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The study used buprenorphine (a partial µ-opioid receptor agonist that also blocks κ-opioid agonists) and samidorphan (a µ-opioid receptor antagonist), developed by Alkermes, which sponsored the clinical trial. Study participants included 142 people with major depressive disorder (MDD) who had been treated with a selective serotonin reuptake inhibitor or a serotonin-norepinephrine reuptake inhibitor but had an “inadequate response” to one or two courses of treatment.
The researchers used a two-stage sequential parallel design in which first-round placebo nonresponders were randomized to placebo or high- or low-dosage levels of the drug combination, wrote Maurizio Fava, M.D. (pictured above), a professor of psychiatry at Harvard Medical School and executive vice chair of psychiatry at Massachusetts General Hospital, and colleagues.
Significant improvements in scores on the Hamilton-Depression Rating Scale, the Montgomery-Åsberg Depression Scale, and the Clinical Global Impressions severity scale were recorded among patients taking a 2mg/2mg combination of buprenorphine/samidorphan compared with placebo after four weeks. There was also evidence of improvement in the 8mg/8mg dosage group, although this evidence did not reach statistical significance. Nausea, vomiting, and dizziness were commonly occurring side effects, and there was no evidence of opioid withdrawal or consistent signal of abuse liability, the authors reported.
“These results support the premise of the sequential parallel comparison design as a strategy to enhance signal detection in relatively smaller samples, and they are consistent with the finding that signal detection is enhanced in placebo nonresponders, as the effect size of buprenorphine/samidorphan was greater in stage 2 than in stage 1,” Fava and colleagues wrote. “These results support the hypothesis of a significant role of opioid dysregulation in major depression and the therapeutic potential of opioid modulation,” they concluded.
For more in Psychiatric News about the use of buprenorphine in treating depression, see “Low-Dose Buprenorphine Found to Decrease Suicidal Ideation, but Experts Remain Cautious.”