For 36 years, I worked as a psychiatrist treating individuals with schizophrenia, and I had the privilege of treating many of my patients continuously for two or three decades. These years taught me the following:
Worldwide, between 10%-20% of individuals with schizophrenia live normal lives if they stay on their antipsychotic medication. The remainder of individuals with schizophrenia have to adjust to being unable to return to work, and being less socially active. Thus it is essential that patients be offered rewarding opportunities for volunteer work and community involvement.
"Recovery" in schizophrenia must be defined as both functional (occupational & social) recovery as well as symptomatic recovery. Thus successful treatments for schizophrenia must show that they decrease: unemployment, social isolation, medical adverse effects, psychotic relapse, hospitalization, and suicide. Unfortunately, apart from antipsychotic medication, most of the other treatments for schizophrenia haven't consistently shown that they bring about both functional and symptomatic recovery.
Early diagnosis and lifelong treatment on antipsychotic medication is absolutely essential for recovery from schizophrenia.
Individuals smoking marijuana (cannabis), abusing alcohol or other drugs do not make a full recovery from schizophrenia.
One of the worst aspects of schizophrenia is its loneliness. Many individuals with schizophrenia lose their job, their friends, and their feeling of self-worth. Antipsychotic medication can't remedy these losses; hence therapists must organize social activities that restore friends, self-worth and laughter. Most patients prefer activities that last only a few hours; rather than activities that last for days. Thus activities like: day-trips, volleyball, craft groups, art groups, choir, cooking groups, movie groups, walking groups, hiking/snowshoeing groups or coffee get-togethers are preferred over longer, more stressful activities (e.g., week-long trips). These social and recreational activities must treat participants as individuals, and not as "patients". These participants should vote on what activities they want, and how these activities should be run. For safety reasons; it is wise to not include an overtly psychotic patient in these recreational activities. Refreshments should be provided at half time, so that participants can sit and socialize with other participants. These supervised activities often provide patients with the only social contact and laughter that they have all week. (On a patient's birthday, my wife always remembered to bring a birthday cake to our activities.)
Therapists must insist that all patients faithfully stay on their antipsychotic medications. Those that find it difficult to stay on oral medication should be switched to long-acting injectable antipsychotic medication. "Drug holidays" always eventually turn out to be a disaster.
Family members should be invited to join the patient's appointments (if the patient approves). If a psychotic patient is undergoing significant deterioration, or is at risk of harming himself or others; family or concerned friends should be permitted to speak to the therapist - even against the expressed wishes of the psychotic patient. A family member's or friend's "right" to get psychiatric help for a psychotic loved one who is relapsing should supersede a psychotic patient's "right" to medical confidentiality.
Psychotic patients should be (voluntarily or involuntarily) hospitalized when they suffer severe deterioration in functioning. Patients should not have to wait until they are "at risk of harming himself or others" before psychiatric help is given. Unfortunately, only a few legal jurisdictions (e.g., British Columbia, Canada) have Mental Health Acts that permit involuntary hospitalization on the basis of severe deterioration in functioning. Most legal jurisdictions have Mental Health Acts that permit involuntary hospitalization only when the psychotic patient "is at risk of harming himself or others". Such antiquated Mental Health Acts prevent many families from getting psychiatric help for their psychotic loved ones, until it is too late.
High rates of rehospitalization can be dramatically reduced if there is continuity of care. When patients are acutely psychotic; they should be seen by their outpatient therapist for one hour every week. Once they are stabilized; the frequency of their outpatient visits should be gradually decreased. Finally, they should be seen for one hour at least once every 3-6 months for the rest of their lives. (This is exactly what I did in my private psychiatric practice, and very few of my patients required rehospitalization.)
Even with the best treatment, only 10%-20% of individuals with schizophrenia will fully recover, 70% will remain single, and 70% will be unemployed (and on some form of disability pension). Tragically, 5% will die due to suicide.
