the manic-like or
hypomanic-like episodes are substance-induced or are attributable to the
physiological effects of another medical condition.
Rating Scheme for the Strength of the Recommendations
Each recommendation is identified as falling into one of three categories of
endorsement, indicated by a bracketed Roman numeral following the statement. The three
categories represent varying levels of clinical confidence:
[I] Recommended with substantial clinical confidence.
[II] Recommended with moderate clinical confidence.
[III] May be recommended on the basis of individual circumstances.
Major Recommendations
Provide Education to the Patient and the Family
With the patient's permission, family members and others involved in the
patient's day-to-day life may also benefit from education about the illness, its
effects on functioning (including family and other interpersonal relationships),
and its treatment [I].
Common misperceptions about antidepressants (e.g., they are addictive) should be
clarified [I].
In addition, education about major depressive disorder should address the need
for a full acute course of treatment, the risk of relapse, the early recognition
of recurrent symptoms, and the need to seek treatment as early as possible to
reduce the risk of
complications
or a full-blown episode of major depression [I].
Patients should also be told about the need to taper antidepressants, rather
than discontinuing them precipitously, to minimize the risk of withdrawal
symptoms or symptom recurrence [I].
Patient education also includes general promotion of healthy behaviors such as
exercise, good sleep hygiene, good nutrition, and decreased use of tobacco,
alcohol, and other potentially deleterious substances [I].
Educational tools such as books, pamphlets, and trusted web sites can augment
the face-to-face education provided by the clinician [I].
Treatment Of Acute Phase Of Major Depressive Disorder
Pharmacotherapy
An antidepressant medication is recommended as an initial treatment choice for
patients with mild to moderate major depressive disorder [I] and definitely
should be provided for those with severe major depressive disorder unless ECT is
planned [I].
Because the effectiveness of antidepressant medications is generally comparable
between classes and within classes of medications, the initial selection of an
antidepressant medication will largely be based on the anticipated side effects,
and additional factors
such
as
medication response in prior episodes, cost, and patient preference [I].
For most patients, a selective serotonin reuptake inhibitor (SSRI), serotonin
norepinephrine reuptake inhibitor (SNRI), mirtazapine, or bupropion is optimal
[I].
In general, the use of nonselective monoamine oxidase inhibitors (MAOIs) (e.g.,
phenelzine, tranylcypromine, isocarboxazid) should be restricted to patients who
do not respond to other treatments [I], given the necessity for dietary
restrictions with these
medications
and
the potential for deleterious drug-drug interactions.
In patients who prefer complementary and alternative therapies,
S-adenosyl methionine (SAMe) [III] or St. John's wort [III] might be
considered, although evidence for their efficacy is modest at best.
Careful attention to drug-drug interactions is needed with St. John's wort [I].
Patients receiving pharmacotherapy should be systematically monitored on a
regular basis to assess their response to treatment and assess patient safety
[I].
If antidepressant side effects do occur, an initial strategy is to lower the
dose of the antidepressant or to change to an antidepressant that is not
associated with that side effect [I].
Other Somatic Therapies
ECT is recommended as a treatment of choice for patients with severe major
depressive disorder that is not responsive to psychotherapeutic and/or
pharmacological interventions, particularly in those who have significant
functional impairment or have not responded
to
numerous medication trials [I].
ECT is also recommended for individuals with major depressive disorder who have
associated psychotic or catatonic features [I], for those with an urgent need
for response (e.g., patients who are suicidal or nutritionally compromised due
to refusal of food or
fluids)
[I],
and for those who prefer ECT or have had a previous positive response to ECT
[II].
Bright light therapy might be used to treat seasonal affective disorder
as well as nonseasonal depression [III].
Psychotherapy
Use of a depression-focused psychotherapy alone is recommended as an initial
treatment choice for patients with mild to moderate major depressive disorder
[I], with clinical evidence supporting the use of cognitive-behavioral therapy
(CBT) [I], interpersonal
psychotherapy
[I], psychodynamic therapy [II], and problem-solving therapy [III] in individual
[I] and in group [III] formats.
In women who are pregnant, wish to become pregnant, or are breastfeeding, a
depression-focused psychotherapy alone is recommended [II] and depending on the
severity of symptoms, should be considered as an initial option [I].
As with patients who are receiving pharmacotherapy, patients receiving
psychotherapy should be carefully and systematically monitored on a regular
basis to assess their response to treatment and assess patient safety [I].
Marital and family problems are common in the course of major depressive
disorder, and such problems should be identified and addressed, using
marital or family therapy when indicated [II].
The combination of psychotherapy and antidepressant medication may be used as an
initial treatment for patients with moderate to severe major depressive disorder
[I].
Combining psychotherapy and medication may be a useful initial treatment
even in milder cases for patients with psychosocial or interpersonal
problems, intrapsychic conflict, or co-occurring personality disorder [II].
Assessing the Adequacy of Treatment Response
Onset of benefit from psychotherapy tends to be a bit more gradual than that
from medication, but no treatment should continue unmodified if there has been
no symptomatic improvement after 1 month [I].
Generally, 4-8 weeks of treatment are needed before concluding that a
patient is partially responsive or unresponsive to a specific intervention
[II].
Strategies to Address Nonresponse
For individuals who have not responded fully to treatment, the acute phase of
treatment should not be concluded prematurely [I], as an incomplete response to
treatment is often associated with poor functional outcomes.
If at least a moderate improvement in symptoms is not observed within 4-8 weeks
of treatment initiation, the diagnosis should be reappraised, side effects
assessed, complicating co-occurring conditions and psychosocial factors
reviewed, and the treatment plan
adjusted
[I]. It is also important to assess the quality of the therapeutic alliance and
treatment adherence [I].
For patients in psychotherapy, additional factors to be assessed include the
frequency of sessions and whether the specific approach to psychotherapy is
adequately addressing the patient's needs [I].
With some TCAs, a drug blood level can help determine if additional dose
adjustments are required [I].
For patients treated with an antidepressant, optimizing the medication dose
is a reasonable first step if the side effect burden is tolerable and the
upper limit of a medication dose has not been reached [II].
Particularly for those who have shown minimal improvement or experienced
significant medication side effects, other options include augmenting the
antidepressant with a depression-focused psychotherapy [I] or with other agents
[II] or changing to another non-MAOI
antidepressant [I].
Patients may be changed to an antidepressant from the same pharmacological
class (e.g., from one SSRI to another SSRI) or to one from a different class
(e.g., from an SSRI to a tricyclic antidepressant [TCA]) [II].
For patients who have not responded to trials of SSRIs, a trial of an SNRI
may be helpful [II].
Augmentation of antidepressant medications can utilize another non-MAOI
antidepressant [II], generally from a different pharmacological class, or a
non-antidepressant medication such as lithium [II], thyroid hormone [II], or
a second-generation antipsychotic
[II].
Additional strategies with less evidence for efficacy include
augmentation using an anticonvulsant [III], omega-3 fatty acids [III],
folate [III], or a psychostimulant medication [III], including modafinil
[III].
If anxiety or insomnia are prominent features, consideration can be
given to anxiolytic and sedative-hypnotic medications [III], including
buspirone, benzodiazepines, and selective gamma-aminobutyric acid (GABA)
agonist hypnotics (e.g., zolpidem,
eszopiclone).
For patients whose symptoms have not responded adequately to medication, ECT
remains the most effective form of therapy and should be considered [I].
In patients capable of adhering to dietary and medication restrictions, an
additional option is changing to a nonselective MAOI [II] after allowing
sufficient time between medications to avoid deleterious interactions [I].
Transdermal selegiline, a relatively selective MAO B inhibitor with fewer
dietary and medication restrictions, or transcranial magnetic stimulation
could also be considered [II].
Vagus nerve stimulation (VNS) may be an additional option for
individuals who have not responded to at least four adequate trials of
antidepressant treatment, including ECT [III].
For patients treated with psychotherapy, consideration should be given to
increasing the intensity of treatment or changing the type of therapy [II]. If
psychotherapy is used alone, the possible need for medications in addition to or
in lieu of psychotherapy
should be
assessed [I].
Patients who have a history of poor treatment adherence or incomplete
response to adequate trials of single treatment modalities may benefit from
combined treatment with medication and a depression-focused psychotherapy
[II].
Treatment Of Continuation Phase Of Major Depressive Disorder
During the continuation phase of treatment, the patient should be carefully
monitored for signs of possible relapse [I].
Systematic assessment of symptoms, side effects, adherence, and functional
status is essential [I] and may be facilitated through the use of clinician-
and/or patient-administered rating scales [II].
To reduce the risk of relapse, patients who have been treated successfully with
antidepressant medications in the acute phase should continue treatment with
these agents for 4-9 months [I].
In general, the dose used in the acute phase should be used in the
continuation phase [II].
To prevent a relapse of depression in the continuation phase, depression-focused
psychotherapy is recommended [I], with the best evidence available for
cognitive-behavioral therapy.
Patients who respond to an acute course of ECT should receive continuation
pharmacotherapy [I], with the best evidence available for the combination of
lithium and nortriptyline. Alternatively, patients who have responded to an
acute course of ECT may be given
continuation ECT, particularly if medication or psychotherapy has been
ineffective in maintaining remission [II].
Treatment Of Maintenance Phase Of Major Depressive Disorder
In order to reduce the risk of a recurrent depressive episode, patients who have
had three or more prior major depressive episodes or who have chronic major
depressive disorder should proceed to the maintenance phase of treatment after
completing the continuation
phase
[I].
Maintenance therapy should also be considered for patients with additional
risk factors for recurrence, such as the presence of residual symptoms,
ongoing psychosocial stressors, early age at onset, and family history of
mood disorders [II].
For many patients, particularly for those with chronic and recurrent major
depressive disorder or co-occurring medical and/or psychiatric disorders, some
form of maintenance treatment will be required indefinitely [I].
During the maintenance phase, an antidepressant medication that produced
symptom remission during the acute phase and maintained remission during the
continuation phase should be continued at a full therapeutic dose [II].
If a depression-focused psychotherapy has been used during the acute and
continuation phases of treatment, maintenance treatment should be
considered, with a reduced frequency of sessions [II].
For patients whose depressive episodes have not previously responded to
acute or continuation treatment with medications or a depression-focused
psychotherapy but who have shown a response to ECT, maintenance ECT may
be considered [III].
Maintenance treatment with vagus nerve stimulation is also appropriate
for individuals whose symptoms have responded to this treatment modality
[III].
Due to the risk of recurrence, patients should be monitored systematically
and at regular intervals during the maintenance phase [I]. Use of
standardized measurement aids is recommended for the early detection of
recurrent symptoms [II].
Discontinuation of Treatment
When pharmacotherapy is being discontinued, it is best to taper the medication
over the course of at least several weeks [I].
To minimize the likelihood of discontinuation symptoms, patients should be
advised not to stop medications abruptly and to take medications with them when
they travel or are away from home [I].
A slow taper or temporary change to a longer half-life antidepressant (e.g.,
fluoxetine) may reduce the risk of discontinuation syndrome [II] when
discontinuing antidepressants or reducing antidepressant doses.
Before the discontinuation of active treatment, patients should be informed of
the potential for a depressive relapse and a plan should be established for
seeking treatment in the event of recurrent symptoms [I].
After discontinuation of medications, patients should continue to be monitored
over the next several months and should receive another course of adequate acute
phase treatment if symptoms recur [I].
For patients receiving psychotherapy, it is important to raise the issue of
treatment discontinuation well in advance of the final session [I], although the
exact process by which this occurs will vary with the type of therapy.
Clinical Factors Influencing Treatment
Psychiatric Factors
Factors to consider in determining the nature and intensity of treatment include
(but are not limited to) the nature of the doctor-patient alliance, the
availability and adequacy of social supports, access to and lethality of suicide
means, the presence of a
co-occurring
substance use disorder, and past and family history of suicidal behavior [I].
For suicidal patients, psychiatrists should consider an increased intensity of
treatment, including hospitalization when warranted [I] and/or combined
treatment with pharmacotherapy and psychotherapy [II].
For patients who exhibit psychotic symptoms during an episode of major
depressive disorder, treatment should include a combination of antipsychotic and
antidepressant medications or ECT [I].
When patients exhibit cognitive dysfunction during a major depressive episode,
they may have an increased likelihood of future dementia, making it important to
assess cognition in a systematic fashion over the course of treatment [I].
Catatonic features that occur as part of a major depressive episode should be
treated with a benzodiazepine [I] or barbiturate [II], typically in conjunction
with an antidepressant [II]. If catatonic symptoms persist, ECT is recommended
[I]. To reduce the
likelihood
of
general medical complications, patients with catatonia may also require
supportive medical interventions, such as hydration, nutritional support,
prophylaxis against deep vein thrombosis, turning to reduce risks of decubitus
ulcers, and passive range of motion to
reduce
risk of contractures [I]. If antipsychotic medication is needed, it is important
to monitor for signs of neuroleptic malignant syndrome, to which patients with
catatonia may have a heightened sensitivity [II].
Benzodiazepines may be used adjunctively in individuals with major
depressive disorder and co-occurring anxiety [II], although these agents do
not treat depressive symptoms, and careful selection and monitoring is
needed in individuals with co-occurring
substance
use
disorders [I].
In patients who smoke, bupropion [I] or nortriptyline [II] may be options to
simultaneously treat depression and assist with smoking cessation.
When possible, a period of substance abstinence can help determine whether
the depressive episode is related to substance intoxication or withdrawal
[II]. Factors that suggest a need for antidepressant treatment soon after
cessation of substance use include a
family
history of major depressive disorder and a history of major depressive
disorder preceding the onset of the substance use disorder or during periods
of sobriety [II].
For patients who have a personality disorder as well as major depressive
disorder, psychiatrists should institute treatment for the major depressive
disorder [I] and consider treatment for personality disorder symptoms [II].
Demographic and Psychosocial Factors
When prescribing medications to women who are taking oral contraceptives, the
potential effects of drug-drug interactions must be considered [I].
For women in the perimenopausal period, SSRI and SNRI antidepressants are
useful in ameliorating depression as well as in reducing somatic symptoms
such as hot flashes [II].
Both men and women who are taking antidepressants should be asked whether sexual
side effects are occurring with these medications [I]. Men for whom trazodone is
prescribed should be warned of the risk of priapism [I].
For women who are currently receiving treatment for depression, a pregnancy
should be planned, whenever possible, in consultation with the treating
psychiatrist, who may wish to consult with a specialist in perinatal psychiatry
[I].
In women who are pregnant, planning to become pregnant, or breast-feeding,
depression-focused psychotherapy alone is recommended [II] and should always
be considered as an initial option, particularly for mild to moderate
depression, for patients who prefer
psychotherapy, or for those with a prior positive response to psychotherapy
[I].
Antidepressant medication should be considered for pregnant women who have
moderate to severe major depressive disorder as well as for those who are in
remission from major depressive disorder, are receiving maintenance
medication, and are deemed to be at high
risk
for a recurrence if the medication is discontinued [II].
When antidepressants are prescribed to a pregnant woman, changes in
pharmacokinetics during pregnancy may require adjustments in medication doses
[I].
Electroconvulsive therapy may be considered for the treatment of depression
during pregnancy in patients who have psychotic or catatonic features, whose
symptoms are severe or have not responded to medications, or who prefer
treatment with ECT [II].
When a woman decides to nurse, the potential benefits of antidepressant
medications for the mother should be balanced against the potential risks to the
newborn from receiving antidepressant in the mother's milk [I].
For women who are depressed during the postpartum period, it is important to
evaluate for the presence of suicidal ideas, homicidal ideas, and psychotic
symptoms [I]. The evaluation should also assess parenting skills for the newborn
and for other children in the
patient's care [I].
In individuals with late-life depression, identification of co-occurring general
medical conditions is essential, as these disorders may mimic depression or
affect choice or dosing of medications [I]. Older individuals may also be
particularly sensitive to
medication
side
effects (e.g., hypotension, anticholinergic effects) and require adjustment of
medication doses for hepatic or renal dysfunction [I]. In other respects,
treatment for depression should parallel that used in younger age groups [I].
