A groundbreaking study led by Dr. Parinda Parikh at Weill Cornell Medical College has revealed promising results for long-acting injectable (LAI) antipsychotics in managing bipolar mania and schizoaffective disorder among adolescents, despite current FDA restrictions on their use in patients under 18.
The research, involving 116 adolescents with a mean age of 16.17 years, demonstrated remarkable improvement in symptom control over a one-year period. The study population comprised 66% males, with 73% diagnosed with bipolar mania and 22% with schizoaffective disorder.
Clinical Outcomes and Efficacy
Patients showed substantial improvement in Young Mania Rating Scale (YMRS) scores, starting from a baseline of 33.8 and progressively decreasing to 21.7 at month 1, 12.3 at month 2, 4.9 at month 6, and ultimately reaching 3.0 at the one-year mark. The treatment's success was further evidenced by 86.2% of participants successfully returning to school or work.
Treatment Protocol and Administration
The study utilized three different LAI antipsychotics - aripiprazole, paliperidone, and risperidone - administered at intervals of one to three months. This approach addressed a critical challenge in adolescent psychiatric care, where poor adherence to daily oral medications often compromises treatment effectiveness.
"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," noted Dr. Parikh and her research team.
Safety Profile and Adverse Events
The treatment demonstrated a manageable safety profile, with increased appetite and weight gain being the most commonly reported side effects. The average BMI increased from 23.4 to 26.3 kg/m². While 12% of participants required formulation changes due to adverse events, notably, no participants discontinued the study due to side effects.
Clinical Implications and Current Treatment Landscape
The findings are particularly significant given the current limitations in treating adolescent bipolar disorder. While several oral second-generation antipsychotics are FDA-approved for this population, adherence remains a major challenge due to factors including anosognosia, cognitive dysfunction, and impulsivity.
Dr. Daniel Greer, from Rutgers Ernest Mario School of Pharmacy, explains the advantage of LAIs: "When you take a pill, the level goes up and then your body metabolizes some of it, and it goes back down. 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."
Monitoring and Long-term Outcomes
During the 4-to-14-month follow-up period, while 28.4% of participants experienced depressive episodes, there were no reported suicide attempts or deaths. This observation suggests the potential for LAIs to provide stable long-term management of bipolar symptoms in adolescents.
The researchers emphasize the need for FDA clinical trials to further explore LAI antipsychotic formulations in adolescents, particularly given the high-risk nature and poor medication adherence in this population. The study's results provide compelling evidence for considering LAIs as a viable treatment option for managing bipolar mania in adolescents, potentially changing the treatment paradigm for this vulnerable population.
