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NEW YORK CITY -- An investigational two-drug tablet for sublingual administration called ALKS 5461 was effective as adjunctive, long-term treatment for major depressive disorder, researchers reported here.

The open-label phase III trial found 52.5% of patients achieved remission of major depression within 12 months of treatment, with a median time to remission of 59 days, in patients with inadequate response to conventional antidepressants, according to Michael Edward Thase, MD, of the University of Pennsylvania Perelman School of Medicine, and colleagues.

Improvements in mean scores on the Montgomery–Åsberg Depression Rating Scale were sustained throughout the 12-month ongoing trial, which was presented at the .

The sublingual ALKS 5461 tablet combined 2 mg of buprenorphine -- a partial mu-opioid receptor agonist and kappa-opioid receptor antagonist -- with 2 mg of samidorphan, a mu-opioid antagonist. Patients in the study continued on conventional antidepressants.

These results confirm prior findings of four short-term randomized clinical trials assessing ALKS 5461. The current study included 1,452 adult de novo participants or patients were enrolled in one of the previous trials. All individuals had a confirmed major depressive disorder diagnosis with symptoms persisting despite standard antidepressant treatment. Among the exclusion criteria were history of drug abuse or opioid agonist or antagonist use, as well electroconvulsive therapy or suicide attempt within the past 2 years.

"Antidepressant medications are taken for months or even years, not weeks, so it's important that longer term observational studies be done for every new medication being evaluated as a potential treatment for depression," Thase told MedPage Today. "This is particularly true for ALKS 5461 because this medication works through the opiate pathway, and other medications that work through this pathway are associated with development of tolerance of effects or dependence/withdrawal symptoms when stopping."

Overall, 49% of participants completed the study, with 11% discontinuing due to an adverse event. The most common adverse events reported were headache, nausea, constipation, dizziness, and somnolence. There weren't, however, any reports of weight changes nor changes in metabolic profile. Additionally, there was no evidence of withdrawal after treatment discontinuation.

"The findings are not surprising," said Thase. "We didn't think the drug would be associated with tolerance of therapeutic effects or signs of dependence -- because of the effects of samidorphan -- but it is important to answer these questions with data, not conjecture."

The adjunctive treatment is currently by the FDA, with a decision expected by January 2019.

"Although there still is some work to do to confirm that ALKS 5461 is an effective adjunct to antidepressants, our findings indicate that, when it is effective on clinical grounds, the benefits are sustained without having to increase the dose -- no tolerance of effect -- there are no late-emerging side effects, and there are not significant withdrawal symptoms when it is time to stop the medication," Thase concluded.

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