It is very important to decrease the stigma of mental illness. (For many years, a mental health community leader, Robert Winram, and myself arranged a Mental Health Christmas Awards Dinner for my city. This dinner gave awards to patients, parents and mental health workers who had made outstanding contributions to mental health. It was held in one of our city's largest hotels, and 800 patients and parents attended. By doing this, we hoped to publicly recognize the "unsung heroes" in mental health.)
What you are about to read about schizophrenia is presented in an honest, and I hope compassionate, manner. Schizophrenia is potentially a very serious mental disorder, but antipsychotic medication and psychosocial treatments can dramatically help two-thirds of the individuals with this disorder. The first step in conquering this illness is to become better informed.
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.
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:
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 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 may 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.
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.
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".
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 very high risk of tragedy if a psychotic individual physically threatens the police.
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
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."
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
Pharmaceutical companies have paid prosecutors $2.7 billion in settlements over their illegal off-label marketing of their antipsychotics. These are the largest criminal fines ever paid by pharmaceutical companies.
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.
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.)
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])
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.)
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.)
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
Cognitive impairment in schizophrenia (Cognitive functioning is moderately to severely impaired in patients with schizophrenia. This impairment is the prime driver of the significant disabilities in occupational, social, and economic functioning in patients with schizophrenia and an important treatment target. The profile of deficits in schizophrenia includes many of the most important aspects of human cognition: attention, memory, reasoning, and processing speed. The effects of antipsychotic medications on cognition in schizophrenia and first-episode psychosis appear to be minimal.)
Innovative treatment approaches in schizophrenia enhancing neuroplasticity: aerobic exercise, erythropoetin and repetitive transcranial magnetic stimulation (Aerobic exercise has been shown to increase hippocampal volume, elevate N-acetyl-aspartate in the hippocampus as neuronal marker, and improve short-term memory in schizophrenia. The hematopoietic growth factor erythropoetin (EPO) is involved in brain development and associated with the production and differentiation of neuronal precursor cells. A first study demonstrated a positive effect of EPO application on cognition in schizophrenia patients. In randomised controlled studies with small sample size, the efficacy of repetitive transcranial magnetic stimulation (rTMS), a biological intervention focussing on the enhancement of LTP, has been shown for the improvement of positive and negative symptoms in schizophrenia.)
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.)
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.)
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.)
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.)
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)
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. )
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.)
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.)
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.)
Cognitive behavioral therapy for schizophrenia: an empirical review (Seven randomized, controlled trial studies testing the efficacy of CBT for schizophrenia demonstrated large clinical effects on measures of positive and negative symptoms of schizophrenia. Patients receiving routine care and adjunctive CBT have experienced additional benefits above and beyond the gains achieved with routine care and adjunctive supportive therapy.)
Cognitive Behavior Therapy Versus Other Psychosocial Treatments for Schizophrenia (The use of CBT has been associated with some reduction in symptoms, particularly affective problems associated with having such a serious illness. However, there is considerable variability in the findings of the various studies and, at present, it is not possible to assert any substantial benefit for cognitive behavioral therapy over other psychological therapies)
Adverse effects of cognitive behavioral therapy and cognitive remediation in schizophrenia: results of the treatment of negative symptoms study (This study examined the frequency and extent of detrimental effects of cognitive behavioral therapy (CBT) for psychosis. In a randomized clinical trial, we investigated the efficacy of CBT for the reduction of negative symptoms as compared with cognitive remediation (CR) in schizophrenia patients (n = 198). Monthly assessments with Positive and Negative Syndrome Scale and Scale for the Assessment of Negative Symptoms allowed for the analysis of symptom increases during the treatment. Increases in negative symptoms occurred in 64 CBT and 58 CR patients. These differences were not significant. The maximum increase in negative symptoms under treatment, as compared with the baseline, was equal to an effect size of -0.66 in CBT patients and -0.77 in CR patients.)
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.)
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.)
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.)
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])
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.)
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.)
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. )
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.)
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.])
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.
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].)
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.)
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. )
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.)
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.)
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.)
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.)
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.)
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.)
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.])
