The management of schizophrenia usually involves many aspects including psychological, pharmacological, social, educational, and employment-related interventions directed to recovery, and reducing the impact of schizophrenia on quality of life, social functioning, and longevity.
Hospitalization Hospitalization may occur with severe episodes of schizophrenia. This can be voluntary or (if mental health legislation allows it) involuntary (called civil or involuntary commitment). Long-term inpatient stays are now less common due to deinstitutionalization, although still occur. Following (or in lieu of) a hospital admission, support services available can include drop-in centers, visits from members of a community mental health team or Assertive Community Treatment team, supported employment and patient-led support groups. Efforts to avoid repeated hospitalization include the obtaining of community treatment orders which, following judicial approval, coerce the affected individual to receive psychiatric treatment including long-acting injections of anti-psychotic medication. This legal mechanism has been shown to increase the affected patient's time out of the hospital.
Medication
The mainstay of treatment for schizophrenia is an antipsychotic medication. Most antipsychotics can take around 7 to 14 days to have their full effect. Medication may improve the positive symptoms of schizophrenia, and social and vocational functioning. However, antipsychotics fail to significantly improve the negative symptoms and cognitive dysfunction. There is evidence of clozapine, amisulpride, olanzapine, and risperidone being the most effective medications. However, a high proportion of studies of risperidone were undertaken by its manufacturer, Janssen-Cilag, and should be interpreted with this in mind. In those on antipsychotics, continued use decreases the risk of relapse. There is little evidence regarding consistent benefits from their use beyond two or three years.
Treatment of schizophrenia changed dramatically in the mid-1950s with the development and introduction of the first antipsychotic chlorpromazine. Others such as haloperidol and trifluoperazine soon followed.
It remains unclear whether the newer antipsychotics reduce the chances of developing neuroleptic malignant syndrome, a rare but serious and potentially fatal neurological disorder most often caused by an adverse reaction to antipsychotics (neuroleptics).
Most people on antipsychotics get side effects. People on typical antipsychotics tend to have a higher rate of extrapyramidal side effects while some atypicals are associated with considerable weight gain, diabetes, and risk of metabolic syndrome; this is most pronounced with olanzapine, while risperidone and quetiapine are also associated with weight gain. Risperidone has a similar rate of extrapyramidal symptoms to haloperidol. The American Psychiatric Association generally recommends that atypicals be used as first line treatment in most patients, but further states that therapy should be individually optimized for each patient.
The response of symptoms to medication is variable; treatment resistant schizophrenia is the failure to respond to two or more antipsychotic medications given in therapeutic doses for six weeks or more. Patients in this category may be prescribed clozapine, a medication that may be more effective at reducing symptoms of schizophrenia, but treatment may come with a higher risk of several potentially lethal side effects including agranulocytosis and myocarditis. Clozapine is the only medication proven to be more effective for people who do not respond to other types of antipsychotics. It also appears to reduce suicide in people with schizophrenia. As clozapine suppresses the development of bone marrow, in turn reducing white blood cells which can lead to infection, blood tests are taken for the first six months on this medication. The risk of experiencing agranulocytosis due to clozapine treatment is higher in elderly people, children, and adolescents. The effectiveness in the studies also needs to be interpreted with caution as the studies may have an increased risk of bias.
Studies have found that antipsychotic treatment following NMS and neutropenia may sometimes be successfully rechallenged (restarted) with clozapine.
Tobacco smoking increases the metabolism of some antipsychotics, by strongly activitating CYP1A2, the enzyme that breaks them down, and a significant difference is found in these levels between smokers and non-smokers. It is recommended that the dosage for those smokers on clozapine be increased by 50%, and for those on olanzapine by 30%. The result of stopping smoking can lead to an increased concentration of the antipsychotic that may result in toxicity, so that monitoring of effects would need to take place with a view to decreasing the dosage; many symptoms may be noticeably worsened, and extreme fatigue, and seizures are also possible with a risk of relapse. Likewise those who resume smoking may need their dosages adjusted accordingly. The altering effects are due to compounds in tobacco smoke and not to nicotine; the use of nicotine replacement therapy therefore has the equivalent effect of stopping smoking and monitoring would still be needed.
Research findings suggested that other neurotransmission systems, including serotonin, glutamate, GABA, and acetylcholine, were implicated in the development of schizophrenia, and that a more inclusive medication was needed. A new first-in-class antipsychotic that targets multiple neurotransmitter systems called lumateperone (ITI-007), was trialed and approved by the FDA in December 2019 for the treatment of schizophrenia in adults. Lumateperone is a small molecule agent that shows improved safety, and tolerance. It interacts with dopamine, serotonin, and glutamate in a complex, uniquely selective manner, and is seen to improve negative and positive symptoms, and social functioning. Lumateperone was also found to reduce potential metabolic dysfunction, have lower rates of movement disorders, and have lower cardiovascular side effects such as a fast heart rate.
The fixed-dose combination medication xanomeline/trospium chloride (Cobenfy) was approved for medical use in the United States in September 2024. It is the first antipsychotic drug approved by the US Food and Drug Administration (FDA) to treat schizophrenia that targets cholinergic receptors as opposed to dopamine receptors, which has long been the standard of care.
Add-on agents Sometimes the use of a second antipsychotic in combination with another is recommended where there has been a poor response. A review of this use found some evidence for an improvement in symptoms but not for relapse or hospitalisation. The use of combination antipsychotics is increasing in spite of limited supporting evidence, with some countries including Finland, France, and the UK recommending its use and others including Canada, Denmark, and Spain in opposition. Anti-inflammatories, anti-depressants, and mood stabilisers are other add-ons used. Other strategies used include ECT, or repetitive transcranial magnetic stimulation (rTMS) but evidence for these is lacking.
Note: Only adjuncts for which at least one double-blind randomized placebo-controlled trial has provided support are listed in this table.