Comparative efficacy of antipsychotics for reducing aggression in schizophrenia: systematic review and network...

Antipsychotics are used to manage hostility and aggressive behaviour in schizophrenia, but their comparative efficacy remains unclear.

To compare the efficacy of antipsychotics for reducing hostility and aggressive behaviour in schizophrenia.

We searched PubMed, PsycINFO, ClinicalTrials.gov, and the Cochrane Schizophrenia Group's register to 25 April 2025. Two reviewers screened studies and extracted data. We included randomised controlled trials in adults with schizophrenia or related psychotic disorders assessing hostility or aggressive behaviour with ≥48 h follow-up. Standardised mean differences (SMDs) were synthesised in a frequentist random-effects network meta-analysis. Confidence was assessed using Confidence In Network Meta-Analysis. The protocol was registered in PROSPERO (CRD42024572272).

Forty-one studies involving 21 025 participants and 18 antipsychotics were included. Most studies were based on double-blind, parallel-group trials (37/41, 90%), with a median follow-up of 8 weeks (interquartile range = 6). The most common outcome measures were hostility items or related subscales from symptom rating scales (36/41, 88%). Compared with placebo, several antipsychotics reduced hostility and aggressive behaviour. Clozapine (SMD -0.75, 95% CI -1.13 to -0.38), paliperidone (-0.62, -0.88 to -0.36), and olanzapine (-0.60, -0.86 to -0.35) showed the largest effects. Smaller but significant effects were observed for asenapine, risperidone, aripiprazole and haloperidol (SMD range -0.52 to -0.30). Confidence in the evidence was low or very low, mainly due to within-study bias and incoherence.

Antipsychotics reduced hostility and aggressive behaviour in predominantly short- to medium-term studies. Clozapine, paliperidone and olanzapine appeared most effective, although low-certainty evidence limits conclusions about differences between antipsychotics. Further trials with aggressive behaviour as the primary outcome and longer follow-up are needed.