Psychoeducation for schizophrenia (Psychoeducational approaches have been developed to increase patients' knowledge of, and insight into, their illness and its treatment. 44 trials (median study duration 12 weeks) of psychoeducation for schizophrenia reported increased clinical improvement rates (NNT 4), lower readmission rates (NNT 5) and greater satisfaction with mental health services (NNT 5). However, psychoeducation did not significantly reduce non-compliance (NNT 11) or relapse (NNT 9) rates.)
The concepts of remission and recovery in schizophrenia (The Remission in Schizophrenia Working Group (RSWG) published operationalized criteria for symptomatic remission in 2005. Reported remission rates vary widely across studies (17-88%). Patients move in and out of remission over time.)
The prevention of schizophrenia--what can we learn from eco-epidemiology? ("We do not currently have sufficient empirical data to design effective prevention strategies." [Editor: I disagree. There is solid evidence that cannabis use causes a near four-fold increase in the incidence of schizophrenia. If cannabis is legalized; the vast majority of new cases of schizophrenia will be due to cannabis use.])
Progressive ventricular expansion in chronic poor-outcome schizophrenia (In comparison with healthy participants, schizophrenia patients displayed significantly enlarged body, and anterior and posterior horns of the lateral ventricles at baseline and follow-up..Progressive enlargement of the posterior horn in the poor-outcome (Kraepelinian) group, however, was more pronounced than in schizophrenia patients with good outcome...Excessive ventricular enlargement in the chronic phase of schizophrenia may be specifically associated with poor functional outcome of the illness.)
Structural neuroimaging in schizophrenia: from methods to insights to treatments ("Ventricular enlargement is one of the earliest and most consistent findings in schizophrenia . The ventricles of patients with schizophrenia are approximately 130% the size of normal controls. This has been interpreted as an indicator of brain shrinkage after the onset of the brain process associated with schizophrenia. Ventricular enlargement is present by the time of first psychotic episodes of schizophrenia. There is no evidence for a loss of neurons and no gliosis in postmortem studies of schizophrenia. These findings, taken together, suggest that schizophrenia is not a neurodegenerative disorder. There are multiple focal brain regions that are abnormal in schizophrenia. These MRI changes occur over time, particularly soon after onset of illness, and these changes may also be evident before the onset of symptoms (ie, in the prodrome period). These MRI abnormalities are also observed, albeit in a more attenuated form, in family members of patients with schizophrenia.")
Treatment of shizophrenic patients and rTMS (Despite appropriate medication, about 1/4 of patients with schizophreia suffer for refractory positive and/or negative symptoms, which are associated with functional handicap. Numerous studies have suggested that the pathophysiology of auditory hallucinations (AH) is related to a hyper activity of the left temporoparietal cortex (TPC). On the other hand, negative symptoms are associated with a prefrontal hypoactivity. When compared to sham, this type of acute course of rTMS has been proven to induce a substantial and significant reduction in auditory hallucinations. But this effect does not seem long-lasting and maintenance protocols must be developed. Concerning negative symptoms, the results are less solid.)
Practical aspects of the use of ziprasidone in schizophrenia (Ziprasidone is used for the treatment of schizophrenia and bipolar manic states in doses 40-80 mg administered twice a day. The i.m. form should be given 40 mg/day only during three days. Ziprasidone shows similar efficacy as olanzapine.)
Antipsychotics and metabolics in the post-CATIE era (CATIE provided clear confirmation of the metabolic liability for olanzapine and also quetiapine, particularly on measures associated with insulin resistance: fasting triglycerides and central adiposity)
Clozapine versus other atypical antipsychotics for schizophrenia (Attrition from these studies was high (overall 30.1%), leaving the interpretation of results problematic. Clozapine was not more efficacious than olanzapine, quetiapine, risperidone and ziprasidone in improving the participants general mental state. There was no significant difference between clozapine and olanzapine or risperidone in terms of positive or negative symptoms of schizophrenia. Clozapine produced an important weight gain not seen with risperidone.
