Last reviewed 2026-04-23 · How we verify

High Dose ALKS 5461

ALKS 5461 is a combination of buprenorphine and samidorphan that acts as a partial mu-opioid receptor agonist while blocking opioid-induced side effects through antagonism at the opioid receptor.

ALKS 5461 is a combination of buprenorphine and samidorphan that acts as a partial mu-opioid receptor agonist while blocking opioid-induced side effects through antagonism at the opioid receptor. Used for Major depressive disorder (Phase 3), Opioid use disorder (earlier development stage).

At a glance

Mechanism of action

ALKS 5461 combines buprenorphine, a partial mu-opioid receptor agonist used for pain and opioid use disorder, with samidorphan, an opioid antagonist. The samidorphan component is designed to mitigate certain opioid-related adverse effects such as respiratory depression, constipation, and abuse potential while maintaining the therapeutic benefits of buprenorphine. This combination approach aims to improve the safety and tolerability profile of opioid therapy.

Approved indications

• Major depressive disorder (Phase 3)
• Opioid use disorder (earlier development stage)

Common side effects

• Nausea
• Headache
• Dizziness
• Constipation
• Sedation

Key clinical trials

• A Study of ALKS 5461 for the Treatment of Major Depressive Disorder (MDD) - FORWARD-5 Study (PHASE3)
• A Study of ALKS 5461 for the Treatment of Major Depressive Disorder (MDD) - the FORWARD-4 Study (PHASE3)

Primary sources

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