Therapeutic effects of antidepressants for global improvement and subdomain symptoms of autism spectrum disorder: a systematic review and meta-analysis

BACKGROUND: No established pharmacological treatment is available for the core symptoms of autism spectrum disorder (ASD). This study aimed at investigating the efficacy of antidepressants for the core and associated symptoms of ASD. METHODS: We searched PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ScienceDirect, Web of Science and ClinicalTrials.gov using the keywords “ASD” and “antidepressants.” We searched from database inception to June 2021 for randomized controlled trials of antidepressant use in patients with ASD. We calculated pooled effect sizes based on a random-effects model. RESULTS: Analysis of 16 studies with 899 participants showed improvements in restricted and repetitive behaviours (effect size = 0.27) and global symptoms (effect size = 1.0) in patients with ASD taking antidepressants versus those taking placebos (p ≤ 0.01). We found no differences between the 2 groups (p ≥ 0.36) in terms of dropout rate (odds ratio [OR] = 1.17) or rate of study discontinuation because of adverse events (OR = 1.05). We also noted improvements in irritability and hyperactivity in the antidepressant group (Hedges g = 0.33 and 0.22, respectively, both p < 0.03). Subgroup analyses showed significant effects of medication type (i.e., clomipramine was better than SSRIs) and age (antidepressants were more effective in adults than in children or adolescents) on both restricted and repetitive behaviours and global improvement (p < 0.05). Meta-regression demonstrated that better therapeutic effects were associated with lower symptom severity and older age. LIMITATIONS: The small effect sizes and variations in treatment response that we found warrant further study. CONCLUSION: Our results supported the effectiveness of antidepressants for global symptoms and symptom subdomains of ASD, with tolerable adverse effects. Low symptom severity and adulthood were associated with better outcomes.