Serotonin Toxicity in Children and Adolescents: A Systematic Review and Meta-Analysis of Cases

Objectives: Serotonin toxicity is a state of central nervous system (CNS) excitation classically featuring altered mental status, neuromuscular excitation, and autonomic instability. While retrospective studies and reviews have characterized serotonin toxicity in adults, there have been no systematic reviews of serotonin toxicity in pediatric populations. The goal of this review was to use published case reports to describe serotonin toxicity in pediatric patients and to consider the impact of age on clinical presentation. Methods: A search for case reports of serotonin toxicity in patients younger than 18 years was conducted. Cases were systematically screened for inclusion using serotonin toxicity diagnostic tools, and a meta-analysis of case characteristics was conducted. Results: Sixty-six cases of serotonin toxicity in pediatric patients were reviewed. Only 56.1% met diagnostic criteria for serotonin toxicity on all three of the most commonly used diagnostic tools. Antidepressants were found to be the most common trigger of toxicity, implicated in 78.8% of cases. While onset of toxicity was rapid following overdose, toxicity was more likely to be delayed in the setting of medication titration (71.8% vs. 0%, p < 0.0001). Signs of neuromuscular excitation were prevalent, occurring in 92.4% of cases with 81.8% showing the full triad of neuromuscular symptoms, altered mental status, and autonomic instability. The only age-related differences occurred in relation to activation symptoms (more likely to be reported in children than in adolescents) and seizures (less likely to be reported in children than in adolescents or toddlers). Treatment was primarily supportive in nature, although 25.8% of patients received cyproheptadine. In all but one reviewed case, the patient survived. Conclusions: The presentation of serotonin toxicity in the pediatric population is similar to that seen in adults. Treatment is supportive with most patients achieving full recovery. Further exploration of the age-related differences in serotonin activity within the CNS is needed.