Where to position clozapine: re-examining the evidence (The hematologic monitoring implemented with clozapine's reintroduction here in North America has proven successful in preventing clozapine-related deaths secondary to agranulocytosis. present evidence does not link clozapine to increased mortality rates; indeed, it appears better than other antipsychotics in this regard.)
Effect of antipsychotic medication alone vs combined with psychosocial intervention on outcomes of early-stage schizophrenia: A randomized, 1-year study (Early-stage patients with schizophrenia were randomly assigned to receive antipsychotic medication treatment only or antipsychotic medication plus 12 months of psychosocial intervention consisting of psychoeducation, family intervention, skills training, and cognitive behavior therapy administered during 48 group sessions. The rates of treatment discontinuation or change due to any cause were 32.8% in the combined treatment group and 46.8% in the medication-alone group. Compared with those receiving medication only, patients with early-stage schizophrenia receiving medication and psychosocial intervention have a lower rate of treatment discontinuation or change, a lower risk of relapse, and improved insight, quality of life, and social functioning.)
Iloperidone for the treatment of schizophrenia (Effective and safe, except cautious dosing and titration schedule is recommended at the initiation of therapy due to the potential for orthostatic hypotension and dizziness. Can have drug interactions through the CYP3A4 and CYP2D6 enzymes, along with the potential for QT prolongation.)
What do large scale studies of medication in schizophrenia add to our management strategies?
(Five large naturalistic trials have compared second generation antipsychotic drugs with first generation antipsychotic drugs. The studies were: * CUTLASS (Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia study); * CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness study); * SOHO (Schizophrenia outpatients Health Outcomes study); * CAFE (Comparison of Atypicals in First Episode study); * EUFEST (European First Episode Schizophrenia Trial). The trials: * CAFE - the trial, although well randomised and blinded, uses discontinuation as a primary endpoint - this is hard to draw conclusions from: patients may discontinue due to side effects, due to lack of efficacy or with against medical advice for a multitude of reasons. As a secondary endpoint, the study does make use of a PANSS scoring system to measure efficacy, adding some weight to the conclusion that olanzapine, quetiaine and risperidone in early psychosis patients have equivalent efficacies. * CATIE - This trial was a comparative study, and so lacked a control arm and used discontinuation of medication an inverse measure of efficacy - an easily quantifiable event, but making for difficult interpretation. However most criticism has been directed at the unusually low (quitiapine, ziprasidone) and high (olanzapine and perphenazine) doses of drug used, which were reflected in their differing rates of efficacy. * CUtLASS This trial allows for less generalisation of its findings to the general population as it makes use a specific sub-population (those switching from one medication to another after a period of treatment). Also some patients were prescribed oral medications and some depot injections - making comparisons difficult due to possible differences in compliance. * EUFEST This trial makes use of discontinuation as an endpoint with the weaknesses we have described. Treatment of first episodes of psychosis is shown to be feasible, but it could not suggest if haloperidol or second generation drugs may be more efficacious. * SOHO - This trial hindered by the observational design of the study and small numbers reaching the primary end point (4%) caution should be exercised in the conclusion that olanzapine is superior to risperidone, quetiapine or typical antipsychotics.)
Treatment of early-onset schizophrenia (Clozapine shows greater efficacy in children and adolescents than it has in adults. Children and adolescents appear to be more likely to develop metabolic abnormalities such as pronounced weight gain, which may significantly impact adherence.)
Olanzapine: a review of rapid and long-acting parenteral formulations (Olanzapine pamoate long acting injection (depot) is given at 2- or 4-weekly intervals. There is also an olanzapine rapid-acting intramuscular injection. Apart from local injection reactions and a postinjection delirium/sedation syndrome, no new adverse events additional to those seen with oral olanzapine.)
Antipsychotic medication, functional outcome and quality of life in schizophrenia: focus on amisulpride (Restoration of quality of life is considered as the ultimate treatment goal in the management of schizophrenia; yet few studies have evaluated the relationship of treatment with quality of life. Amisulpride treatment improvements in quality of life are consistently greater than those observed in patients treated with haloperidol and similar in magnitude to those seen with olanzapine, ziprasidone and risperidone.)
