Safety and Tolerability of Brexpiprazole in Adolescents With Schizophrenia: A Long-Term, Open-Label Study

Abstract

Objective

This study aimed to characterize long-term safety and tolerability of brexpiprazole, an atypical antipsychotic, as maintenance treatment in adolescents with schizophrenia.

Method

This was an interim analysis of an ongoing, 24-month, multicenter, single-arm, open-label, outpatient study of oral brexpiprazole 1 to 4 mg/day (flexible dose) in adolescents aged 13 to 17 years with schizophrenia. Primary end points were incidence of treatment-emergent adverse events (TEAEs), TEAEs by severity, serious TEAEs, and adverse events leading to study discontinuation.

Results

At the time of interim analysis, 169 patients had entered the study, 114 (67.5%) were ongoing, 23 (13.6%) had completed the full 24 months, and 32 (18.9%) had discontinued—most commonly due to withdrawal by the patient. Study participants were 52.7% female and 79.9% White, with a mean age of 15.6 years. Overall, 95 of 167 treated patients (56.9%) reported ≥1 TEAEs, most commonly somnolence (10.2%), headache (9.0%), weight increase (9.0%), and nasopharyngitis (6.6%). Most TEAEs were mild or moderate in severity. Clinically meaningful weight gain after adjusting for natural growth occurred in 33 patients (19.8%). Five patients (3.0%) reported a serious TEAE (2 psychotic disorder; 1 each of nonfatal suicide attempt, pilonidal cyst, and psychomotor hyperactivity), all of which resolved during the study. Two patients (1.2%) discontinued the study due to adverse events: one following the serious nonfatal suicide attempt and the other due to hyperpituitarism and weight increase, which were considered stable at the time of discharge.

Conclusion

Brexpiprazole, when used as maintenance treatment for adolescents with schizophrenia, has a safety profile generally consistent with that observed in adult patients. Any weight gain in adolescent patients should be carefully monitored and compared against weight gain associated with normal growth.

Plain language summary

Long-term antipsychotic treatment is often standard of care for adolescents with schizophrenia, although side effects leading to treatment discontinuation are common. The aim of this study was to identify the frequency and severity of adverse events associated with the antipsychotic brexpiprazole in adolescents aged 13 to 17 years with schizophrenia. Among 167 treated patients, most adverse events were mild or moderate in severity, with two patients discontinuing treatment because of adverse events. One in 5 patients gained more weight than expected for growing adolescents. Overall, the long-term safety of brexpiprazole in adolescents with schizophrenia is like that in adults.

Clinical guidance

• This study aimed to answer the question of whether oral doses of brexpiprazole, 1-4 mg once-daily, were safe and tolerated maintenance treatment in adolescents with schizophrenia.

• In an interim analysis of a 24-month study (67.5% of patients ongoing; 13.6% completed; 18.9% discontinued), 1.2% of adolescents with schizophrenia reported an adverse event that led to treatment discontinuation.

• Clinicians should consider safety profiles when selecting an antipsychotic for the treatment of adolescents with schizophrenia; brexpiprazole has a similar safety profile in adolescents as in adults.

Clinical trial registration information

Safety and Tolerability of Open-Label Flexible-Dose Brexpiprazole as Maintenance Treatment in Adolescents With Schizophrenia; https://www.clinicaltrials.gov/study/NCT03238326?cond=NCT03238326.