Supplementary Material for: Excessive Mood Elevation and Behavioral Activation with Antidepressant Treatment of Juvenile Depressive and Anxiety Disorders: A Systematic Review

Background: The prevalence, characteristics and implications of excessive arousal-activation in children and adolescents treated with antidepressants for specific illnesses have not been systematically examined. Methods: We compared reports of antidepressant trials (n = 6,767 subjects) in juvenile depressive (n = 17) and anxiety disorders (n = 25) for consensus-based indications of psychopathological mood elevation or behavioral activation. Results: Rates of excessive arousal-activation during treatment with antidepressants were at least as high in juvenile anxiety (13.8%) as depressive (9.79%) disorders, and much lower with placebos (5.22 vs. 1.10%, respectively; both p < 0.0001). The antidepressant/placebo risk ratio for such reactions in paired comparisons was 3.50 (12.9/3.69%), and the meta-analytically pooled rate ratio was 1.7 (95% confidence interval: 1.2-2.2; both p ≤ 0.001). Overall rates for ‘mania or hypomania', specifically, were 8.19% with and 0.17% without antidepressant treatment, with large drug/placebo risk ratios among depressive (10.4/0.45%) and anxiety (1.98/0.00%) disorder patients. Conclusions: Risks of excessive mood elevation during antidepressant treatment, including mania-hypomania, were much greater than with placebo, and similar in juvenile anxiety and depressive disorders. Excessive arousal-activation in children or adolescents treated with antidepressants for anxiety as well as depressive disorders calls for particular caution and monitoring for potential risk of future bipolar disorder.