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Before the development of antidepressants, opioid agonists were used to treat depression. This practice was consistent with recent findings of depression-related dysregulation of the opioid receptor and with mood improvement in treatment-resistant depression after treatment with the mixed agonist/antagonist buprenorphine in uncontrolled trials. In the current placebo-controlled study involving 32 depressed subjects who had failed a single antidepressant trial, researchers tested a medication combining an opioid agonist (buprenorphine, 8 mg) with an opioid antagonist (samidorphin; not FDA-approved). Several authors are employees of the manufacturer.
The trial used two doses (agonist:antagonist ratios, 8:1 and 1:1) based on a preliminary study…