Medication Adherence Among Children and Adolescents with Severe Mental Illness: A Systematic Review and Meta-Analysis

Objective: To perform a systematic review and meta-analysis of studies investigating predictors of medication adherence in children and adolescents with severe mental illness (SMI). Method: A systematic literature search was conducted in PubMed/MEDLINE, Web of Science, and PsycINFO from 1980 through October 1st, 2017, for original peer-reviewed articles that investigated predictors of adherence to psychopharmacologic treatment among children (<= 18-years-old) with a primary psychotic disorder, bipolar disorder, depression, recent suicide attempt, or psychiatric hospitalization. Effect sizes (ESs) for individual predictors were extracted and combined using DerSimonian-Laird random-effects meta-analysis. Meta-regression and moderator analyses were conducted to investigate subgroups. This review complied with Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines. Results: A total of 28 studies (n=180,870) met inclusion criteria; 65.9% (+/- 20.9%) of children and adolescents with SMI were medication adherent. Adherence was associated with patient and family attitudes toward care, adherence to psychotherapy, and insight. Nonadherence was associated with illness severity, substance use, and attention-deficit/hyperactivity disorder. Heterogeneity was moderate-to-large for most ES estimates (I-2 > 50%). Age, sex, underlying diagnosis, and study methodology emerged as significant moderators. Conclusion: Medication nonadherence among youth with SMI is highly prevalent. Children and adolescents with more severe illness and higher comorbidity burden are at greater risk for nonadherence. Positive interpersonal care processes and adherence to nonpharmacological treatment may be protective. These findings inform development of a risk profile for nonadherence among youth with SMI. Future prospective research is needed to address the shortcomings in the existing literature and inform interventions to improve adherence.