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Objectives: Pediatric bipolar disorder is a severe disabling condition affecting 1%-3% of youth worldwide. Both acute and maintenance treatment with medications are mainstays of treatment. It is well established in adult literature that adherence to medications improves outcomes and many adult studies have examined factors impacting adherence. This systematic review set out to identify the current state of research examining adherence to medications and characteristics influencing adherence in pediatric bipolar disorder. Methods: We performed a systematic literature review in the Medline, PsycINFO, CINAHL, EMBASE, Wiley Clinical Trials, and Cochrane databases. New research regarding characteristics and measurement of adherence to psychotropic medication for bipolar disorder (I, II, or not otherwise specified) in patients ≤18 years old were included for review. Exclusion criteria included no bipolar diagnosis, inclusion of patients >18 years old, no pharmacologic treatment, and lack of adherence measurements. Results: Initial search generated 439 articles after duplicate removal. One hundred thirty-three full-text articles were reviewed, 16 underwent additional review and 6 were selected for final inclusion. The majority of articles were excluded for patients >18 years old. Included articles were extremely heterogeneous for multiple measures, including methodology, determination of adherence, adherence rates, and characteristics influencing adherence. Of medications evaluated, 6/6 studies included mood stabilizers, 4/6 antidepressants, 3/6 antipsychotics, and 2/6 psychostimulants. Three out of six articles included patients <12 years old. Some significant factors affecting adherence included polypharmacy, comorbid psychiatric diagnoses, socioeconomic status, sex, family history and functioning, side effects, race, stability of bipolar diagnosis, and number of follow-up visits attended. Conclusions: Pediatric-specific information on medication adherence in bipolar disorder is very limited. Information on patient characteristics that may influence adherence rates is critical to target interventions to improve adherence. No articles reported on interventions to improve adherence. Given the different psychosocial situations of pediatric patients versus adults, it is likely that targets for improving adherence differ in pediatric patients.

Objective: To determine if acute treatment with aripiprazole (APZ) would be superior to treatment with placebo in reducing dysfunctional symptoms of elevated mood and/or irritability in symptomatic children and adolescents at familial high risk for bipolar disorder (BPD) whose mood episodes occur spontaneously. These are patients we have previously referred to as suffering from "cyclotaxia.", Methods: This was single-site, randomized, double-blind, placebo-controlled outpatient clinical trial in which youths aged 5-17 years who met diagnostic criteria for either cyclothymic disorder (CYC) or BPD not otherwise specified (BP-NOS) were randomly assigned to receive either APZ or placebo. Eligible participants had at least one parent with BPD, another first- or second-degree relative afflicted with a mood disorder, and also had not responded to psychotherapy. Treatment with APZ was initiated at a dose of approximately 0.1 mg/kg/day and could be increased by approximately 0.05 mg/kg/day at each study visit. Patients were seen weekly for 4 weeks and then every other week thereafter for 12 weeks. The primary outcome measure was mean change from baseline on Young Mania Rating Scale (YMRS) total score., Results: A total of 59 patients (30 APZ, 29 placebo) aged 11.8 (SD = 2.7) years were randomized and returned for at least one postbaseline assessment. The mean total daily doses of active APZ and placebo were 7.1 mg (SD = 3.7) and 7.4 mg (SD = 4.2), respectively. At the 12-week time point, APZ was superior to placebo on the primary outcome measure (p < 0.005). Most adverse events were mild and transient in nature. There was a significant difference in weight gain from baseline between patients who received APZ (2.3 kg [SD = 3.3]) and those who received placebo (0.7 kg [SD = 1.8])., Conclusion: This double-blind trial found that APZ was significantly more efficacious than placebo in reducing symptoms of mania in children and adolescents with cyclotaxia.

Objective: While a number of articles have reviewed the use of long-acting injectable antipsychotics (LAIs) in first-episode psychosis, there has been extremely limited focus on LAIs in children and adolescents. This review of the literature evaluated use of LAIs in children and youth under the age of 18., Methods: We conducted a comprehensive search of the PubMed, PsychINFO, CINAHL, and EMBASE databases using keywords related to LAIs, children, and psychiatric conditions, including schizophrenia, bipolar disorder, and schizoaffective disorder. Reports were included if they were in English, conducted between 1971 and 2015, and reported on use of LAIs in individuals less than the age of 18., Results: The search identified seven reports including one open-label trial, three case reports, and three case series. No controlled trials were found. Sample sizes ranged from 1 to 19 with a total of 36 individuals in all cases combined. Mean sample age was 12.1 ± 2.2 in the open-label trial and calculated to be 14.9 ± 1.5 in the remainder of the reports. Most patients (80.6%) were boys. Primary diagnoses included bipolar I disorder (n = 18; 50%), schizophrenia (n = 7; 19.4%), and bipolar spectrum disorders (n = 6; 16.6%). The LAIs used were risperidone long-acting injection (n = 24; 66.7%), paliperidone palmitate (n = 8; 22.2%), fluphenazine decanoate (n = 1; 2.8%), aripiprazole extended-release injectable (n = 1; 2.8%), zuclopenthixol decanoate (n = 1; 2.8%), and olanzapine extended release (n = 1; 2.8%). Most cases reported clinical improvement and the majority of individuals (n = 14; 82.4%) were reported to tolerate the medication well. The most common side effects were weight gain (mean 5.7 ± 4.1 kg in the open-label trial), tremor (n = 2; 5.6%), and oculogyric crisis (n = 2; 5.6%)., Conclusions: This literature review suggests that LAI use in youth with serious mental illness may improve clinical outcomes and adherence. Side effects of LAIs among youth appear are similar to oral preparations. However, there is a paucity of data despite issues with nonadherence in youth and the fact that they have much to lose and much to gain. Existing reports have substantial methodological limitations, and research is needed to guide the use of LAIs in children and adolescents.

The article discusses two research studies on child and adolescent psychopharmacology. The study "Effect of Antipsychotic Medication Alone vs Combined With Psychosocial Intervention on Outcomes of Early-Stage Schizophrenia" examined the effects of antipsychotic medication with and without psychosocial intervention on functional outcomes of early-stage schizophrenia. It also details the study "Effects of Atomoxetine With and Without Behavior Therapy on the School and Home Functioning of Children With Attention Deficit/Hyperactivity Disorder."