Antipsychotic choice for a first episode of psychosis in adults and young people

If antipsychotic therapy for a first episode of psychosis is considered necessary after observing the patient for 24 to 48 hours, if possible, discuss the following with the patient and, if the patient consents, their family, carers or significant others:

  • the purpose of the antipsychotic and its place in multifaceted treatment
  • which antipsychotic adverse effects are acceptable to the patient and how these effects are monitored, prevented and addressed
  • the importance of treatment adherence—approximately 50% of patients who have a first episode of psychosis are not adherent to antipsychotic therapy. Advise the patient that poor adherence is the largest single cause of relapse, especially in young people with a first episode of psychosis.
Antipsychotic choice must balance efficacy, and short- and long-term tolerability. For drugs with similar efficacy, choice should be guided by the adverse effect profile and patient factors, including their physical health (see Baseline parameters potentially affected by antipsychotic therapy) and which adverse effects are acceptable to the patient. Also consider the availability of a long-acting injectable formulation. Use an antipsychotic for its antipsychotic properties, not sedation. If short-term management of agitation is required, it is preferable to add a benzodiazepine; see here.

Amisulpride, aripiprazole, olanzapine, quetiapine, risperidone and ziprasidone have been shown in randomised controlled trials to have efficacy in treating a first episode of psychosis—there is minimal difference in efficacy between these antipsychotics. However, for people younger than 18 years, data suggest ziprasidone is not effective for schizophrenia. Do not use olanzapine as first-line therapy, despite evidence of efficacy, because it has severe metabolic adverse effects. For this reason, olanzapine is a third-line treatment option in these guidelines.

Note: Do not use olanzapine as first-line therapy for a first episode of psychosis because it has severe metabolic adverse effects.

Although asenapine, brexpiprazole, cariprazineBajouco 2022Coentre 2021Csehi 2022Durgam 2014Durgam 2015Durgam 2016Generoso 2023Kane 2015Marder 2019Schneider-Thoma 2022, lurasidone and paliperidone are effective antipsychotics, these drugs are ranked second line in these guidelines because, at the time of writing, randomised controlled trial data for a first episode of psychosis are lacking.

Sequential trials of monotherapy may be required until the best balance of effectiveness and adverse effects is achieved. For antipsychotic regimens, see here.

Occasionally, because of cost or availability, the older antipsychotics chlorpromazine, haloperidol, periciazine or zuclopenthixol are used to treat psychosis. These drugs are effective but more likely to cause extrapyramidal adverse effects and lead to treatment discontinuation, and have been associated with lower quality of life.

For additional considerations in antipsychotic choice, see: