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Endogenous opioid neurotransmission has been clearly implicated in analgesic responses to placebo in patients with chronic pain. Could it also play a role in placebo response in depressed patients? This randomized, crossover study involving 35 unmedicated patients with major depression compared patients' reactions to 1 week of receipt of “active placebo” (daily oral placebo that patients were told was a fast-acting antidepressant, ending with one intravenous infusion) or placebo that patients were told was inactive (daily oral placebo; no infusion). Patients were then crossed over to the other condition. Afterwards, 25 patients completed 10 weeks of citalopram, sertraline, mirtazapine, fluoxetine, or bupropion.
Active placebo significantly r…