Adverse Effects of Antidepressant Medications and their Management in Children and Adolescents

Introduction: Selective serotonin reuptake inhibitors (SSRIs) and, to a lesser extent, serotonin-norepinephrine reuptake inhibitors (SNRIs) are the cornerstone of pharmacotherapy for children and adolescents with anxiety and depressive disorders. These medications alleviate symptoms and restore function for many youths; however, they are associated with a distinct adverse effect profile, and their tolerability may complicate treatment or lead to discontinuation. Yet, SSRI/SNRI tolerability has received limited attention in the pediatric literature. Methods: This review examines the early- (e.g., activation, gastrointestinal symptoms, sedation) and late-emerging (e.g., weight gain) adverse effects of SSRIs and some SNRIs in pediatric patients. Results: We provide a framework for discussing SSRI/SNRI tolerability with patients and their families and describe the pharmacologic basis, course, and predictors of adverse events in youth. Strategies to address specific tolerability concerns are presented. For selected adverse events, using posterior simulation of mean differences over time, we describe their course based on Physical Symptom Checklist measures in a prospective, randomized trial of anxious youth aged 7–17 years who were treated with sertraline (n = 139) or placebo (n = 76) for 12 weeks in the Child/Adolescent Anxiety Multimodal Study (CAMS). Main Results: In CAMS, the relative severity/burden of total physical symptoms (p < 0.001), insomnia (p = 0.001), restlessness (p < 0.001), nausea (p = 0.002), abdominal pain (p < 0.001), and dry mouth (p = 0.024) decreased from baseline over 12 weeks of sertraline treatment, raising the possibility that these symptoms are transient. No significant changes were observed for sweating (p = 0.103), constipation (p = 0.241), or diarrhea (p = 0.489). Finally, we review the antidepressant withdrawal syndrome in children and adolescents and provide guidance for SSRI discontinuation, using pediatric pharmacokinetic models of escitalopram and sertraline—two of the most used SSRIs in youth. Conclusion: SSRI/SNRIs are associated with both early-emerging (often transient) and late-emerging adverse effects in youth. Pharmacokinetically-informed appraoches may address some adverse effects and inform SSRI/SNRI discontinuation strategies.