PMID- 17445831 OWN - NLM STAT- MEDLINE DCOM- 20080201 LR - 20151119 IS - 0022-3956 (Print) IS - 0022-3956 (Linking) VI - 42 IP - 1 DP - 2008 Jan TI - A randomized, double-blind comparison of duloxetine and venlafaxine in the treatment of patients with major depressive disorder. PG - 22-34 AB - BACKGROUND: Clinical trials assessing antidepressant therapies typically include separate assessments of efficacy (benefit) and adverse events (risk). Global benefit-risk (GBR) assessment allows the simultaneous evaluation of both efficacy and adverse events. The objective was to compare the serotonin and norepinephrine reuptake inhibitors (SNRIs) duloxetine and venlafaxine using GBR assessment. METHODS: Data were combined from two similarly designed, multicenter, randomized, double-blind, parallel group studies in which patients with major depressive disorder were randomized to either duloxetine 60 mg/day or venlafaxine extended release (XR) 150 mg/day (75 mg/day for the first 2 weeks) for a 6-week fixed dosing period followed by an additional 6 weeks of treatment in which the dose could be increased up to 120 mg/day for duloxetine and 225 mg/day for venlafaxine. Patients completing the study (or receiving study drug for 2 weeks or more) were eligible to enter a taper period where the dose of study drug was gradually reduced over 1-2 weeks prior to drug discontinuation. The primary outcome measure (defined a priori) was the GBR comparison of duloxetine 60 mg/day and venlafaxine XR 150 mg/day after 6 weeks of treatment. In the GBR analysis, benefit was defined as remission at endpoint [17-item Hamilton Depression Rating Scale (HAMD17) 7]. Risk was defined by four categories: patients having either no adverse events (AEs), AEs with no severity rating greater than moderate, AEs with at least one severity rating of severe, or having discontinued with a reason of self-reported adverse event (regardless of any AE severity). Additional efficacy measures included HAMD17 total score and subscales, HAMA, CGI-S, and PGI-I. Safety and tolerability were assessed via analysis of reasons for discontinuation, treatment-emergent adverse events (TEAEs), discontinuation-emergent adverse events, and changes in vital signs, weight, and laboratory analytes. RESULTS: There were no significant differences between duloxetine 60 mg/day and venlafaxine 150 mg/day as measured by GBR assessment at the end of 6 weeks (-1.418 vs. -1.079, P = 0.217) or 12 weeks (-0.349 vs. -0.121, P = 0.440), nor were there significant differences between treatment groups on the majority of efficacy measures. Significantly more venlafaxine-treated patients (74.5%) completed 12 weeks of treatment compared with duloxetine-treated patients (64.8%, P =.006). Nausea was the most common treatment-emergent adverse event (TEAE) for both drugs, and was significantly higher with duloxetine 60 mg/day compared to venlafaxine 150 mg/day during the first 6 weeks of treatment (43.6% vs. 35.0%, P0.05). During the taper period, significantly more venlafaxine-treated patients reported discontinuation-emergent adverse events (DEAEs) than duloxetine-treated patients. From a safety perspective, significantly more venlafaxine-treated patients (n = 4) than duloxetine-treated patients (n=0, P =.047) experienced sustained elevations of systolic blood pressure during the fixed dosing period. Otherwise, there were few significant differences in safety measures found between treatment groups during 6 and 12 weeks of therapy. CONCLUSIONS: Duloxetine 60 mg/day and venlafaxine XR 150 mg/day have similar benefit-risk profiles on the basis of a comparison utilizing GBR assessment. The implications of the more subtle differences between these drugs, as well as for interpreting the GBR assessment, are discussed. FAU - Perahia, David G S AU - Perahia DG AD - Lilly Research Centre, Erl Wood, Sunninghill Road, Windlesham, Surrey GU20 6PH, UK. d.perahia@lilly.com FAU - Pritchett, Yili Lu AU - Pritchett YL FAU - Kajdasz, Daniel K AU - Kajdasz DK FAU - Bauer, Michael AU - Bauer M FAU - Jain, Rakesh AU - Jain R FAU - Russell, James M AU - Russell JM FAU - Walker, Daniel J AU - Walker DJ FAU - Spencer, Kimberly A AU - Spencer KA FAU - Froud, Debbie M AU - Froud DM FAU - Raskin, Joel AU - Raskin J FAU - Thase, Michael E AU - Thase ME LA - eng PT - Clinical Trial PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20070418 PL - England TA - J Psychiatr Res JT - Journal of psychiatric research JID - 0376331 RN - 0 (Antidepressive Agents) RN - 0 (Cyclohexanols) RN - 0 (Thiophenes) RN - 7D7RX5A8MO (Venlafaxine Hydrochloride) RN - 9044SC542W (Duloxetine Hydrochloride) SB - IM MH - Adolescent MH - Adult MH - Antidepressive Agents/*therapeutic use MH - Cyclohexanols/*therapeutic use MH - Depressive Disorder, Major/*drug therapy MH - Double-Blind Method MH - Duloxetine Hydrochloride MH - Female MH - Humans MH - Male MH - Middle Aged MH - Psychiatric Status Rating Scales MH - Severity of Illness Index MH - Thiophenes/*therapeutic use MH - Treatment Outcome MH - Venlafaxine Hydrochloride EDAT- 2007/04/21 09:00 MHDA- 2008/02/02 09:00 CRDT- 2007/04/21 09:00 PHST- 2006/09/13 00:00 [received] PHST- 2006/12/19 00:00 [revised] PHST- 2007/01/05 00:00 [accepted] PHST- 2007/04/21 09:00 [pubmed] PHST- 2008/02/02 09:00 [medline] PHST- 2007/04/21 09:00 [entrez] AID - S0022-3956(07)00051-9 [pii] AID - 10.1016/j.jpsychires.2007.01.008 [doi] PST - ppublish SO - J Psychiatr Res. 2008 Jan;42(1):22-34. doi: 10.1016/j.jpsychires.2007.01.008. Epub 2007 Apr 18.