Internet Mental Health
 
SCHIZOPHRENIA
 


Prediction: Episodic/Chronic For Lifetime

      Occupational-Economic:       Wisdom vs Irrationality:
  • Continuous cognitive impairment (distractibility, apathy, forgetfulness, impaired executive functioning [planning, problem-solving], impaired social communication)
  • Episodic/continuous psychosis (unless on antipsychotic medication)
      Courage vs Negative Emotion:
  • Flat or blunted emotions, 5% suicide rate
      Helping Others vs Detachment:
  • Schizoid traits: intimacy avoidance, social withdrawal, lack of emotional expression
  • Paranoid traits: suspiciousness, bearing grudges, feeling victimized
      Self-Control vs Disinhibition: N/A
      Justice vs Antagonism:
  • Majority are nonviolent, but overall there is an above average risk of physical violence. (NOTE: Alcoholics and drug addicts are much more violent than individuals with schizophrenia.)
      Medical:
  • Denial of illness; increased risk of death due to accident or other illness


SYNOPSIS

Schizophrenia F20 - ICD10 Description, World Health Organization
The schizophrenic disorders are characterized in general by fundamental and characteristic distortions of thinking and perception, and affects that are inappropriate or blunted. Clear consciousness and intellectual capacity are usually maintained although certain cognitive deficits may evolve in the course of time. The most important psychopathological phenomena include thought echo; thought insertion or withdrawal; thought broadcasting; delusional perception and delusions of control; influence or passivity; hallucinatory voices commenting or discussing the patient in the third person; thought disorders and negative symptoms.

The course of schizophrenic disorders can be either continuous, or episodic with progressive or stable deficit, or there can be one or more episodes with complete or incomplete remission. The diagnosis of schizophrenia should not be made in the presence of extensive depressive or manic symptoms unless it is clear that schizophrenic symptoms antedate the affective disturbance. Nor should schizophrenia be diagnosed in the presence of overt brain disease or during states of drug intoxication or withdrawal. Similar disorders developing in the presence of epilepsy or other brain disease should be classified under F06.2 (organic delusional disorder), and those induced by psychoactive substances under F10-F19 (mental and behavioural disorders due to substance abuse) with common fourth character .5 (psychotic disorder).

    F20.0 Paranoid schizophrenia

    Paranoid schizophrenia is dominated by relatively stable, often paranoid delusions, usually accompanied by hallucinations, particularly of the auditory variety, and perceptual disturbances. Disturbances of affect, volition and speech, and catatonic symptoms, are either absent or relatively inconspicuous.

    F20.1 Hebephrenic schizophrenia

    A form of schizophrenia in which affective changes are prominent, delusions and hallucinations fleeting and fragmentary, behaviour irresponsible and unpredictable, and mannerisms common. The mood is shallow and inappropriate, thought is disorganized, and speech is incoherent. There is a tendency to social isolation. Usually the prognosis is poor because of the rapid development of "negative" symptoms, particularly flattening of affect and loss of volition. Hebephrenia should normally be diagnosed only in adolescents or young adults.

    F20.2 Catatonic schizophrenia

    Catatonic schizophrenia is dominated by prominent psychomotor disturbances that may alternate between extremes such as hyperkinesis and stupor, or automatic obedience and negativism. Constrained attitudes and postures may be maintained for long periods. Episodes of violent excitement may be a striking feature of the condition. The catatonic phenomena may be combined with a dream-like (oneiroid) state with vivid scenic hallucinations.

    F20.3 Undifferentiated schizophrenia

    Psychotic conditions meeting the general diagnostic criteria for schizophrenia but not conforming to any of the subtypes in F20.0-F20.2, or exhibiting the features of more than one of them without a clear predominance of a particular set of diagnostic characteristics.

    F20.4 Post-schizophrenic depression

    A depressive episode, which may be prolonged, arising in the aftermath of a schizophrenic illness. Some schizophrenic symptoms, either "positive" or "negative", must still be present but they no longer dominate the clinical picture. These depressive states are associated with an increased risk of suicide. If the patient no longer has any schizophrenic symptoms, a depressive episode should be diagnosed (F32.-). If schizophrenic symptoms are still florid and prominent, the diagnosis should remain that of the appropriate schizophrenic subtype (F20.0-F20.3).

    F20.5 Residual schizophrenia

    A chronic stage in the development of a schizophrenic illness in which there has been a clear progression from an early stage to a later stage characterized by long- term, though not necessarily irreversible, "negative" symptoms, e.g. psychomotor slowing; underactivity; blunting of affect; passivity and lack of initiative; poverty of quantity or content of speech; poor nonverbal communication by facial expression, eye contact, voice modulation and posture; poor self-care and social performance.

    F20.6 Simple schizophrenia

    A disorder in which there is an insidious but progressive development of oddities of conduct, inability to meet the demands of society, and decline in total performance. The characteristic negative features of residual schizophrenia (e.g. blunting of affect and loss of volition) develop without being preceded by any overt psychotic symptoms.
Schizophrenia - Diagnostic Criteria, American Psychiatric Association

An individual diagnosed with schizophrenia needs to meet all of the following criteria:

  • Active-Phase Symptoms: Two (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated). At least one of these symptoms must be delusions, hallucinations, or disorganized speech:

    • Delusions.

    • Hallucinations.

    • Disorganized speech (e.g. frequent derailment or incoherence).

    • Grossly disorganized or catatonic behavior.

    • Negative symptoms (i.e., diminished emotional expression or avolition).

  • For a significant portion of the time since the onset of the disturbance, level of functioning in one or more major areas, such as work, interpersonal relations, or self-care, is markedly below the level achieved prior to the onset (or when the onset is in childhood or adolescence, there is failure to achieve expected level of interpersonal, academic, or occupational functioning).

  • Continuous signs of the disturbance persist for at least 6 months. This 6-month period must include at least 1 month of symptoms (or less if successfully treated) that meet the above criterion for active-phase symptoms and may include periods of prodromal or residual symptoms. During these prodromal or residual periods, the signs of the disturbance may be manifested by only negative symptoms or by two or more active-phase symptoms present in an attenuated form (e.g., odd beliefs, unusual perceptual experiences).

  • Schizoaffective disorder and depressive or bipolar disorder with psychotic features have been ruled out because either (1) no major depressive or manic episodes have occurred concurrently with the active-phase symptoms; or (2) if mood episodes have occurred during active-phase symptoms, they have been present for a minority of the total duration of the active and residual periods of the illness.

  • The disturbance is not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition.

  • If there is a history of autistic spectrum disorder or a communication disorder of childhood onset, the additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations, in addition to the other required symptoms of schizophrenia, are also present for at least 1 month (or less if successfully treated).

Schizophrenia affects between 0.55 and 1 percent of the population. In 2002, the overall cost of schizophrenia in America was estimated to be USD $62.7 billion.

Schizophrenia usually starts in late adolescence or early adulthood, and may be preceded by years of gradual social and academic deterioration. The diagnosis requires that a one-month psychotic phase of the illness be associated with at least a 6-month period of decline in interpersonal, academic, or occupational functioning. The risk of suicide is high; 5% of individuals with this disorder kill themselves. The suicide risk is highest at the onset of the illness. In schizophrenia, an individual can have depressive or manic episodes. However, schizophrenia is not diagnosed if the total duration of these mood episodes last longer than 50% of the total duration of the illness.
What Are The Core Features Of Schizophrenia?

Until recently, schizophrenia was thought to be "just" a psychotic disorder; hence research was aimed at finding better ways to prevent its psychotic symptoms. Antipsychotic medications now can prevent psychotic symptoms in two-thirds of individuals with schizophrenia. However, even on antipsychotic medication, 70% of individuals with schizophrenia are not competitively employed, are single, and have a poor level of psychosocial functioning 10 years after first admission.

Thus the psychotic symptoms of schizophrenia are "just the top of the iceberg", and not its core features.

Researchers have now found the cognitive impairments that are the core features of schizophrenia (that cause unemployment, being single, and having a low level of psychosocial functioning). The psychotic symptoms of schizophrenia often are episodic and come and go. However, the cognitive impairments that are the core features of schizophrenia are chronic and unwavering. Research has shown that there is significant loss of brain mass in schizophrenia and disruption of connection within the brain. These underlying anatomical deficits are now believed to cause the cognitive impairments that are the core features of schizophrenia (e.g., impaired executive functioning, cognitive slowing, apathy, memory impairment, and poor concentration).

Antipsychotic medication is dramatically effective in preventing psychotic relapse and rehospitalization. Unfortunately, antipsychotic medication does little to improve the cognitive impairments caused by schizophrenia. However, there is evidence that antipsychotic medication does prevent the worsening of these cognitive impairments. Thus, in order to protect the brain from further neurological deterioration, every effort should be made to keep individuals with schizophrenia on their antipsychotic medication.

Implications Of Schizophrenia Being A Lifelong Neurological Disorder

There are many expensive frauds that promise miracle-like recovery from schizophrenia with vitamins or other treatment fads. These bogus therapies do have an initial placebo effect, but it soon becomes obvious that they do little to reduce the psychosis, unemployment, and low psychosocial functioning of individuals with schizophrenia. Since schizophrenia is a lifelong neurological disorder which usually results in unemployment and social isolation; governments should ensure that there is adequate mental health funding for: disability pensions, government subsidized housing, supervised psychiatric group homes, free psychiatric medication and healthcare, mental health drop-in centers and clubhouses, sheltered employment, and supervised recreational activities.

It is now obvious that there will not be a "quick cure" for schizophrenia. Our best therapies can protect our patients from further harm, and significantly improve their quality of life. These therapies can ensure that most of our patients will have an active social life. Unfortunately, our current therapies are unable to return the majority of our patients to competitive employment.


Effective Therapies

Pharmacotherapy

Recent research has shown that: (1) the newer, "atypical" or "second generation", antipsychotic medications are no more effective than the first generation antipsychotic medications; (2) most antipsychotic medications are equally effective, but only differ in adverse effects; (3) half of patients refuse to stay on their antipsychotic medication - and this is a major reason for treatment failure; (4) antipsychotic medication is effective in symptom control in up to two-thirds of patients, but in at least one-third of patients the response is poor; (5) antipsychotic medications are the most effective means of preventing relapse and rehospitalization, and should be taken continuously for a lifetime (since 90% of first-episode patients with schizophrenia relapse within 2 years if not on antipsychotic medication).

