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“Antidepressants are not all created equal”

Cipriani and colleagues published a major multiple-treatments meta-analysis of new generation antidepressants last week - see abstract below.  As Parikh wrote in his linked editorial (see below) "Andrea Cipriani and colleagues provide the field with a major answer.  Free of any potential funding bias (and including an analysis of studies based on pharmaceutical-company sponsorship), these researchers used a newer methodology, multiple treatments meta-analysis, to examine 117 head-to-head randomised trials in almost 26 000 patients ... Of 12 newer antidepressants, four emerged as superior in efficacy: escitalopram, mirtazapine, sertraline, and venlafaxine ... In terms of acceptability, four agents were better tolerated: bupropion, citalopram, escitalopram, and sertraline.  Balancing efficacy and acceptability and lower drug costs, the researchers concluded that sertraline might be particularly appropriate as a first-choice treatment ... "  This is superbly useful information.  Parikh's editorial goes on to raise helpful queries about next step questions, however Cipriani et al have done antidepressant prescribers and users a major service with this very important paper.

Cipriani, A., T. A. Furukawa, et al. (2009). "Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis." Lancet 373(9665): 746-758. [Abstract/Full Text]
Summary - Background: Conventional meta-analyses have shown inconsistent results for efficacy of second-generation antidepressants. We therefore did a multiple-treatments meta-analysis, which accounts for both direct and indirect comparisons, to assess the effects of 12 new-generation antidepressants on major depression.  Methods: We systematically reviewed 117 randomised controlled trials (25,928 participants) from 1991 up to Nov 30, 2007, which compared any of the following antidepressants at therapeutic dose range for the acute treatment of unipolar major depression in adults: bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, mirtazapine, paroxetine, reboxetine, sertraline, and venlafaxine.  The main outcomes were the proportion of patients who responded to or dropped out of the allocated treatment.  Analysis was done on an intention-to-treat basis.  Findings: Mirtazapine, escitalopram, venlafaxine, and sertraline were significantly more efficacious than duloxetine (odds ratios [OR] 1.39, 1.33, 1.30 and 1.27, respectively), fluoxetine (1.37, 1.32, 1.28, and 1.25, respectively), fluvoxamine (1.41, 1.35, 1.30, and 1.27, respectively), paroxetine (1.35, 1.30, 1.27, and 1.22, respectively), and reboxetine (2.03, 1.95, 1.89, and 1.85, respectively).  Reboxetine was significantly less efficacious than all the other antidepressants tested.  Escitalopram and sertraline showed the best profile of acceptability, leading to significantly fewer discontinuations than did duloxetine, fluvoxamine, paroxetine, reboxetine, and venlafaxine.  Interpretation: Clinically important differences exist between commonly prescribed antidepressants for both efficacy and acceptability in favour of escitalopram and sertraline.  Sertraline might be the best choice when starting treatment for moderate to severe major depression in adults because it has the most favourable balance between benefits, acceptability, and acquisition cost.  (Funding None).  (Note both the study protocol and the data set are freely viewable)

Parikh, S. V. (2009). "Antidepressants are not all created equal." Lancet 373(9665): 700-701. [Extract/Full Text - select issue 9665 from list]
In The Lancet today, Andrea Cipriani and colleagues provide the field with a major answer.  Free of any potential funding bias (and including an analysis of studies based on pharmaceutical-company sponsorship), these researchers used a newer methodology, multiple treatments meta-analysis, to examine 117 head-to-head randomised trials in almost 26 000 patients.  They did two types of analysis: of efficacy (at least 50% symptom reduction at week 8) and acceptability (dropout rates for any reason during the first 8 weeks of treatment).  As the researchers stress, these outcomes were chosen for clinical reasons, because evidence-based medicine calls for rigorous studies and statistics while providing treatment recommendations on the basis of comprehensibility and ease of implementation.  Of 12 newer antidepressants, four emerged as superior in efficacy: escitalopram, mirtazapine, sertraline, and venlafaxine.  One agent, reboxetine, was significantly less effective than the 11 other agents.  In terms of acceptability, four agents were better tolerated: bupropion, citalopram, escitalopram, and sertraline.  Balancing efficacy and acceptability and lower drug costs, the researchers concluded that sertraline might be particularly appropriate as a first-choice treatment  ...  A new gold standard of reliable information has been compiled for patients to review, particularly because these researchers have also made their data and analyses available on a public website.  Such research invites a key clinical question: is superiority at 8 weeks meaningful and sustained over a treatment that minimally lasts 6 months?  A similar meta-analysis could answer this vital question.  Additional clinical questions include clarifying the effect of using the identified stronger agents, or the best tolerated agents, in combination studies with psychotherapy.  Historically, combination strategies have not always been superior, but perhaps future ones will be by choosing a more appropriate antidepressant.  A key challenge now involves the issue of costs and benefits; although the generic agents are cheaper to buy, proper studies are needed to aid societal choices among the four strongest antidepressants. As Patel and colleagues have emphasised, such cost concerns are particularly crucial from a global perspective, because most people live in low-income and middle-income countries.

 

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