Effects of ADHD and ADHD medications on depression and anxiety in children and adolescents: A systematic review and meta-analysis

This systematic review and meta-analysis aimed to comprehensively assess the effects of attention-deficit/hyperactivity disorder (ADHD) and ADHD medications on the risk of depression and anxiety in children and adolescents. A comprehensive search of PubMed, Embase, Cochrane Library, and Web of Science was conducted up to January 30, 2024. The outcomes were depression and anxiety. Subgroup analysis was performed according to outcome population as youth onset, sex and duration of medication. Sensitivity analysis and publication bias assessment were also performed. Thirty-three studies were included. The children and adolescents with ADHD had a significantly higher risk of depressive disorder than those without ADHD [pooled relative risk (RR) = 2.27, 95% confidence interval (CI) = 1.57-3.29, P < 0.001]. The children and adolescents with ADHD were at a higher risk of major depressive disorder than those without ADHD (pooled RR = 2.20, 95%CI = 1.47-3.29, P = 0.002). The children and adolescents with ADHD had an 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 group was higher than that in the non-ADHD group (pooled RR = 1.71, 95%CI = 1.13-2.61, P = 0.012). The children and adolescents with ADHD were at an elevated risk of agoraphobia compared with those without ADHD (pooled RR = 4.99, 95%CI = 1.51-16.56, P = 0.009). Children and adolescents with stimulant medications had a significantly lower risk of depression than those without stimulant medications (pooled RR = 0.80, 95%CI = 0.72-0.89, P < 0.001). In 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. Stimulant medications for ADHD were associated with a reduced risk for depression.