When antidepressants are prescribed, the psychiatrist should recognize that
ethnic groups may differ in their metabolism and response to medications
[II].
A family history of bipolar disorder or acute psychosis suggests a need for
increased attention to possible signs of bipolar illness in the patient (e.g.,
with antidepressant treatment) [I].
A family history of recurrent major depressive disorder increases the
likelihood of recurrent episodes in the patient and supports a need for
maintenance treatment [II].
Family history of a response to a particular antidepressant may
sometimes help in choosing a specific antidepressant for the patient
[III].
Because problems within the family may become an ongoing stressor that
hampers the patient's response to treatment, and because depression in a
family is a major stress in itself, such factors should be identified and
strong consideration given to educating
the
family
about the nature of the illness, enlisting the family's support, and
providing family therapy, when indicated [II].
For patients who have experienced a recent bereavement, psychotherapy or
antidepressant treatment should be used when the reaction to a loss is
particularly prolonged or accompanied by significant psychopathology and
functional impairment [I].
Support groups may be helpful for some bereaved individuals [III].
Co-occurring General Medical Conditions
Communication with other clinicians who are providing treatment for general
medical conditions is recommended [I].
The clinical assessment should include identifying any potential interactions
between medications used to treat depression and those used to treat general
medical conditions [I].
Assessment of pain is also important as it can contribute to and co-occur with
depression [I]. In addition, the psychiatrist should consider the effects of
prescribed psychotropic medications on the patient's general medical conditions,
as well as the effects of
interventions for such disorders on the patient's psychiatric condition [I].
In patients with preexisting hypertension or cardiac conditions, treatment with
specific antidepressant agents may suggest a need for monitoring of vital signs
or cardiac rhythm (e.g., electrocardiogram [ECG] with TCA treatment; heart rate
and blood pressure
assessment
with SNRIs and TCAs) [I].
When using antidepressant medications with anticholinergic side effects, it is
important to consider the potential for increases in heart rate in individuals
with cardiac disease, worsening cognition in individuals with dementia,
development of bladder outlet
obstruction
in men with prostatic hypertrophy, and precipitation or worsening of narrow
angle glaucoma [I].
Some antidepressant drugs (e.g., bupropion, clomipramine, maprotiline)
reduce the seizure threshold and should be used with caution in individuals
with preexisting seizure disorders [II].
In individuals with Parkinson's disease, the choice of an antidepressant
should consider that serotonergic agents may worsen symptoms of the disease
[II], that bupropion has potential dopamine agonist effects (benefitting
symptoms of Parkinson's disease but
potentially worsening psychosis) [II], and that selegiline has
antiparkinsonian and antidepressant effects but may interact with L-dopa and
with other antidepressant agents [I].
In treating the depressive syndrome that commonly occurs following a stroke,
consideration should be given to the potential for interactions between
antidepressants and anticoagulating (including antiplatelet) medications [I].
Given the health risks associated with obesity and the tendency of some
antidepressant medications to contribute to weight gain, longitudinal monitoring
of weight (either by direct measurement or patient report) is recommended [I],
as well as calculation of body
mass
index (BMI) [II]. If significant increases are noted in the patient's weight or
BMI, the clinician and patient should discuss potential approaches to weight
control such as diet, exercise, change in medication, nutrition consultation, or
collaboration with the
patient's
primary care physician [I].
In patients who have undergone bariatric surgery to treat obesity, adjustment of
medication formulations or doses may be required because of altered medication
absorption [I].
For diabetic patients, it is useful to collaborate with the patient's
primary care physician in monitoring diabetic control when initiating
antidepressant therapy or making significant dosing adjustments [II].
Clinicians should be alert to the possibility of sleep apnea in patients with
depression, particularly those who present with daytime sleepiness, fatigue, or
treatment-resistant symptoms [II]. In patients with known sleep apnea, treatment
choice should consider
the
sedative side effects of medication, with minimally sedating options chosen
whenever possible [I].
Given the significant numbers of individuals with unrecognized human
immunodeficiency virus (HIV) infection and the availability of effective
treatment, consideration should be given to HIV risk assessment and screening
[I]. For patients with HIV infection who are
receiving antiretroviral therapy, the potential for drug-drug interactions needs
to be assessed before initiating any psychotropic medications [I]. Patients who
are being treated with antiretroviral medications should be cautioned about
drug-drug interactions with
St.
John's wort that can reduce the effectiveness of HIV treatments [I].
In patients with hepatitis C infection, interferon can exacerbate depressive
symptoms, making it important to monitor patients carefully for worsening
depressive symptoms during the course of interferon treatment [I].
Because tamoxifen requires active 2D6 enzyme function to be clinically
efficacious, patients who receive tamoxifen for breast cancer or other
indications should generally be treated with an antidepressant (e.g.,
citalopram, escitalopram, venlafaxine,
desvenlafaxine)
that
has minimal effect on metabolism through the cytochrome P450 2D6 isoenzyme [I].
When depression occurs in the context of chronic pain, SNRIs and TCAs may be
preferable to other antidepressive agents [II].
When ECT is used to treat major depressive disorder in an individual with a
co-occurring general medical condition, the evaluation should identify
conditions that could require modifications in ECT technique (e.g., cardiac
conditions, hypertension, central nervous
system
lesions) [I]; these should be addressed insofar as possible and discussed with
the patient as part of the informed consent process [I].
[Editor: A few antidepressant medications have potentially severe withdrawal syndromes,
especially Paxil (paroxetine) and Effexor (venlafaxine). This video correctly reports
that physicians were not warned of these severe withdrawal syndromes. Most patients
never
experience
this problem if they slowly withdraw from Paxil or Effexor over 3 months. Often
simultaneously starting Prozac (fluoxetine) while withdrawing from Paxil or Effexor can
minimize this withdrawal syndrome. It should be remembered that 60% of severely
depressed individuals
recover on
antidepressant medication, and most antidepressant medications do not have severe
withdrawal syndromes.]
"The U.S. Food and Drug Administration approved Spravato (esketamine) nasal
spray, in conjunction with an oral antidepressant, for the treatment of
depression in adults who have tried other antidepressant medicines but have not
benefited from them (treatment-resistant depression). Because of the risk of
serious adverse outcomes resulting from sedation and dissociation caused by
Spravato administration, and the potential for abuse and misuse of the drug, it
is only available through a restricted distribution system, under a Risk
Evaluation and Mitigation Strategy (REMS).
The Spravato labeling contains a Boxed Warning that cautions that patients are
at risk for sedation and difficulty with attention, judgment and thinking
(dissociation), abuse and misuse, and suicidal thoughts and behaviors after
administration of the drug. Because of the risk of sedation and dissociation,
patients must be monitored by a health care provider for at least two hours
after receiving their Spravato dose. The REMS requires the prescriber and the
patient to both sign a Patient Enrollment Form that clearly states that the
patient understands they should make arrangements to safely leave the health
care setting to get home and that the patient should not drive or use heavy
machinery for the rest of the day on which they received the drug.
The efficacy of Spravato was evaluated in three short-term (four-week) clinical
trials and one longer-term maintenance-of-effect trial. In the three short-term
studies, patients were randomized to receive Spravato or a placebo nasal spray.
In light of the serious nature of treatment-resistant depression and the need
for patients to receive some form of treatment, all patients in these studies
started a new oral antidepressant at the time of randomization and the new
antidepressant was continued throughout the trials. The primary efficacy measure
was the change from baseline on a scale used to assess the severity of
depressive symptoms. In one of the short-term studies, Spravato nasal spray
demonstrated statistically significant effect compared to placebo on the
severity of depression, and some effect was seen within two days.
The two other short-term trials did not meet the
pre-specified statistical tests for demonstrating effectiveness
. In the longer-term maintenance-of-effect trial, patients in stable
remission or with stable response who continued treatment with Spravato
plus an oral antidepressant
experienced a statistically significantly longer time to relapse of
depressive symptoms than patients on placebo nasal spray plus an oral
antidepressant.
The most common side effects experienced by patients treated with Spravato in
the clinical trials were disassociation, dizziness, nausea, sedation, vertigo,
decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased
blood pressure, vomiting and feeling drunk.
Patients with unstable or poorly controlled hypertension or pre-existing
aneurysmal vascular disorders may be at increased risk for adverse
cardiovascular or cerebrovascular effects. Spravato may impair attention,
judgment, thinking, reaction speed and motor skills. Patients should not drive
or operate machinery until the next day after a restful sleep. Spravato may
cause fetal harm and women of reproductive potential should consider pregnancy
planning and prevention; women should not breastfeed while being treated.
Esketamine is the s-enantiomer of ketamine. Ketamine is a mixture of two
enantiomers (mirror image molecules)."
WARNING:
This FDA approval of ketamine for the treatment of severe depression was
based on the success of one longer-term maintenance-of-effect trial - despite
the failure of two other short-term trials.
Ketamine is an illegal hallucinogenic dance drug for clubbers. At a low dose, it
causes elation, and at higher doses it causes dissociation (i.e., an unreal,
trace-like state) and hallucinations. Long-term use and abuse of ketamine
is associated with liver inflammation, destruction of the bladder lining,
cognitive problems and other serious medical complications. Ethically, an
effective treatment for clinical depression must do more than make a patient
"feel good". All of the illegal drugs (e.g., heroin, crack cocaine) make people
"feel good" - at least initially. To be acceptable, a treatment for clinical
depression must also significantly improve the depressed patient's ability to
work, love and play - in addition to being nonaddictive and medically safe. The
government approved treatments for depression should differ from addictive,
illegal "recreational drugs".
Remember that nearly every US state is now suing OxyContin maker Purdue
Pharma because Purdue Pharma fraudulantly claimed that OxyContin was
nonaddictive. It turned out that OxyContin was highly addictive and its
widespread prescription triggered the current opioid crisis. The acute
antidepressant effects of ketamine are blocked when the patient is
pretreated with oral naltrexone, indicating that ketamine acts like an opioid. Ketamine is addictive,
thus it is essential that physicians not repeat the mistake that was made with
OxyContin. The addiction potential of ketamine and esketamine requires more
long-term scientific study before these opioid-like medications receive
widespread use in the treatment of treatment resistent depression.
In the phase 3 study of the use of esketamine for the treatment of treatment
resistent depression (TRD), more than 200 adult patients with TRD were enrolled
at 39 sites in five countries. They were randomly assigned to receive daily for
4 weeks a newly initiated open-label, oral antidepressant plus either twice
weekly esketamine starting at 56 mg and possibly titrating up to 84 mg (n = 114)
or matching intranasal placebo (n = 109).
The newly initiated antidepressant was either duloxetine, escitalopram,
sertraline, or extended-released venlafaxine.
The mean baseline scores on the Montgomery–Åsberg Depression Rating Scale
(MADRS) were 37.0 for the experimental group and 37.3 for the placebo control
group; and follow-up continued for all patients to week 24.
The primary efficacy outcome was change on MADRS total score from baseline to
day 28. Results showed that the active treatment group had a significantly
greater change at this endpoint vs the placebo group (adjusted mean difference,
–4.0 points; 95% confidence interval [CI], –7.31 to –0.64; P = .02). The effect
size from baseline to day 28 was 0.3 which represents
only a mild treatment effect
.
Remission, which was defined as a total score of 12 or less at day 28 on the
MADRS, was achieved by 52.5% of the active treatment group vs 31.0% of the
placebo group (P = .001). A 50% improvement over baseline on the MADRS,
signifying the response rate, was achieved by 69.3% vs 52.0%, respectively.
Dizziness, dissociation, a distortion of the sense of taste, nausea, and vertigo
were the most commonly reported adverse events (AEs) in the esketamine group and
ranged from 20.9% to 26.1%. Although there was a transient increase in blood
pressure up to 40 minutes after each dose of esketamine was administered, it
commonly returned to normal ranges about an hour and a half after dosing.
IV ketamine has been shown to be effective for refractory depression but has not
been approved by the FDA. Ketamine has also been used for decades as a
recreational party drug.
Intranasal esketamine, on the other hand, represents a novel administration
method for ketamine. However:
Janssen provided just one successful short-term, double-blind trial of
esketamine. Two other short-term, double-blind trials were unsuccessful.
Thus
only one-third of the short-term, double-blind
trials were successful
- yet the FDA approved this medication.
A longer study is required in order to assess whether the long-term use
of intranasal esketamine can become addictive. (Remember that the highly
addictive property of OxyContin wasn't noticed until years after it was
approved by the FDA.)
The suicide risk of intranasal esketamine must be further investigated.
Another study of nasal esketamine reported that
3 patients committed suicide 4–20 days after their last dose of
esketamine (whereas none committed suicide in the placebo group). Two of
the patients who died by suicide showed no previous signs of suicidal
activity during the study prior to their esketamine withdrawal. This
suggests a protracted withdrawal reaction, as has been reported with
opioids. This represents
an alarmingly high rate of suicide
for patients withdrawing from nasal esketamine
treatment.
Another study showed that
relapse rates on discontinuing esketamine reached
40%
by 3–4 months even though patients were receiving other
antidepressants. This suggests that intranasal esketamine treatment will
have to be long-term - yet no long-term study beyond 60 weeks of its
safety has been conducted.
Stand Up For Mental
Health - Stand up comic David Granirer has established a very successful
training course in stand up comedy for mental health consumers. “We use comedy to
give mental health consumers a powerful voice and help reduce the stigma and
discrimination around mental illness,” says Granirer. “The idea is that laughing at
our setbacks raises us above them. It makes people go from despair to hope, and hope
is crucial to anyone struggling with adversity." David trains the comics via Skype
and then flies in at the end of the course to perform with the group. In this way,
David has established Stand Up For Mental Health comedy groups across North America.
Self-Blaming vs. Self-Compassion
Some individuals are constantly at war with themselves.
They believe: "I am stupid", "I am a failure", "Nothing goes right for me". They constantly
analyze themselves and their behavior for flaws. They are cynical and pessimistic. Because
of their gloomy, depressed or angry mood, they withdraw and socially isolate themselves.
This
lack of cooperation with others makes them feel even more hopeless, depressed or angry.
These individuals are at a high risk for developing Persistent Depressive Disorder or Major
Depressive Disorder. Healthy people are self-confident, optimistic, sociable, and feel
accepted and supported by friends. Individuals suffering from excessive self-blaming are
pessimistic,
socially withdrawn, and feel rejected by others.
If you suffer from excessive self-blaming; here are ways you can remedy this by learning
increased self-compassion and social cooperation:
Self-Confidence vs. Self-Blaming:
You must be kind towards yourself, instead of always blaming yourself for
everything. Accept and love yourself for who you are - with all your human
imperfections. You must strive to have a good opinion of yourself and your
abilities, and to be socially confident.
Quit
constantly comparing yourself to others.
Optimism vs. Pessimism:
Strive to replace your unrealistic, pessimistic, negative thinking with more
realistic, optimistic, positive thinking.
Sociality vs. Social Withdrawal:
In order to feel good, you have to do good. Thus to feel better, you have to get out
and help others (and remember to frequently smile).
Feeling Accepted vs. Feeling Rejected:
You can not control how other people behave towards you. All you can do is control
how you behave towards other people. Much of your life is not under your control;
hence you can not change it. You are only responsible for the small part of your
life which is under
your
control - the part you can change. Thus remain friendly and out-going - especially
towards people that haven't accepted you.
Monitoring Your Progress
NOTE: When each of the following presentations finish; you must exit
by manually closing its window in order to return to this webpage.
The Healthy Social Behavior Scale lists social behaviors that research has
found to be associated with healthy social relationships. You can keep score (totaling its
4-point scale answers) on a separate piece of paper to monitor your progress.
The Mental Health Scale lists behaviors and symptoms that research has found
to be associated with mental health (or disorder). You can keep score (totaling its 4-point
scale answers) on a separate piece of paper to monitor your progress.
The Life Satisfaction Scale lists the survey questions often used to measure
overall satisfaction with life. You can keep score (totaling its 4-point scale answers) on a
separate piece of paper to monitor your progress.