Antipsychotic Effectiveness

Equal Effectiveness Of Antipsychotic Drugs In Treating Hallucinations

Thus antipsychotic medication is not a cure for schizophrenia, but these drugs significantly help to control schizophrenia. Off antipsychotic medication, individuals with schizophrenia live very isolated, tormented lives.

A review of 65 randomised controlled trials involving 6493 patients with schizophrenia found that, at 1-year follow-up:

  • Antipsychotic drugs prevent relapse (relapse rate: drug 27%, placebo 64%, NNT 3)

  • Antipsychotic drugs prevent hospitalization (hospitalization rate: drug 10%, placebo 26%, NNT 5)

  • More participants in the placebo group than in the antipsychotic drug group left the studies early due to inefficacy of treatment (left prematurely: drug 20%, placebo 50%, NNT 3)

  • Quality of life was better in antipsychotic drug-treated participants (SMD -0.62)

Antipsychotic medication decreases the risk of violent behavior in individuals with schizophrenia. Clozapine has a specific anti-aggressive effect in schizophrenia.

Because olanzapine causes very significant weight gain; it is not a first-line treatment for this disorder. For individuals with this disorder who refuse to take their antipsychotic medication, there is the option of giving them injections of long-lasting antipsychotic medication (that can last one month). Clozapine is often effective for patients that have failed to respond to two previous antipsychotic medications. In combination with antipsychotic medication, mood stabilizers are used to control mood swings and impulsivity, and antidepressants are used to treat depression. "Drug holidays" are usually disastrous; thus it is essential that medication be taken continuously without significant dose reduction. Often involuntary hospitalization with forced medication saves lives. There is a wonderful article written by a neuroscientist telling how, when she developed schizophrenia, "Forced medication saved my life".


Inspirational Speech Given By Neuroscientist Who Herself Developed Schizophrenia

The vast majority of psychotic individuals are never at risk of harming themselves or others. However, a small minority of individuals with schizophrenia become violent. Sadly, their violent, bizarre behavior sometimes leads to their death. This is a terrible tragedy because, with treatment, such deaths are totally preventable. In a psychiatric emergency, parents should first call their son's or daughter's psychiatrist or mental health clinic before calling the police. If the police arrive without being accompanied by a psychiatrist and ambulance; there is a risk of tragedy if a psychotic individual physically threatens the police.

Electroconvulsive Therapy

Electroconulsive therapy (ECT) may provide months of benefit, but this benefit is not sustained.

Psychotherapy

No therapy is a substitute for antipsychotic medication, but a number of psychological and social therapies do increase the effectiveness of antipsychotic medication. Cognitive behavioral therapy (CBT) is mildly effective against hallucinations (with small effect sizes ranging from 0.35 to 0.44). CBT appears to be no more effective than other, less expensive, social therapies. Other effective psychological treatments include: psychoeducation, assertive community treatment, supported employment, skills training, token economy interventions, and family-based psychosocial intervention. Intensive case management (ICM) reduces hospitalization, improves adherence to care, and improves social functioning. Educating the patient and the patient's family about schizophrenia and its treatment is always beneficial. Whenever possible, the patient's family should be included and supported in the patient's therapy. The more psychotic the patient, the greater is the need for family involvement in treatment.


Excellent Very Honest Documentary On Bellevue Psychiatric Hospital

Ineffective Therapies

Vitamins, dietary supplements, computer-assisted cognitive rehabilitation, and cognitive remediation have all proven to be ineffective in improving occupational or psychosocial functioning, decreasing psychotic symptoms, or preventing relapse in schizophrenia. Playing mindless brain training games is ineffective.

Medical Complications

Schizophrenia shortens lifespan by up to 15 years, primarily due to cardiovascular disease, and this excess mortality is getting worse. Cardiovascular risk increases after first exposure to any antipsychotic drug. Smoking and obesity are also major risk factors for this excess mortality.

Brain Changes In Schizophrenia

Cognitive impairment, especially of verbal memory and processing speed, is a core feature of schizophrenia. What brain changes could cause these cognitive impairments? Research has found that there are progressive brain changes during the early phases of psychosis. Structural alterations in medial temporal, prefrontal, anterior cingulate and insular cortex plus superior temporal gyrus volume reductions often occur during the acute process of transition to psychosis. These brain structural changes show marked progression at the initial stage of schizophrenia, but less in chronic schizophrenia.

"In the development of schizophrenia, the earliest structural deficits in the brain are found in parietal brain regions, supporting visuospatial and associative thinking. Over 5 years, these deficits progress anteriorly into temporal lobes, engulfing sensorimotor and dorsolateral prefrontal cortices, and frontal eye fields. These structural deficits in the brain correlate with psychotic symptom severity and mirror the neuromotor, auditory, visual search, and frontal executive impairments in the disease. In temporal regions, gray matter loss is completely absent early in the disease but becomes pervasive later. Later, the dorsolateral prefrontal cortex and superior temporal gyri, develop structural deficits that are found consistently in adult studies. These structural deficits of the brain were found to be independent of antipsychotic therapy." Overall, the findings suggest continuous progressive brain tissue decreases and lateral ventricle volume increases in chronically ill patients, up to at least 20 years after their first symptoms. Progressive volume loss seems most pronounced in the frontal and temporal (gray matter) areas. Progressive lateral ventricle volume increases are also found. More pronounced progressive brain changes in patients is associated with poor outcome, more negative symptoms, and a decline in neuropsychological performance in one or some of the studies, but not consistently so. Higher daily cumulative dose of antipsychotic medication intake is either not associated with brain volume changes or with less prominent brain volume changes. "In patients with schizophrenia as a group, higher illness severity was associated with frontotemporal gray matter reduction and frontoparietal white matter expansion in both brain hemispheres."

Insula-Frontal Lobe

Recovery and Relapse In Schizophrenia

The topic of recovery in schizophrenia is very controversial. There are many dishonest recovery claims made about vitamins or treatments that "cure schizophrenia". For more about recovery in schizophrenia, (click here)

Cannabis And Schizophrenia

Cannabis (pot) has been proven to nearly quadruple the risk of developing schizophrenia. In 1969-70, Swedish military conscripts (>97% of the country's male population aged 18-20) were followed for 35 years. At the start of this study, none of the conscripts had schizophrenia. Over 35 years, those who had used cannabis more than 50 times at the beginning of the study had 3.7 times the normal rate of developing schizophrenia. This association was not explained by use of other psychoactive drugs or personality traits. Schizophrenia normally occurs in 1% of the population. 86% of individuals with schizophrenia are disabled and unemployed. Thus, if cannabis was legalized, the prevalence of schizophrenia could more than triple. This would cause a massive increase in the national unemployment rate.

Legalizing Illicit Drugs

Some people argue that illicit drugs should be legalized to decrease the crime associated with these drugs. Historically, tobacco and alcohol were once illegal drugs. Tobacco smoking is now the leading cause of death in America, and alcoholism is the third leading cause of death. Thus legalizing illicit drugs does not make them any less medically and socially harmful. In fact the opposite is true; legalizing illicit drugs increases their use and the harm they cause. The Government of Finland is passing legislation that will gradually ban all tobacco use by 2040.

Lack Of Social Skills During Schizophrenia

There are certain social skills that are essential for healthy social functioning. During schizophrenia, individuals may develop schizoid personality traits; thus lack the essential social skills of intimacy, sociability, and emotional expressiveness.

    Social Skills That Are Lacking In Schizophrenia With Schizoid Personality Traits

    SOCIAL SKILL LOW LEVEL HIGH LEVEL
    Intimacy Intimacy avoidance Wanting close friendships or intimate romantic relationships
    Sociability Social withdrawal Friendly; interested in social contacts and activities
    Emotional Expressiveness Lack of emotional expression Open expression of emotions; full range of emotions

During schizophrenia, individuals may also develop paranoid personality traits; thus lack the essential social skills of trust, forgiveness, and gratitude.

    Social Skills That Are Lacking In Schizophrenia With Paranoid Personality Traits

    SOCIAL SKILL LOW LEVEL HIGH LEVEL
    Trust Suspiciousness Trusting the loyalty and good intentions of significant others (e.g., family, friends)
    Forgiveness Bearing grudges Forgiving other peoples’ mistakes; not bearing grudges or seeking revenge
    Gratitude Feeling victimized Being thankful for the good things in life; expressing thanks to others

Which Behavioral Dimensions Are Involved?

The ancient Greek civilization lasted for 1,300 years (8th century BC to 6th century AD). The ancient Greek philosophers taught that the 5 pillars of their civilization were: wisdom, courage, helping others, self-control, and justice. Psychiatry named the opposite of each of these 5 ancient themes as being a major dimension of psychopathology (i.e., irrationality, negative emotion, detachment, disinhibition, and antagonism). (Psychology named these same factors the "Big 5 dimensions of personality": "intellect", "neuroticism", "extraversion", "conscientiousness", and "agreeableness")

    Schizophrenia: Irrationality, Negative Emotion And Detachment
            Wisdom vs Irrationality:
      • Continuous cognitive impairment (distractibility, apathy, forgetfulness, impaired executive functioning [planning, problem-solving], impaired social communication)
      • Episodic/continuous psychosis (unless on antipsychotic medication)
            Courage vs Negative Emotion:
      • Flat or blunted emotions, 5% suicide rate
            Helping Others vs Detachment:
      • Schizoid traits: intimacy avoidance, social withdrawal, lack of emotional expression
      • Paranoid traits: suspiciousness, bearing grudges, feeling victimized
            Self-Control vs Disinhibition: N/A
            Justice vs Antagonism:
      • Majority are nonviolent, but overall there is an above average risk of physical violence. (NOTE: Alcoholics and drug addicts are much more violent than individuals with schizophrenia.)
Diagnostic Features

This disorder, at some point in the illness, involves a psychotic phase (with delusions, hallucinations, or grossly bizarre/disorganized speech and behavior). This psychotic phase must last for at least one month (or less if successfully treated). Schizophrenia also causes impairment in social or vocational functioning which must last for at least 6 months. The psychotic phase is not due to a medical condition, medication, or illegal drug.

