Joel Yager, MD reviewing Fava M et al. Am J Psychiatry 2016 Feb 12.
Even after adjusting for placebo responders, adjunctive treatment with combined buprenorphine and samidorphan offered moderate benefits.
Some depressions remain treatment-resistant to selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) even when treatment is augmented with atypical antipsychotics, lithium, or other medications. Opiates alleviate melancholia associated with depression, and some conventional antidepressants have opioid effects. Therefore, opioid modulators merit attention as potential antidepressant agents (NEJM JW Psychiatry Feb 2015 and Neuropsychopharmacology 2014; 40:1448). This industry-sponsored, multisite study was conducted in two phases, each with a 4-week treatment period followed by a 1-week taper.
First, 142 inadequate responders to ≥8 weeks of SSRIs or SNRIs were randomized to adjunctive treatment either with buprenorphine (a µ- and κ-opioid partial agonist) plus samidorphan (a µ-opioid antagonist that blocks the addictive potential of buprenorphine) or with placebo in a 2:2:9 ratio. Buprenorphine/samidorphan combination was given at either the previously studied dose (8 mg each) or lower dose (2 mg each).
The stage 1 placebo arm was designed to weed out placebo responders; 65 placebo nonresponders were rerandomized in stage 2 to the three arms. After the 4-week treatment period, the 2-mg group had significant improvement, with a medium effect size of 0.50. Response rates were significantly greater with the 2-mg preparation on a secondary measure, the Montgomery–Åsberg Depression Rating Scale in stage 2 (2 mg, 50%; 8 mg, 28%; placebo, 5%). Adverse events (mostly vomiting) were recorded in 66%, 81%, and 90% in the placebo, 2-mg, and 8-mg groups, respectively, and led to discontinuation in 2% of placebo recipients and 19% of buprenorphine/samidorphan recipients. No opiate withdrawal was noted.
Citation(s):
Fava M et al. Opioid modulation with buprenorphine/samidorphan as adjunctive treatment for inadequate response to antidepressants: A randomized double-blind placebo-controlled trial. Am J Psychiatry 2016 Feb 12; [e-pub].
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