Clozapine leads again, while quetiapine did no better than placebo
STUDY: Lamsma J et al, Br J Psychiatry 2026
STUDY TYPE: Systematic review and network meta-analysis
FUNDING: Independent
Background
Antipsychotics are used for psychotic symptoms in schizophrenia and may treat aggression as well. This network analysis compared them.
The Study
- 41 studies (60 randomized trials) with 21,025 adults with schizophrenia and related disorders, median follow-up 8 weeks.
- 18 antipsychotics compared with placebo and with each other, using direct and indirect comparisons.
Results
Compared with placebo, these antipsychotics reduced hostility, with moderate effects:
- Clozapine (effect size 0.75)
- Paliperidone (0.62)
- Olanzapine (0.60)
- Asenapine, risperidone, aripiprazole, and haloperidol (0.30 to 0.52)
Quetiapine, ziprasidone, amisulpride, brexpiprazole, and lurasidone were little different from placebo.
Limitations
- Confidence was low or very low for every comparison.
- Most trials measured hostility as a secondary item, so the results may partly reflect overall symptom improvement.
- The clozapine estimate rests on 124 patients.
- Few trials included forensic patients or people with substance use, who account for much of the violence.
Practice Implications
- Clozapine is generally used after two antipsychotic failures, but guidelines recommend it first or second line in schizophrenia with significant aggression or suicidality.
- Paliperidone and olanzapine are reasonable choices before that, and a long-acting injectable form improves adherence and long-term recovery.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
