Despite unclear evidence to support the long-term use of antipsychotics to treat challenging (problem) behaviours in people with autism in the absence of a psychiatric disorder, this practice is common.

We conducted a systematic review and meta-analysis of all randomised controlled trials (RCTs) involving antipsychotics for people with autism of all ages, irrespective of the outcomes assessed. We searched seven databases and hand-searched ten relevant journals. Two authors independently screened titles, abstracts and full papers and extracted data using the Cochrane Handbook template. We conducted meta-analyses of outcomes and the rate of adverse events.

We included 39 papers based on 21 primary RCTs that recruited 1482 people with autism. No RCT assessed any psychiatric disorder outcome, such as psychoses or bipolar disorder. A meta-analysis of ten placebo-controlled RCTs showed a significantly improved Aberrant Behaviour Checklist-Irritability score in the antipsychotic group with an effect size of −6.45 [95% confidence interval (CI) −8.13 to −4.77] (low certainty). Pooled Clinical Global Impression data on 11 placebo-controlled RCTs showed an overall effect size of 0.84 (95% CI 0.48 to 1.21) (moderate certainty). There was a significantly higher risk of overall adverse effects (p = 0.003) and also weight gain (p < 0.00001), sedation (p < 0.00001) and increased appetite (p = 0.001) in the antipsychotic group.

There is some evidence for risperidone and preliminary evidence for aripiprazole to significantly improve scores on some outcome measures among children with autism but not adults or for any other antipsychotics. There is a definite increased risk of antipsychotic-related different adverse effects.

Despite the widespread use of psychotropic medications in people with autism spectrum disorder (ASD), there is limited evidence to suggest that psychotropic medications including mood stabilisers are effective in individuals with ASD.

To carry out a systematic review and meta-analysis of randomised controlled trials (RCTs) that assessed the effectiveness of mood stabilisers in people with ASD.

We searched the following databases: Cochrane Library, MEDLINE, Embase, CINAHL, PsycINFO, ERIC, DARE, and ClinicalTrials.gov. In addition, we hand-searched 12 relevant journals. We used the Cochrane Risk of Bias and Jadad scores to assess the quality of included RCTs. We carried out a meta-analysis using a random-effects model.

We included eight RCTs (four on valproate, two on levetiracetam, and one each on lamotrigine and topiramate) that included a total of 310 people with ASD, primarily children. Outcomes were based on core and associated ASD symptoms including irritability and aggression but not bipolar disorder. Only two small studies (25%) from the same group showed definite superiority over placebo and one over psychoeducation alone. Meta-analysis of pooled data on the Aberrant Behaviour Checklist-irritability, Clinical Global Impression Scale-improvement, and Overt Aggression Scale (OAS)/OAS-modified did not show any significant inter-group difference. The rates of adverse effects did not show any significant inter-group difference.

Given the methodological flaws in the included studies and the contradictory findings, it is difficult to draw any definitive conclusion about the effectiveness of mood stabilisers to treat either ASD core symptoms or associated behaviours. Robust large-scale RCTs are needed in the future to address this issue.

PROSPERO registration: CRD42021255467 on 18 May 2021.

Although widely used, the current evidence for the efficacy of antidepressant and anti-anxiety medications for people with autism spectrum disorder (ASD) is limited and conflicting.

We carried out a systematic review and meta-analysis of randomised controlled trials that assessed the effectiveness of these medications in people with ASD.

We searched the following databases: Cochrane Library, Medline, EMBASE, CINAHL, PsycINFO, ERIC, DARE and ClinicalTrials.gov. Additionally, we hand-searched 11 relevant journals. We used the Cochrane risk-of-bias tool and Jadad score to assess the quality of each included study. We carried out a meta-analysis using a random effects model.

We included 15 randomised controlled trials (13 on antidepressants and two on anti-anxiety medications) for a total of 958 people with ASD. Data showed contradictory findings among the studies, with larger studies mostly showing a non-significant difference in outcomes between the treatment and the placebo groups. Meta-analysis of pooled Yale-Brown Obsessive Compulsive Scale and Clinical Global Impression Scale data from nine studies (60%) did not show any statistically significant inter-group difference on either of the outcome measures. The adverse effects reported were mild and, in most studies, their rates did not show any significant inter-group difference.

Given the methodological flaws in the most included studies and contradictory findings, it is difficult to draw any definitive conclusion about the effectiveness of either antidepressant or anti-anxiety medications to treat either ASD core symptoms or associated behaviours. Robust, large-scale, randomised controlled trials are needed to address this issue.