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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 treatmen…