Effects of ADHD and its medication on depression and anxiety in children and adolescents: a systematic review and meta-analysis

Background: To comprehensively assess the effects of attention-deficit/hyperactivity disorder (ADHD) and its medication on the risks of depression and anxiety in children and adolescents. Methods: : Comprehensive search was conducted in PubMed, Embase, Cochrane Library, and Web of Science until May 19, 2022. The outcomes were depression (depressive disorder, dysthymic disorder, major depressive disorder) and anxiety (anxiety disorder, generalized anxiety disorder, specific phobia, social phobia, separation anxiety disorder, panic disorder, agoraphobia, obsessive-compulsive disorder). Subgroup analysis was performed according to population (children <18 years old, adults ≥18 years old), sex (male, female) and duration of medication (<1 year, ≥1 year). Outcomes assessed by more than 10 studies were tested for publication bias through the Begg’s test. Results: : Thirty-one studies were included in this systematic review and meta-analysis, with three only included for qualitative analysis. Individuals with ADHD had a significantly higher risk of depressive disorder than those without ADHD (pooled relative risk (RR)=2.26, 95% confidence interval (CI)=1.34-3.80, P =0.002). Subjects with ADHD were at a significantly higher risk of major depressive disorder than those without ADHD (pooled RR=2.24, 95%CI=1.31-3.82, P =0.003). Individuals with ADHD had a significantly increased risk of specific phobia versus those without ADHD (pooled RR=1.68, 95%CI=1.16-2.44, P =0.006). The risk of social phobia in the ADHD groupwas significantly higher than that in the non-ADHD group (pooled RR=1.71, 95%CI=1.13-2.61, P =0.012). Subjects with ADHD were at a significantly elevated risk compared with those without ADHD (pooled RR=4.99, 95%CI=1.51-16.56, P =0.009). No significant associations were observed between ADHD stimulant or non-stimulant medication and the risk of depression, and between ADHD stimulant medication and the risk of anxiety (all P >0.05). Conclusion: Children and adolescents with ADHD had higher risks of depressive disorder, major depressive disorder, specific phobia, social phobia, and agoraphobia than those without; ADHD medication had no significant effect on depression and anxiety.