1 Boring Old Man

Benefits From Antidepressants:
^{Synthesis of 6-Week Patient-Level Outcomes From Double-blind Placebo-Controlled Randomized Trials of Fluoxetine and Venlafaxine
by Robert D. Gibbons, PhD; Kwan Hur, PhD; C. Hendricks Brown, PhD; John M. Davis, MD; and J. John Mann, MD}
Archives of General Psychiatry. Published online March 5, 2012.

^{Context: Some meta-analyses suggest that efficacy of antidepressants for major depression is overstated and limited to severe depression.
Objective: To determine the short-term efficacy of antidepressants for treating major depressive disorder in youth, adult, and geriatric populations.
Data Sources: 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.
Study Selection: All sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine.
Data Extraction: 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.
Data Synthesis: 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.
Conclusions: 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first research synthesis in this area to use complete longitudinal person-level data from a large set of published and unpublished studies.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.}

^{A detailed description of the study data is available on request from the authors and will be available in a related publication.}

^{[only Child and Adolescent data shown]}

Let’s linger here for a moment [don’t worry – it’s the only table in the paper]. Here’s what I had guessed before based on FDA approval documents and the publications from the TADS Study [see coming soon?…]:

And here’s what Gibbons used in his analysis:

Some of the differences are clear. His group only analyzed the first six weeks because that was the shortest study [including adult studies]. They wanted complete data for all studies in their analysis [?]. Studies X065 and HCJE were part of the  FDA Medical Review. They were both published by Dr. Emslie et al [A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression, Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled, randomized clinical trial, reviewed on this blog in tuning the quartet…]. I don’t have a clue where Study LYAQ came from. It’s not listed on Lilly’s Clinical Trial site. If you figure it out, let me know [from the text of the article, I think it was an in-patient study]. The TADS trial [Fluoxetine, Cognitive-Behavioral Therapy, and Their Combination for Adolescents With Depression] had four groups – Placebo, Prozac, Cognitive Behavior Therapy [CBT], and Prozac+CBT. In this analysis, they only used the Placebo and the Prozac groups, explaining the different numbers in the two tables, again truncating the trial to the first six weeks [the first part of TADS lasted 12 weeks]. Note that Dr. Emslie was a member of the TADS group as well.