Randomised controlled trials of antidepressant and anti-anxiety medications for people with autism spectrum disorder: systematic review and meta-analysis

Abstract

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

Benefits and harms of interventions to improve anxiety, depression, and other mental health outcomes for autistic people: A systematic review and network meta-analysis of randomised controlled trials

“…In terms of pharmacological interventions, this review found that some medications (ADH, MDMA, SNRI) were associated with increased adverse events, although there is no evidence these medications improve mental health. This is in line with existing meta-analyses that suggest that the evidence for the use of antidepressants or anti-anxiety medications in autistic people is inconsistent ( D’Alò et al, 2021 ; Deb et al., 2021 ), and antipsychotics are not effective for anxiety or depression ( D’Alò et al, 2021 ).…”

“…School-based interventions for anxiety show some promise for improving anxiety, although further evidence is needed. Finally, evidence for the use of anti-anxiety medications in autistic people is inconsistent (D'Alò et al, 2021;Deb et al, 2021). only a short period of time.…”

“…Previous meta-analyses looking at interventions for anxiety in autistic people have focused on children and adolescents, and have examined specific interventions such as CBT ( Kreslins et al, 2015 ; Perihan et al., 2020 ; Sukhodolsky et al, 2013 ; Ung et al, 2015 ), school-based interventions ( Perihan et al, 2022 ), or use of specific medications ( D’Alò et al, 2021 ; Deb et al, 2021 ). From this evidence, there is some indication that CBT may be effective compared to no intervention for autistic youth without intellectual disability (ID), although there is significant heterogeneity in findings.…”

“…A recent systematic review of the evidence on treatment for depression in autistic people concluded that there is some suggestion that mindfulness-based therapy may be beneficial; however, the strength of evidence is poor and studies have inconsistent findings ( Menezes et al, 2020 ). A meta-analysis looking at evidence for the effectiveness of antidepressants in autistic people, which focused on outcomes other than depression, found that evidence for the use of antidepressants is also contradictory ( Deb et al, 2021 ).…”

Autism and mental illness in children and young people require standardised approaches for assessment and treatment

“… 6 A 2021 systematic review on 13 RCTs on antidepressants and two on anxiolytics observed contradictory results on efficacy; their meta-analysis demonstrated no significant inter-group difference between the placebo and antidepressants in children. 7 An alternative approach, cognitive-behavioural therapy (CBT), can be effective but requires modification for those with ASD. 8 …”