Long-Acting Injectable Antipsychotics in Adolescents with Bipolar Disorder

Bipolar disorder often begins in adolescence or early adulthood, characterized by recurrent manic episodes that can lead to neurodegenerative brain changes and functional decline. While several oral second-generation antipsychotics are Food and Drug Administration (FDA)-approved for mania, adherence to maintenance treatment is frequently poor due to factors such as anosognosia, cognitive dysfunction, impulsivity, side effects aversion, and substance use. Long-acting injectable (LAI) antipsychotics, approved for adults with bipolar mania or schizoaffective disorder (bipolar type), offer a potential solution for adolescents with similar conditions. This study reports on the efficacy of LAI antipsychotics in managing bipolar mania in adolescents, tracking outcomes over up to a year with baseline and follow-up Young Mania Rating Scale (YMRS) assessments. The study included 116 adolescents with a mean age of 16.17 years (66% male, 48% white, 23% black). Of these, 73% were diagnosed with bipolar mania and 22% with schizoaffective disorder, bipolar type. The mean illness duration was 1.9 years, with a baseline YMRS score of 33.8 and a body mass index (BMI) of 23.4 kg/m². LAI antipsychotics administered included aripiprazole, paliperidone, and risperidone, given at intervals of 1, 2, or 3 months. YMRS scores showed substantial improvement, declining to 21.7 at 1 month, 12.3 at 2 months, 4.9 at 6 months, and 3.0 at 1 year. Common side effects were increased appetite and weight gain (mean BMI rose to 26.3 kg/m²). There were no dropouts, although 12% of participants switched formulations due to side effects. Notably, 86.2% of adolescents improved sufficiently to return to school or work. While 28.4% experienced depressive episodes, there were no suicide attempts or deaths during the 4- to 14-month follow-up. This study demonstrates that LAI antipsychotics can effectively stabilize adolescents with bipolar mania or schizoaffective disorder, bipolar type, showing a marked decline in YMRS scores and high rates of remission and functional recovery. Despite the lack of FDA approval for LAI antipsychotics in those younger than 18, our results from off-label use suggest significant efficacy and tolerability. Further FDA clinical trials are needed to explore LAI antipsychotic formulations in adolescents to address the needs of this high-risk, nonadherent population.