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.

Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.

To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.

The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.

These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.

Substance use disorder explains much of the excess risk of violent behaviour in psychotic disorders. However, it is unclear to what extent the pharmacological properties and subthreshold use of illicit substances are associated with violence.

Individuals with psychotic disorders were recruited for two nationwide projects: GROUP (N = 871) in the Netherlands and NEDEN (N = 921) in the United Kingdom. Substance use and violent behaviour were assessed with standardized instruments and multiple sources of information. First, we used logistic regression models to estimate the associations of daily and nondaily use with violence for cannabis, stimulants, depressants and hallucinogens in the GROUP and NEDEN samples separately. Adjustments were made for age, sex and educational level. We then combined the results in random-effects meta-analyses.

Daily use, compared with nondaily or no use, and nondaily use, compared with no use, increased the pooled odds of violence in people with psychotic disorders for all substance categories. The increases were significant for daily use of cannabis [pooled odds ratio (pOR) 1.6, 95% confidence interval (CI) 1.2–2.0), stimulants (pOR 2.8, 95% CI 1.7–4.5) and depressants (pOR 2.2, 95% CI 1.1–4.5), and nondaily use of stimulants (pOR 1.6, 95% CI 1.2–2.0) and hallucinogens (pOR 1.5, 95% CI 1.1–2.1). Daily use of hallucinogens, which could only be analysed in the NEDEN sample, significantly increased the risk of violence (adjusted odds ratio 3.3, 95% CI 1.2–9.3).

Strategies to prevent violent behaviour in psychotic disorders should target any substance use.