Complications

Individuals with this disorder may develop significant loss of interest or pleasure. Likewise, some may develop mood abnormalities (e.g., inappropriate smiling, laughing, or silly facial expressions; depression, anxiety or anger). Often there is day-night reversal (i.e., staying up late at night and then sleeping late into the day). The individual may show a lack of interest in eating or may refuse food as a consequence of delusional beliefs. Often movement is abnormal (e.g., pacing, rocking, or apathetic immobility). Frequently there are significant cognitive impairments (e.g., poor concentration, poor memory, and impaired problem-solving ability). The majority of individuals with Schizophrenia are unaware that they have a psychotic illness. This poor insight is neurologically caused by illness, rather than simply being a coping behavior. This is comparable to the lack of awareness of neurological deficits seen in stroke. This poor insight predisposes the individual to noncompliance with treatment and has been found to be predictive of higher relapse rates, increased number of involuntary hospitalizations, poorer functioning, and a poorer course of illness. Depersonalization, derealization, and somatic concerns may occur and sometimes reach delusional proportions. Motor abnormalities (e.g., grimacing, posturing, odd mannerisms, ritualistic or stereotyped behavior) are sometimes present.

The life expectancy of individual with Schizophrenia is shorter than that of the general population for a variety of reasons. Suicide is an important factor, because approximately 5% of individuals with Schizophrenia commit suicide - and between 20% and 40% make at least one suicide attempt. There is an increased risk of assaultive and violent behavior. The major predictors of violent behavior are male gender, younger age, past history of violence, noncompliance with antipsychotic medication, and excessive substance use. However, it should be noted that most individuals with Schizophrenia are not more dangerous to others than those in the general population.

Comorbidity

Alcoholism and drug abuse worsen the course of this illness, and are frequently associated with it. From 80% to 90% of individuals with Schizophrenia are regular cigarette smokers. Anxiety and phobias are common in Schizophrenia, and there is an increased risk of Obsessive-Compulsive Disorder and Panic Disorder. Schizotypal, Schizoid, or Paranoid Personality Disorder may sometimes precede the onset of Schizophrenia.

Diagnostic Tests

No laboratory test has been found to be diagnostic of this disorder. However, individuals with Schizophrenia often have a number of (non-diagnostic) neurological abnormalities. They have enlargement of the lateral ventricles, decreased brain tissue, decreased volume of the temporal lobe and thalamus, a large cavum septum pellucidi, and hypofrontality (decreased blood flow and metabolic functioning of the frontal lobes). They also have a number of cognitive deficits on psychological testing (e.g., poor attention, poor memory, difficulty in changing response set, impairment in sensory gating, abnormal smooth pursuit and saccadic eye movements, slowed reaction time, alterations in brain laterality, and abnormalities in evoked potential electrocephalograms).

Prevalence

Schizophrenia is the fourth leading cause of disability in the developed world (for ages 15-44), and Schizophrenia is observed worldwide. Lifetime prevalence varies from 0.5% to 1.5%. The incidence of Schizophrenia is slightly higher in men than women. Negative symptoms (e.g., social withdrawal, lack of motivation, flat emotions) tend to predominate in men; whereas depressive episodes, paranoid delusions, and hallucinations tend to predominate in women.

Course

Schizophrenia usually starts between the late teens and the mid-30s, whereas onset prior to adolescence is rare (although cases with age at onset of 5 or 6 years have been reported). Schizophrenia can also begin later in life (e.g., after age 45 years), but this is uncommon. Usually the onset of Schizophrenia occurs a few years earlier in men than women. The onset may be abrupt or insidious. Usually Schizophrenia starts gradually with a prepsychotic phase of increasing negative symptoms (e.g., social withdrawal, deterioration in hygiene and grooming, unusual behavior, outbursts of anger, and loss of interest in school or work). A few months or years later, a psychotic phase develops (with delusions, hallucinations, or grossly bizarre/disorganized speech and behavior). Individuals who have an onset of Schizophrenia later in their 20's or 30's are more often female, have less evidence of structural brain abnormalities or cognitive impairment, and display a better outcome. Schizophrenia usually persists, continuously or episodically, for a life-time. Complete remission (i.e., a return to full premorbid functioning) is uncommon. Some individuals appear to have a relatively stable course, whereas others show a progressive worsening associated with severe disability. The psychotic symptoms usually respond to treatment with antipsychotic medication, whereas the negative symptoms are less responsive to antipsychotic medication. Often the negative symptoms steadily become more prominent during the course of Schizophrenia.

Outcome

The best outcomes are associated with early and persistent treatment with antipsychotic medication soon after the onset of Schizophrenia. Other factors that are associated with a better prognosis include good premorbid adjustment, acute onset, later age at onset, good insight, being female, precipitating events, associated mood disturbance, brief duration of psychotic symptoms, good interepisode functioning, minimal residual symptoms, absence of structural brain abnormalities, normal neurological functioning, a family history of Mood Disorder, and no family history of Schizophrenia.

Familial Pattern

The first-degree biological relatives of individuals with Schizophrenia have a risk for Schizophrenia that is about 10 times greater than that of the general population. Concordance rates for Schizophrenia are higher in monozygotic (identical) twins than in dizygotic (fraternal) twins. The existence of a substantial discordance rate in monozygotic twins also indicates the importance of environmental factors.

Treatment

Antipsychotic medication shortens the duration of psychosis in Schizophrenia, and prevents recurrences (but psychotic relapses can still occur under stress). Usually it takes years before individuals can accept that they have Schizophrenia and need medication. When individuals stop their antipsychotic medication, it may take months (or even years) before they suffer a psychotic relapse. Most, however, relapse within weeks. After each psychotic relapse there is increased intellectual impairment.

Antipsychotic medication (+/- antidepressant medication +/- antianxiety medication) usually prevents suicide, minimizes rehospitalization, and dramatically improves social functioning. Unfortunately, even on antipsychotic medication, most individuals with Schizophrenia can't return to gainful employment due to the intellectual impairments caused by this illness (e.g., poor concentration, poor memory, impaired problem-solving, inability to "multi-task", and apathy).

Life-long treatment with antipsychotic medication is essential for recovery from Schizophrenia. Individuals also require long-term emotional and financial support from their families. Most individuals with Schizophrenia qualify for government (or insurance) disability pensions. Social rehabilitation (e.g., club-houses, supervised social activities) and sheltered/volunteer employment are also essential. Certain illicit drugs, especially cannabis ("pot"), have been shown to actually cause Schizophrenia.

Prepsychotic (Prodromal) Or
Postpsychotic (Residual) Phase

Psychotic (Active) Phase

Core Problems in Prepsychotic or Postpsychotic Phase
  • Social and/or Occupational Impairment
  • Apathy
Core Problems in Psychotic Phase
Common Associated Problems in Prepsychotic or Postpsychotic Phase
  • Lack of Physical Exercise
  • Poor Sexual Interest or Ability
  • Increased Smoking
  • Sad or Depressed Mood
  • Poor Concentration or Attention
  • Poor Memory
  • Impaired Executive Functioning (planning, problem-solving)
  • Lack of Insight
  • Solitary Lifestyle
  • Indifference To Others
  • Lack of Self-Confidence
  • Shyness
Common Associated Problems in Psychotic Phase
  • Lack of Physical Exercise
  • Poor Sexual Interest or Ability
  • Distrust or Suspiciousness
  • Increased Smoking
  • Sad or Depressed Mood
  • Poor Concentration or Attention
  • Generalized Worry
  • Poor Memory
  • Impaired Executive Functioning (planning, problem-solving)
  • Lack of Insight
  • Mistrust of Friends
  • Solitary Lifestyle
  • Indifference To Others
  • Lack of Emotion
  • Lack of Self-Confidence
  • Shyness
  • Difficulty Handling Conflict
Problems in Prepsychotic or Postpsychotic Phase When Severe
  • Distrust or Suspiciousness
  • Mistrust of Friends
  • Difficulty Handling Conflict
  • Poor Money Management
  • Risk of Harming Self
  • Impaired Communication With Words
  • Impaired Communication With Emotions
  • Poor Grooming and Hygiene
  • Need for Institutional Care
Problems in Psychotic Phase When Severe
  • Poor Money Management
  • Physical Violence
  • Obsessive Thinking or Compulsive Rituals
  • Risk of Harming Self
  • Poor Grooming and Hygiene
  • Need for Institutional Care

