Samidorphan
[Olanzapine] is an effective atypical antipsychotic that, like other antipsychotics, is associated with weight gain, metabolic dysfunction, and increased risk of type II diabetes. Samidorphan is a novel opioid antagonist structurally related to [naltrexone], with a higher affinity for opioid receptors, more potent μ-opioid receptor antagonism, higher oral bioavailability, and a longer half-life, making it an attractive candidate for oral dosing. Although antipsychotic-induced weight gain is incompletely understood, it is thought that the opioid system plays a key role in feeding and metabolism, such that opioid antagonism may be expected to ameliorate these negative effects. Samidorphan has been shown in animal models and clinical trials to ameliorate [olanzapine]-induced weight gain and metabolic dysfunction.  Samidorphan was first approved as a variety of fixed-dose combination tablets with [olanzapine] by the FDA on May 28, 2021, and is currently marketed under the trademark LYBALVI™ by Alkermes Inc.