Brexpiprazole for schizophrenia and as adjunct for major depressive disorder

In clinical trials for MDD, brexpiprazole dosage was not adjusted for strong CYP2D6 inhibitors (eg, paroxetine, fluoxetine). Therefore, CYP considerations are already factored into general dosing recommenda­tions and brexpiprazole could be adminis­tered without dosage adjustment in patients with MDD; however, under these circum­stances, it would be prudent to start brexpip­razole at 0.5 mg, which, although “on-label,” represents a low starting dosage. (Whenever 2 drugs are co-administered and 1 agent has the ability to disturb the metabolism of the other, using smaller increments to the target dosage and possibly waiting longer between dosage adjustments could help avoid poten­tial drug–drug interactions.)

No dosage adjustment for brexpiprazole is required on the basis of sex, race or eth­nicity, or smoking status. Although clinical studies did not include patients age ≥65, the product label recommends that in general, dose selection for a geriatric patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, and cardiac function, concomitant diseases, and other drug therapy.
 

Bottom Line
Brexpiprazole, an atypical antipsychotic, is FDA-approved for schizophrenia and as an adjunct to antidepressants in major depressive disorder. For both indications, brexpiprazole demonstrated positive results compared with placebo in phase-III trials. Brexpiprazole is more potent at serotonin 5-HT1A and 5-HT2A receptors and displays less intrinsic activity at D2 receptors than aripiprazole, which could mean that the drug may be better-tolerated.

Related Resources
• Citrome L. Brexpiprazole: a new dopamine D2 receptor par­tial agonist for the treatment of schizophrenia and major de­pressive disorder. Drugs Today (Barc). 2015;51(7):397-414.
• Citrome L, Stensbøl TB, Maeda K. The preclinical profile of brexpiprazole: what is its clinical relevance for the treat­ment of psychiatric disorders? Expert Rev Neurother. In press.

Drug Brand Names
Aripiprazole • Abilify
Brexpiprazole • Rexulti
Fluoxetine • Prozac
Paroxetine • Paxil

Disclosure
Dr. Citrome is a consultant to Alexza Pharmaceuticals, Alkermes, Allergan, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, Forum Pharmaceuticals, Genentech, Janssen, Jazz Pharmaceuticals, Lundbeck, Merck, Medivation, Mylan, Novartis, Noven, Otsuka, Pfizer, Reckitt Benckiser, Reviva, Shire, Sunovion, Takeda, Teva, and Valeant Pharmaceuticals; and is a speaker for Allergan, AstraZeneca, Janssen, Jazz Pharmaceuticals, Lundbeck, Merck, Novartis, Otsuka, Pfizer, Shire, Sunovion, Takeda, and Teva.