Addition of Opioid Antagonist Deflects Abuse Potential of Novel Antidepressant

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In a poster presentation at the 73rd Annual Scientific Convention of the Society of Biological Psychiatry meeting in New York, New York, May 10 to 12, and at Psych Congress 2018, held October 25-28 in Orlando Florida, researchers reported on the ability of the addition of an opioid receptor antagonist to address the abuse potential of an adjunctive investigational drug therapy for major depressive disorder (MDD).

ALKS 5461 is an investigational drug therapy for MDD and is made up of buprenorphine (BUP) and samidorphan (SAM), a µ-opioid receptor antagonist added to address the abuse/dependence potential of BUP. Researchers reported on the ability of SAM to to address the abuse potential of BUP in the ALKS 5461.

The study examined evaluated abuse potential in 38 nondependent, opioid-experienced volunteers.

Participants were randomized to 6 treatments in a blinded crossover design: placebo (PBO), ALKS 5461 at the therapeutic dose (BUP/SAM 2mg/2mg), at 4 times the therapeutic dose (8mg/8mg), and at 8 times the therapeutic dose, or at supratherapeutic dose (16mg/16mg), or BUP (8mg and 16mg).

Separately, safety data from 4 PBO-controlled MDD studies (n = 961) were examined for adverse events (AEs) that may be associated with euphoria, dependence, and withdrawal.

The maximum effect (E_max) or “drug liking” scores—a standard index for how much a subject might like a drug in the moment—for the ALKS 5461 2mg/2mg dose were similar to those for the placebo group (median within-subject difference [90% CI]: 2.5 [0.0-9.0]).

E_max scores for the ALKS 5461 dose groups, including supratherapeutic doses, were significantly lower than those observed for either BUP dose.

In MDD controlled studies, the incidence of euphoria-related AEs was low for ALKS 5461 2mg/2mg and placebo (1.6% vs 0.2%, respectively) and there was no evidence of dependence or withdrawal. No patients randomized to ALKS 5461 reported abuse-behavior adverse events.

The researchers reported that the findings indicate that SAM mitigates the abuse potential of BUP in the ALKS 5461 2mg/2mg combination.

Reference

Setnik B, Mathew SJ, Nangia N. Clinical evaluation of abuse potential of ALKS 5461. Presented at the The 73rd Annual Scientific Convention of the Society of Biological Psychiatry Meeting, May 11, 2018; New York, New York. Abstract #F172.