This website uses these 5 major dimensions of human behavior (i.e., Agreeableness,
Conscientiousness, Openness/Intellect, Extraversion/Sociability, and Emotional
Stability) to describe all mental disorders. This website adds one more dimension,
"Physical Health", to create the "Big 6" dimensions of mental health.
The behaviors of the "Five Factor Model of Personality" represent five adaptive functions
that are vital to human survival. For example, when one individual approaches another, the
individual must: (1) decide whether the other individual is friend or foe [
"Agreeableness"
], (2) decide if this represents safety or danger [
"Emotional Stability"
], (3) decide whether to approach or avoid the other individual [
"Extraversion/Sociability"
], (4) decide whether to proceed in a cautious or impulsive manner [
"Conscientiousness"
], and (5) learn from this experience [
"Openness/Intellect"
].
"In physical science a first essential step in the direction of learning any
subject is to find principles of numerical reckoning and practicable methods for
measuring some quality connected with it. I often say that
when you can measure what you are speaking about and express it in
numbers you know something about it; but when you cannot measure it,
when you cannot express it in numbers, your knowledge is of a meagre and
unsatisfactory kind: it may be the beginning of knowledge,
but you have scarcely, in your thoughts, advanced to the stage of science,
whatever the matter may be."
Lord Kelvin (1824 – 1907)
The best
summary on bad research is given by Laura Arnold in this TEDx lecture.
If you read nothing else about research, you owe it to
yourself to watch this short video - it is excellent!
The active placebo effect: 2300 years ago, the Greek Stoic philosophers
taught that it is not the objective event, but our subjective
judgment about the event, that determines our behavior. The active placebo
effect bears witness to this ancient wisdom.
Randomized Controlled Trial:
Ask: Was the trial randomized? Was the randomization
procedure described and was it appropriate?
The best research design is to have research subjects randomly assigned
to an experimental or control group. It is essential that confounding
factors be controlled for by having a control group or comparator condition
(no intervention, placebo, care as usual etc.).
Representative Sample:
Ask: Do the research subjects represent a normal
cross-section of the population being studied?
Many psychological research studies using university students are
flawed because their subjects are not representative of the normal
population since they are all W.E.I.R.D. (White, Educated, Intelligent,
Rich, and living in a Democracy).
Single Blind Trial:
Ask: Was the treatment allocation concealed?
It is essential that the research subjects are kept "blind" as to
whether they are in the experimental or control group (in order to control
for any placebo effects).
Double Blind Trial (Better Than Single Blind Trial):
Ask: Were blind outcome assessments conducted?
In a double blind study, neither the research subjects nor the outcome
assessors know if the research subject is in the experimental or control
group. This controls for both the placebo effect and assessor bias.
Baseline Comparability:
Ask: Were groups similar at baseline on prognostic
indicators?
The experimental and control groups must be shown to be comparable at
the beginning of the study.
Confounding Factors:
Ask: Were there factors, that weren't controlled for,
that could have seriously distorted the study's results?
For example, research studies on the effectiveness of mindfulness cognitive therapy in
preventing depressive relapse forgot to control for whether the research
subjects were also simultaneously receiving antidepressant medication or
other psychological treatments for depression.
Intervention Integrity:
Ask: Was the research study protocal strictly
followed?
The research subjects must be shown to be compliant (e.g., taking their
pills, attending therapy) and the therapists must be shown to be reliably
delivering the intervention (e.g., staying on the research protocol).
Statistical analysis:
Ask: Was a statistical power calculation described?
The study should discuss its statistical power analysis; that is
whether the study size is large enough to statistically detect a difference
between the experimental and control group (should it occur) and usually
this requires at least 50 research subjects in the study.
Ask: Are the results both statistically
significant and clinically significant?
Many medical research findings are statistically significant
(with a p-value <0.05), but they are not clinically significant
because the difference between the experimental and control groups is
too small to be clinically relevant.
For example, the effect of a
new drug may be found to be 2% better than placebo. Statistically (if
the sample size was large enough) this 2% difference could be
statistically significant (with a p-value <0.05). However,
clinicians would say that this 2% difference is not
clinically significant (i.e., that it was too small to really
make any difference).
Statistically, the best way to test for
clinical significance is to test for effect size (i.e., the
size of the difference between two groups rather than confounding
this with statistical probability).
When the outcome of
interest is a dichotomous variable, the commonly used measures of
effect size include the odds ratio (OR), the relative risk (RR), and
the risk difference (RD).
When the outcome is a continuous
variable, then the effect size is commonly represented as either the
mean difference (MD) or the standardised mean difference (SMD)
.
The MD is the difference in the means of the treatment
group and the control group, while the SMD is the MD divided by the
standard deviation (SD), derived from either or both of the groups.
Depending on how this SD is calculated, the SMD has several versions
such, as Cohen's d, Glass's Δ, and Hedges' g.
Clinical Significance: With Standard Mean Difference, the
general rule of thumb is that a score of 0 to 0.25 indicates
small to no effect, 0.25-0.50 a mild benefit, 0.5-1 a moderate
to large benefit, and above 1.0 a huge benefit. It is a
convention that a SMD of
0.5
or larger is a standard threshold for clinically
meaningful benefit.
The statistical summary
should report what percentage of the total variance of the dependent
variable (e.g., outcome) can be explained by the independent
variable (e.g., intervention).
In clinical studies, the study
should report the number needed to treat for an additional
beneficial outcome (NNTB), and the number needed to treat for
an additional harmful outcome (NNTH).
Number Needed To Benefit (NNTB): This is defined as the
number of patients that need to be treated for one of them to
benefit compared with a control in a clinical trial. (It is
defined as the inverse of the absolute risk reduction.)
Note: Statistically, the NNTB depends on which control group is used for
comparison - e.g., active treatment vs. placebo
treatment, or active treatment vs. no
treatment.
Number Needed To Harm (NNTH): This is
defined as the number of patients that need to be treated for
one of them to be harmed compared with a control in a clinical
trial. (It is defined as the inverse of the absolute increase in
risk.)
Ask: Does the researcher accept full
responsibility for the study's statistical analysis?
The researcher should not just hand over the study's raw
data to a corporation (that may have $1,000 million invested in the
study) to do the statistical analysis.
Completeness of follow-up data:
Ask: Was the number of withdrawals or dropouts in each
group mentioned, and were reasons given for these withdrawals or
dropouts?
Less than 20% of the research subjects should drop out of the study.
The intervention effect should persist over an adequate length of time.
Handling of missing data:
Ask: Was the statistical analysis conducted on the
intention-to-treat sample?
There must be use of intention-to-treat analysis (as opposed to a
completers-only analysis). In this way, all of the research subjects that
started the study are included in the final statistical analysis. A
completers-only analysis would disregard those research subjects that
dropped out.
Replication of Findings:
Ask: Can other researchers replicate this study's
results?
The research study's methodology should be clearly described so that
the study can be easily replicated. The researcher's raw data should be
available to other researchers to review (in order to detect errors or
fraud).
Fraud:
Ask: Is there a suspicion of fraud?
In a research study, examine the independent and dependent variables
that are always measured as a positive whole number (e.g., a variable
measured on a 5-point Likert-type scale ranging from "1 = definitely
false to 5 = definitely true" etc.). For each of these
variables, look at their sample size (
n
), mean (
M
) and standard deviation (
SD
) before they undergo statistical analysis. There is a high suspicion of
fraud in a study's statistics:
If the M is mathematically impossible (online
calculator): This is one of the easiest ways to
mathematically detect fraud. The mean (
M
) is defined as "the sum (
Sum
) of the values of each observation divided by the total number
(
n
) of observations". So:
M
=
Sum
/
n
. Thus: (
Sum
) = (
M
) multiplied by (
n
). We know that, if a variable is always measured as a positive
whole number, the sum of these observations always has to be a whole
number. For these variables to test for fraud: calculate (
M
) multiplied by (
n
). This calculates the
Sum
which MUST be a positive whole number. If the calculated
Sum
isn't a positive whole number; the reported mean (
M
) is mathematically impossible - thus the researcher either
cooked the data or made a mistake. A recent study of 260 research papers
published in highly reputable psychological journals found that
1 in 2 of these research papers reported at
least one impossible value
, and 1 in 5 of these research papers reported multiple
impossible values. When the authors of the 21 worst offending
research papers were asked for their raw data (so that its
reliability could be checked) - 57% angrily refused. Yet such
release of raw data to other researchers is required by most
scientific journals. (Here is an example of a research paper filled with mathematically
impossible means.)
If the SD is mathematically impossible (online
calculator): When researchers fraudulently "cook" their
data, they may accidently give their data a mean and standard
deviation that is mathematically impossible.
If the
SD/M is very small
(i.e., the variable's standard deviation is very small compared
to the mean suggesting data smoothing).
If the
SD's are almost identical
(i.e., the variables have different means but almost identical
standard deviations).
If the 4th digit of the values of the variables aren't uniformly
distributed - since each should occur 10% of the time (Benford's Law).
If the researcher is
legally prevented from publishing negative
findings
about a drug or therapy because that would violate the
"nondisclosure of trade secrets" clause in the research contract
(i.e., it is a "trade secret" that the drug or therapy is
ineffective - hence this can not be "disclosed"). Approximately half of all registered clinical
trials fail to publish their results.
If the
researcher refuses to release his raw data to
fellow researchers
(so that they can check its validity). In order to be published
in most scientific journals, a researcher must promise to share his
raw data with fellow researchers. Thus a researcher's refusal to do
so is almost a sure indicator of fraud.
If the
research study's data contradicts the study's
own conclusions
- surprisingly, this often occurs.
Calling Bullshit
In The Age of Big Data - "Bullshit is language, statistical figures,
data graphics, and other forms of presentation intended to persuade by
impressing and overwhelming a reader or listener, with a blatant disregard for
truth and logical coherence." Reading the syllabus of this university course
should be required reading for every student of mental health. This syllabus is
absolutely fantastic!
Major pharmaceutical company fined $3 billion US for making
false claims - (text and video) [Editor: This is an
example of how a major pharmaceutical company purposely produced fraudulant
research in order to increase its sales.] In 2001, GlaxoSmithKline, the
manufacturer of the antidepressant Paxil, published research that falsely
claimed that Paxil was effective in the treatment of adolescent
depression. This claim and others were found to be fraudulant, and in 2012
GlaxoSmithKline was fined $3 billion
US in court settlements. Subsequent independent reanalysis of the
original Paxil research data clearly proved that the original study was fraudulant. This fraudulant research
paper was published in a top psychiatric journal, and has never been retracted
or corrected.
Cochrane Review (The best evidence-based, standardized
reviews available)
Strong evidence of effectiveness:
Paroxetine versus other anti-depressive agents for
depression (2014) (There was no clear evidence that paroxetine was
better or
worse compared with
other antidepressants at increasing response to treatment at any time point.
Most of included studies were at unclear or high risk of bias, and were
sponsored by the drug industry. The potential for overestimation of treatment
effect due to sponsorship bias should
be
borne in mind.)
Pharmacological treatment for psychotic depression
(2013) (We found only 12 randomised controlled trials (RCTs) that met
our inclusion
criteria. These trials
involved a total of 929 people. From these trials, we found evidence that the
combination of an antidepressant plus an antipsychotic provides more effective
treatment for psychotic depression than either treatment alone. However, our
confidence in this conclusion
is
limited because the information came from only a small number of RCTs, which
included small numbers of people.)
Fluoxetine compared with other antidepressants for
depression in adults (2013) (The present study detected differences
in terms of
efficacy
and tolerability between fluoxetine and certain ADs, but the clinical meaning of
these differences is uncertain. Moreover, the assessment of quality with the
risk of bias tool showed that the great majority of included studies failed to
report details on
methodological
procedures. Of consequence, no definitive implications can be drawn from the
studies' results. The better efficacy profile of sertraline and venlafaxine (and
possibly other ADs) over fluoxetine may be clinically meaningful, as already
suggested by other systematic
reviews. In addition to efficacy data, treatment decisions should also be based
on considerations of drug toxicity, patient acceptability and cost.)
Fluvoxamine versus other anti-depressive agents for
depression (2013) (We found no strong evidence that fluvoxamine was
either
superior or
inferior to
any other antidepressants in terms of efficacy and tolerability in the acute
phase treatment of depression. However, differing side effect profiles were
evident.)
Citalopram versus other antidepressants for depression
(2012) (Thirty-seven randomised controlled trials (more than 6000
participants)
were included in
the
present review. In terms of efficacy, citalopram was more efficacious than other
reference compounds like paroxetine or reboxetine, but worse than escitalopram.
In terms of side effects, citalopram was more acceptable than older
antidepressants, like tricyclics.
As
with
most systematic reviews in psychopharmacology, the potential for overestimation
of treatment effect due to sponsorship bias and publication bias should be borne
in mind when interpreting review findings. Economic analyses were not reported
in the included studies,
however, cost effectiveness information is needed in the field of antidepressant
trials.)
Amitriptyline for the treatment of depression (2012)
(Amitriptyline is a tricyclic antidepressant drug that has been used for decades
in the
treatment of
depression.
The current review includes 39 trials with a total of 3509 participants and
confirms its efficacy compared to placebo or no treatment. This finding is
important, because the efficacy of antidepressants has recently been questioned.
However, the review also
demonstrated
that amitriptyline produces a number of side effects such as vision problems,
constipation and sedation.)
Duloxetine versus other antidepressive agents for depression
(2012) (In the present review we assessed the evidence for the
efficacy, acceptability
and
tolerability of duloxetine in comparison with all other antidepressants in the
acute-phase treatment of major depression. Sixteen randomised controlled trials
(5735 participants) were included. Duloxetine was not more effective than some
other new antidepressant
agents in
the acute-phase treatment of major depression, and it was less well tolerated
than escitalopram and venlafaxine as more patients allocated to duloxetine
withdrew treatment before study end. However, due to the limited number of
studies per comparison these results
should
be interpreted with caution.)
Psychological and pharmacological interventions for
depression in patients with diabetes mellitus
(2012) (This
review
examined clinical trials on psychological treatments and antidepressant drugs in
depressed patients with diabetes. The objective was to determine the effects of
these treatments on depression, blood sugar, adherence to diabetic treatment
regimens, diabetes
complications,
death from any cause, healthcare costs and health-related quality of life.
Nineteen trials with 1592 participants were identified as relevant for the
review. Eight trials with 1122 participants investigated psychological
treatments versus usual care (duration of
therapy
three weeks to 12 months, follow-up after treatment zero to six months). Eight
trials with 377 participants examined antidepressant drugs versus placebo
(duration of intervention three weeks to six months, no follow-up after
treatment). Three trials with 93
participants
compared the effects of two different antidepressant medications (duration of
intervention 12 weeks, no follow-up after treatment). In summary, psychological
treatments and antidepressant drugs have a moderate, yet positive, effect on
depression outcomes in
diabetes
patients. Antidepressant drugs have a positive effect on blood glucose, whereas
effects on blood glucose are inconclusive for psychological treatments.
Patient-rated quality of life did not benefit from psychological or
antidepressant drug treatments. Healthcare
costs,
death from any cause and diabetes complications have not been examined
sufficiently. Serious or severe adverse effects were either rare
(pharmacological treatments) or not reported (psychological treatments). )
Mirtazapine versus other antidepressive agents for
depression (2011) (The evidence from this review, which included
findings from
29 randomised
controlled trials (4974 participants in total), suggests that mirtazapine is
likely to have a faster onset of action than the most frequently used type of
antidepressants, which are the selective serotonin reuptake inhibitors (SSRIs).
It would appear that
mirtazapine
is
superior to SSRIs at the end of treatment over 6 to 12 weeks. Mirtazapine causes
adverse events that lead to a similar frequency of dropouts as SSRIs and
tricyclic antidepressants, although adverse event profile of mirtazapine is
unique. Mirtazapine is likely to
cause
weight gain or increased appetite and somnolence but is less likely to cause
nausea or vomiting and sexual dysfunction than SSRIs.)
