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Medications for first-episode psychosis

What is first-episode psychosis?

People with a first episode of psychosis experience distressing symptoms such as unusual beliefs or abnormal behaviour (positive symptoms) and/or withdrawal or loss of interest in work or school (negative symptoms). Early intervention programs for schizophrenia and psychosis often combine many elements comprising both pharmaceutical and psychosocial therapies, and may involve enriched therapies that are tailored to an individual’s needs. The conclusions presented here are based on group data, and as such individual treatment programs need to be tailored by trained clinicians. Individual response to treatment can vary in terms of both symptoms and adverse effects.

What is the evidence on medications for first-episode psychosis?

For targeted early intervention services that include both antipsychotics and psychosocial components, moderate to high quality evidence finds small effects of greater improvements in symptoms, functioning, quality of life, and more remission and recovery than with treatment as usual.

Overall, there is a reasonable response to antipsychotics after a first-episode of psychosis; moderate quality evidence finds antipsychotics are associated with an 81% response rate when measured as a 20% reduction in symptoms, and a 52% response rate when measured as a 50% reduction in symptoms. For specific antipsychotics, high quality evidence finds greater improvement in overall symptoms with olanzapine than with haloperidol, and moderate to high quality evidence finds greater improvement in negative symptoms with olanzapine than with haloperidol, with no differences in positive symptoms. Moderate to high quality evidence finds greater improvement in overall symptoms with amisulpride or risperidone than with haloperidol. Moderate quality evidence finds greater improvement in overall symptoms with amisulpride than with quetiapine, and with ziprasidone than with haloperidol. There was greater improvement in negative symptoms with olanzapine than with risperidone, and greater improvement in positive symptoms with olanzapine than with quetiapine. There was greater improvement in both positive and negative symptoms with quetiapine than with haloperidol, and greater improvement in positive symptoms with risperidone than with quetiapine.

For relapse prevention, moderate to high quality evidence finds small effects of fewer relapses and hospitalisations with targetted early intervention services. Second-generation antipsychotics in general were found to be more effective than first-generation antipsychotics. Moderate quality evidence finds relapse and rehospitalisation rates were higher after discontinuation rather than maintenance of antipsychotics in people in remission following a first-episode of psychosis.

For treatment adherence, moderate to high quality evidence finds less all-cause discontinuation with targeted early intervention services. There was less all-cause discontinuation with risperidone than with haloperidol and less all-cause discontinuation with quetiapine than with haloperidol. Moderate to low quality evidence finds less all-cause discontinuation with aripiprazole or olanzapine than with haloperidol.

For side effects, olanzapine was associated with at least one use of drugs to treat parkinsonian symptoms. Quetiapine was associated with less akathisia than haloperidol, aripiprazole, risperidone, and olanzapine. Molindone resulted in less weight gain than risperidone, haloperidol, and olanzapine and less increase in prolactin release than risperidone.

October 2020

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Last updated at: 2:16 pm, 15th February 2022
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Fact Sheet Technical Commentary
Tags:  Early detection Early intervention First-episode psychosis

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