Long-Acting Injectables Effectively Manage Bipolar Mania in Adolescents

A recent study found long-acting injectable antipsychotics can effectively reduce symptoms of bipolar mania or schizoaffective disorder in adolescents.1 The effectiveness was demonstrated through patients’ decline in the Young Mania Rating Scale over a year.

“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,” wrote investigators, led by Parinda Parikh, MD, assistant clinical professor at Weill Cornell Medical College.

Bipolar disorder often develops in adolescence or early adulthood, yet the US Food and Drug Administration (FDA) has not approved any long-acting injectable antipsychotics for patients < 18 years. This leaves adolescents with bipolar disorder vulnerable to neurodegenerative brain changes and functional decline.

Individuals < 18 years have several oral second-generation antipsychotics at their disposal for easing symptoms of bipolar disorder, but these FDA-approved drugs for mania have poor adherence rates. Anosognosia, cognitive dysfunction, impulsivity, adverse event aversion, and substance use explain these poor adherence rates.

Long-acting injectable antipsychotics improve adherence rates since patients do not need to take an oral pill every day but rather get an injection approximately every 2 weeks. Last year HCPLive spoke with Daniel Greer, PharmD, a clinical assistant professor at the Rutgers Ernest Mario School of Pharmacy, about a study finding that antipsychotic injections were linked to a 75% reduction in 30-day rehospitalizations compared with oral antipsychotics.2

“When you take a pill, the level goes up and then your body metabolizes some of it, and it goes back down,” Greer said. “So, there’s like a little bit of sawtooth pattern with your drug levels, whereas the long-acting injectables release really smoothly and slowly over a long period of time.”

For adolescents who experience anosognosia, cognitive dysfunction, impulsivity, and adverse event aversion, Parikh and colleagues sought to examine the efficacy of long-acting injectables in managing bipolar mania in 116 adolescents for ≥ 1 year.1 The sample had a mean age of 16.17 years and comprised 66% males, 48% white participants, and 23% black participants.

Among the sample, 73% of the participants were diagnosed with bipolar mania and 22% with schizoaffective disorder. Participants had these disorders for an average of 1.9 years. At baseline, participants had Young Mania Rating Scale scores of 33.8 and a body mass index (BMI) of 23.4 kg/m2.

Investigators administered a long-acting injectable, either aripiprazole, paliperidone, or risperidone, to participants at the intervals of months 1, 2, or 3. On long-acting injectables, participants demonstrated substantial improvement in managing bipolar disorder or schizoaffective disorder, as seen by the Young Mania Rating Scale score at follow-up. On average, Young Mania Rating Scale scores reduced to 21.7 at month 1, 12.3 at month 2, 4.9 at month 6, and 3.0 at 1 year.

Following treatment, 86.2% of adolescents could return to school or work. More than a quarter (28.4%) experienced depressive episodes, but there were no suicide attempts or deaths during the 4-to-14-month follow-up.

Commonly reported adverse events included increased appetite and weight gain, defined when the BMI rose to 26.3 kg/m². Adverse events did not lead to any study discontinuations; however, 12% of participants switched formulations due to this reason.

“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,” investigators concluded. “Further FDA clinical trials are needed to explore LAI antipsychotic formulations in adolescents to address the needs of this high-risk, nonadherent population.”

References

1. Parikh P, Sood K, Bansal LR, Abraham J, Eichbaum A, Shoda EK, Buddhavarapu M, Oza M, Chandra AP, Simanowitz C, Witriol M, Nasrallah H. Long-Acting Injectable Antipsychotics in Adolescents with Bipolar Disorder. J Child Adolesc Psychopharmacol. 2025 Jan 6. doi: 10.1089/cap.2024.0088. Epub ahead of print. PMID: 39761033.
2. Derman, C. Daniel Greer, PharmD: Reduction in Rehospitalizations with Antipsychotic Injections for Schizophrenia. HCPLive. February 3, 2024. https://www.hcplive.com/view/daniel-greer-pharmd-reduction-in-rehospitalizations-with-antipsychotic-injections-for-schizophrenia. Accessed January 7, 2025.