Strain et al. (2023) Adverse Effects of Antidepressant Medications and their Management in Children and Adolescents

[Addax]

Pharmacotherapy, 2023 DOI: 10.1002/phar.2767, Stawn, Mills, Poweleit, Ramsey,  and Croarkin

 

Abstract
Introduction: Selective serotonin reuptake inhibitors (SSRIs) and, to a lesser extent, serotonin-norepinephrine reuptake inhibitors (SNRIs) are the cornerstone of pharma- cotherapy 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 com- plicate 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 pre- sented. 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), abdomi- nal 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 pedi- atric 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.

 

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