Description


Stories

Free Diagnosis Of This Disorder

Rating Scales

Web Community

Treatment

Review Articles On The Effectiveness Of Treatment

  • 2013 Research Review Articles
    • Physical Therapies
    • Pharmaceutical Therapies
      • The nature of relapse in schizophrenia (Relapse rates are very high when treatment is discontinued, even after a single psychotic episode; a longer treatment period prior to discontinuation does not reduce the risk of relapse; many patients relapse soon after treatment reduction and discontinuation; transition from remission to relapse may be abrupt and with few or no early warning signs; once illness recurrence occurs symptoms rapidly return to levels similar to the initial psychotic episode; while most patients respond promptly to re-introduction of antipsychotic treatment after relapse, the response time is variable and notably, treatment failure appears to emerge in about 1 in 6 patients.)
          Editor's Comment: This superb review is published online free. It is a must read.
      • The association between schizophrenia and violent or homicidal behaviour: the prevention and treatment of violent behaviour in these patients (The risk of homicidal behaviours is higher in patients with schizophrenia compared to the overall population. The following factors increase the risk of violence in schizophrenia: young age, alcoholism, substance abuse, noncompliance with treatment, fulfillment of the criteria for antisocial personality disorder and paranoid subtype, history of suicidal ideation and attempts and history of frequent hospitalization. There are many trials showing the efficacy of clozapine on violent and aggressive behaviour.)
      • Treatment of adolescents with early-onset schizophrenia spectrum disorders: in search of a rational, evidence-informed approach (Antipsychotics are efficacious in the treatment of early onset schizophrenia (except for ziprasidone). Clozapine is reserved for those with treatment-refractory early onset schizophrenia.)
      • Detection of metabolic syndrome in schizophrenia and implications for antipsychotic therapy : is there a role for folate? (the presence of metabolic syndrome is associated with significant cardiovascular mortality and represents a growing public health concern in the USA. Patients with schizophrenia have a three times greater risk of death than the general population, with cardiovascular disease being the most common cause of this mortality. Use of atypical antipsychotics (AAPs) to treat schizophrenia contributes significantly to this cardiovascular risk.)
      • Clozapine: key discussion points for prescribers (Clozapine is the most effective antipsychotic medication for treatment-refractory schizophrenia and is also approved for suicidality in schizophrenia patients. However, it can cause significant medical morbidity and requires intensive medical monitoring once prescribed.)
      • Schizophrenia past clozapine: what works? (In patients who discontinue clozapine, considering a trial of olanzapine would be worthwhile)
      • Asenapine, iloperidone and lurasidone: critical appraisal of the most recently approved pharmacotherapies for schizophrenia in adults (All three agents are similar in terms of overall efficacy and low propensity for clinically significant weight gain or adverse changes in glycemic or lipid profile. For each drug, comparative and real-world effectiveness studies are lacking, as are effectiveness and safety data in elderly, young and pregnant/nursing patients.)
      • Lurasidone: in the treatment of schizophrenia (In two placebo-controlled, phase II trials, lurasidone 40-120 mg/day was efficacious in reducing the acute symptoms of schizophrenia. In a third phase II trial, the lurasidone groups and haloperidol control group failed to separate from placebo on key endpoints. In two placebo- and active treatment-controlled, phase III trials, lurasidone at dosages of 40-160 mg/day, olanzapine 15 mg/day and quetiapine extended-release (XR) 600 mg/day were efficacious in reducing the symptoms of schizophrenia. In a 12-month, double-blind extension trial, the relapse rate in lurasidone recipients was noninferior to that in quetiapine XR recipients. In a third phase III trial, lurasidone 80 mg/day, but not 40 or 120 mg/day, was more efficacious than placebo for the primary endpoint. In an unpublished trial, there were no significant differences between lurasidone, active comparator and placebo groups on the primary endpoint. Lurasidone was generally well tolerated over the short and longer term. Extrapyramidal symptoms and akathisia occurred in ˜10-13 % of patients. Lurasidone was associated with a low risk of QT interval prolongation, weight gain, metabolic disturbances and hyperprolactinaemia. [Editor: In 3 out of these 8 trials, lurasidone was no better than placebo])
      • Efficacy of olanzapine in comparison with clozapine for treatment-resistant schizophrenia: evidence from a systematic review and meta-analyses (clozapine is significantly more efficacious than olanzapine for treatment-resistant schizophrenia)
      • A review of paliperidone palmitate (Risperidone long-acting injection (RLAI) was the first second-generation antipsychotic available as a long-acting injection. Paliperidone is the active metabolite of risperidone, is available either as an extended release oral formulation (Invega) or long-acting injection (Invega Sustenna) which is administered monthly by intramuscular injection (deltoid or gluteal). Doses of PLAI can be expressed either in milligram equivalents (mg eq) of paliperidone palmitate or in milligrams of the active fraction of paliperidone. The recommended initiation regimen of 150 mg eq (234 mg) on day 1 and 100 mg eq (156 mg) on day 8 (both administered in the deltoid) achieves therapeutic blood levels rapidly and without the necessity of oral supplementation. No refrigeration or reconstitution prior to administration is required. PLAI has been shown in to be effective in controlling the acute symptoms of schizophrenia as well as delaying time to relapse. Safety and tolerability are comparable to RLAI with no new safety signals. Thus, PLAI may represent the rational development of RLAI with greater ease of use.)
      • Assessing the prospect of donepezil in improving cognitive impairment in patients with schizophrenia (Even though cognitive impairment is manifested in almost all patients with schizophrenia, the Clinical Antipsychotic Trials for Intervention Effectiveness (CATIE) study showed no significant difference between first- and second-generation psychotropic drugs in improving cognitive abilities. Donepezil is not recommended as an adjunct to antipsychotic medication targeting cognitive deficits in schizophrenia subjects.)
      • Efficacy and safety of second-generation long-acting injections in schizophrenia: a meta-analysis of randomized-controlled trials (The present meta-analysis shows superior efficacy for the second-generation long-acting injections over placebo on psychotic symptoms, although with a relatively small effect size; no evidence of superiority in efficacy over oral antipsychotics; and modest evidence of greater symptoms of extrapyramidal side effects.)
      • Interventions to reduce antipsychotic polypharmacy: a systematic review (Antipsychotic polypharmacy remains controversial but is common. Careful switching from polypharmacy to monotherapy seems feasible in a majority of patients with schizophrenia. Directly cautioning physicians not to use polypharmacy is more effective than a less assertive educational approach.)
      • Blonanserin for schizophrenia: systematic review and meta-analysis of double-blind, randomized, controlled trials (Safe and effective antipsychotic medication, but has a 1.62 higher risk of akathisia than risperidone)
    • Psychological Therapies
    • Miscellaneous
      • “Meta-guidelines” for the management of patients with schizophrenia (A "guideline of guidelines" for the treatment of schizophrenia which not only reconcile the various existing standards but also update them to include the use of several newer agents, most of which were marketed following the publication of existing standards)
      • Improving treatment adherence in your patients with schizophrenia: the STAY initiative (Six principles to improve Treatment Adherence in Your patients are: (1) recognizing that most patients with schizophrenia are at risk of partial/non-adherence at some time during the course of their illness; (2) the benefits of a good therapeutic alliance for identifying potential adherence issues; (3) tailored treatment plans to meet an individual's needs, including the most suitable route of delivery of antipsychotic medication; (4) involving family/key persons in care and psychoeducation of the patient, assuming the patient agrees to this; (5) ensuring optimal effectiveness of care; and (6) ensuring continuity in the care of patients with schizophrenia.)
      • Five-year clinical course and outcome of schizophrenia in Ethiopia (Patients with schizophrenia (n=321) were identified systematically after screening 68378 adults, ages 15-49 years, in rural Ethiopia. The majority (74.9%) had chronic illness at entry and were treatment naïve (89.6%). During 5-year follow-up, 96% had received treatment at least once although only about 6% had received antipsychotic treatments continuously. Forty five percent of participants were continuously symptomatic with 30.3% having had continuous psychotic episode. About 20% had experienced continuous remission. Treatment has been a consistent predictor of a favorable outcome.)
      • Remission in schizophrenia: critical and systematic review (In 2005, the Remission in Schizophrenia Working Group published consensus criteria to define remission. Remission has a reported rate of 17% to 78% (weighted mean = 35.6%) in first-episode schizophrenia and 16% to 62% (weighted mean = 37%) in multiple-episode patients, with no statistical difference between the two weighted means (p = .79). Patients who were treated with long-acting injectable risperidone showed high maintenance of remission status. Studies comparing second-generation antipsychotics versus haloperidol showed higher remission rates for the former. The variables most frequently associated with remission were better premorbid function, milder symptoms at baseline (especially negative symptoms), early response to treatment, and shorter duration of untreated psychosis. Rates of symptomatic remission exceeded reported rates for functional recovery. )
  • 2012 Research Review Articles
    • Biological Factors
    • Physical Therapies
    • Pharmaceutical Therapies
      • Risk factors for relapse following treatment for first episode psychosis: a systematic review and meta-analysis of longitudinal studies. (Relapse of positive symptoms was 28% (range=12-47%), 43% (35-54%), 54% (40-63%) at 1, 1.5-2, and 3 years follow-up, in that order. Medication non-adherence, persistent substance use disorder, carers' critical comments (but not overall expressed emotion) and poorer premorbid adjustment, increased the risk for relapse 4-fold, 3-fold, 2.3-fold and 2.2-fold, respectively.)
      • Predicting relapse after a first episode of non-affective psychosis: a three-year follow-up study. (The relapse rates at 1 year and 2 years were 20.7% and 40.7%, respectively. Adherence to medication was the only significant predictor of relapse after a three-year follow-up [hazard ratio (HR) 4.8, 95% confidence interval (CI) 2.9-7.7; p < 0.001]. Comparison of the mean time of relapse between adherent and non-adherent patients also revealed statistically significant differences (933 and 568 days, respectively). 50% of patients will relapse despite being categorized as treatment adherents.)
      • Flupenthixol versus placebo for schizophrenia (We were surprised that this well-established drug had so few data from trials investigating its absolute effects. We think this is unlikely to be rectified some 50 years after its launch and know that this would not happen today. However, even though data are very limited, flupenthixol may well be worthy of careful investigation - partly to ensure that this inexpensive active drug is not forgotten.)
      • Bromperidol decanoate (depot) for schizophrenia (Minimal poorly reported trial data suggests that bromperidol decanoate may be better than placebo injection but less valuable than fluphenazine or haloperidol decanoate)
      • Managing the prodrome of schizophrenia (All evidence taken together makes it difficult to justify specific interventions at the prodromal stage of schizophrenia from the perspective of preventing or delaying the onset of the disorder)
      • Antipsychotic treatment response in schizophrenia (Early nonresponse to antipsychotic treatment may predict subsequent non-response, though early response is not necessarily indicative of future response. If patients do not respond to treatment within the first two weeks of an acute exacerbation, clinicians should consider switching antipsychotic agents, except in patients with first-episode psychosis, for whom a longer trial of the initially prescribed therapy appears to be appropriate.)
      • Information and communication technology in patient education and support for people with schizophrenia (Information and communication technology (ICT) is increasingly being used to deliver information, treatment or both for people with severe mental disorders. Using ICT to deliver psychoeducational interventions has no clear effects compared with standard care, other methods of delivering psychoeducation and support, or both.)
      • Treatment of schizophrenia in pregnancy and postpartum (50-60% of women with schizophrenia will become pregnant; fifty percent of these pregnancies will be unplanned or unwanted. The majority of antipsychotic medications used to treat schizophrenia appear to be relatively safe for use during pregnancy and breastfeeding. There appears to be greater risk for the mother and the fetus/infant in not treating schizophrenia during pregnancy and postpartum.)
      • Anticholinergic effects of oral antipsychotic drugs of typicals versus atypicals over medium- and long-term: systematic review and meta-analysis (Over the medium- and long-term there were no statistically significant differences between the typicals and atypicals in the main anticholinergic side-effects with one exception. We found that in the long-term, the typical antipsychotics were associated with a significantly higher prevalence of blurred vision.)
      • Clozapine: balancing safety with superior antipsychotic efficacy (The primary indications for clozapine are: 1) treatment-resistant schizophrenia or schizoaffective disorder, defined as persistent moderate to severe delusions or hallucinations despite two or more clinical trials with other antipsychotic drugs; and, 2) patients with schizophrenia or schizoaffective disorder who are at high risk for suicide. Concerns over a number of safety considerations are responsible for much of the underutilization of clozapine: 1) agranulocytosis; 2) metabolic side effects; and, 3) myocarditis. These side effects can be detected, prevented, minimized and treated, but there will be a very small number of fatalities. Nevertheless, clozapine has been found in two large epidemiologic studies to have the lowest mortality of any antipsychotic drug, mainly due to its very large effect to reduce the risk for suicide.)
      • Optimizing outcome with antipsychotic treatment in first-episode schizophrenia: balancing efficacy and side effects ( For best clinical long-term outcomes: 1) start with a well-tolerated first-generation antipsychotic medication (thereby avoiding weight gain, insulin resistance, and prolactin-induced changes in gender-specific physiology); then, 2) switch to clozapine if patients are nonresponsive to a trial of 2 first-generation antipsychotic medications.)
