Deprescribing Antidepressants in Children and Adolescents: A Systematic Review of Discontinuation Approaches, Cross-Titration, and Withdrawal Symptoms

Abstract

Background: Antidepressant medications, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are commonly used to treat depressive, anxiety, and obsessive-compulsive disorders in youth. Yet, data on discontinuing these medications, withdrawal symptoms, and strategies to switch between them are limited. Methods: We searched PubMed and ClinicalTrials.gov through June 1, 2024, to identify randomized controlled trials assessing antidepressant discontinuation in youth. We summarized pediatric pharmacokinetic data to inform tapering and cross-titration strategies for antidepressants and synthesized these data with reports of antidepressant withdrawal. Results: Our search identified 528 published articles, of which 28 were included. In addition, 19 records were obtained through other methods, with 14 included. The corpus of records included 13 randomized, double-blind, placebo-controlled trials (3026 patients), including SSRIs (K = 10), SNRIs (K = 4), and TCAs (K = 1), ranging from 4 to 35 weeks. Deprescribing antidepressants requires considering clinical status, treatment response, and, in cross-titration cases, the pharmacokinetics and pharmacodynamics of both medications. Antidepressant withdrawal symptoms are related to the pharmacokinetics of the medication, which vary across antidepressants and may include irritability, palpitations, anxiety, nausea, sweating, headaches, insomnia, paresthesia, and dizziness. These symptoms putatively involve changes in serotonin transporter expression and receptor sensitivity, impacting the serotonin, dopamine, and norepinephrine pathways. Conclusions: Although approaches to deprescribing antidepressants in pediatric patients are frequently empirically guided, accumulating data related to the course of relapse and withdrawal symptoms, as well as the pharmacokinetic and pharmacodynamic properties of medications, should inform these approaches. Recommendations within this review support data-informed discussions of deprescribing-including when and how-that are critically important in the clinician-family-patient relationship.

Keywords: antidepressant; anxiety; depression; selective serotonin reuptake inhibitor (SSRI); serotonin-norepinephrine reuptake inhibitor (SNRI).