Benefits From Antidepressants Synthesis of 6-Week Patient-Level Outcomes From Double-blind Placebo-Controlled Randomized Trials of Fluoxetine and Venlafaxine

Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Archives of general psychiatry (Impact Factor: 14.48). 03/2012; 69(6):572-9. DOI: 10.1001/archgenpsychiatry.2011.2044
Source: PubMed


Some meta-analyses suggest that efficacy of antidepressants for major depression is overstated and limited to severe depression.
To determine the short-term efficacy of antidepressants for treating major depressive disorder in youth, adult, and geriatric populations.
Reanalysis of all intent-to-treat person-level longitudinal data during the first 6 weeks of treatment of major depressive disorder from 12 adult, 4 geriatric, and 4 youth randomized controlled trials of fluoxetine hydrochloride and 21 adult trials of venlafaxine hydrochloride.
All sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine.
Children's Depression Rating Scale-Revised scores (youth population), Hamilton Depression Rating Scale scores (adult and geriatric populations), and estimated response and remission rates at 6 weeks were analyzed for 2635 adults, 960 geriatric patients, and 708 youths receiving fluoxetine and for 2421 adults receiving immediate-release venlafaxine and 2461 adults receiving extended-release venlafaxine.
Patients in all age and drug groups had significantly greater improvement relative to control patients receiving placebo. The differential rate of improvement was largest for adults receiving fluoxetine (34.6% greater than those receiving placebo). Youths had the largest treated vs control difference in response rates (24.1%) and remission rates (30.1%), with adult differences generally in the 15.6% (remission) to 21.4% (response) range. Geriatric patients had the smallest drug-placebo differences, an 18.5% greater rate of improvement, 9.9% for response and 6.5% for remission. Immediate-release venlafaxine produced larger effects than extended-release venlafaxine. Baseline severity could not be shown to affect symptom reduction.
To our knowledge, this is the first research synthesis in this area to use complete longitudinal person-level data from a large set of published and unpublished studies. The results do not support previous findings that antidepressants show little benefit except for severe depression. The antidepressants fluoxetine and venlafaxine are efficacious for major depressive disorder in all age groups, although more so in youths and adults compared with geriatric patients. Baseline severity was not significantly related to degree of treatment advantage over placebo.

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Available from: J. John Mann, Aug 11, 2014
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    • "In addition, it is possible that medication is prescribed for a variety of conditions associated with a referral to psychiatric services not directly linked to self-injurious behavior in any case, exploration of potential medication effects on suicidality is important as there has been some evidence for increased risk of self-harm among young people aged under 18, who are taking serotonin reuptake inhibitors (SSRIs) for depression unlike other age groups (Martinez et al., 2005). However, this has been recently disputed in a reanalysis of all randomised placebo-control trials of fluoxetine and venlafaxine (Gibbons et al., 2012). "
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    Journal of Mental Health 07/2015; DOI:10.3109/09638237.2015.1022249 · 1.01 Impact Factor
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    • "However, there are several limitations to the reported meta-analyses. First, they rely on a limited number of studies, thus Gibbons et al. (2012) included 4 geriatric studies, whereas Nelson et al. (2013) included 10 trials of second-generation antidepressants in patients with late-life depression. Second, the authors included only a restricted range of baseline severity scores as they focused on MDD. "
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    Journal of Affective Disorders 04/2015; 181:50-60. DOI:10.1016/j.jad.2015.03.062 · 3.38 Impact Factor
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    • "The placebo effect has been explored across a variety of diseases and medical conditions but it is in psychiatry - and most of all in depression - that the placebo response may play a major clinical role. This has generated concerns and a long-lasting debate around the real efficacy of antidepressants, with very conflicting opinions [4,5]. In antidepressant trials with adults, the mean response rate for active treatment is 50%, while the mean placebo response is 31%, with an absolute difference of 19% [6]. "
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