Efficacy, Tolerability, and Acceptance of Long-Lasting Antipsychotics in Children and Adolescents: A Systematic Review

Objectives: While long-lasting antipsychotics (LLA) were specifically developed to address the problem of adherence in patients with chronic psychiatric disorders, their role in pediatric populations is not clear. Methods: To document the efficacy, tolerance, and acceptance of LLAs in children and adolescents, a literature search was conducted using several databases for published studies (PubMed, PsycINFO) from January 1965 to December 2020. Twenty-two studies were identified (16 case reports/series, 3 open label studies, 2 controlled studies, and 1 retrospective analysis of national database). Results: Demographic features were widely heterogeneous across studies (total N = 480, 58% male, mean age = 15.0 +/- 1.8). Case reports/series presented positive therapeutic outcomes in noncompliant youths with severe mental illness. Three open-label one-arm studies supported the clinical efficacy of risperidone long-acting injection in patients previously stabilized with oral risperidone. One study showed lower clinical symptoms and higher functioning at 12 months in youths treated for an acute psychotic episode with paliperidone palmitate compared to oral risperidone. The types and rates of side effects of LLA were comparable to those observed for oral antipsychotics. Two studies suggested better metabolic and neurological tolerance of LLA compared to an oral form. Preliminary evidence supported a satisfactory level of treatment satisfaction in patients treated with LLA and their families, while concerns were raised regarding practical administration in outpatient services. However, the average quality of the evidence based on the RoB2 tool was low. Conclusions: The level of evidence was low for the efficacy of LLA in pediatric populations and very low for the tolerance and acceptance. It concerned mostly the effect of risperidone long-acting injection in adolescents with psychotic disorders. Randomized maintenance clinical trials using noninferiority analysis would be more appropriate for further research.