      • Drug safety and efficacy evaluation of sertindole for schizophrenia (Sertindole is generally well tolerated, but is associated with a dose-related QTc interval prolongation (+22 ms). Sertindole can be an important second-line option for the treatment of schizophrenia for patients intolerant to at least one other antipsychotic.)
      • Body weight and metabolic adverse effects of asenapine, iloperidone, lurasidone and paliperidone in the treatment of schizophrenia and bipolar disorder: a systematic review and exploratory meta-analysis (Preliminary data suggest the lowest weight gain potential with lurasidone and potentially relevant short-term metabolic effects for asenapine and iloperidone)
      • Antipsychotics in adults with schizophrenia: comparative effectiveness of first-generation versus second-generation medications: a systematic review and meta-analysis (Clear benefits of FGAs versus SGAs for treating schizophrenia remain inconclusive)
      • Clozapine for the treatment of schizophrenia (Clozapine is the treatment of choice for schizophrenic patients who are refractory to treatment, display violent behaviors, or who are at high risk of suicide. However, it is also the antipsychotic with the worst side effect profile, the highest risk of complications, and the most difficult to prescribe.)
      • Paliperidone palmitate for schizophrenia (When flexibly dosed with a mean doses of approximately 70 to 110 mg every four weeks, paliperidone palmitate appears comparable in efficacy and tolerability to risperidone long-acting injection flexibly dosed with mean doses of approximately 35 mg every two weeks)
      • Exploratory analyses of efficacy data from schizophrenia trials in support of new drug applications submitted to the US Food and Drug Administration (A high and increasing placebo response and a declining treatment effect are of great concern in schizophrenia trials conducted in North America.)
      • Comparative effectiveness of atypical antipsychotics in schizophrenia: what have real-world trials taught us? (The CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness), CUtLASS (Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study) and SOHO (Schizophrenia Outpatient Health Outcomes) programmes confirmed the superiority of clozapine over other antipsychotics; CATIE and SOHO also confirmed olanzapine as probably the second most effective antipsychotic. Effectiveness studies have confirmed the high incidence of adverse metabolic effects with clozapine, olanzapine and (with less certainty) quetiapine.)
      • Overdose of atypical antipsychotics: clinical presentation, mechanisms of toxicity and management (Patients with significant CNS depression with associated loss of airway reflexes and respiratory failure need advanced airway management. Hypotension should be treated first with intravenous fluids, with the use of direct acting vasopressors reserved for persistent hypotension. Benzodiazepines should be used for seizures, with barbiturates used for refractory seizures. Intravenous magnesium can be administered for patients with a corrected QT interval exceeding 500 milliseconds.)
      • Anticholinergics in the era of atypical antipsychotics: short-term or long-term treatment? (Some studies suggest improvement in tardive dyskinesia with cessation of anticholinergics. Four studies examined the effects of anticholinergic agent discontinuation on cognition and all observed an improvement post-discontinuation. Changes in symptoms of schizophrenia with anticholinergic discontinuation are conflicting, with more recent studies suggesting an improvement. Given their questionable benefit with continued use, clinicians should consider a gradual withdrawal of anticholinergic agents in stable patients receiving antipsychotics.)
      • Maintenance treatment with antipsychotic drugs for schizophrenia (The review currently includes 65 randomised controlled trials (RCT(s)) and 6493 participants comparing antipsychotic medication with placebo. Antipsychotic drugs were significantly more effective than placebo in preventing relapse at seven to 12 months (primary outcome; drug 27%, placebo 64%, number needed to treat for an additional beneficial outcome (NNTB 3 CI 2 to 3) ...Hospitalisation was also reduced, however, the baseline risk was lower (drug 10%, placebo 26%, NNT 5 CI 4 to 9). .. More participants in the placebo group than in the antipsychotic drug group left the studies early due to any reason (at 7-12 months: drug 38%, placebo 66%, NNTB 4 CI 3 to 5) and due to inefficacy of treatment (at 7-12 months: drug 20%, placebo 50%, NNTB 3 CI 2 to 4). Quality of life was better in drug-treated participants (SMD -0.62). Conversely, antipsychotic medication as a group and irrespective of duration, were associated with more participants experiencing movement disorders (e.g. at least one movement disorder: drug 16%, placebo 9%,NNTH 25 CI 13 to 100), sedation (drug 13%, placebo 9%, (NNTH) not significant) and weight gain (drug 10%, placebo 6%, NNTH 20)... The results clearly demonstrate the superiority of antipsychotic drugs compared to placebo in preventing relapse. )
      • Atypical antipsychotic drugs, schizophrenia, and metabolic syndrome in non-Euro-American societies (The metabolic syndrome development profile in patients with schizophrenia receiving atypical antipsychotic drugs in non-Euro-American societies seems to be comparable to that in European and North American societies)
      • Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents (The D(2) receptor has been the target for the development of antipsychotic drugs. The relative success of antipsychotics in treating positive symptoms is limited by the fact that a substantial number of patients are refractory to current medications and by their lack of efficacy for negative and cognitive symptoms, which often determine the level of functional impairment. In addition, while the newer antipsychotics produce fewer motor side effects, safety and tolerability concerns about weight gain and endocrinopathies have emerged.)
      • Zuclopenthixol acetate for acute schizophrenia and similar serious mental illnesses (This review did not find any suggestion that zuclopenthixol acetate is more or less effective in controlling aggressive acute psychosis, or in preventing adverse effects than intramuscular haloperidol, and neither seemed to have a rapid onset of action.)
      • Asenapine: a clinical review of a second-generation antipsychotic (Is safe and effective. Its most common side effects are: somnolence (13%-24%), extrapyramidal symptoms (EPS) (7%-12%), and dizziness (11%).)
      • Antipsychotics in pediatric and adolescent patients: a review of comparative safety data (Quetiapine and ziprasidone display a better tolerability profile than risperidone and olanzapine in terms of weight gain, glucose metabolism, increases in prolactin levels, and EPS, while aripiprazole seems to be the most weight-neutral.)
      • The treatment of hallucinations in schizophrenia spectrum disorders (The first treatment option for hallucinations in schizophrenia is antipsychotic medication, which can induce a rapid decrease in severity. Only 8% of first-episode patients still experience mild to moderate hallucinations after continuing medication for 1 year. Olanzapine, amisulpride, ziprasidone, and quetiapine are equally effective against hallucinations, but haloperidol may be slightly inferior. If the drug of first choice provides inadequate improvement, it is probably best to switch medication after 2-4 weeks of treatment. Clozapine is the drug of choice for patients who are resistant to 2 antipsychotic agents. For relapse prevention, medication should be continued in the same dose. Depot medication should be considered for all patients because nonadherence is high. Transcranial magnetic stimulation (TMS) currently has the status of a potentially useful treatment method for auditory hallucinations, but only in combination with state of the art antipsychotic treatment. Electroconvulsive therapy (ECT) is considered a last resort for treatment-resistant psychosis. Although several studies showed clinical improvement, a specific reduction in hallucination severity has never been demonstrated.)
      • Lurasidone for schizophrenia: what's different? (Lurasidone is associated with minimal weight gain and no clinically meaningful alterations in glucose, lipids, or the ECG QT interval. As per the product label, the recommended starting dose is 40 mg/day and the maximum recommended dose is 80 mg/day. Higher doses do not appear to be more efficacious, and may be associated with increases in adverse effects, such as somnolence and akathisia. It is recommended that lurasidone be administered once daily with at least 350 calories of food.)
      • A systematic review of the evidence of clozapine's anti-aggressive effects (Clozapine can reduce violence and persistent aggression in patients with schizophrenia and other psychiatric disorders. It may offer an advantage over other antipsychotics, although perhaps exclusively in the case of traditionally defined 'treatment resistance')
      • Practical guidelines on the use of paliperidone palmitate in schizophrenia (Paliperidone palmitate is useful in both the acute and maintenance phases of treatment. Paliperidone palmitate offers some advantages in terms of tolerability, simplicity of treatment initiation and long duration between injections.)
      • Aripiprazole: a review of its use in the management of schizophrenia in adults (Aripiprazole has a lower incidence of extrapyramidal symptoms than haloperidol and fewer weight-gain issues than olanzapine. Aripiprazole also showed a favourable cardiovascular tolerability profile and its use was associated with a reduced risk of metabolic syndrome than placebo or olanzapine.)
      • Treating impaired cognition in schizophrenia (Although current antipsychotic drugs treat psychosis in schizophrenia rather well, their impact on cognitive dysfunction is minimal)
      • Asenapine: a synthesis of efficacy data in bipolar mania and schizophrenia (Asenapine is taken sublingually and is associated with sedation and/or somnolence; it has a lower propensity to weight gain and metabolic disruption than olanzapine. Extrapyramidal side effects (EPS) are associated with asenapine and may be dose-dependent. Asenapine is not associated with sustained hyperprolactinemia or cardiovascular toxicity. Dysgeusia and oral hypoesthesia/paresthesia is associated with asenapine)
      • Antipsychotic treatment for schizophrenia in the maintenance phase: a systematic review of the guidelines and algorithms (Fourteen guidelines and algorithms were identified...Ten of 11 guidelines and algorithms did not recommend discontinuation of antipsychotics within five years; six of them partially recommended antipsychotic discontinuation for patients with first-episode schizophrenia exclusive. All nine guidelines and algorithms that referred to intermittent or targeted antipsychotic strategy endorsed against this strategy. Although being a hot topic of controversy, dose reduction of antipsychotics or lower dose therapy in the maintenance phase compared to the acute dosage is not recommended on the whole concerning atypical antipsychotics, whereas dose reduction appears sometimes considered acceptable for typical antipsychotics.)
      • Clinical pharmacology of paliperidone palmitate a parenteral long-acting formulation for the treatment of schizophrenia (Paliperidone palmitate is a long-acting intramuscular atypical antipsychotic drug indicated for the acute maintenance treatment of schizophrenia in adults. Its mechanism of action, like all other atypical agents, is attributed to the antagonism of brain dopamine D2 and serotonin 5-HT2A receptors.)
      • Clozapine resistance: augmentation strategies (There is scarce evidence of efficacy and safety as regards adjunctive strategies for clozapine-resistant patients)
      • A systematic review of meta-analyses of the efficacy of oral atypical antipsychotics for the treatment of adult patients with schizophrenia (Clozapine had superior efficacy over typical antipsychotics, trailed behind by olanzapine and risperidone. Meta-analyses generally do not support efficacy differences between the other atypical antipsychotics compared with the older typical agents.)
      • Interventions to improve adherence to antipsychotic medication in patients with schizophrenia--a review of the past decade (Interventions that offered more sessions during a longer period of time, and especially those with a continuous focus on adherence, seem most likely to be successful, as well as pragmatic interventions that focus on attention and memory problems. The positive effects of adapted forms of Motivational Interviewing found in earlier studies, such as compliance therapy, have not been confirmed.)
      • Descriptive analyses of the aripiprazole arm in the risperidone long-acting injectable versus quetiapine relapse prevention trial (ConstaTRE) (Clinically stable adults with schizophrenia or schizoaffective disorder previously treated with oral risperidone, olanzapine, or an oral conventional antipsychotic were randomized to risperidone long-acting injectable (RLAI) or aripiprazole and monitored for up to 24 months. Relapse occurred in 27.3% of aripiprazole-treated and 16.5% of RLAI-treated patients. Remission was achieved by 34.1% of aripiprazole and 51.1% of RLAI patients. Clinical global impression-change was improved ("minimally improved" to "very much improved") in 26.4% with RLAI and 15.9% with aripiprazole patients.)
    • Psychological Therapies
    • Other Therapies
    • Miscellaneous
      • Outcomes that matter: A qualitative study with persons with schizophrenia and their primary caregivers in India (32 persons with schizophrenia and 38 primary caregivers were asked what benefits they expected from treatment. Eleven outcomes were desired by both groups: symptom control; employment/education; social functioning; activity; fulfilment of duties and responsibilities; independent functioning; cognitive ability; management without medication; reduced side-effects; self-care; and self-determination. Social functioning, employment/education and activity were the most important outcomes for both groups; symptom control and cognitive ability were more important to persons with schizophrenia while independent functioning and fulfilment of duties were more important to caregivers.)
      • Long-Term Follow-Up of the TIPS Early Detection in Psychosis Study: Effects on 10-Year Outcome (Early detection of first-episode psychosis appears to increase the chances of milder deficits and superior functioning)
      • Clinical instruments to evaluate and guide treatment in schizophrenia (For many treatment studies it is unrealistic to expect a change in actual functioning. Most treatment trials are too brief to permit subjects to change their level of vocational or social functioning. In addition, real-world functioning is influenced by factors such as an individual's financial status or the availability of community services. This has led to the use of functional capacity measures which monitor an individual's ability to perform functionally meaningful tasks even if they do not complete these tasks. Attention has also focused on interview-based measures of cognition and negative symptoms. Both of these psychopathological domains are related to functioning and both are the focus of drug development.)
