Probing opioid effects in major depression hydromorphone (HM) challenge

Abstract

The opioid system may play a role in some symptoms of major depressive disorder (MDD). We hypothesized that depressed individuals would exhibit an altered response to the agonist HM compared to controls due to an altered function of opioid pathways. In a double-blind, placebo-controlled, randomized study, the effects of HM (6mg, oral) were measured before and 30, 60, 90, 120, 180 and 240 min. after HM intake. Patients with MDD (N=39; HM: 17; placebo: 22) were compared to controls (N=22; HM: 9; placebo: 13) using well-validated scales (e.g. Addiction Research Center Inventory), and psychomotor tasks (e.g. Tracking Test). HM produced time-dependent changes in subjective effects (e.g. VAS-Liking, ARCI-PCAG). Severely depressed (HAMD>24) subjects receiving HM showed significant improvement on negative symptoms compared to controls: differences in the ARCI negative effects composite scale in both peak - baseline and baseline-corrected area-under-the-curve (AUC) mean scores of subjective HM effects were significantly reduced in severely depressed vs. controls (peak - baseline: 96.5 vs. 201.1, p=0.05; AUC: 128.8 vs. 358.2, respectively, p=0.05). Tracking Test mean baseline-corrected % time over the road AUC scores were 10.4 for the severely depressed vs. −13.4 for moderately depressed (p<0.05) and vs. −0.02 for controls (NS). These findings suggest involvement of opioids in the neurobiology of depression. Clinical Pharmacology & Therapeutics (2004) 75, P3–P3; doi: 10.1016/j.clpt.2003.11.009