Sertraline versus other antidepressive agents for depression
(2010) ( In the present review we assessed the evidence for the
efficacy, acceptability
and
tolerability of sertraline in comparison with all other antidepressants in the
acute-phase treatment of major depression. Fifty-nine randomised controlled
trials (about 10,000 participants) were included in the review. The review
showed evidence of differences in
efficacy, acceptability and tolerability between sertraline and other
antidepressants, with meta-analyses highlighting a trend in favour of sertraline
over other antidepressants, both in terms of efficacy and acceptability, in a
homogeneous sample of clinical
trials,
using conservative statistical methods. The included studies did not report on
all the outcomes that were pre-specified in the protocol of this review.
Outcomes of clear relevance to patients and clinicians, in particular, patients
and their carers' attitudes to
treatment, their ability to return to work and resume normal social functioning,
were not reported in the included studies.)
Antidepressants for depression in physically ill people
(2010) (We extracted information on fifty-one studies in the review. Our
results
found that
antidepressants are better than a placebo (inactive) drug in treating depression
in physically ill people. Both the two main classes of antidepressant, tricyclic
antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), were
shown to be more
effective
than a placebo. Antidepressants improved depressive symptoms within 4-5 weeks of
treatment, and this benefit persisted after 18 weeks. However, patients taking
an antidepressant were more likely to experience sexual dysfunction and dry
mouth, and were more likely
to
stop
taking their medication after 6-8 weeks of treatment. There are no grounds to
recommend one antidepressant over another on the basis of this review. We
conclude that antidepressants appear to be useful in treating depression and
should be considered for physically
ill
patients. )
Amitriptyline for depression (2009) (This present
systematic review indicates that amitriptyline is at least as efficacious as
other tricyclics or newer compounds.
However, the
burden
of side-effects in patients receiving it was greater. In comparison with
selective serotonin reuptake inhibitors amitriptyline was less well tolerated,
and although counterbalanced by a higher proportion of responders, the
difference was not statistically
significant. )
Antidepressants plus benzodiazepines for major depression
(2009) (The reviewers report that a combination of benzodiazepines with
antidepressants works
in
favour for the treatment of depression, because it decreases drop outs from
treatment and it increases short-term response up to four weeks. However, there
are downsides to this combination therapy because benzodiazepines can induce
dependence, which is estimated
to
occur
in one third of patients, as well as a decline in the drug's effect over time.
Benzodiazepines have been associated with an increase in accident proneness.)
Antidepressants for depressed older people (2009) (This
review compared the efficacy, withdrawal rates and side effects of different
antidepressant
classes in the
treatment of depression in older people. Thirty-two studies provided data for
the review. Our main findings indicate that tricyclic antidepressants (classical
and tricyclic related) and selective serotonin reuptake inhibitors (SSRIs) are
equally efficacious.
However,
when
comparing the two tricyclic groups with SSRIs we found that tricyclic related
antidepressants were similar to SSRIs in terms of overall withdrawal rate, and
classical tricyclic antidepressants were associated with a higher withdrawal
rate due to side effects.
These
findings are reflected in the differing side effect profiles when comparing both
tricyclic groups with SSRIs. The findings of the review must be interpreted with
some caution in view of the relatively low patient numbers and lack of side
effect data.)
Escitalopram versus other antidepressive agents for
depression (2009) (Twenty-two randomised controlled trials (about 4000
participants) were
included
in the present review. Escitalopram appears to be suitable as first-line
antidepressant treatment for people with moderate to severe major depression. It
has been compared with only a few other antidepressants and so we are unable to
say whether it is better,
worse or
the
same as many of the other drugs used in practice. However, it did perform better
than citalopram when we brought together the results of six studies in nearly
two thousand patients)
Low dose tricyclic antidepressants (TCAs) for depression
(2009) (This systematic review of 39 studies (2564 participants) found
that
tricyclic
antidepressants
between 75-100 mg/day and possibly below this range result in more reduction in
depression than placebo. On the other hand, there was no strong evidence to show
that standard dosage tricyclic brings about more response than low dosage
tricyclic. The findings
suggest
that
administration of low dosage tricyclic antidepressant is a defensible practice.)
Antidepressants compared with placebos for depressed older
people (2009) (TCAs, SSRIs and MAOIs are effective in the treatment
of older
community
patients and inpatients likely to have severe physical illness. At least six
weeks of antidepressant treatment is recommended to achieve optimal therapeutic
effect. There is little evidence concerning the efficacy of low dose TCA
treatment. Further trials are
required
before low dose TCA treatment is routinely recommended.)
Antidepressants versus placebo for depression in primary
care (2009) (We found 14 studies conducted in adults (not the elderly)
in
primary care
setting, in which tricyclic antidepressants (TCAs) or selective serotonin
reuptake inhibitors (SSRIs) were compared against a placebo control group in the
treatment of depression. The results showed that both TCAs and SSRIs were
effective for depression. Most of
the
studies were supported by funds from pharmaceutical companies and were of short
duration. There appeared to be more adverse effects with TCAs than with SSRIs,
however rates of withdrawal from study medication due to adverse effects were
very similar between the
two
antidepressant classes. Adverse effects not leading to medication cessation
seemed to be more common with TCAs than SSRIs.)
Some evidence of effectiveness:
Antidepressants for postnatal depression (2014) (We were
able to combine data from three studies comparing a type of commonly used
antidepressant
called selective
serotonin
reuptake inhibitors (SSRIs) with placebo. The results showed that women with
postnatal depression who were given SSRIs were more likely to improve or recover
than those given placebo. We were unable to combine the data from studies
comparing antidepressants with
other
treatments or treatment as usual due to the very small number of studies
identified for these comparisons. There was insufficient evidence to conclude
whether, and for whom, antidepressant or psychosocial/psychological treatments
are more effective, or whether
some
antidepressants are more effective or better tolerated (or both) than others.
Conclusions were also limited by the lack of data on long-term follow-up, the
safety of breastfeeding or child outcomes.)
Interventions to help depressed people resume work
(2014) (We evaluated the effectiveness of interventions that can help
depressed workers
to resume work
activities. In three studies with 251 participants, researchers looked at
changes at work such as work modification or coaching in addition to regular
care and found that these reduced sickness absence to a moderate extent. In
three studies with 326 participants,
researchers found that cognitive behavioural therapy that was provided online or
by telephone reduced sickness absence to a moderate extent compared to regular
care. Three studies compared antidepressant pills with each other but there were
no consistent effects
on
sickness absence. One study found that participants had a reduction in sick
leave after doing stretching exercises. Two other studies did not find an effect
on sick leave after physical exercises such as running or using the gymnasium. A
structured telephone
outreach
and
care management program that included medication reduced sickness absence
compared to usual care.)
Pharmacological treatment for psychotic depression
(2013) (We found only 12 randomised controlled trials (RCTs) that met
our inclusion
criteria. These trials
involved a total of 929 people. From these trials, we found evidence that the
combination of an antidepressant plus an antipsychotic provides more effective
treatment for psychotic depression than either treatment alone. However, our
confidence in this conclusion
is
limited because the information came from only a small number of RCTs, which
included small numbers of people.)
Treatments for preventing the recurrence of depression in
children and adolescents (2013) (Currently, there
is little evidence
to
conclude which type of treatment approach is most effective in preventing
relapse or recurrence of depressive episodes in children and adolescents.
Limited trials found that antidepressant medication reduces the chance of
relapse-recurrence in the future, however,
there
is considerable diversity in the design of trials, making it difficult to
compare outcomes across studies. Some of the research involving psychological
therapies is encouraging, however at present more trials with larger sample
sizes need to be conducted in order
to
explore this treatment approach further.)
Exercise for depression (2013) (Exercise is moderately
more effective than a control intervention for reducing symptoms of depression,
but analysis of methodologically
robust trials
only
shows a smaller effect in favour of exercise. When compared to psychological or
pharmacological therapies, exercise appears to be no more effective, though this
conclusion is based on a few small trials.)
Behavioural therapies versus other psychological therapies
for depression (2013) (We found low- to moderate-quality
evidence that
behavioural therapies and other psychological therapies are equally effective.
The current evidence base that evaluates the relative benefits and harms of
behavioural therapies is very weak. This limits our confidence in both the size
of the effect and its
precision
for
our key outcomes related to response and withdrawal. Studies recruiting larger
samples with improved reporting of design and fidelity to treatment would
improve the quality of evidence in this review.)
Alprazolam for depression (2012) (Alprazolam appears to
reduce depressive symptoms more effectively than placebo and as effectively as
tricyclic antidepressants.
However, the studies
included in the review were heterogeneous, of poor quality and only addressed
short-term effects, thus limiting our confidence in the findings. Whilst the
rate of all-cause withdrawals did not appear to differ between alprazolam and
placebo, and withdrawals were
less
frequent in the alprazolam group than in any of the conventional antidepressants
combined group, these findings should be interpreted with caution, given the
dependency properties of benzodiazepines.)
Newer antidepressants for depression in children and
adolescents (2012) (Depression is common in young people and can
contribute to a variety of
negative outcomes, such as poor academic functioning, difficulties in peer and
family relationships, increases in substance use, and both attempted and
completed suicide. This review contained 19 trials (with a total of 3353
participants) testing the effectiveness
of
newer generation antidepressants (these are antidepressants developed and used
since tricyclic antidepressants were developed). Based on 14 of the trials (2490
participants in total), there was evidence that those treated with an
antidepressant had lower
depression
severity scores than those on placebo, however, the size of this difference
was small. Based on 17 trials (3229 participants in total), there was
evidence of an increased risk (64%) of suicide-related outcomes for those on
antidepressants compared with
those
given
placebo. Where rates of adverse events were reported, this was higher for those
prescribed an antidepressant. There was no evidence that one particular type
of newer generation antidepressant had a larger effect than the others when
compared to placebo. It
is
unclear how meaningful the results regarding the effectiveness of these
medications are in terms of a young person's day-to-day functioning. Children
and adolescents with other conditions (such as anxiety, substance use disorder
or a conduct disorder) as well as
depression, and those at risk of suicide, were often excluded from trials.
However, these young people are more representative of the population who
present to clinical services, therefore it is not possible to predict how they
would respond to antidepressants.
There
was
often insufficient information to judge the quality of the trials accurately.
With these limitations, it is difficult to answer questions about the
effectiveness and safety of antidepressants for treating depression in children
and adolescents. Clinicians need to
provide
accurate information to children and adolescents, and their families, about the
uncertainties regarding the benefits and risks of newer generation
antidepressant medication as a treatment option for depression. If a decision to
use medication is agreed then
fluoxetine
might be the medication of first choice given guideline recommendations and, if
used, the risk of suicide should be assessed and monitored particularly
closely.)
Collaborative care for people with depression and anxiety
(2012) ("Collaborative care" is an innovative way of treating depression
and
anxiety. It
involves
a number of health professionals working with a patient to help them overcome
their problems. Collaborative care often involves a medical doctor, a case
manager (with training in depression and anxiety), and a mental health
specialist such as a psychiatrist. The
case
manager has regular contact with the person and organises care, together with
the medical doctor and specialist. The case manager may offer help with
medication, or access to a "talking therapy" to help the patient get better. In
this review we found 79 randomised
controlled trials (RCTs) (90 comparisons) including 24,308 patients worldwide,
comparing collaborative care with routine care or alternative treatments (such
as consultation-liaison) for depression and anxiety. There were problems with
the methods in some of the
studies.
For example, the methods used to allocate patients to collaborative care or
routine care were not always free from bias, and many patients did not complete
follow-up or provide information about their outcomes. Most of the studies
focused on depression and the
evidence
suggests that collaborative care is better than routine care in improving
depression for up to two years. A smaller number of studies examined the effect
of collaborative care on anxiety and the evidence suggests that collaborative
care is also better than usual
care
in
improving anxiety for up to two years. Collaborative care increases the number
of patients using medication in line with current guidance, and can improve
mental health related quality of life. Patients with depression and anxiety
treated with collaborative care
are
also
more satisfied with their treatment.)
Tricyclic antidepressants compared with active placebos for
depression (2012) (This review examined trials which compared
antidepressants
with
'active' placebos, that is placebos containing active substances which mimic
side effects of antidepressants. Small differences were found in favour of
antidepressants in terms of improvements in mood. This suggests that the effects
of antidepressants may
generally be
overestimated and their placebo effects may be underestimated.)
St. John's wort for treating depression (2009) (We have
reviewed 29 studies in 5489 patients with depression that compared treatment
with extracts of
St. John's wort for
4
to 12 weeks with placebo treatment or standard antidepressants. The studies came
from a variety of countries, tested several different St. John's wort extracts,
and mostly included patients suffering from mild to moderately severe symptoms.
Overall, the St. John's
wort
extracts tested in the trials were superior to placebo, similarly effective as
standard antidepressants, and had fewer side effects than standard
antidepressants. However, findings were more favourable to St. John's wort
extracts in studies form German-speaking
countries
where these products have a long tradition and are often prescribed by
physicians, while in studies from other countries St. John's wort extracts
seemed less effective. This differences could be due to the inclusion of
patients with slightly different types of
depression,
but it cannot be ruled out that some smaller studies from German-speaking
countries were flawed and reported overoptimistic results.)
Psychostimulants for depression (2009) (This review
evaluated the evidence from randomised controlled trials (RCTs) evaluating the
effectiveness of
psychostimulants (PS) in the
treatment of depression. Twenty-four RCTs were identified, of which 14 had data
for meta-analysis. Five drugs were evaluated, including dexamphetamine,
methylphenidate, methylamphetamine, pemoline and modafinil. Modafinil was
evaluated separately as its
pharmacology
differs from other PS. Three small trials of PS involving a total of 62
participants indicated that oral treatment with PS in the short term (up to four
weeks) significantly reduced depressive symptoms when compared with placebo,
however, the overall quality of
the
trials
was poor, limiting confidence in the findings. Two trials involving 411
participants compared modafinil against placebo when combined with
antidepressant treatment at 6-8 weeks, and showed a non-significant difference
in reducing depression symptoms. One small
trial
of 50
participants compared oral modafinil against placebo after 12 weeks of
treatment, and also showed a non-significant difference in reducing depression
symptoms. No trials examined the longer-term effect of PS. Further well
conducted trials with long term follow-up
are
required to find out which PS may be more effective in the treatment of
depression, and whether PS are more effective in certain subgroups of depressed
patients.)
Relaxation for depression (2009) (Many people with
depression do not get treatment or delay getting treatment. One reason for this
is that they do not like
antidepressants. Another is
the
limited availability of specialized psychological treatments, such as
cognitive-behavior therapy. Relaxation techniques are a simple psychological
treatment that can be administered after brief training. The review of 15 trials
found that it was better than no
treatment
or minimal treatment, but not as effective as psychological therapies like
cognitive-behavior therapy. Relaxation techniques have potential as a simple
first-line psychological treatment for depression. Those who do not respond
within a set time could be offered
more
complex psychological treatment such as cognitive-behavior therapy.)
Tryptophan and 5-Hydroxytryptophan for depression (2009)
(Available evidence does suggest these substances are better than placebo at
alleviating depression.
Further studies are needed to evaluate the efficacy and safety of 5-HTP and
tryptophan before their widespread use can be recommended. The possible
association between these substances and the potentially fatal
Eosinophilia-Myalgia Syndrome has not been
elucidated.
Because alternative antidepressants exist which have been proven to be effective
and safe the clinical usefulness of 5-HTP and tryptophan is limited at present.)
Psychotherapeutic treatments for older depressed people
(2009) ( In this review we included seven small trials, involving a
total of 153
participants,
that
examined psychotherapeutic treatments for depression in older people. Five
trials compared a form of cognitive behavioural therapy (CBT) against control
conditions, and the findings showed that CBT was more effective than control.
Two individual trials compared
CBT
against psychodynamic therapy, with no significant difference in effectiveness
indicated between the two approaches. If taken on their own merit, the findings
do not provide strong support for psychotherapeutic treatments in the management
of depression in older
people.)
