Acute and persistent withdrawal syndromes following discontinuation of antidepressants in children and adolescents: a systematic review

Antidepressants are commonly prescribed for children and adolescents, but their discontinuation may result in withdrawal symptoms, though rarely described for this age group in the literature. Systematically examining the types and prevalence of withdrawal syndromes in children and adolescents in accordance with PRISMA guidelines is the aim of the present paper. A search of PubMed, Embase, Web of Science, and Cochrane Library was conducted from inception to December 2024. Inclusion criteria were: clinical populations; subjects aged 2–18; antidepressant discontinuation; assessment of withdrawal symptoms; randomized controlled trials (RCTs) or observational studies; rate/type of withdrawal symptoms. A total of 6227 citations were screened, leading to 12 studies, encompassing 690 participants aged 2–18 years, with eight RCTs and four observational studies. The analysis revealed common withdrawal symptoms across various antidepressant classes, predominantly affecting the central nervous and gastrointestinal systems. Symptoms such as nausea (14.6%–22.0%), headache (14.6%–15.0%), diarrhea (10.0%–22.0%), depression (10%), inner tension (44%), anxiety/worry (44%), and cough (33%) were frequently observed, especially after discontinuation of selective serotonin reuptake inhibitors. Such symptoms clustered in new withdrawal symptoms according to a diagnostic classification of withdrawal syndromes at discontinuation of antidepressants used in adults. Withdrawal symptoms and withdrawal syndromes following antidepressant discontinuation in children and adolescents are still neglected but pose significant clinical challenges, often resembling or exacerbating underlying conditions. Future research is needed, as well as a systematic assessment of these symptoms in the clinical realm (registered in OSF DOI: https://doi.org/10.17605/OSF.IO/GYQ9Z).