The relationship between antidepressant and analgesic responses: findings from six placebo-controlled trials assessing the efficacy of duloxetine in patients with major depressive disorder

Abstract

Objective: Debate continues regarding whether onset of analgesia is faster than antidepressant effect in antidepressants with both properties. Duloxetine hydrochloride (from here on referred to as duloxetine) is effective in both major depressive disorder and diabetic peripheral neuropathic pain. This post-hoc analysis of six placebo-controlled duloxetine trials in patients with major depressive disorder was designed to compare onset of antidepressant activity to pain relief.Research design and methods: Duloxetine was administered at 40–120 mg/day versus placebo for up to 9 weeks in outpatient clinic settings. The primary depression measure was the HAMD17 and pain severity was measured using visual analog scale (VAS) measuring overall pain, headache, back and shoulder pain, and pain while awake. The time course of improvement was profiled using repeated measures modeling and Kaplan–Meier product limit estimation.Results: In all but one case, significant reductions in HAMD17 and VAS scores were seen within 2 weeks of treatment. Median time to VAS response was consistently shorter across all VAS measures than that to HAMD17 response in both placebo- and duloxetine-treated patients with at least modest levels of pain at study entry. Regression analyses consistently demonstrated little association between analgesic and antidepressant responses. Limitations of these findings include that the studies used in these analyses did not require the patients to enroll with any specific level of pain. Moreover, the type of pain exhibiting at presentation was not routinely identified; therefore, the impact of different pain types on these findings is unknown.Conclusions: Duloxetine's analgesic effect is independent of the drug's antidepressant effect. Additionally, faster onset of the analgesic effect appears to be a population-specific phenomenon that is unmodified in the presence of active agents.