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ABSTRACT
Introduction
Onset of psychotic symptoms occurs prior to age 19 in 39% of patients with schizophrenia. There are limited approved treatment options for adolescents with schizophrenia. Brexpiprazole was approved by the United States Food and Drug Administration (FDA) for treatment of schizophrenia in adolescents in 2022.
Areas covered
Extrapolation of adult data to youth and use of pharmacologic modeling coupled with open long-term safety data were used by the FDA to approve brexpiprazole for adolescent schizophrenia. These were all reviewed herein.
Expert opinion
D2 receptor partial agonist antipsychotic agents are preferred in the early phase of treatment of psychotic disorders. Approval of brexpiprazole in adolescent schizophrenia provides an additional option. Brexpiprazole was approved by the FDA on the basis of extrapolation of adult data without controlled trials in adolescents. This reduces placebo exposure in young people. Two previous agents (asenapine and ziprasidone) approved for adult schizophrenia failed to separate from placebo in adolescent schizophrenia studies; this partially undermines the process of extrapolation. For brexpiprazole, the paucity of data in adolescents relegates it to second-line agent. More research on brexpiprazole is needed to delineate its relative role in the management of adolescent schizophrenia.
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There is an unmet need for antipsychotic agents to treat psychosis in adolescents with schizophrenia
Both clinical and pharmacologic data suggest that D2 receptor partial agonist antipsychotic agents may be preferred agents for treatment early in the course of psychotic illness.
Brexpiprazole, a D2 receptor partial agonist approved for adults with schizophrenia, has been approved for adolescents 13 years of age or older, based on extrapolation of adult data and pharmacokinetic modeling.
Approval of psychotropic agents for adolescents based on extrapolation of adult data is a new model that will probably grow in use.
Despite FDA approval, and good evidence for both efficacy and safety in adults, the lack of placebo-controlled evidence of brexpiprazole in youths relegates it to a second-line agent until additional data are available.
Abbreviations
| 5HT | = | Serotonin |
| CDC | = | Centers for Disease Control and Prevention |
| CI | = | confidence interval |
| CYP | = | cytochrome P450 enzymes |
| D1 | = | the dopamine D1 receptor |
| D2 | = | the dopamine D2 receptor |
| FDA | = | United States Food and Drug Administration |
| NDA | = | new drug application |
| PANSS | = | Positive and Negative Syndrome Scale |
| PRISMA | = | Preferred Reporting Items for Systematic reviews and Meta-Analyses |
| SD | = | standard deviation |
Declaration of Interest
RS El-Mallakh has received research funding from Sumitomo Pharma, and is a speaker for Axsome, Intracellular, Janssen Pharmaceuticals, Lundbeck, Myriad, Noven, Otsuka, and Teva. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer Disclosures
One reviewer declares that they have served as a consultant and speaker for Otsuka and Lundbeck, the companies that have commercialized brexpiprazole. Another reviewer declares that have received manuscript or speaker’s fees from Astellas, Eisai, Eli Lilly and Company, Elsevier Japan, Janssen Pharmaceuticals, Kyowa Yakuhin, Lundbeck Japan, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, Merck Sharp and Dohme, Nihon Medi-Physics, Novartis, Otsuka, Shionogi, Shire, Sumitomo Pharma, Takeda, Tsumura, Viatris, Wiley Japan, and Yoshitomi Yakuhin as well having received research grants from Eisai, Mochida, Meiji Seika Pharma, Shionogi and Sumitomo Pharma. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.