Efficacy of SSRIsand SNRIs in depression is generally comparable. Desvenlafaxine is an SNRI that have been marketed in US since 2008. 50 mg/day is the recommended therapeutic dose. As a fixed dose schedule, is it effective? Papakostas GI, Culpepper L, Fayyad RS, Musgnung J and Guico-Pabia CJ report the results of a metaanlysis of all 6 RCTs that sued fixed dose against placebo in this article.
Six randomized, double-blind, placebo-controlled trials that evaluate the efficacy of desvenlafaxine 50mg/day versus placebo in moderately depressed and severely depressed patient populations were included in the analysis.Study durations were 8 weeks for all but one trial, which had a duration of 12 weeks. Primary efficacy endpoint in the current analysis was change from baseline in HAM-D17 total score at week 8. Pooled population included 2274 patients. The duration of the current depressive episode was less than 12 months for 64%. Groups were similar on base line characteristics. One third of participants were severely depressed.
Results: Among those with severe depression, the HAMD scores reduced significantly. ( -11.91 in active arm Vs -9.85 in placebo arm). Adjusted mean difference being 2.07, In mdoerately depreese patiets this was 1.37.
Remission rates: In severe depression 22% achieved remission in active arm with 15% in placebo arm. In moderate depression this was 30% vs 24%. 46% of those with severe depression showed response compared to 35% in placebo arm.
Generalisability is limited. (patients with any physical health problems, substance use, comorbid psychiatric disorders ( other than Anxiety disorder) and those with suicidal behaviours were excluded). Short term studies. The analysis / writing/ studies included were sponsored by the manufacturer Pfizer.
Comment: It is important to note that the company ( originally Wyeth) withdrew application for licensing for depression in Europe. The EMA ( European Medicines Agency) observed that the flexible dose regime ( which more closely resembles clinical practice) found non significant difference from placebo. There was also no advantage from safety and tolerability angles. Greater part of venlafaxine is converted in body to desvenlafaxine, and hence no advantage is being offered. The application for extending the license to post menopausal symptoms were also withdrawn in USA.
Papakostas GI, Culpepper L, Fayyad RS, Musgnung J, Guico-Pabia CJ. Int Clin Psychopharmacol. 2013 Nov;28(6):312-21