Light treatment for non-seasonal depression (2009) (For
patients suffering from non-seasonal depression, light therapy offers modest
though
promising antidepressive
efficacy, especially when administered during the first week of treatment, in
the morning, and as an adjunctive treatment to sleep deprivation responders.
Hypomania as a potential adverse effect needs to be considered. Due to limited
data and heterogeneity of
studies
these results need to be interpreted with caution. )
Psychosocial and psychological interventions for postpartum
depression (2009) (Postpartum depression affects
approximately 13% of all new
mothers. Many women desire to try treatment options other than medication. This
review examined nine trials involving 956 women which studied either
psychosocial (e.g., peer support, non-directive counselling) or psychological
(e.g., cognitive behavioural therapy
and
interpersonal psychotherapy) treatments for postpartum depression. Although the
methodological quality of the majority of trials was, in general, not strong,
the meta-analysis results suggest that psychosocial and psychological
interventions are an effective
treatment
option for women suffering from postpartum depression. The long-term
effectiveness remains unclear.)
Lithium for maintenance treatment of mood disorders
(2009) (This systematic review investigated the efficacy of lithium
compared to that of
placebo in the
maintenance treament of mood disorders (unipolar and bipolar disorder). Nine
randomised studies (reporting on 825 participants) were included in the review.
Lithium was more effective than placebo in preventing relapse in mood disorder
overall. Lithium was more
effective
than placebo in bipolar disorder, though estimates of the size of the effect
varied between studies. In unipolar disorder, lithium appeared to be more
effective than placebo but the evidence for this was less clear cut. Lithium
should be considered for maintenance
treatment in bipolar disorder and, although the evidence is less reliable, it
may be considered as one of a range of treatments with possible benefit in
preventing relapse in unipolar disorder. Caution should be exercised in
abruptly
stopping lithium therapy in patients who have been taking it successfully for
some time, due to the high risk of relapse.)
No evidence of effectiveness:
Antidepressants for people with epilepsy and depression
(2014) (We found eight studies that included 471 patients with epilepsy
treated
with an
antidepressant. Three were randomised controlled trials and five were
non-randomised prospective cohort studies. Taking all the evidence into account,
the review found that there is very limited evidence demonstrating a significant
effect of antidepressants on
depressive
symptoms in epilepsy. There was limited information on the effect of
antidepressants on seizure control, however in the studies reporting this
outcome there did not appear to be any significant worsening of seizures.)
Psychotherapy for depression among cancer patients who are
incurable (2013) (Evidence from RCTs of moderate quality suggest
that psychotherapy
is
useful for treating depressive states in advanced cancer patients. However, no
evidence supports the effectiveness of psychotherapy for patients with
clinically diagnosed depression.)
Tricyclic drugs for depressed children and adolescents
(2013) (Data suggest tricyclic drugs are not useful in treating
depression in
children. There is
marginal evidence to support the use of tricyclic drugs in the treatment of
depression in adolescents.)
Dietary supplements for preventing postnatal depression
(2013) (There is insufficient evidence to conclude that selenium, DHA or
EPA prevent
postnatal
depression. There is currently no evidence to recommend any other dietary
supplement for prevention of postnatal depression.)
Second-generation antipsychotic drugs for major depressive
disorder (2012) (This review found 28 studies on five
second-generation
antipsychotic
drugs (amisulpride, aripiprazole, olanzapine, quetiapine and risperidone)
comparing the effects of the drugs alone or adding them or placebo to
antidepressants for major depressive disorder and dysthymia. There is evidence
that amisulpride might lead to symptom
reduction
in dysthymia, while no important differences were seen for major depression.
There is limited evidence that aripiprazole leads to symptom reduction when
added to antidepressants. Olanzapine had no beneficial effects for treatment of
depression when compared to
antidepressants or compared to placebo but there was limited evidence for the
benefits of olanzapine as additional treatment. Data on quetiapine indicated beneficial effects for
quetiapine alone or as additional treatment when
compared to placebo; data on quetiapine versus duloxetine did not show
beneficial effects in terms of symptom reduction for either group, but
quetiapine treatment was less well tolerated. The data, however, are very
limited. Slight benefits of risperidone
as
additional treatment, in terms of symptom reduction, are also based on a rather
small number of randomised participants. Generally, treatment with
second-generation antipsychotic drugs was associated with worse tolerability,
mainly due to sedation, weight gain or
laboratory values such as prolactin increase.)
Drug treatment for depression in multiple sclerosis
(2011) (Many patients with multiple sclerosis (MS) suffer from
depression. In this review we
summarized studies
of
antidepressant drug treatments in patients with MS. We found two studies that
met the inclusion criteria of methodological quality, comprising of a total of
70 participants: one (28 participants) reported the effects of desipramine, the
other (42 participants) the
effects
of paroxetine. The two studies showed no improvement of depression with both
treatments in the short term (five/twelve weeks). Adverse effects, such as
nausea or headache occurred frequently. Further studies on drug treatment of
depression in MS with a longer
duration
are
clearly needed, as the results may be affected by the small size of participants
and by the fact that many participants did not complete the studies.)
Acupuncture for depression (2010) (We found insufficient
evidence to recommend the use of acupuncture for people with depression. The
results are limited by the high
risk of bias in
the
majority of trials meeting inclusion criteria.)
Screening and case finding instruments for depression
(2009) (The use of depression screening or case finding instruments has
little or no
impact on the
recognition, management or outcome of depression in primary care or the general
hospital.)
Transcranial magnetic stimulation (TMS) for depression
(2009) (There is no strong evidence for benefit from using transcranial
magnetic
stimulation to treat
depression, although the small sample sizes do not exclude the possibility of
benefit. )
Not yet possible to draw any definite conclusions due to insufficient evidence:
Is dance movement therapy an effective treatment for
depression? A review of the evidence (2015) (The
low-quality
evidence
from three small trials with 147 participants does not allow any firm
conclusions to be drawn regarding the effectiveness of DMT for depression.
Larger trials of high methodological quality are needed to assess DMT for
depression, with economic analyses and
acceptability
measures and for all age groups.)
Alternating current cranial electrotherapy stimulation in
the treatment of depression (2014) (Cranial
electrotherapy
stimulation (CES) has been proposed as an alternative treatment for symptoms of
depression. CES is a treatment in which a low intensity electrical current is
administered to the head through the use of a small, portable electrical device.
A sample treatment
regimen
might
consist of daily application of the device for 30 minutes for a month, but
treatment instructions vary with the device and condition being treated. In the
United States CES devices require a prescription. In most other countries,
marketing of CES devices is
approved
for
stress reduction but not specific medical conditions such as depression. We
found no high quality clinical trials comparing CES with sham CES in people with
acute depression. Currently, there is insufficient evidence to support the use
of CES in treatment of acute
depression.
)
Long term treatment for depression in older people
(2012) (This systematic review evaluated the efficacy and acceptability
of antidepressant
drugs,
psychological
therapies (talking treatments) and combinations of these treatments in
preventing the recurrence of depression in people aged 60 and over who had
recovered from depression while taking antidepressant medication. Remaining on
antidepressant drugs for one year
appears
to
reduce the risk of depression returning from 61% to 42% but the benefits at
other time intervals could not be determined. Antidepressant treatment appeared
to be as well tolerated as placebo treatment. The benefits of psychological
therapies were not clear, due to
the
small number of research studies. This review cannot be used to make firm
recommendations on the optimal long-term treatment of depression in older people
due to the limited number and small size of research studies involved.)
Second-generation antidepressants for winter depression
(2011) (Evidence for the effectiveness of second generation
antidepressants
(SGAs) is limited to
one
small trial of fluoxetine compared with placebo, which shows a non-significant
effect in favour of fluoxetine, and two small trials comparing fluoxetine
against light therapy, which suggest equivalence between the two interventions.
The lack of available evidence
precludes the ability to draw any overall conclusions on the use of SGAs for
winter depression.)
Psychosocial and psychological interventions for treating
antenatal depression (2010) (Although for many women
pregnancy was once
thought
of as a time of emotional wellbeing, approximately 12% of women will suffer from
antenatal depression. Research suggests that women who are on low-income, lack
social support, experience significant stress or negative life events, and have
poor relationships may
be at
higher risk of developing antenatal depression.
Unfortunately, depression during the pregnancy is related to poor maternal
self-care behaviours, which may influence the baby's health, and it places a
woman at significant risk of developing postpartum depression. Many women are
unwilling to take medication
during
their
pregnancy and are often interested in psychosocial and psychological
interventions as a form of treatment. The review found only one trial involving
50 US women evaluating interpersonal psychotherapy for the treatment of
antenatal depression. This trial provided
insufficient evidence to determine if psychological therapies are effective
treatment for antenatal depression. Further research is needed.)
Inositol for depression (2009) (Inositol is a
nutritional supplement that has been suggested as a treatment for depressive
disorders. The reviewers found the current
evidence is unclear
whether or not inositol is of benefit in the treatment of depression.)
Folate for depression (2009) (This systematic review was
undertaken to see if giving folate to people with depressive disorders reduced
their depressive symptoms. Three
randomized trials
were
identified, involving a total of 247 people. In all three trials, folate was
well tolerated. In two of these trials, folate was added to other antidepressant
drug treatment and there was limited evidence that folate helped. In the third
trial, folate was compared
to
trazodone, an antidepressant drug. No difference was found. There is therefore
limited evidence that adding folate to other antidepressant may be helpful, but
larger trials are needed before patients and clinicians can be confident that it
will be helpful. )
The involvement of paraprofessionals for anxiety and
depressive disorders (2009) (The few studies included in the
review did not allow
conclusions about the effect of paraprofessionals compared to professionals, but
three studies (women only) indicated a significant effect for paraprofessionals
(all volunteers) compared to no treatment. The evidence to date may justify the
development and
evaluation
of
programs incorporating paraprofessionals in treatment programs for anxiety and
depressive disorders.)
Music therapy for depression (2009) (Findings from
individual randomised trials suggest that music therapy is accepted by people
with depression and is associated
with improvements
in
mood. However, the small number and low methodological quality of studies mean
that it is not possible to be confident about its effectiveness. High quality
trials evaluating the effects of music therapy on depression are required.)
Family therapy for depression (2009) (The current
evidence base is too heterogeneous and sparse to draw conclusions on the overall
effectiveness of family therapy
in the treatment
of
depression. At this point, use of psychological interventions for the treatment
of depression for which there is already an evidence-base would seem to be
preferable to family therapy. Further high quality trials examining the
effectiveness and comparative
effectiveness
of explicitly defined forms of family therapy are required. )
Marital therapy for depression (2009) (There is no
evidence to suggest that marital therapy is more or less effective than
individual psychotherapy or drug
therapy in the
treatment
of depression. Improvement of relations in distressed couples might be expected
from marital therapy. Future trials should test whether marital therapy is
superior to other interventions for distressed couples with a depressed partner,
especially considering the
role
of
potential effect moderators in the improvement of depression. )
Antidepressant prevention of postnatal depression (2009)
(Only two small trials met the criteria for inclusion. Both trials used
medication
immediately
postpartum.
The drugs were nortriptyline, a tricylic antidepressant (TCA) and sertraline, a
selective serotonin reuptake inhibitor (SSRI). Both drugs were compared only to
placebo. Nortripyline was not shown to have any benefit over placebo; there was
some evidence that
sertraline
was effective both in reducing the incidence of recurrent postpartum depression
and in increasing the time to recurrence. However, both trials involved only
very small numbers of women and did not use intention to treat analyses. There
is, therefore, no clear
evidence
for
the use of these antidepressants in the prevention of postnatal depression.)
Milnacipran versus other antidepressive agents for
depression (2009) (A total of 16 randomised controlled trials (2277
participants) were included
in
this review. Currently, there is inadequate evidence to conclude whether
milnacipran is superior, inferior or the same as other antidepressive agents in
terms of efficacy, acceptability and tolerability in the acute phase treatment
of major depression. However,
there
is
some evidence in favour of milnacipran over TCAs in terms of dropouts due to
adverse events (acceptability) and the rates of experiencing adverse events
(tolerability). Information about other clinically meaningful outcomes such as
cost-effectiveness and social
functioning, including the ability to return to work, is lacking. Further study
is needed to answer whether milnacipran would be the better choice of
antidepressant for acute major depression.)
Electroconvulsive therapy (ECT) for depression in elderly
people (2009) (This review involved searching the literature for
well-conducted
(randomised)
studies that compared ECT to both simulated ECT and to antidepressants. The
review found only four studies, all of which had serious problems in their
methods. At present, therefore, it is not possible to draw firm conclusions on
whether ECT is more effective than
antidepressants,.or on the safety or side effects of ECT in elderly people with
depression.)
Note: The Cochrane Reviews are the best in psychiatry, but they do not cover all
psychiatric topics. Thus it is essential that you also read the following Research
Review Articles.
[Editor: Notice that the remission rate for the treatment of major
depressive disorder with ECT is the same as the remission rate for
antidepressant medication.]
The use of
ECT and MST in treating depression. - Magnetic seizure therapy (MST) has
been used successfully in the treatment of depression, yet there is a dearth of
literature in comparison
with
electroconvulsive
therapy (ECT).
Therapeutic interventions for vascular depression: a
systematic review. - Efficacy trials suggested that nimodipine,
transcranial magnetic stimulation, carotid stent placement, and
citalopram were effective for
vascular depression. Exploratory studies suggested that white-matter
hyperintensities and global vascular risk are predictors of poor response.
Deep brain
stimulation for intractable psychiatric disorders. - The overall
response rate appears to exceed 50% in intractable obsessive-compulsive disorder
(OCD) for some deep brain
stimulation (DBS) targets.
In
treatment-resistant depression (TRD), >50% of patients responded during acute
and long-term bilateral electrical stimulation in a different target. DBS was
generally well tolerated in both OCD and TRD, but some unique, target- and
stimulation-specific adverse
effects
were
observed (e.g., hypomania).
Rapid-acting antidepressant strategies: mechanisms of
action. - Sleep deprivation therapy (SDT) has been investigated in over
60 studies with a 40-60% response rate within 48 h. Although SDT
is often used in
Europe
to initiate a rapid response, it is less utilized within the USA, in part,
because it has a short duration when administered alone. We review data
concerning chronotherapeutic strategies of bright-light therapy (BLT) and
sleep-phase advance (SPA) which
successfully
sustain the antidepressant efficacy of SDT.
Antidepressants and suicide in adolescents. - SSRIs
antidepressants better than placebo, but the effect size is unreported. They are
generally safe in the treatment of adolescent depressive
disease.
[Editor: The fact that, after 24 weeks,
only 46-52% of patients with major depressive disorder achieve full
remission testifies to how many depressed patients don't respond to
antidepressant medications (or other treatments).]
Management of
treatment-resistant depression. - Setting unrealistic goals for the
treatment of treatment-resistant depression may lead to overtreatment and
demoralization. Patients
must accept that
treatment-resistant depression is a chronic illness that can be effectively managed
but not likely cured. The focus should be less on eliminating depressive symptoms
and more on learning to function better in spite of them. It is important to
maintain hope
for
improvement without setting unrealistic expectations. Significant others and family
members can be invaluable in providing support. Patients with a wide range of
chronic medical illnesses can and do learn to function effectively and to achieve a
satisfying quality
of
life
in spite of their illness.
Combination of
antidepressants in the treatment of major depressive disorder: a systematic
review and meta-analysis. - Antidepressant combination was shown to be
better than a single
antidepressant
considering
remission (relative risk [RR], 2.71) and response (RR, 1.55). Mirtazapine
plus selective serotonin reuptake inhibitor (SSRI) was superior to an isolated SSRI
for remission (RR, 1.88). Tricyclic antidepressant plus SSRI was superior to SSRI
for remission and
response (RR, 8.58). There was no difference between combined and
monotherapy groups in dropouts owing to adverse effects.
[ Editor: This research shows that there is a dramatic increase in the
effectiveness of antidepressant treatment when a tricyclic antidepressant is
used in combination with a SSRI antidepressant.]