A systematic review of the effects of antipsychotic drugs on brain volume (People with schizophrenia are often found to have smaller brains and larger brain ventricles than normal, but the role of antipsychotic medication remains unclear. Some evidence points towards the possibility that antipsychotic drugs reduce the volume of brain matter and increase ventricular or fluid volume. Antipsychotics may contribute to the genesis of some of the abnormalities usually attributed to schizophrenia.)
Catatonia and its treatment (Catatonia is present in about 10% of acutely ill psychiatry patients, only a minority of whom have schizophrenia. Catatonia typically resolves dramatically and completely with benzodiazepine therapy. The majority of patients with catatonia have concurrent psychosis. Failure to treat the catatonia before institution of antipsychotic medication may increase the risk of inducing neuroleptic malignant syndrome.)
Paliperidone palmitate - review of the efficacy, safety and cost of a new second-generation depot antipsychotic medication (Paliperidone palmitate is a newly available depot formulation of paliperidone (the 9-OH metabolite of risperidone). Maximum concentration following deltoid injection is approximately 28% higher compared with injection into the gluteal muscle, and thus paliperidone palmitate requires initiation by two initial deltoid injections spread 1 week apart to achieve therapeutic concentrations rapidly. Subsequent injections are at 4-week intervals. Optimal dose is between 39 and 156 mg IM (deltoid) every 4 weeks. The cost of a 4-week dose of paliperidone palmitate is 19 times the cost of a 4-week supply of oral generic risperidone.)
A controlled, evidence-based trial of paliperidone palmitate, a long-acting injectable antipsychotic, in schizophrenia (All paliperidone palmitate dose groups showed significant improvement vs placebo in the Positive and Negative Syndrome Scale (PANSS) total score (25 and 50 mg equiv., p=0.02; 100 mg equiv., p<0.001), as well as Clinical Global Impression Severity scores (p< or =0.006). Parkinsonism, the most frequently reported extrapyramidal symptom, was reported at similar rates for placebo (5%) and paliperidone palmitate (5-6% across doses). The mean body mass index and mean weight showed relatively small dose-related increases during paliperidone palmitate treatment. All doses of once-monthly paliperidone palmitate were efficacious and generally tolerated, both locally and systemically. [Editor: Notice that there is only a 20% difference between the effectiveness of medication and that of placebo. This is the usual difference found between antipsychotic medication and placebo.])
Family intervention for schizophrenia (Family intervention decreases the frequency of relapse (NNT 7), reduces hospital admission (NNT 8), and encourages compliance with medication (NNT 6). It does not affect the tendency of individuals/families to leave care. Family intervention also seems to improve general social impairment and the levels of expressed emotion within the family.)
The 2009 schizophrenia PORT psychosocial treatment recommendations and summary statements (Systems of care serving persons with schizophrenia should include a program of assertive community treatment (ACT). This intervention should be provided to individuals who are at risk for repeated hospitalizations or have recent homelessness. The key elements of ACT include a multidisciplinary team including a medication prescriber, a shared caseload among team members, direct service provision by team members, a high frequency of patient contact, low patient-to-staff ratios, and outreach to patients in the community. ACT has been found to significantly reduce hospitalizations and homelessness among individuals with schizophrenia.)
Periods of recovery in deficit syndrome schizophrenia: a 20-year multi-follow-up longitudinal study (Cumulatively, over the 20-year period, 13% of patients classified as meeting criteria for the deficit syndrome showed 1 or more 1-year periods of global recovery, in comparison to 63% of nondeficit schizophrenia patients and 77% of depressed patient controls. Results indicate that the deficit syndrome represents a persistently impaired subsample of schizophrenia patients, with continuous social, occupational, and symptom impairment. In contrast, nondeficit syndrome schizophrenia patients showed at least some periods of remission or recovery, with the likelihood of these periods increasing as they became older. Findings provide further support for the validity of the deficit syndrome concept and suggest that deficit status is characterized by a more persistently impaired course of illness and particularly poor long-term prognosis.)
