Antipsychotics (APs) are not officially approved for the treatment of depressive, anxiety, obsessive-compulsive, emotional dysregulation, or sleep disorders among children and adolescents. Despite this, the treatment of these common and comorbid disorders is likely to partially explain the increased AP use. We assessed all studies reporting changes in symptoms or functioning during antipsychotic treatment for these diagnoses among patients < 18 years old. We systematically searched MEDLINE, EBM reviews and PsycINFO databases for all studies published by October 30, 2025, reporting on the effectiveness of APs for obsessive-compulsive, mood dysregulation, depression, anxiety, and sleep-related disorders among patients < 18 years. We evaluated evidence using the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). Of the 2237 identified studies, 119 were eligible for full-text review, and 13 were included in the final review. One study compared two antipsychotics, while the rest were uncontrolled open-label studies, case series, or case reports. No randomized controlled trials nor studies on sleep or anxiety disorders were identified. While there were reported changes in standardized mean scores between baseline and endpoint, the level of evidence in obsessive-compulsive, mood dysregulation, and depression related disorders was very low. The identified very low level of evidence stands in stark contrast to clinical practice, where APs are increasingly prescribed. Future methodologically robust studies are needed to demonstrate efficacy. Given the side effects of APs, physicians should carefully consider the benefits and harms when prescribing them for off-label indications.
Holopainen et al. (Mon,) studied this question.
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