Emerging drugs
for major depressive disorder. - Drugs that modulate glutamatergic
neurotransmission may hold the greatest promise for exerting rapid and large
antidepressant effects.
[ Editor: In this study, a NNT=14 for remission vs. placebo would mean that
there was only a 7% difference in effect. This small difference is clinically
insignificant.]
Pharmacological treatment of unipolar depression during
pregnancy and breast-feeding--a clinical overview. - Citalopram and
sertraline can be used during pregnancy, while some controversy
remains over in utero
exposure to paroxetine and fluoxetine, which might be associated with an increased
risk of foetal cardiovascular malformation. Less data is available concerning
fluvoxamine and escitalopram use but current data does not indicate a specific risk.
Citalopram,
paroxetine
and sertraline can be used during breast-feeding, while fluoxetine probably
should be avoided. Nortriptyline, amitriptyline and clomipramine can be used
during pregnancy and lactation, although data are more abundant for SSRI
treatment. Venlafaxine can be
used
during pregnancy, while caution is advised during breast-feeding. Other
antidepressants should be avoided because of lack of data on their effect. A
strongly indicated lithium therapy should be continued. Close monitoring of lithium
levels throughout pregnancy is
mandatory, as is detailed foetal echocardiography in weeks 18-22 of gestation.
Lithium should not be used during breast-feeding. Electroconvulsive therapy (ECT) is
a valid option if indicated, both during pregnancy and breast-feeding.
[ Editor: In summary, in terms of antidepressant medication, only citalopram,
sertraline, nortriptyline, amitriptyline, clomipramine, and lithium (with close
monitoring of levels) can be used during pregnancy and lactation.]
Newer
generation antidepressants for depressive disorders in children and
adolescents. - Remission rates increased from 380 per 1000 to 448 per 1000
for those treated with an antidepressant.
There was evidence
of
an increased risk of suicide-related outcome for those on antidepressants (40 in
1000) compared with a placebo (25 in 1000). Fluoxetine is the medication of first
choice.
Psychodynamic treatment of depression. - Brief
psychodynamic treatment of depression has been found to be superior to control
conditions, and equally effective as other active psychological
treatments. The
effect
size of this treatment is not reported.
Mindfulness-based cognitive therapy: theory and
practice. - Research findings from several randomized controlled trials
suggest that MBCT is a useful intervention for relapse prevention in
patients with
recurrent
depression. However the effect size of this treatment isn't reported.
Clinical
depression: an evidence-based integrative complementary medicine treatment
model. - Cognitive behavioral therapy, interpersonal therapy, St John's
wort, S-adenosyl methionine, and
exercise are more
effective than placebo in the treatment of clinical depression. However, the
effect size is not reported. Evidence is not conclusive that acupuncture,
omega-3 fish oils, and L-tryptophan is effective for clinical depression.
[Editor: The fact that only 9% of primary care patients with major
depressive disorder receive adequate treatment, and only 6% achieve
remission is a public health disaster.]
Tackling
anxiety and depression in older people in primary care. - In older
people, anxiety tends to follow threats or traumatic events, whereas depression
follows loss events. Older
patients often deny feeling
anxious or depressed and are more likely to present with insomnia, irritability,
agitation and multiple somatic complaints.
Borderline
personality disorder and depression: an update. - Similar temperamental
features have been demonstrated in borderline personality disorder (BPD) and
major depression. The strong
link between the two
disorders seems to be widely recognized by scientific community.
Executive
dysfunction and treatment response in late-life depression. - Executive
dysfunction in geriatric depression has been shown to predict poor response to
antidepressant medication.
From our review, the
aspects of executive functioning that appear to be associated with
antidepressant response rates are verbal fluency and response inhibition.
Differences between effects of psychological versus
pharmacological treatments on functional and morphological brain alterations
in anxiety disorders and major depressive disorder: a systematic
review. - The
most
prevalent mental disorders, anxiety and mood disorders, are associated with both
functional and morphological brain changes that commonly involve the 'fear
network' including the (medial) prefrontal cortex, hippocampus and amygdala.
Patients suffering from anxiety
disorders and major depressive disorder often show excessive amygdala and
reduced prefrontal cortex functioning. Pharmacotherapy particularly decreases
over-activity of limbic structures (bottom-up effect) while psychotherapy tends
to increase activity and
recruitment
of
frontal areas (top-down effect), especially the anterior cingulate cortex.
Additionally, pharmacotherapy, but not psychotherapy, has been associated with
morphological changes, depending on the disorder.
Exercise
for the treatment of depression and anxiety. - Exercise compares
favorably to antidepressant medications as a first-line treatment for mild to
moderate depression and has also been
shown to improve
depressive symptoms when used as an adjunct to medications. While effective,
exercise has not been shown to reduce anxiety to the level achieved by
psychopharmaceuticals.
Deep brain
stimulation in the treatment of depression. - Deep brain stimulation
(DBS) for treatment-resistant major depressive disorder has resulted in 30%-40%
remission rates at one-year
followup. The
published
experience is, however, limited, and the method is at present an experimental
therapy.
Pharmaceutical Treatments:
Solving
the antidepressant efficacy question: effect sizes in major depressive
disorder. - Relative antidepressant versus placebo benefit increased
linearly from 5% in mild depression to 12%
in moderate
depression to 16% in severe depression. Thus antidepressants are effective
in acute depressive episodes that are moderate to severe, but are not
effective in mild depression. These considerations only apply to acute
depression, however. For maintenance, the long-term
efficacy of antidepressants is unproven, but research shows they are not
harmful.
[ Editor: The finding that antidepressant medications are only 12% more
effective than placebo for moderate depression is very important (and
humbling). The remission rate for antidepressant treatment of moderate
depression is 52%; whereas on active
placebo the remission rate is 40%. Obviously we should study what
makes this (active) placebo effect of seeing a physician so effective, in
that this placebo effect causes three-quarters of the remission.]
What do
the terms "drug-specific response/remission rate" and "placebo" really
mean? - Placebo is frequently misrepresented by the media as
representing nothing. In fact, placebo represents
everything except
the
investigational treatment. That is an important distinction. The second is the
concept of the drug-specific response/remission rate. While manufacturers
frequently cite the overall response/remission rate observed in the group
treated with their drug in their clinical
trials, that is not the true rate specifically attributable to the drug.
Instead, it represents the combined rate due to both the drug and the non-drug
(or "placebo") therapeutic aspects of the trial. To determine the drug-specific
response/remission rate, the placebo
response/remission rate must be subtracted from the overall response/remission
rate observed in the drug treated group. That is because the drug treated group
receives both the therapeutic benefit of the drug and all of the nondrug
therapeutic benefit of the trial
(i.e.,
the "placebo" condition). Viewed from this perspective, only about one out of
four patients with major depression responds specifically to either selective
serotonin or serotonin-norepinephrine reuptake inhibitors. These principles are
important if one is to put the
recent controversy about the effectiveness of modern antidepressant treatment
into perspective. The critical issue is not how good the drugs are but rather
how serious our diseases are. When evaluating the current antidepressants, the
principal issue is not how many
patients with major depression they treat but instead how well they treat the
patients they do treat. The Sequenced Treatment Alternatives to Relieve
Depression (STAR*D) study has clearly documented that approximately 40% of
patients with major depression do not
respond
to existing antidepressants. That finding is consistent with the concept that
there are likely many forms of depressive illness, only a fraction of which are
responsive to drugs that work via effects on biogenic amines.
Agomelatine for the treatment of major depressive
disorder. - Agomelatine (Valdoxan/Thymanax), is a melatonin (MT1/MT2)
agonist and serotonin (5-HT2c) receptor antagonist. Agomelatine produces
strong
effects
on circadian sleep phase disturbances, improving time to sleep onset and quality
of sleep. It has been shown to be superior to placebo and similar to existing
antidepressants. However, 3 - 4.5% of patients treated with 50 mg/day showed
elevated transaminases. Although
none of these reactions so far seem to have been serious, the adverse effects in
the liver may present a regulatory and marketing challenge.
Pharmacotherapy in depressed children and adolescents. -
In the treatment of mild and moderate depressive symptoms, non-pharmacological
approaches such as psychotherapy play a major role, a
severe
symptomatology
may demand a combination with antidepressants. As first-choice medication for
the treatment of juvenile depression, the selective serotonin reuptake inhibitor
(SSRI) fluoxetine is recommended, due to its efficacy and approval. As
second-choice antidepressants the
SSRIs
sertraline, escitalopram and citalopram might be used. Other antidepressants -
such as tricyclic antidepressants, ?(2)-adrenoceptor antagonists, selective
noradrenalin reuptake inhibitors (SNRI) - may be alternatively used, but not as
first- or second-choice
medications.
Escitalopram for the treatment of major depressive disorder
in youth. - The efficacy of escitalopram in adolescent major depressive
disorder was demonstrated in a double-blind, randomized,
controlled trial. The
optimal dose is 10 mg/day and the magnitude of the antidepressant effect is
modest. Escitalopram treatment is generally well tolerated by adolescents, but
treatment-emergent agitation, suicidal behavior and manic symptoms should be
closely monitored.
A guide to
the treatment of depression in women by estrogens. - Transdermal
estrogens in the appropriate dose will suppress ovulation and suppress the
cyclical hormonal changes that produce
premenstrual
depression.
Estrogens also have a mood-enhancing effect in postnatal depression and the
depression in the transitional phase of the menopause. It is possible to add
transdermal testosterone which will improve mood, energy and libido. The problem
is the progestogen as these women
are
often progestogen-intolerant. Progestogen should be used in the lowest dose and
for the shortest duration necessary to prevent endometrial hyperplasia or the
return of premenstrual syndrome-type symptoms if the women are
progestogen-intolerant. The use of estrogens
for
depression in these women does not exclude the use of antidepressants.
Hormone-responsive depression cannot be diagnosed by measuring hormone levels
but can only be diagnosed by a careful history relating depression to the
menstrual cycle, pregnancies and the
perimenopausal years.
Quetiapine
extended release: adjunctive treatment in major depressive disorder. -
Quetiapine extended release (XR) is a once-daily oral formulation of the
atypical antipsychotic quetiapine that
is available for
use
as adjunctive therapy in major depressive disorder (MDD). The numbers needed to
treat to achieve an additional response over antidepressant plus placebo were
11-18 and 8-9 in the quetiapine XR 150 and 300?mg/day dosage groups,
respectively. Treatment-emergent adverse
events were mostly of mild to moderate severity; 1% of adjunctive quetiapine XR
and 1.3% of antidepressant plus placebo recipients reported serious adverse
events.
[ Editor: In mental health, a number needed to treat (NNT) above 8 is
considered clinically insignificant. Thus this medication's NNT of 8-9 for
300 mg/day to produce a response would mean that it's antidepressant effect
was on the border of clinical
insignificance.]
Agomelatine: a narrative review. - Agomelatine, a
melatonergic receptor agonist (MT(1)/MT(2)) and 5HT(2C) receptor antagonist. It
is efficacious in both the acute phase and the continuation
phase of treatment
of
depression and anxiety symptoms associated with major depression. It has
comparable efficacy with other antidepressants. It has a low incidence of
treatment emergent sexual dysfunction and weight gain. Transient
aminotransferase elevations without clinical signs of
liver
damage have been observed more frequently than with placebo (1.1% versus 0.7%),
and a hepatic monitoring schedule is therefore recommended.
A
benefit-risk assessment of agomelatine in the treatment of major
depression. - Six European trials demonstrated a small, statistically
significant, marginally clinically relevant difference in
efficacy
favouring
agomelatine over placebo. The only placebo-controlled study in elderly patients
did not demonstrate a significant benefit for agomelatine. Because elevated
liver enzymes are common, and there is a rare risk of more serious liver
reactions, routine laboratory
monitoring of
liver function is recommended. Agomelatine does not have clinically significant
advantages compared with other antidepressant drugs. It should only be
considered as an alternative drug for patients who do not respond to or
cannot tolerate other antidepressant
drugs.
[ Editor: This article conveniently failed to mention that agomelatine
increases liver enzymes, and there is a rare risk of more serious liver
reactions.]
Vilazodone
for the treatment of depression. - Vilazodone is a new agent recently
approved by the FDA for treating major depressive disorder. Response rates seen
with vilazodone are similar to
those of currently
available antidepressants.
Therapeutic options in treatment-resistant depression. -
Treatment-resistant depression responds to antidepressant medication combined
with lithium, atypical antipsychotics or electroconvulsive
therapy (ECT).
The
use of cognitive behavior therapy is recommended for unipolar
treatment-resistant depression (TRD), but there is no evidence supporting its
use in bipolar TRD.
Therapy
for prevention of post-stroke depression. - Depression is the most
common psychiatric disorder after stroke that adversely affects stroke outcomes.
Antidepressants and psychological
therapies may be
effective and safe in preventing post-stroke depression.
A
systematic review of treatments for refractory depression in older
people. - Half of the participants responded to pharmacological
treatments, indicating the importance of managing
treatment-refractory
depression
actively in older people. The only treatment for which there was replicated
evidence was lithium augmentation. The authors found no double-blind randomized
placebo-controlled trials of treatments for refractory depression in older
people.
Switch
antidepressants: when? How? Why? - It is recommended to wait 4 to 8
weeks before changing treatment if the response is insufficient. However, an
early switch is possible in case of
non-response at 2-4
weeks.
Direct switch is possible and well tolerated in most instances, except for
situations implicating a monoamine oxidase inhibitor (MAOI) or a tricyclic
antidepressant.
Treatment-resistant depression: no panacea, many
uncertainties. Adverse effects are a major factor in treatment choice. -
At least 50% of patients with depression do not enter remission after
several weeks of
antidepressant therapy. Depression should only be considered drug-resistant
after at least 6 weeks of therapy. Increasing the dose of the first-line
antidepressant is only based on weak evidence. Trials comparing continuing the
first-line antidepressant versus
switching
to another pharmacological class have yielded conflicting results. Combining two
antidepressants mainly increases the risk of adverse effects, without a tangible
clinical benefit. Two meta-analyses suggest that adding a so-called atypical
neuroleptic to ongoing
antidepressant therapy leads to 1 extra remission per 7 to 10 treated patients,
but also to treatment cessation due to adverse effects in 8% to 9% of cases.
Older neuroleptics have not been properly evaluated in this setting. There is no
firm evidence that adding
lithium
increases the chances of remission. Adding an antiepileptic or a psychostimulant
is more harmful than beneficial. Adding a thyroid hormone, a benzodiazepine,
buspirone or pindolol has no proven antidepressive effect. There is no firm
evidence that adding psychotherapy
increases the chances of remission. Electroconvulsive therapy is probably
effective for some patients with refractory depression but it necessitates
general anaesthesia and carries a risk of memory disorders. Vagal nerve
electrostimulation has no proven efficacy.
Transcranial magnetic stimulation seems to have some efficacy and few adverse
effects.
The role
of the glutamatergic system in pathophysiology and pharmacotherapy for
depression: preclinical and clinical data - Glutamate is the most
important excitatory neurotransmitter in the
central nervous
system.
Glia cells are crucial regulators of the glutamatergic metabolism. Several
studies have reported a dysfunction or reduced number of glia cells in patients
suffering from depression. This could result in hyperfunctioning of the
glutamatergic system leading to a toxic
accumulation of glutamate. Commonly used antidepressants influence the glutamate
metabolism and antiglutamatergic substances [e. g., riluzol] and NMDA-receptor
antagonists [e. g., ketamine] have shown antidepressant properties in mostly
preclinical and some clinical
trials.
Efficacy
of antidepressants: a re-analysis and re-interpretation of the Kirsch
data. - Recently there has been much debate on the true usefulness of
antidepressant therapy especially after the
publication of a
meta-analysis by Kirsch et al. (PLoS Medicine 2008, 5, e45). It seems that the
Kirsch et al.'s meta-analysis suffered from important flaws in the calculations;
reporting of the results was selective and conclusions unjustified and
overemphasized.