Schizophrenia (Genetic vulnerability is shared in part with bipolar disorder and recent molecular genetic findings also indicate an overlap with developmental disorders such as autism. The diagnosis of schizophrenia is associated with demonstrable alterations in brain structure and changes in dopamine neurotransmission, the latter being directly related to hallucinations and delusions. Pharmacological treatments, which block the dopamine system, are effective for delusions and hallucinations but less so for disabling cognitive and motivational impairments.)
Glial cells in schizophrenia: pathophysiological significance and possible consequences for therapy (Schizophrenia lacks the neuronal degeneration seen in typical degenerative brain diseases. However, many studies show abnormalities in the connecting elements between the nerve cell bodies (synapses, dendrites and axons) and in all three types of glial cells. There is accumulating evidence of reduced numbers of oligodendrocytes and altered gene expression of myelin/oligodendrocyte-related genes that might explain white matter abnormalities
Aripiprazole versus other atypical antipsychotics for schizophrenia (Aripiprazole premature discontinuation rate was considerable (38.5%), limiting the validity of the findings. Aripiprazole may be somewhat less effective than olanzapine, but more tolerable in terms of metabolic effects and sedation. There is no evidence for a difference in efficacy compared to risperidone.)
Review of the efficacy of placebo in comparative clinical trials between typical and atypical antipsychotics (The pooled efficacy rates observed were 40.8%, 34.9% and 21.3% for the atypical antipsychotics, typical antipsychotics and placebo, respectively. One hundred and sixty six patients would have to be included when a new drug is compared with placebo if calculation is based on a difference of 20% found between the atypical antipsychotic and placebo and 2,054 if the difference sought were that found between the atypical antipsychotic and the typical antipsychotic, i.e. 6%. The estimated therapeutic failures would be 115 of the 166 patients when the study drug is compared with placebo, and 1,274 failures in the 2,054 patients when the study drug is compared to the typical antipsychotic. Placebo controlled studies may reduce the number of individuals exposed to the harmful effects of ineffective drugs.)
Clinical recovery in first-episode psychosis
(For first-episode patients, at 2-year followup, 52.0% attained symptomatic remission and 26.4% attained functional remission, while 19.2% met both criteria sets and were considered recovered. Recovery was significantly associated with short duration of untreated psychosis and better baseline functioning.)
Are second generation antipsychotics a distinct class? ("Aside from clozapine, first-generation and second-generation antipsychotics represent a diverse group of medications that have heterogenous receptor profiles and side effects but comparable clinical efficacy and potential to cause extrapyramidal symptoms." )
Clozapine use in children and adolescents. ("Despite a higher incidence of adverse effects in children, clozapine appears to be a uniquely beneficial second-line agent for treating children with refractory schizophrenia.")
Antipsychotic safety and efficacy concerns. ("Both the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and the Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1) sought to determine if atypical antipsychotics were truly safer and more effective than typical antipsychotics, but the evidence provided did not support the superiority of the atypical antipsychotics as expected.")
Blood glucose and schizophrenia: a systematic review of prospective randomized clinical trials. (Editor: Eli Lilly and Co. Ltd, the makers of olanzapine, have lost more than $1 billion in legal actions against them for denying that olanzapine increases the risk of diabetes. Thus I find this study's conclusion incredible; namely: "No consistent significant glucose differences were found between any comparator antipsychotics or placebo in any trial." This is simply untrue. Olanzapine definitely increases the risk of diabetes mellitus.")
The costs of schizophrenia. ("The cost of schizophrenia in the United States in 2002 was estimated to be $62.7 billion. Compared with a 1991 estimate, inpatient costs have declined, whereas outpatient costs and medication costs have increased.")
Refractory schizophrenia ("Refractory schizophrenia affects at least one third of patients with schizophrenia and the best evidence shows that is monotherapy with clozapine remains the mainstay for the treatment of such condition.")