      • Is early intervention for psychosis feasible and effective? (Excellent review of the research basis for early intervention for psychosis)
      • Clinical interventions for women with schizophrenia: pregnancy (During pregnancy, adjust antipsychotic dose to clinical status, link the patient with prenatal care services, and help her prepare for childbirth. There are pros and cons to breastfeeding while on medication, and these need thorough discussion. During the postpartum period, mental health home visits should be provided. Parenting support is critical.)
      • Overview of violence to self and others during the first episode of psychosis (A substantial proportion of psychotic patients examined after violent suicide attempts (49%), major self-mutilation (54%), homicide (39%), and assault resulting in serious injury (38%) are in their first episode of psychosis)
      • Maternal schizophrenia: psychosocial treatment for mothers and their children (Women with schizophrenia are at risk for not engaging in treatment due to fears of barriers and losing their children. Minimal outpatient psychosocial treatments are available to this population.)
      • Placebo-related effects in clinical trials in schizophrenia: what is driving this phenomenon and what can be done to minimize it? (In recent years there has been a trend towards increasing placebo effects in clinical trials. This has been associated with diminishing drug–placebo differences in clinical trials, which, in turn, has interfered with signal detection for new therapies. Consequences of this increasing placebo effect are increased costs for drug development, more inconclusive and failed trials, delays in the development of new antipsychotics or even the abandonment of the search for new therapies because the risks and costs are seen as too great. There may also be a reduction in the perceived value of newer therapies as poor signal detection is sometimes inappropriately interpreted as newer therapies being less potent relative to older therapies or that treatments are losing their effects over time. More recent trials had an approximate 1.6-fold greater risk for placebo effects. This increase in placebo effect has been greater in trials performed in the US. [Editor: Excellent review of why the placebo effect is rising due to poor experimental methodology])
  • 2011 Research Review Articles
    • Biological Factors
      • Correlations between ventricular enlargement and gray and white matter volumes of cortex, thalamus, striatum, and internal capsule in schizophrenia (Patients with schizophrenia had increased ventricular size associated with decreased cortical gray matter volumes widely across the brain, but not directly correlated with volume loss in the immediately adjacent caudate, putamen, or internal capsule)
      • Schizophrenia as a disorder of too little dopamine: implications for symptoms and treatment (Antipsychotics represent the first effective therapy for schizophrenia, with their benefits linked to dopamine D2 blockade. Schizophrenia was soon identified as a hyperdopaminergic disorder, and antipsychotics proved to be reasonably effective in controlling positive symptoms. However, over the years, schizophrenia has been reconceptualized more broadly, now defined as a heterogeneous disorder with multiple symptom domains. Negative and cognitive features, not particularly responsive to antipsychotic therapy, have taken on increased importance--current thinking suggests that these domains predate the onset of positive symptoms and are more closely tied to functional outcome. That they are better understood in the context of decreased dopamine activity suggests that schizophrenia may fundamentally represent a hypodopaminergic disorder.)
      • Subjective well-being in schizophrenia as measured with the Subjective Well-Being under Neuroleptic Treatment scale: a review (Striatal dopamine D(2) receptor occupancy is correlated with subjective well-being. Early positive response of subjective well-being is predictive of a better outcome.)
      • Maternal infection and schizophrenia: implications for prevention (Accumulating evidence suggests that maternal infection is a risk factor for schizophrenia. Prospective epidemiological studies indicate that maternal influenza, toxoplasmosis, and genital/reproductive infection are associated with this disorder in offspring. Previous studies suggest that treatment or prophylactic efforts targeting these and other infections could have significant effects on reducing the incidence of schizophrenia, given that they are common in the population and the effect sizes derived from epidemiological studies of these and other microbial pathogens and schizophrenia, to date, are not small.)
    • Physical Therapies
    • Pharmaceutical Therapies
      • Preventing the second episode: a systematic review and meta-analysis of psychosocial and pharmacological trials in first-episode psychosis ("The analysis of 3 RCTs of psychosocial interventions comparing specialist First Episode Psychosis (FEP) programs vs treatment as usual involving 679 patients demonstrated the former to be more effective in preventing relapse (odds ratio [OR]=1.80, 95% confidence interval [CI]=1.31-2.48; P<.001; number needed to treat [NNT]=10). While the analysis of 3 different cognitive-behavioral studies not specifically intended at preventing relapse showed no further benefits compared with specialist FEP programs (OR=1.95, 95% CI=0.76-5.00; P=.17), the combination of specific individual and family intervention targeted at relapse prevention may further improve upon these outcomes (OR=4.88, 95% CI=0.97-24.60; P=.06). Exploratory analysis involving 1055 FEP patients revealed that relapse rates were significantly lower with second-generation antipsychotics (SGAs) compared with FGAs (OR=1.47, 95% CI=1.07-2.01; P<.02; [NNT]=10).")
          Editor's Comment: A number needed to treat greater than 8 is generally accepted as not being clinically significant. Thus this review's conclusion that second-generation antipsychotics were superior to first-generation antipsychotics is highly suspect.
      • Lurasidone: a clinical overview (The recommended dose is 40-80 mg given once daily, with no titration needed. Lurasidone should be taken with food. The tolerability profile of lurasidone is noteworthy in terms of a good weight and metabolic profile and no cardiovascular adverse effects such as orthostatic hypotension or prolongation of the QTc interval. )
      • Iloperidone: a clinical overview (The target dose of 6 mg bid can be achieved in 4 days, with titration recommended to minimize postural hypotension. The maximum recommended dose is 12 mg bid. The tolerability profile of iloperidone is noteworthy in terms of modest weight gain, no medically important changes in lipid and glucose levels, little in the way of prolactin elevation, and absence of extrapyramidal side effects, including akathisia. However, iloperidone can prolong the QTc interval on electrocardiogram. )
      • Asenapine: a clinical overview (It is administered as sublingual tablets in doses of 5 or 10 mg bid. It is well tolerated, with a dropout rate for adverse events similar to that of placebo. Asenapine is associated with a mean weight gain of less than 1 kg over a year and a relatively neutral effect on lipid and glucose levels. It can cause sedation and mild extrapyramidal side effects.)
      • Antipsychotics in the treatment of schizophrenia: an overview (Schizophrenia is characterized by positive, negative, cognitive, disorganization, and mood symptoms. Antipsychotics are the mainstay in the pharmacologic treatment of schizophrenia. Findings concerning efficacy for positive symptoms and disorganization suggest no consistent differences among available antipsychotics, with the exception of clozapine's superior efficacy for treatment-resistant schizophrenia. Although second-generation antipsychotics (SGAs) have generally been believed to be associated with a lower risk of EPS but a higher risk of metabolic adverse effects than first-generation agents (FGAs), the substantial variation in these and other side effects among agents within both classes indicates that it is not clinically useful to make a categorical distinction between FGAs and SGAs. )
      • Schizophrenia, psychotropic drugs and cognition (Differences between atypical and conventional drugs appear far less contrasted than initially suggested)
      • Time course of improvement with antipsychotic medication in treatment-resistant schizophrenia (The majority of improvement with antipsychotics occurs during the first 4 weeks)
      • Pharmacotherapy of schizophrenia (The typical-atypical classification is an outworn concept because there are pharmacological differences not only between the two groups but within the groups too. There are no significant differences among the antipsychotics with respect to efficiency but their side effect profiles are very different. )
      • Lurasidone: a new treatment option for schizophrenia (The incidence of extrapyramidal symptoms (excluding akathisia/restlessness) was greater with lurasidone (14.7%) than placebo (5.1%). Akathisia and somnolence were dose-related adverse events. Lurasidone appears to have relatively little effect on weight, plasma glucose or lipids to date. No evidence of QTc prolongation was seen and orthostatic hypotension was uncommon. Raised prolactin levels in short-term studies were dose-dependent, greater in females and occurred overall in 3.7 and 0.7% of lurasidone and placebo recipients, respectively.)
      • Management of schizophrenia in late life with antipsychotic medications: a qualitative review (Treatment of non-resistant, late-life schizophrenia with olanzapine and risperidone appears to be supported by the available evidence)
      • A review and Bayesian meta-analysis of clinical efficacy and adverse effects of 4 atypical neuroleptic drugs compared with haloperidol and placebo (clozapine, olanzapine, risperidone and aripiprazole show only small differences in overall efficacy. Olanzapine and clozapine produce the most weight gain and haloperidol produces the most extrapyramidal symptoms. Even aripiprazole and risperidone, however, induce considerable weight gain compared with placebo.)
      • Aripiprazole treatment for patients with schizophrenia: from acute treatment to maintenance treatment (The most current treatment guidelines for schizophrenia recommend more than 1 year of maintenance therapy after the first psychotic episode, and more than 5 years of maintenance therapy after multiple psychotic episodes. (Yet) Approximately two-thirds of such patients are known to relapse within 1 year and almost 90% of such patients may recur within 2 years.)
      • Treatment resistant schizophrenia and response to antipsychotics: a review (Treatment resistant schizophrenia usually is defined as at least 2 failed adequate antipsychotic trials (at chlorpromazine equivalent doses of = 1000 mg/day for = 6 weeks). Treatment response has been defined by a relative change in the representative scales (most commonly = 20% decrease in the Positive and Negative Syndrome Scale), but it sometimes included the absolute criteria such as post-treatment score of = 35 in the Brief Psychiatric Rating Scale or Clinical Global Impression-severity score of = 3 (mild or less severe). Social functioning has not been a primary outcome measure in past pivotal trials, and other important domains of the illness such as cognition and subjective perspectives have not been incorporated into definitions of treatment resistance or response. [Editor: It is a glaring omission not to use social/occupational/cognitive functioning in definitions of recovery/relapse.])
      • Adjunct mirtazapine for negative symptoms of schizophrenia (A few small studies found the addition of mirtazapine to antipsychotics to be effective at doses of 30 mg/day)
      • Dosing and switching strategies for paliperidone palmitate: based on population pharmacokinetic modelling and clinical trial data (The approved recommended initiation regimen for paliperidone palmitate is 234?mg on day 1 followed by 156?mg on day 8, each administered into the deltoid muscle, using a 1-inch 23-gauge needle in those weighing < 90?kg and a 1.5-inch 22-gauge needle in those weighing =90?kg. No oral supplementation is required. Monthly maintenance dosing is in the range of 39-234?mg; recommended dose of 117?mg injected into the deltoid (needle size is weight adjusted) or gluteal (using a 1.5-inch 22-gauge needle) muscle. The day 8 dose may be administered ±2 days and monthly doses ±7 days, without a clinically significant impact on plasma concentrations. In patients with mild renal impairment (creatinine clearance [CL(CR)]: 50-80?mL/min), dosage should be adjusted. No dose adjustment is required in patients with mild or moderate hepatic impairment; no data currently exist regarding severe hepatic impairment. Elderly patients with normal renal function should receive the same dosage as younger adult patients with normal renal function. Paliperidone palmitate can be initiated the day after discontinuing previous oral antipsychotic treatment. In patients switching from other long-acting injectable (LAI) antipsychotics, (including long-acting risperidone), paliperidone palmitate dosing should be initiated at the time of what would have been the next scheduled injection of the previous LAI, and continued monthly thereafter. )
      • Extent of attaining and maintaining symptom remission by antipsychotic medication in the treatment of chronic schizophrenia: evidence from the CATIE study (For patients with chronic schizophrenia, the CATIE study showed it was very difficult for them to attain symptom remission. At the start of the study, 16.2% of patients were already in symptomatic remission. During the following 18 months, only 11.7% attained and then maintained at least 6 months of symptomatic remission, and 55.5% (n = 623) experienced no symptom remission at any visit. Attaining and maintaining remission for 6 months was highest for the olanzapine (12.4%) medication group followed by the quetiapine (8.2%), perphenazine (6.8%), ziprasidone (6.5%), and risperidone (6.3%) groups.)
      • Difference in early prediction of antipsychotic non-response between risperidone and olanzapine in the treatment of acute-phase schizophrenia (In newly admitted patients with acute schizophrenia, non-response to risperidone using CGI-I at 2 weeks can predict subsequent response. It looks like there is significant response to olanzapine that doesn't occur until 4 weeks. Thus, clinicians may want to switch to another drug earlier when risperidone is the first drug, and later when olanzapine is the first drug.)
      • Predictors of response and remission in the acute treatment of first-episode schizophrenia patients--is it all about early response? (First-episode schizophrenia patients were treated for 43 days with either haloperidol or risperidone. Early response was defined as a = 30% improvement in the PANSS total score by week 2, response as a = 50% reduction in the PANSS total score from admission to discharge and remission according to the consensus criteria. 52% of the patients were responders and 59% remitters at discharge. A shorter duration of untreated psychosis (p=0.0167), a lower PANSS general psychopathology subscore (p<0.0001), and early treatment response (p=0.0002) were identified as significant predictors of remission.)
      • Early intervention for psychosis (6 studies of early intervention in the prodromal (prepsychotic) phase of schizophrenia found that nothing worked [olanzapine, cognitive behavioal therapy (CBT), family therapy, and seeing a specialized team].)