Herbal
medicines, other than St. John's Wort, in the treatment of depression: a
systematic review. - Saffron stigma was found to be significantly more
effective than placebo and equally as
efficacious as
fluoxetine
and imipramine. Saffron petal was significantly more effective than placebo and
was found to be equally efficacious compared to fluoxetine and saffron stigma.
Lavender was found to be less effective than imipramine, but the combination of
lavender and imipramine was
significantly more effective than imipramine alone. When compared to placebo,
Echium was found to significantly decrease depression scores at week 4, but not
week 6. Rhodiola was also found to significantly improve depressive symptoms
when compared to placebo.
[Editor: These studies fail to report the treatment effect sizes; thus these
findings may be statistically significant, but not clinically significant.]
Efficacy
of escitalopram compared to citalopram: a meta-analysis. - In this
meta-analysis, the statistically significant superior efficacy of escitalopram
compared to citalopram was shown to be
clinically
relevant,
with a number-needed-to-treat (NNT) value of 5.7 (p<0.0001) for the difference
in remission rates.
Aripiprazole as adjunctive therapy for patients with major
depressive disorder: overview and implications of clinical trial data. -
In November 2007, aripiprazole was approved by the US FDA as
an adjunctive
therapy
to antidepressants for treating MDD. Aripiprazole was demonstrated to be safe
and well tolerated, and showed a minimal trend for weight gain over the course
of a 6-week treatment. The incidence of akathisia was higher than that reported
in studies of patients with
schizophrenia; however, most cases were mild to moderate and infrequently lead
to discontinuation (5 patients out of 1090).
Use of
risperidone as augmentation treatment for major depressive disorder. -
Use of risperidone as adjunctive therapy for treatment-resistant depression may
improve rates of response and
remission, but
long-term
effectiveness and safety cannot be determined at this time. Risperidone
augmentation may be effective and safe when used at low doses (0.25 to 2
mg/day). The most common adverse effects associated with risperidone therapy
were headache, dry mouth, and increased
appetite.
If at
first you don't succeed: a review of the evidence for antidepressant
augmentation, combination and switching strategies. - In
treatment-resistant depression, the strength of evidence
supporting a trial of
augmentation or a switch to a new agent is very similar, with remission rates
between 25% and 50% in both cases. although it is true that adjunctive lithium
and thyroid hormone have established efficacy, we can only be confident that
this is true for use in
combination
with tricyclic antidepressants (TCAs), and the trials were done in less
treatment-resistant patients than those who typically receive TCAs today. Of
these two options, triiodothyronine augmentation seems to offer the best
benefit/risk ratio for augmentation of modern
antidepressants. After failure of a first-line selective serotonin reuptake
inhibitor (SSRI), neither a switch within class nor a switch to a different
class of antidepressant is unequivocally supported by the data, although
switching from an SSRI to venlafaxine or
mirtazapine may potentially offer greater benefits. Interestingly, switching
from a newer antidepressant to a TCA after a poor response to the former is not
supported by strong evidence. Of all strategies to augment response to
new-generation antidepressants,
quetiapine
and aripiprazole are best supported by the evidence, although neither the cost
effectiveness nor the longer-term benefit of these strategies has been
established.
Second-generation antipsychotics in major depressive
disorder: update and clinical perspective. - In major depressive
disorder, second-generation antipsychotics (SGA) monotherapy or adjunctive
therapy to
conventional antidepressants showed rapid onset of antidepressant efficacy.
Although maintenance data are limited, quetiapine monotherapy, risperidone
adjunctive therapy, and amisulpride adjunctive therapy significantly delayed the
time to relapse as compared with
placebo. In general, extrapyramidal symptoms appeared to be low with SGAs, but a
higher incidence of akathisia was observed with aripiprazole. An elevated risk
of weight gain was observed with olanzapine-fluoxetine combination, risperidone,
aripiprazole, and
quetiapine
compared with placebo.
The effect
of mindfulness-based cognitive therapy for prevention of relapse in
recurrent major depressive disorder: a systematic review and
meta-analysis. - Mindfulness-based cognitive therapy
(MBCT) is an
effective intervention for relapse prevention in patients with recurrent major
depressive disorder (MDD) in remission, at least in cases of three or more
previous MDD episodes. The relative risk reduction was 43% for participants with
three or more previous episodes,
while no risk reduction was found for participants with only two episodes. In
two studies, MBCT was at least as effective as maintenance antidepressant
medication.
A
systematic review of non-pharmacological treatments for depression in people
with chronic physical health problems. - The largest and strongest
evidence base supports individual- and
group-based cognitive and
behavioral interventions (18 trials). The evidence was strongest for those
interventions aimed solely at reducing depression in comparison to those aimed
more broadly at reducing the psychosocial stress associated with having a
chronic physical health problem.
Interpersonal psychotherapy for depression: a
meta-analysis. - The overall effect size (Cohen's d) of the 16 studies
that compared IPT and a control group was 0.63, corresponding to a number
needed to treat of
2.91. Ten studies comparing IPT and other psychological treatments showed a
nonsignificant differential effect size of 0.04 (number needed to treat=45.45).
Pharmacotherapy (after removal of one outlier) was more effective than IPT
(number needed to treat=9.43).
Combination maintenance treatment with pharmacotherapy and IPT was more
effective in preventing relapse than pharmacotherapy alone (number needed to
treat=7.63).
[ Editor: In mental health, a number needed to treat larger than 8 usually
means the treatment effect/difference is insignificant. Thus I disagree with
the authors statement that: "pharmacotherapy was more effective than IPT".]
The
efficacy of short-term psychodynamic psychotherapy for depressive disorders
with comorbid personality disorder. - Short-term Psychodynamic
Psychotherapy (STPP) has been shown to be effective
for depressive
disorders with comorbid personality disorder. Pre- to post- treatment effects
sizes were large (d = 1.00-1.27), and these gains were maintained in follow-ups
averaging over 1.5 years. For major depression, no differences were found
comparing STPP to other
psychotherapies,
and STPP was found superior to a wait-list condition.
Computer-aided cognitive behavioral therapy for
depression. - While patients with Major Depression seem to benefit from
computer-based therapy with regular therapist contact, it remains unclear
whether
unattended
self-help interventions over the internet are effective for this patient
population. However, these interventions are effective in patients with mild to
moderate depressive symptomatology.
Internet-delivered psychotherapy for depression in
adults. - Randomized controlled trials have confirmed the efficacy of
guided internet-delivered psychotherapy (iPT) in treating people with
diagnosed or
elevated
symptoms of depression with equivalent results obtained by programs based on
cognitive behavioural or problem solving models. With guidance, effect sizes are
comparable to those obtained in face-to-face psychotherapy.
Group
treatment for postpartum depression: a systematic review. - Postpartum
depression (PPD) is a serious public health problem affecting 10% to 15% of
women during the first year after
delivery with negative
consequences for both mother and infant. Research shows that group treatment is
effective in reducing PPD symptoms.
Is group
psychotherapy effective in older adults with depression? A systematic
review. - Group psychotherapy is an effective intervention in older
adults with depression in comparison to waiting
list controls,
the
overall effect size is very modest. The reported benefits of group intervention
in comparison to other active interventions did not reach statistical
significance. The benefits of group psychotherapy were maintained at follow-up.
Effectiveness of interventions to improve antidepressant
medication adherence: a systematic review. - The interventions which
showed significant improvement in outcomes were primarily
multifaceted and complex,
with
proactive care management and involvement of mental health specialists. The most
commonly used elements of multifaceted interventions included patient
educational strategies, telephone follow-up to monitor patients' progress, as
well as providing medication support
and
feedback to primary care providers. Overall, educational interventions alone
were ineffective in improving antidepressant medication adherence.
Highlights
of the international consensus statement on major depressive disorder. -
The following recommendations were made by the consensus group: periodically
screen all patients for
depression, use
measurement-based tools and full psychiatric assessments to complete
differential diagnoses, refer patients to psychiatric specialists when
appropriate, establish a therapeutic alliance with patients and their
families, begin treatment with an antidepressant for
moderate
or severe depression, treat patients to remission, and continually monitor
patients' symptomatic improvement.
[Editor: These are excellent guidelines for adequate treatment of major
depressive disorder.]
Quality of
life: the ultimate outcome measure of interventions in major depressive
disorder. - Patients with major depressive disorder (MDD) have a
significantly diminished quality-of-life (QOL)
. Treatment for
MDD
has been shown to improve QOL in the acute treatment phase, but QOL remains low
compared to healthy controls even when symptoms are in remission following
treatment. Future treatment studies of MDD should track QOL as the ultimate
outcome measure of treatment success.
Psychomotor retardation in depression: biological
underpinnings, measurement, and treatment. - Manifestations of
psychomotor retardation include slowed speech, decreased movement, and impaired
cognitive
function.
It is common in patients with melancholic depression and those with psychotic
features. Biological correlates may include abnormalities in the basal ganglia
and dopaminergic pathways. Available evidence suggests that depressed patients
with psychomotor retardation may
respond well to electroconvulsive therapy (ECT). Current literature regarding
antidepressants is inconclusive, though tricyclic antidepressants may be
considered for treatment of patients with psychomotor retardation.
Postpartum
depression: an essential overview for the practitioner. - Postpartum
depression (PPD) may have a variety of etiologies, which include changing plasma
levels of estrogen and
progesterone, postpartum
hypothyroidism, sleep deprivation, or difficult life circumstances. Standard
treatments for PPD include psychotherapy and antidepressants. However, treatment
of a thyroid condition or insomnia, or even regular exercise or massage may also
be beneficial. PPD is
underdiagnosed, therefore more screening is needed.
Pharmacogenetics of antidepressant response. - The small
effect sizes of genetic variants and heterogeneity between studies have
significantly hindered attempts to find robust genetic predictors
of response to
antidepressants.
Vascular
depression: where do we go from here? - Vascular depression encompasses
not only depression with small vessel disease of the brain, but also poststroke
depression, and depression
related to myocardial
infarction. The treatment outcome and natural course of vascular depression have
been much worse than that of the nonvascular depression. Poststroke
antidepressant and psychoeducation therapy and vascular preventive interventions
can probably improve outcome.
(Editor: This study shows that studies comparing cognitive-behavioral therapy vs.
imipramine will be biased, since imipramine [unlike an SSRI antidepressant] is
ineffective against atypical depression - and 25% of patients with Major Depressive
Disorder have atypical
depression).
This website uses these 5
major dimensions of human behavior to describe all mental disorders. (This website adds
one more dimension, "Physical Health", to create the "Big 6" dimensions of mental health.)
The behaviors of the "Five Factor Model of Personality" represent five adaptive functions that
are vital to human survival. For example, when one individual approaches another, the individual
must: (1) decide whether the other individual is friend or foe [
"Agreeableness"
], (2) decide if this represents safety or danger [
"Emotional Stability"
], (3) decide whether to approach or avoid the other individual [
"Extraversion/Sociability"
], (4) decide whether to proceed in a cautious or impulsive manner [
"Conscientiousness"
], and (5) learn from this experience [
"Openness/Intellect"
].
Which "Big 6" Dimensions of Mental Health Are Impaired in Major Depressive Disorder?
THE POSITIVE SIDE OF THE "BIG 6" DIMENSIONS OF MENTAL HEALTH
THE NEGATIVE SIDE OF THE "BIG 6" DIMENSIONS OF MENTAL HEALTH
THIS DISORDER
Agreeableness Being kind and honest.
Antagonism Being unkind or dishonest.
Conscientiousness Being diligent and self-disciplined.
Disinhibition Being distractible,
impulsive, or undisciplined.
Disinhibition
Openness/Intellect Showing good creativity, problem-solving, and learning ability
Impaired Intellect Showing decreased creativity, problem-solving, or learning ability.
Impaired Intellect (Psychosis)
Extraversion Being gregarious, assertive and
enthusiastic.
Detachment Being detached,
unassertive, and unenthusiastic.
Detachment
Emotional Stability Being emotionally stable and calm.
Emotional Distress Being emotionally unstable/distressed.
Emotional Distress
Physical Health Being physically fit and healthy.
Physical Symptoms Being physically unfit or ill.
Physical Symptoms
The Following Will Only Discuss The Dimensions of Mental Illness That Are Abnormal In This Disorder
The problems that
are characteristic of this disorder are highlighted with this pink
background color.
CONSCIENTIOUSNESS VS. DISINHIBITION
CONSCIENTIOUSNESS (Self-Control)
Description:
Conscientiousness is synonymous with being
industrious and orderly. The Conscientiousness dimension
measures the behaviors that are central to the concept of
SELF-CONTROL - organizing and controlling one's behavior in order to
achieve one's goals. This involves traits like paying attention, controlling
impulses, and delaying gratification. Individuals with high
Conscientious work hard to achieve goals, pursue accuracy and
perfection, show prudent, careful decision making, and are orderly with
things and time. High Conscientiousness is associated with better:
longevity, health, school and job performance. (This dimension appears to
measure the behaviors that differentiate industriousness from
distractibility [or order from chaos]).
Descriptors:
Cautious, self-disciplined, industrious, efficient, organized,
responsible.
Chimpanzees:
The Conscientious-Disinhibited dimension of human behavior is also
evident in chimpanzees. Chimpanzees can plan for the future and control their
impulses (video). Goal-directed behavior requires good impulse
control, otherwise it becomes distracted and disorganized.
Executive Functioning:
The human brain's problem-solving and planning ability is the most
advanced in all of the animal kingdom. This ability is called executive
functioning (defined as “the ability to maintain an appropriate
problem-solving set for attainment of a future goal”). Individuals with poor
executive functioning have difficulty with problem-solving, planning,
impulse control, avoiding distraction, and maintaining goal-oriented
behavior. Thus the "Big 5" personality dimension of Conscientiousness
appears to describe the brain's executive functioning ability. Language Characteristics: Many positive emotion
words (e.g. happy, good), few emotional distress words (e.g. hate, bad),
more perspective, careful to check that information is conveyed correctly,
straight to the point, formal, few negations, few swear words, few
references to friends, few disfluencies or filler words, many insight words,
not impulsive.
Research:
Higher scores on Conscientiousness predict greater success in
school and at work. *MRI research found that Conscientiousness was
associated with increased volume in the lateral prefrontal cortex, a region
involved in planning and the voluntary control of behavior.
Video Example:
Here is an example of a very conscientious person - President Obama discussing the Iranian nuclear
treaty.
"I do a thorough job. I want everything to be 'just right'. I want every
detail taken care of."
"I am careful."
"I am a reliable hard-worker."
"I am organized. I follow a schedule and always know what I am doing."
"I like order. I keep things tidy."
"I see that rules are observed."
"I do things efficiently. I get things done quickly."
"I carry out my plans and finish what I start."
"I am not easily distracted."
DISINHIBITION (Impaired Self-Control)
Description:
Disinhibition is synonymous with being distractible, impulsive and
disorganized. Individuals with high Disinhibition avoid difficult tasks
or challenging goals, don't mind incompleteness or inaccurracy, act without
thinking of the consequences, have disorganized surroundings and
schedules.
ICD-11 Description:
The core feature of the Disinhibition trait domain is the tendency
to act rashly based on immediate external or internal stimuli (i.e., sensations,
emotions, thoughts), without consideration of potential negative consequences.
Common manifestations of Disinhibition include: impulsivity;
distractibility; irresponsibility; recklessness; and lack of planning.
Descriptors:
Impulsive, uncontrolled, distractible, inefficient, disorganized,
irresponsible.
Language Characteristics: Few positive emotion
words, many emotional distress words, less perspective, less careful, more
vague, informal, many negations, many swear words, many references to friends
(e.g. pal, buddy), many disfluencies or filler words, few insight words,
impulsive.Few positive emotion words, many emotional distress words, less
perspective, less careful, more vague, informal, many negations, many swear
words, many references to friends (e.g. pal, buddy), many disfluencies or filler
words, few insight words, impulsive. Screening Questions:
"People would describe me as reckless."
"I feel like I act totally on impulse."
"Even though I know better, I can’t stop making rash decisions."
