Dose-response relationship of duloxetine in placebo-controlled clinical trials in patients with major depressive disorder

Abstract

Rationale: The optimal dose for achieving the maximum antidepressive effect of selective serotonin reuptake inhibitors (SSRIs) or serotonin-noradrenalin reuptake inhibitors (SNRIs) remains a controversial issue. The varying sensitivity of scales that measure the severity of depression is one of the many factors affecting the evaluation of the dose-response relationship with antidepressants.

Objectives: To determine if the 6-item Hamilton rating scale for depression (HAM-D6) demonstrates a clearer association between dose and antidepressive effect compared with the 17-item Hamilton rating scale for depression (HAM-D17) for fixed doses of duloxetine hydrochloride (40, 60, 80, and 120 mg daily) from six double-blind, randomized, placebo-controlled clinical trials assessing safety and efficacy in the acute treatment of patients with DSM-IV-defined major depressive disorder (MDD).

Methods: Mantel-Haenszel adjusted effect sizes were determined by dose for change from baseline to endpoint in HAM-D6 and HAM-D17 scores from the six studies. To confirm, assessments were repeated on the subset of the population corresponding to the 70% of patients with the longest duration of treatment regardless of study, treatment, dose, geography, or completion status.

Results: For the majority of assessments, HAM-D6 effect sizes were numerically larger than those estimated from the HAM-D17. Findings support that duloxetine 60 mg daily is the best effective dose.

Conclusions: In this assessment of patients with MDD, the HAM-D6 was shown to be more sensitive compared with the HAM-D17 at detecting treatment effects. These findings are consistent with published results of other effective antidepressants.