Brexpiprazole-Induced Gynecomastia in a Thirteen-Year Old Male

This case reports involves a thirteen-year-old male with a history of anxiety, depression, autism spectrum disorder, and attention deficit hyperactivity disorder (ADHD) who developed significant weight gain and gynecomastia ten months after starting brexpiprazole. He had prior trials of quetiapine and aripiprazole which caused significant weight gain but did not cause gynecomastia. He had been taking sertraline and guanfacine for almost two years prior to starting brexpiprazole. Eight months later he was started on dexmethylphenidate for ADHD symptoms. There were no other recent exposures. After these symptoms developed, brexpiprazole and dexmethylphenidate were discontinued and several weeks later his gynecomastia resolved. Dexmethylphenidate is not known to cause gynecomastia. Although atypical antipsychotics have been known to cause gynecomastia, no case reports have identified brexpiprazole causing gynecomastia. Sertraline, a known cytochrome P450 2D6 inhibitor, is one of the primary metabolizers of brexpiprazole. We hypothesize that sertraline may have delayed the metabolism of brexpiprazole through inhibition of cytochrome P450 2D6 which led to elevated levels of brexpiprazole. This may have contributed to development of gynecomastia. This case report emphasizes the importance of closely monitoring drug-drug interactions as well as uncommon adverse effects of medications.