Differential Antidepressant Symptom Efficacy: Placebo-Controlled Comparisons of Duloxetine and SSRIs (Fluoxetine, Paroxetine, Escitalopram)

Abstract

Objective: To test the hypothesis that in patients with major depressive disorder (MDD), the response for specific Hamilton Depression Rating Scale items will differ for duloxetine compared with selective serotonin reuptake inhibitors (SSRIs) and that patterns of response will differ based on symptom severity at baseline. Method: Data were pooled from all Lilly-sponsored clinical trials where duloxetine was compared with placebo and an SSRI in patients with MDD: 7 randomized, double-blind, fixed-dose, 8-week studies of duloxetine (n = 1,133) versus SSRI (n = 689) versus placebo (n = 641). Duloxetine doses were 40, 60, 80 and 120 mg/day. SSRI doses were 10 mg/day (escitalopram) and 20 mg/day (fluoxetine and paroxetine). Results: Compared to SSRI-treated patients, duloxetine-treated patients had a significantly greater (p ≤ 0.05) reduction in the 17-item Hamilton Depression Rating Scale (HAMD₁₇) total score and HAMD₁₇ items of work and activities, psychomotor retardation, genital symptoms and hypochondriasis. Differences favoring the SSRIs approached significance for middle insomnia (p = 0.057) and late insomnia (p = 0.06), with effect sizes at least twice the magnitude of the corresponding effect sizes for duloxetine. Similarly, the advantage for duloxetine versus the SSRIs approached significance for general somatic symptoms (p = 0.056), with an effect size twice that observed for the SSRIs. The HAMD₁₇total score difference was driven mostly by patients with lower baseline MDD severity (HAMD₁₇ total score ≤19), where the HAMD₁₇ effect size advantage for duloxetine over combined SSRIs was statistically significant (p = 0.031). Conclusion: Potentially important differences in symptom response patterns were found between duloxetine and the combined SSRIs depending on symptom severity, and different HAMD₁₇ items responded differently to duloxetine compared with SSRIs. Understanding these differences may be useful in tailoring antidepressant therapy for individual patients.