Predictors of Antidepressant Response

We performed a single-blinded two-week cross-over randomized controlled trial of two identical oral placebos (described as having either potentially "active" fast-acting antidepressant-like effects or to be "inactive") followed by a 10-week open-label treatment with a selective serotonin reuptake inhibitor (SSRI) or in some cases, another agent as clinically indicated. The volunteers were studied with PET and the µ-opioid receptor selective radiotracer \[11C\]carfentanil after each 1-week "inactive" and "active" oral placebo treatment. In addition, 1 mL of isotonic saline was administered intravenously (i.v.) within sight of the volunteer during PET scanning every 4 min over 20 min only after the 1-week active placebo treatment, with instructions that the compound may be associated with the activation of brain systems involved in mood improvement. This challenge stimulus was utilized to test the individual capacity to acutely activate endogenous opioid neurotransmission under expectations of antidepressant effect.