Olanzapine and haloperidol in first episode psychosis: Two-year data. (Olanzapine and haloperidol treatment were both associated with substantial and comparable reductions in symptom severity. Remission rates were greater in patients treated with olanzapine as compared to those treated with haloperidol (57.2% vs. 43.9%, p<0.036). While extrapyramidal side effects were greater in those treated with haloperidol, weight gain, cholesterol level and liver function values were greater in patients treated with olanzapine.)
Electroconvulsive therapy for schizophrenia(Reports: "When ECT is compared with placebo or sham ECT, more people improved in the real ECT group." [Editor:
This study found a 16.7% difference in effectiveness between ECT and placebo (i.e., sham ECT). Clinically, this is a significant difference, but not that robust. Also, this study didn't identify how long the benefit from ECT lasted. Experience with ECT for depression, is that the benefit from ECT wears off in 6 months or less.])
(For psychosis, outcome was generally poor with only 10% achieving a 25% reduction in total PANSS scores from pretreatment to long-term follow-up, also cost-effectiveness analysis showed no advantages of CBT over non-CBT.)
Early-onset schizophrenia: a 15-year follow-up (The study describes the psychopathological and social outcome of patients treated for schizophrenia in adolescence (mean age at onset 16.0 years/SD 1.52) after a mean follow-up period of 15.4 years (10.2-21.2 years). Out of 55 patients consecutively admitted to hospital, 47 (85 %) could be traced and 39 (71 %) could be re-examined. At follow-up, 33/39 patients (85 %) had had at least one readmission. Full remission of global psychopathological symptoms [Clinical Global Impression (CGI) < or = 2] was found in 3/39 (8 %),a moderate outcome (CGI=3-5) in 22/39 (56 %), and a poor outcome (CGI=6-8) was seen in 14/39 (36 %). Severe or very severe impairments of global social functioning [Global Assessment of Social Function (GAS)< 51] were observed in 20/39 (51 %). The best predictor of global psychopathological and psychosocial outcome was type of onset (CGI: Beta=0.36, GAS: Beta=-0.37). A poor outcome was seen in 22 out of 25 cases with insidious onset. )
Long-term course of adolescent schizophrenia (The mean duration of schizophrenia at followup was 9.5 +/- 2.2 years. Assessment of the highest level of adaptive functioning revealed very good or good outcome in 19.8 percent of the patients, fair or poor outcome in 38.2 percent, and very poor outcome and gross impairment in 42.0 percent. Premorbid adjustment was the best predictor of outcome in our schizophrenia sample. A poor prognosis was found in patients with premorbid developmental delays and those who were introverted and withdrawn before their psychotic state.)
Long-term outcome of patients with schizophrenia: a review (Like other mental illnesses and medical illness in general, the natural course of schizophrenia showed itself to have a threefold division of mild, moderate, and severe. Although a great deal of variance in outcome occurred across the studies reviewed, schizophrenia is nevertheless a disorder with relatively poor outcome. Patients with schizophrenia consistently showed poorer courses and outcomes than patients with other psychotic and nonpsychotic psychiatric disorders. On the positive side, subgroups of schizophrenia patients had extended periods of recovery-some without the benefit of extensive mental health aftercare treatment-and patients with schizophrenia did not show a progressive downhill course.)
Long-term diagnostic stability and outcome in recent first-episode cohort studies of schizophrenia (The predominant course of illness includes chronically poor functioning, with little evidence of long-term improvement. Mortality due to suicide is significant at about 10% over 10-year periods of follow-up. Within studies, outcome domains are interrelated, and the relatively consistent predictors of poorer outcome include family history of schizophrenia, insidious onset, poor premorbid functioning, severity of negative symptoms, and severity and duration of untreated psychosis. Residing in a developed rather than a developing country is also associated with a poorer long-term course.
Do patients with schizophrenia ever show periods of recovery? A 15-year multi-follow-up study. (Cumulatively, over the 15-year period slightly over 40% of patients with schizophrenia showed 1 or more periods of recovery. Over 50% of the schizophrenia patients did not have a disorder that was chronic and continuous. Rather, their disorder was episodic, although for many more vulnerable and less resilient schizophrenia patients the episodes were more frequent and severe, with slower recovery.)
