buprenorphine + samidorphan

**Buprenorphine + samidorphan** is an investigational fixed-dose opioid-system modulator developed by Alkermes as adjunctive therapy for adults with major depressive disorder and an inadequate response to antidepressant treatment. ALKS 5461 combined buprenorphine and samidorphan in a 1:1 weight ratio in a once-daily sublingual tablet. Buprenorphine provides partial agonism at the mu-opioid receptor and antagonism at the kappa-opioid receptor, while samidorphan antagonizes the mu-opioid receptor to attenuate opioid agonist effects and abuse liability. The program reached phase 3 and phase 3b studies, but the FDA issued a Complete Response Letter in February 2019 requesting additional clinical evidence of effectiveness; the product was not approved and is no longer listed in Alkermes' active pipeline. ([cdn.clinicaltrials.gov](https://cdn.clinicaltrials.gov/large-docs/99/NCT02141399/Prot_000.pdf))

Brand names

ALKS 5461ALKS5461ALKS-5461

Other names

BUP/SAMbuprenorphine + samidorphanbuprenorphine/samidorphan