"Others see me as irresponsible."
"I’m not good at planning ahead."
*
Distractibility:
"I can't focus on things for very long."
"I am easily distracted."
"I have trouble pursuing specific goals even for short periods of time."
"I can't achieve goals because other things capture my attention."
"I often make mistakes because I don't pay close attention."
Description:
Intellect is synonymous with being open to
experience and being intellectual. Openness to experience
reflects appreciation for art, music, nature, beauty, adventure, and variety
of experience. These individuals are willing to learn, be innovative, and be
flexible. Intellect reflects one's cognitive capacity (e.g.,
reasoning, memory, attention, language and learning). Individuals with high
Intellect are intellectually curious, quick to learn things,
creative, formulate ideas clearly, and have a rich vocabulary. Humans are
set apart from all other species by their intellectual curiosity and their
need to tell stories as a form of social bonding. The Intellect
dimension measures the behaviors that are central to the concept of
WISDOM - having curiosity, experience, knowledge, and good judgment.
(Science requires openness, intellectual curiosity, experimentation, and the
free exchange of information.) High Intellect is associated with
better: longevity, school and creative performance.
Descriptors:
Intelligent, good problem-solving, open-minded, open to new ideas,
creative, innovative.
Chimpanzees:
Human babies vs. chimps: who's smarter? Chimps,
orangutans, and human toddlers perform about equally well on
"physical learning" (e.g., locating hidden objects, figuring out the
source of a noise, understanding the concepts of more and less, using a
stick to get something that's out of reach). Chimpanzees are far superior to humans in "working
memory" (video) (i.e., the brain's ability to temporarily store and
use information). Where human toddlers are far superior to these apes is on
"social learning" tasks (e.g., understanding how to solve a problem
by watching someone else do it, figuring out someone else's state of mind
from their actions, or using nonverbal communication to explain or
understand how to find something). Thus what
makes human intelligence special is our ability to cooperate and
communicate to share expertise. This has allowed us to build complex
societies, collaborate and learn from each other at a high level, and use
symbolic representation (writing, numerals, imagery) to communicate
ideas.
Evolution:
The brains of intelligent species evolved the ability to detect correlational patterns in their perceptions. Then a few intelligent species evolved the
ability to logically detect causal patterns in their perceptions (and later in their abstract or semantic
information). [But will the human brain destroy itself?] Language Characteristics: Many positive
emotion words (e.g. happy, good), high meaning elaboration, more
perspective, politeness, few self-references, complex sentence
constructions, few causation words, many inclusive words (e.g. with, and),
few third person pronouns, many tentative words (e.g. maybe, guess), many
insight words (e.g. think, see), few filler words and within-utterance
pauses, stronger uncommon verbs.
Research:
Higher scores on Intellect are associated with greater
creativity and general intelligence. *MRI research found that
Intellect did not have any significant correlation with the volume of
any localized brain structure. However cognitive testing has shown that "dorsolateral
prefrontal cortex function as well as both fluid and crystalized cognitive
ability was positively related to Intellect but no other personality
trait." Relationship To General Intelligence: The "Big 5" personality dimension of Intellect appears to
describe the individual's general intelligence (g). Research has
shown that Intellect can be separated into 2 factors: Openness and
Intellect. Intellect was independently associated with general
intelligence (g) and with verbal and nonverbal intelligence about equally.
Openness was independently associated only with verbal
intelligence. Example: This video shows how we see what we want to see. What we pay
attention to (or what we believe about the world) blinds us to reality.
(Exit YouTube after first video.) Being Smart Is About Being Adaptive And Open
To New Ideas: When facts prove them wrong, successful people are smart enough to
admit that they are wrong and change their mind. Multi-billionaire Jeff
Bezos said "that the smartest people are constantly revising their
understanding, reconsidering a problem they thought they'd already
solved." He said that people who are right a lot often change their
minds a lot as well. According to Bezos, being truly smart is about
being adaptive and open to new perspectives and ways of thinking. Bezos
encourages people to "look for new ideas from everywhere." Our IQs Are Increasing: IQ gains have averaged 0.28 IQ points annually since 1908. That
would mean that the average person in 1908 would be borderline retarded
by today's standards. Likewise, the average person today would have a
higher IQ that 98 percent of people in 1908. This could explain why
modern moral judgments differ so dramatically from those of our Bronze
Age ancestors. For example, the Bible condoned genocide (Deuteronomy
20:16–18, Joshua 10:40), slavery (Leviticus 25:44, Ephesians 6:5, 1
Timothy 6:1), and insisted on the death penalty for extramarital affairs
(Deuteronomy 22:22) and for being a subborn and rebellious son
(Deuteronomy 21:18-21).
"I am original, and come up with new ideas."
"I am curious about many different things."
"I am quick to understand things."
"I can handle a lot of information."
"I like to solve complex problems."
"I have a rich vocabulary."
"I think quickly and formulate ideas clearly."
"I Enjoy the beauty of nature"
"I believe in the importance of art."
"I love to reflect on things."
"I get deeply immersed in music."
"I see beauty in things that others might not notice."
"I need a creative outlet."
CLOSED-MINDEDNESS (Impaired Intellect)
Description:
Low Intellect is synonymous with being closed to
experience and being unintellectual. Individuals that are closed to
experience are rather unimpressed by most works of art, prefer routine
over variety, stick to what they know, and prefer less abstract arts and
entertainment. Individuals with low intellect are not intellectually
curious, learn things slowly, have difficulty understanding abstract ideas,
avoid creative pursuits, and feel little attraction toward ideas that may seem
radical or unconventional.
Descriptors:
Unwise, poor problem-solving, closed-minded, not open to new ideas,
uncreative, not innovative.
Language Characteristics: Few positive emotion
words, low meaning elaboration, less perspective, less politeness, few positive
emotion words, many self-references, simple sentence construction, many
causation words (e.g. because, hence), many third person pronouns, few tentative
words, few insight words, many filler words and within-utterance pauses, milder
verbs.
"I prefer work that is routine."
"I have difficulty understanding abstract ideas."
"I think slowly."
"People find it hard to follow my logic or understand my thoughts."
"I avoid philosophical discussions."
"I avoid difficult reading material."
"People find it hard to follow my logic or understand my thoughts."
"I have few artistic interests."
"I seldom notice the emotional aspects of paintings and pictures."
"I do not like poetry."
"I seldom get lost in thought."
"I seldom daydream."
Cognitive Impairment
* Memory
Impairment: [When Severely Depressed]
"I have difficulty learning new things, or remembering things that
happened a few days ago."
"I often forget a conversation I had the day before."
"I often forget to take my medications, or to keep my appointments."
* Impaired
Reasoning: [When Severely Depressed]
"My judgment or ability to solve problems isn't good."
"I have difficulty understanding abstract ideas."
"I think slowly."
"People find it hard to follow my logic or understand my thoughts."
Psychoticism
Description:
Psychoticism is the state of being psychotic or of being predisposed
to develop psychosis.
Descriptors:
Unusual beliefs and experiences, eccentricity, perceptual
dysregulation. Screening Questions:
"My thoughts often don’t make sense to others."
"I have seen things that weren’t really there."
"I often have thoughts that make sense to me but that other people say
are strange."
"I often “zone out” and then suddenly come to and realize that a lot of
time has passed."
"Things around me often feel unreal, or more real than usual."
* Unusual
Beliefs and Experiences [When Severely Depressed]:
"I often have unusual experiences, such as sensing the presence of
someone who isn't actually there."
"I've had some really weird experiences that are very difficult to
explain."
"I have seen things that weren’t really there."
"I have some unusual abilities, like sometimes knowing exactly what
someone is thinking."
"I sometimes have heard things that others couldn’t hear."
"Sometimes I can influence other people just by sending my thoughts to
them."
"I often see unusual connections between things that most people miss."
Description:
Extraversion is synonymous with being outgoing, gregarious, enthusiastic
and assertive. Assertiveness encompasses traits relating to
leadership, dominance, and drive. Enthusiasm encompasses both
sociability and the tendency to experience and express positive emotion.
Individuals with high Extraversion feel positively about themselves,
feel confident when leading or addressing groups of people, enjoy social
gatherings and interactions, and experience positive feelings of enthusiasm
and energy. The Extraversion dimension measures the behaviors that
are central to the concept of SOCIALITY - the tendency to associate
in or form social groups. High Extraversion is associated with
better: longevity, leadership, job [sales] performance. (This dimension
appears to measure the behaviors that differentiate approach from
avoidance.)
Descriptors:
Sociable, talkative, enthusiastic, energetic, assertive,
self-confident.
Evolution:
Humans have always depended on social cooperation for their survival.
Our earliest caveman ancestors were too physically weak to survive without
the help of their social group. Research has shown that our
brains can't remain sane without social and/or environmental
stimulation. A person undergoing mild sensory and total social
deprivation in a room for 3-4 days will become confused and start to lose
contact with reality. To remain sane, our brains must be connected to a
social network. The relative social and sensory deprivation of astronauts in
space may become a major problem. Martin Seligman (in his book "Flourish"
p.147) states:
"One American astronaut almost aborted an entire earth orbit mission
by shutting off communications for several orbits, out of pique that
his music player had not yet been repaired in spite of his repeated
requests."
The brains of animal social species evolved
an opioid neurotransmitter system that produces positive emotion
which is important for social affiliation. These species also evolved a
dopamine neurotransmitter system that produces drive and heightened
approach behavior. Language Characteristics: Many topics,
higher verbal output, think out loud, pleasure talk, agreement, compliment,
positive emotion words, sympathetic, concerned about hearer, simple
constructions, few unfilled pauses, few negations, few tentative words,
informal language, exaggeration, many words related to humans (e.g. "man",
"pal"), poor vocabulary.
Research:
Higher scores on Extraversion are associated with greater
happiness and broader social connections. *MRI research found that
Extraversion was associated with increased volume of medial
orbitofrontal cortex, a region involved in processing reward
information.
Video Example:
Here is an example of a delightful extraverted, sociable couple proudly
showing their catamaran sailboat which they are sailing around the world.
"I'm talkative"
"I'm not reserved."
"I'm full of energy."
"I generate a lot of enthusiasm."
"I'm not quiet."
"I have an assertive personality."
"I'm not shy or inhibited."
"I am outgoing and sociable."
"I make friends easily."
"I warm up quickly to others."
"I show my feelings when I'm happy."
"I have a lot of fun."
"I laugh a lot."
"I take charge."
"I have a strong personality."
"I know how to captivate people."
"I see myself as a good leader."
"I can talk others into doing things."
"I am the first to act."
DETACHMENT (Impaired Sociality)
Description:
Detachment is synonymous with low enthusiasm and low assertiveness.
Individuals with high Detachment consider themselves unpopular, feel
awkward when they are the center of social attention, are indifferent to social
activities, and feel less lively and optimistic than others do.
ICD-11 Description:
The core feature of the Detachment trait domain is the tendency to
maintain social detachment (interpersonal distance) and emotional detachment
(emotional distance). Common manifestations of Detachment include: social
detachment (avoidance of social interactions, lack of friendships, and avoidance
of intimacy); and emotional detachment (reserve, aloofness, and limited
emotional expression and experience).
Descriptors:
Withdrawn, quiet, unenthusiastic, apathetic, unassertive, shy.
Reserved Rarely get caught up in the excitement Am not a very
enthusiastic person Am hard to get to know Keep others at a
distance Reveal little about myself
Unassertive:
Do not have an assertive personality Lack the talent for
influencing people Wait for others to lead the way Hold back
my opinions.
Language Characteristics: Single topic, doesn't
think out loud, problem talk, dissatisfaction, emotional distress words, not
sympathetic, elaborated sentence constructions, many unfilled pauses, formal
language, many negations, many tentative words (e.g. maybe, guess), few swear
words, little exaggeration, few words related to humans, rich vocabulary. Screening Questions:
"I often feel down, depressed, or hopeless."
"I steer clear of romantic relationships."
"I’m not interested in making friends."
"I don’t like to get too close to people."
"I rarely get enthusiastic about anything."
* Loss of
Interest or Pleasure:
"I often feel like nothing I do really matters."
"I almost never enjoy life."
"Nothing seems to make me feel good."
"Nothing seems to interest me very much."
"I almost never feel happy about my day-to-day activities."
"I rarely get enthusiastic about anything."
"I don't get as much pleasure out of things as others seem to."
Description:
Emotional Stability is synonymous with stability and
calm. The Emotional Stability dimension measures the
behaviors that are central to the concept of COURAGE - having calm
composure and endurance when confronting adversity. Individuals with high
Emotional Stability are relatively tough, brave, and insensitive to
physical pain, feel little worry even in stressful situations, and have
little need to share their concerns with others. High Emotional
Stability is associated with better: longevity, leadership, job
[team] performance, and marital success. (This dimension appears to measure
the behaviors that differentiate safety from danger.)
Descriptors:
Calm, rarely angry, rarely depressed or moody, rarely anxious or
embarrassed.
Language Characteristics: Pleasure talk,
agreement, compliment, low verbal productivity, few repetitions, neutral
content, calm, few self-references, many short silent pauses, few long
silent pauses, many tentative words, few aquiescence, little exaggeration,
less frustration, low concreteness.
"I am relaxed, and I handle stress well."
"I am emotionally stable, and not easily upset."
"I remain calm in tense situations."
"I rarely get irritated."
"I keep my emotions under control."
"I rarely lose my composure."
"I am not easily annoyed."
"I seldom feel blue."
"I feel comfortable with myself."
"I rarely feel depressed."
"I am not embarrassed easily."
EMOTIONAL DISTRESS (Impaired Stability)
Description:
Emotional Distress is synonymous with emotional volatility and
negative emotion. Individuals with high emotional volatility are
easily upset or angered. They often are very moody and emotionally labile.
Individuals that have high negative emotion exhibit over-sensitivity
to threat or stress. They exhibit excessive fear, anxiety, depression, or
irritability.
ICD-11 Description:
The core feature of the Emotional Distress (or Negative
Affectivity) trait domain is the tendency to experience a broad
range of negative emotions. Common manifestations of Emotional
Distress include: experiencing a broad range of negative emotions
with a frequency and intensity out of proportion to the situation; emotional
lability and poor emotion regulation; negativistic attitudes; low
self-esteem and self-confidence; and mistrustfulness.
Descriptors:
Easily upset, angry, depressed, moody, anxious, embarrassed.
Evolution:
All animals have evolved a "fight or flight" response to threat to
ensure their survival. Mammals went one step further and evolved a "fight,
flight, or freeze" response to threat. In humans, this mammalian "freeze"
response to threat involves inhibition of behavior in response to threat,
punishment, and emotional distress. This threat response of "freezing",
shutting down or passively avoiding is commonly seen in human anxiety or
depression (e.g., freezing with fear or being immobilized by indecision,
worry or depression).
Language Characteristics: Problem talk,
dissatisfaction, high verbal productivity, many repetitions, polarised
content, stressed, many self-references, few short silent pauses, many long
silent pauses, few tentative words, more aquiescence, many self references,
exaggeration, frustration, high concreteness. Screening Questions:
"I worry about almost everything."
"I get emotional easily, often for very little reason."
"I fear being alone in life more than anything else."
"I get stuck on one way of doing things, even when it’s clear it
won’t work."
"I get irritated easily by all sorts of things."
Research:
Lower scores on Emotional Stability are associated with
unhappiness, dysfunctional relationships, and mental health problems. *MRI
research found that Low Emotional Stability (= Emotional Distress or
Neuroticism) was associated with increased volume of brain regions
associated with threat, punishment, and emotional distress.
* Depressed
Mood:
"I have no worth as a person."
"Everything seems pointless to me."
"I often feel like a failure."
"The world would be better off if I were dead."
"The future looks really hopeless to me."
"I often feel just miserable."
"I'm very dissatisfied with myself."
"I often feel like nothing I do really matters."
"I know I'll commit suicide sooner or later."
"I talk about suicide a lot."
"I feel guilty much of the time."
"I'm so ashamed by how I've let people down in lots of little ways."