      • Bromperidol decanoate (depot) for schizophrenia (Patients allocated to fluphenazine decanoate and haloperidol decanoate had fewer relapses than those given bromperidol decanoate (NNH 6))
      • Old patients suffering from long-standing schizophrenia: clinical aspects (Firstly, some display high levels of all schizophrenic symptoms, while others experience changes in the symptom profile with aging, i.e. a reduction in positive symptoms and an increase in negative ones. Secondly, the occurrence of significant depressive symptoms among elderly patients with schizophrenia is well recognized. Lastly, aged persons with schizophrenia often have side effects due to long-term antipsychotic medications and medical co-morbidity, more untreated somatic disorders (diabetes, cardiovascular diseases) and higher mortality rates.)
      • Clinical usefulness of second-generation antipsychotics in treating children and adolescents diagnosed with bipolar or schizophrenic disorders (There is now evidence that aripiprazole, olanzapine, and risperidone are effective in the short-term treatment of children and adolescents with either early-onset schizophrenia or bipolar mania. "The use of clozapine should be strictly limited to patients with non-affective, psychotic symptoms who do not respond to aripiprazole, olanzapine, and risperidone." Due to the lack of research with quetiapine or ziprasidone; it is not possible to arrive at definitive conclusions.)
      • Aripiprazole versus placebo for schizophrenia (Despite the fact that 2585 people participated in nine randomised aripiprazole studies, we were unable to extract any usable data on death, service outcomes, general functioning, behaviour, engagement with services, satisfaction with treatment; economic outcomes or cognitive functioning. In general, study attrition was very large for all studies over four weeks' duration. Fewer people left the aripiprazole group compared with those in the placebo group. Compared with placebo, aripiprazole significantly decreased relapse in both the short and medium term. )
      • Antipsychotic medication for early episode schizophrenia (People with early episode schizophrenia treated with typical antipsychotic medications are less likely to leave the study early, but more likely to experience medication-related side effects)
      • Specialised first-episode psychosis services: a systematic review of the literature (A two-year treatment period is not long enough to enable patients to maintain the improvements obtained during the active phase of an integrated treatment)
      • Iloperidone for the management of adults with schizophrenia (Prescribing information recommends a starting dosage of 1 mg twice daily and then titrated over 7 days to reach a target dosage of 12 to 24 mg/d. The titration is necessary to reduce the risk of orthostatic hypotension-related dizziness. Slow initial titration and twice-daily dosing are potential disadvantages.)
      • Pathways to aggression in schizophrenia affect results of treatment (Schizophrenia elevates the risk for aggressive behavior and violent crime. Clozapine has superior antiaggressive activity in comparison with other antipsychotics and with all other pharmacological treatments. It is usually effective when aggressive behavior is related to psychotic symptoms. However, in many patients, aggression is at least partly based on other factors such as comorbid substance use disorder, comorbid antisocial personality disorder/psychopathy, or current stress. These conditions which are sometimes underdiagnosed in clinical practice must be addressed by appropriate adjunctive psychosocial approaches or other treatments. Treatment adherence has a crucial role in the prevention of aggressive behavior in schizophrenia patients.)
      • Optimizing clozapine treatment (Plasma levels above the therapeutic threshold of 350-420 ng/ml are necessary to determine non-response to clozapine. Patients not responding to a high dose of clozapine should be tried on a lower dose. Augmentation with lamotrigine, antipsychotics, or electroconvulsive therapy may be beneficial in case of partial response to clozapine.)
      • Weight gain and changes in metabolic variables following olanzapine treatment in schizophrenia and bipolar disorder (The proportions of patients who gained at least 7%, 15% or 25% of their baseline weight with long-term exposure were 64%, 32% and 12%, respectively.)
      • Iloperidone, asenapine, and lurasidone: a brief overview of 3 new second-generation antipsychotics (Iloperidone, asenapine, and lurasidone are approved for the treatment of acute schizophrenia in adults, and asenapine is also approved for the maintenance treatment of schizophrenia and as a monotherapy or as an adjunct to lithium or valproate for the treatment of bipolar manic or mixed episodes. Asenapine is a sublingual preparation, in contrast to iloperidone and lurasidone, which are swallowed. Iloperidone and asenapine are dosed twice daily, in contrast to lurasidone, which is dosed once daily with food. Both asenapine and lurasidone can be initiated at a dose that is possibly therapeutic, but iloperidone requires 4 days of titration to reach its recommended target dose range. Although both asenapine and lurasidone can be associated with dose-related treatment-emergent akathisia, iloperidone is essentially free of extrapyramidal adverse effects or akathisia throughout its recommended dose range. Sedation and/or somnolence have been reported with each medication.)
      • Paliperidone extended-release: does it have a place in antipsychotic therapy? (In the absence of direct comparisons with risperidone, it remains difficult to come to a final verdict on the potential additional therapeutic benefits of Paliperidone extended-release which would justify its substantially higher costs as compared with risperidone (its parent compound).)
      • Risperidone in schizophrenia: is there a role for therapeutic drug monitoring? (The routine use of risperidone levels does not seem warranted in all patients with schizophrenia. Therapeutic drug monitoring of risperidone may be beneficial in certain circumstances, including assessing potential noncompliance and supporting compliance, ruling out therapeutic failure as a result of low drug concentrations, and identifying and managing drug interactions and adverse effects.)
      • Pharmacological augmentation strategies for schizophrenia patients with insufficient response to clozapine: a quantitative literature review (There is no combination of clozapine plus some other pharmaceutical agent that yet has been proven superior to clozapine alone)
      • Psychopharmacological treatment of schizophrenia: what do we have, and what could we get? (The effectiveness of second generation antipsychotics is comparable to that of first generation antipsychotics)
      • A tipping point in drug dosing in late-life schizophrenia (In treating individuals with late-life schizophrenia: avoid polypharmacy, gradual dose titration, and timely and thorough assessments of therapeutic and side effects.)
      • Typical and atypical antipsychotics: Is there a difference in their influence on neurocognition? (The reported positive, cognitive effects of atypical antipsychotics are slight, particularly compared to the severity of neurocognitive dysfunction found in schizophrenia. In clinical practice there seem to be no convincing reason for attaching much weight to any differential effects that typical or atypical antipsychotics may have on neurocognition.)
      • Iloperidone: A new drug for the treatment of schizophrenia (Iloperidone has established tolerability at recommended dosages of up to 24 mg daily; however, the dosage must be slowly increased over seven days, and twice-daily administration is required to avoid orthostatic hypotension. The most common adverse effects associated with iloperidone were dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia, and weight gain. Safety studies have also found that iloperidone increases the risk of Q-Tc interval prolongation, similar to that seen with ziprasidone. Minimal changes in glucose and lipid abnormalities were seen in short-term (4- and 6-week) and long-term (52-week) studies, indicating a low chance of metabolic disturbance with iloperidone. iloperidone lacks a clear benefit over other antipsychotic agents.)
      • Placebo response in clinical trials with schizophrenia patients (There is ample evidence of the impact of elevated placebo response in trials of major depression. Placebo response in schizophrenia trials has similarly increased over the past several years.)
      • Oral versus depot antipsychotic drugs for schizophrenia--a critical systematic review and meta-analysis of randomised long-term trials (Depot formulations significantly reduced relapses (NNT 10, P=0.0009), and dropout due to inefficacy. Limited data on non-adherence, rehospitalisation and dropout due to any reason and adverse events revealed no significant differences.)
      • Olanzapine pamoate for the treatment of schizophrenia (The side-effect profile is comparable to that of oral olanzapine. The most relevant adverse event is the post-injection delirium/sedation syndrome, occurring at a rate of 1.4% of patients. It requires administration by qualified personnel in settings where a post-injection observation period for 3 h by medical personnel is available.)
      • Managing suicide risk in patients with schizophrenia (Compared with the general population, these patients have an 8.5-fold greater risk of suicide. Clozapine is the only medication approved by the US FDA for preventing suicide in patients with schizophrenia. Selective serotonin receptor inhibitors (SSRIs) decrease depressive symptoms and suicidal thoughts in patients with schizophrenia.)
      • Risperidone versus other atypical antipsychotics for schizophrenia (The review currently includes 45 blinded RCTs with 7760 participants. Attrition from these studies was high (46.9%). The large proportion of participants leaving studies early and incomplete reporting of outcomes makes it difficult to draw firm conclusions. Risperidone produces somewhat more extrapyramidal side effects and clearly more prolactin increase than most other second generation antipsychotics.)
      • Evidence-based pharmacotherapy of schizophrenia (Withdrawing antipsychotics from patients who have been stable for up to 6 yr leads to more relapses than continuing medication. In effect, continuous treatment is more effective than intermittent strategies. )
      • An open, large, 6-month naturalistic study of outcome in schizophrenic outpatients, treated with olanzapine (The review currently includes 50 studies and 9476 participants. The overall attrition from the included studies was considerable (49.2%) leaving the interpretation of results problematic. Olanzapine may be a somewhat more efficacious drug than some other second generation antipsychotic drugs. This small superiority in efficacy needs to be weighed against a larger weight gain and associated metabolic problems than most other second generation antipsychotic drugs, except clozapine.)
      • Lurasidone for schizophrenia: a brief review of a new second-generation antipsychotic (Efficacy within the dose range of 40-120 mg/d was established in four 6-week, randomized, controlled trials. The recommended starting dose is 40 mg/d and the maximum recommended dose is 80 mg/d. Doses above 80 mg/d do not appear to confer added benefit and may be associated with a dose-related increase in certain adverse reactions such as somnolence and akathisia. Lurasidone is administered once daily with at least 350 calories of food in order to optimize bioavailability. Lurasidone is associated with minimal weight gain and no clinically meaningful alterations in glucose, lipids, or the ECG QT interval.)
      • Elderly patients with schizophrenia and depression: diagnosis and treatment (Augmentation of an antipsychotic medication with an antidepressant medication can be helpful for the elderly patient with schizophrenia and depressive symptoms)
      • The pharmacological management of violence in schizophrenia: a structured review (Although the increased risk of violent behavior in individuals with schizophrenia is now well-established, there is considerable uncertainty in pharmacological strategies to reduce this risk. The main findings included the association of nonadherence to antipsychotic medication to violent outcomes, a specific anti-aggressive effect of clozapine and short-term benefits of adjunctive ß-blockers. There was little evidence on the efficacy of adjunctive mood stabilizers, depot medication or electroconvulsive therapy.)
      • Lurasidone for schizophrenia: a review of the efficacy and safety profile for this newly approved second-generation antipsychotic (Recommended starting dose of 40 mg/day administered once daily with food (=350 calories). The maximum recommended dose is 80 mg/day. NNT vs. placebo was 3-6 for response as defined by =20% reduction in psychopathological rating scale total scores from baseline. Response as defined by a =30% improvement yielded NNTs ranging from 7 to 13. The most common adverse events in the clinical trials were somnolence (broadly defined), akathisia, nausea, parkinsonism and agitation. Lurasidone is associated with minimal weight gain and no clinically meaningful alterations in glucose, lipids, prolactin or the ECG QT interval. Principal advantages over some other second-generation antipsychotics are lurasidone's highly favourable metabolic profile and once-daily dosing regimen.)
      • The treatment of cognitive impairment in schizophrenia (No treatment has yet demonstrated efficacy in large replication trials)
      • Predictors of relapse in Chinese schizophrenia patients: a prospective, multi-center study (The study confirmed the importance of maintenance medication in preventing relapse in Chinese schizophrenia patients underscoring the risk of relapse associated with lack of treatment adherence, severe side effects and the patients' paranoid attitude.)
    • Psychological Therapies
      • Schizophrenia, cognition and psychoeducation (Cognitive remediation targets elementary cognitive impairment, mostly with repetitive cognitive tasks, and studies show an improvement in these specific tasks, but without positive effect on functional and social aspects of the illness. (Whereas) overall approaches, such as psychoeducation or therapeutic education, obtain real gains in quality of life for the patients, autonomy and clinical improvement.)
      • A randomized, controlled trial of computer-assisted cognitive remediation for schizophrenia (Cognitive remediation for people with schizophrenia was effective in improving memory, concentration and executive functioning. "However, there were no significant benefits of cognitive remediation on non-verbal working memory and learning and speed of processing or functional outcome measures." Thus this computer-assisted training did not cause any clinically significant improvement in psychosocial functioning. [Editor: Psychosocial research has shown that patients do significantly benefit from exercise, social skills training, occupational therapy, music therapy and psychoeducation; whereas computer-assisted cognitive remediation appears to accomplish little.])
    • Other Therapies
    • Miscellaneous
  • 2010 Research Review Articles
  • 2009 Research Review Articles
  • 2008 Research Review Articles
  • 2007 Research Review Articles
  • 2006 Research Review Articles
  • 2005 Research Review Articles
  • Prior to 2005 Research Review Articles
  • Articles On Weight Gain