Cerebral ventricular change over the first 10 years after the onset of schizophrenia (During the first 10 years of illness, greater enlargement of lateral ventricles and reduction of hemispheric volume was observed over time in the patients compared with controls. Some patients exhibited ventricular enlargement only early in their illness or not at all after their first episode, while others continue to exhibit ventricular enlargement spanning the decade subsequent to their first episode.)
Superior temporal gyrus in schizophrenia: a volumetric magnetic resonance imaging study (The left superior temporal gyrus (STG) has been reported to be smaller in patients with schizophrenia. The volume of the STG has been found to correlate negatively with severity of hallucinations and thought disorder. Dysfunction of the primary auditory cortex in the anterior and middle STG and auditory association cortex in the posterior STG may play a role in the production of auditory perceptual abnormalities and poor organization of thought respectively.)
A randomized double-blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorder (Both treatments were well tolerated and efficacious. The frequency and severity of extrapyramidal symptoms were similar in the two treatment groups. Greater reductions in severity of positive and affective symptoms were seen with risperidone than with olanzapine treatment among study completers. There was no measure on which olanzapine was superior. Greater weight gain was associated with olanzapine than with risperidone treatment ... An increase in body weight of > or =7% was seen in 27% of olanzapine participants and 12% of risperidone participants.)
Risperidone versus typical antipsychotic medication for schizophrenia (Risperidone may be more acceptable to those with schizophrenia than older antipsychotics and have marginal benefits in terms of limited clinical improvement. Any marginal benefits this drug may have have to be balanced against its greater cost and increased tendency to cause side effects such as weight gain. )
Characteristics of outcome in schizophrenia at 13 years (Four of the original 67 patients with ICD-9 schizophrenia were lost to follow-up and five were dead: 52% were without psychotic symptoms in the last two years of follow-up, 52% were without negative symptoms and 55% showed good/fair social functioning. However, only 17% were alive at follow-up, without symptoms and disability, and receiving no treatment.)
Marital and labor market status in the long run in schizophrenia (Individuals who were later hospitalized were more frequently living alone, unemployed, receiving social benefits, or otherwise outside the labor market when compared with controls, as early as 19 years before their first admission. For individuals with schizophrenia, the odds ratios of being unmarried or not being fully employed were significantly increased even 25 years after admission. This pattern was especially pronounced for men and for individuals who had more admissions.)
Long-term trends of symptoms and disability in schizophrenia and related disorders (60 subjects with non-affective psychosis were monitored over 16 years. The severity of their psychotic symptoms and social disability were rated on a 3-point scale ("improvement, deterioration, and no change or fluctuating"). At 16-year follow-up, 55% of the subjects showed improvement in their psychotic symptoms; whereas 45% of the subjects showed deterioration in their social functioning. A trend of improvement of psychotic symptoms correlated significantly with a negative family history of severe psychiatric disorder and with an acute type of illness onset. Psychotic symptoms and social disability are relatively autonomous descriptors of the course of schizophrenia.)
A separate disease within the syndrome of schizophrenia (If schizophrenia is a clinical syndrome rather than a single disease, the identification of specific diseases within the syndrome would facilitate the advance of knowledge and the development of more specific treatments. We propose that deficit psychopathology (ie, enduring, idiopathic negative symptoms) defines a group of patients with a disease different from schizophrenia without deficit features, as the deficit and nondeficit groups differ in their signs and symptoms, course, biological correlates, treatment response, and etiologic factors.)
Course and outcome for schizophrenia versus other psychotic patients: a longitudinal study (The results indicate that, during the early course, schizophrenia patients still show relatively poor outcomes, although a small number of schizophrenia patients enter into complete remission. Over time, many schizophrenia patients fluctuate between severe disability and moderate disability rather than always showing severe disability. Schizophrenia patients tend to recover more slowly then other psychotic patients.)
(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?)
(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.)