Samidorphan (INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name) is an opioid antagonist that in the form of olanzapine/samidorphan (sold as Lybalvi) is used in the treatment of schizophrenia and bipolar disorder.

[7] Buprenorphine/samidorphan for the treatment of major depressive disorder was rejected by the US Food and Drug Administration (FDA) due to insufficient evidence of effectiveness, but remains in preregistration as of September 2021.

[9] Samidorphan has been investigated for the treatment of alcoholism and cocaine addiction by its developer, Alkermes,[10][11] showing similar efficacy to naltrexone, but possibly with reduced side effects.

[14] A Phase III study found that the addition of samidorphan to olanzapine significantly reduced weight gain compared to olanzapine alone,[15] and the combination was approved for the treatment of schizophrenia and bipolar disorder by the FDA in May 2021, under the brand name Lybalvi.

[1][18][19] In accordance with this profile, samidorphan has been observed to produce some side effects that are potentially consistent with activation of the KOR such as somnolence, sedation, dizziness, and hallucinations in some patients in clinical trials.