    • External Links
      • The Metabolic Effects of Antipsychotic Medications - Canadian Journal of Psychiatry July 2006
          (Editor: At least a decade ago, clinicians became alarmed by the 20 to 40 lb weight gains experienced by many of our patients on the newer antipsychotic medications [especially clozapine, olanzapine, and to a lesser extent, respiridone and quetiapine]. Many older, equally effective, antipsychotic medications [e.g., flupenthixol, sulpiride, amisulpiride] had much less, or no, weight gain. Initially, the manufacturers of these newer, obesity-inducing antipsychotic medications assured clinicians that the weight gain on their medications was minimal. Now, many years later, researchers have finally acknowleged the full magnitude of this serious weight gain problem. My question is why did pharmaceutical company sponsored researchers and lecturers minimize this serious weight gain problem for so long?)
      • Metabolic Monitoring for Patients Treated With Antipsychotic Medications - Canadian Journal of Psychiatry July 2006
          (Editor: It now is essential that clinicians follow these guidelines to metabolically monitor their patients on obesity-inducing antipsychotic medications.)
      • Pharmacologic and Nonpharmacologic Strategies for Weight Gain and Metabolic Disturbance in Patients Treated With Antipsychotic Medications - Canadian Journal of Psychiatry July 2006
          (Editor: The best way, in my opinion, to avoid weight gain on antipsychotic medications is to: (1) use antipsychotic medications which cause minimal weight gain [e.g., flupenthixol, aripiprazole, loxapine, sulpiride, amisulpiride], (2) minimize sugar and starch in the diet, and (3) walk briskly 30 minutes per day. Unfortunately, not all patients respond to the antipsychotics which cause minimal weight gain; hence must be tried on other antipsychotic medications which induce obesity. Nevertheless, many patients on these obesity-inducing medications normalize their weight following steps #2 and #3.)

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