Efficacy of 12 New-Generation Antidepressants Assessed
News Author: Laurie Barclay, MD
CME Author: Charles Vega, MD, FAAFP
Disclosures
Release Date: February 3, 2009; Valid for credit through February 3, 2010
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Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™ for physicians;
Family Physicians - up to 0.25 AAFP Prescribed credit(s) for physicians; Nurses - 0.25 ANCC contact hours (0.25 contact hours are in the area of pharmacology) |
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February 3, 2009 — When balancing benefits, acceptability, and cost, sertraline may be the best initial treatment option for moderate to severe major depression in adults,
according to the results of a meta-analysis of 12 new-generation antidepressants reported in the January 28 Online First issue of The Lancet.
"Conventional meta-analyses have shown inconsistent results for efficacy of second-generation antidepressants," write Andrea Cipriani, PhD, from the University of Verona, in Verona, Italy, and colleagues. "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."
This systematic review included 117 randomized controlled trials, enrolling a total of 25,928 participants, from 1991 up to November 30, 2007. Inclusion criteria for the review were comparison of 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 primary outcome measures were the percentages of patients who responded to or withdrew from the assigned treatment, with analysis by intent-to-treat.
Efficacy was significantly better for mirtazapine, escitalopram, venlafaxine, and sertraline vs duloxetine (odds ratios [ORs], 1.39, 1.33, 1.30, and 1.27, respectively), fluoxetine (ORs, 1.37, 1.32, 1.28, and 1.25, respectively), fluvoxamine (ORs, 1.41, 1.35, 1.30, and 1.27, respectively), paroxetine (ORs 1.35, 1.30, 1.27, and 1.22, respectively), and reboxetine (ORs, 2.03, 1.95, 1.89, and 1.85, respectively).
Compared with all of the other antidepressants tested, reboxetine was significantly less effective. Acceptability profile was best for escitalopram and sertraline, with significantly fewer discontinuations than were observed with duloxetine, fluvoxamine, paroxetine, reboxetine, and venlafaxine.
"Clinically important differences exist between commonly prescribed antidepressants for both efficacy and acceptability in favour of escitalopram and sertraline," the study authors write. "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."
Limitations of this meta-analysis include lack of comparison of adverse effects, toxic effects, discontinuation symptoms, and social functioning; applicability only to acute-phase treatment (8 weeks) of depression; lack of adequate information about randomization and allocation concealment in most included studies; presence of sponsorship bias; and lack of cost-effectiveness analysis.
In an accompanying comment, Sagar V. Parikh, from the University of Toronto and University Health Network in Toronto, Ontario, Canada, notes the "enormous implications" of these findings, but he recommends further meta-analysis to compare 6-month outcomes.
"Intriguingly, Cipriani and colleagues also challenge the field of clinical trials to use sertraline as a benchmark in the development of new compounds; by raising the efficacy bar beyond 'beating placebo,' they hope to discourage the development of drugs of routine efficacy and also side-step the ethically challenging position of using placebos in an era of multiple proven treatments for depression," Dr. Parikh writes. "With such a host of clinical and research implications, this pivotal meta-analysis of antidepressant efficacy and acceptability will surely change the tune of psychiatrists."
This study received no external funding. Four of the study authors have disclosed various financial relationships with GlaxoSmithKline; sanofi-aventis; the UK Department of Health and Medical Research Council; the Stanley Medical Research Institute; Bristol-Myers Squibb; Asahi Kasei; Astellas; Dai-Nippon Sumitomo; Eisai; Eli Lilly; Janssen; Kyowa Hakko; Meiji; Nikken Kagaku; Organon; Otsuka; Pfizer; Yoshitomi; the Japanese Ministry of Education, Science and Technology; the Japanese Ministry of Health, Labour and Welfare; Roche; and and/or Novartis. The remaining study authors have disclosed no relevant financial relationships.
Dr. Parikh has received honoraria or grant support from Apotex, AstraZeneca, Biovail, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Lilly, Lundbeck, Novartis, Pfizer, and Wyeth.
Lancet. Published online January 28, 2009.
Clinical Context
Depression is one of the most common conditions treated in primary care practices, in part because of a rapid expansion of pharmaceutical treatment options in the last 2 decades. However, the proliferation of treatment choices for depression has also led to confusion as to which medication is best for an individual patient.
A previous analysis by Hansen and colleagues of newer antidepressants found significant design and methodologic problems among trials comparing these medications. This review, which was published in the September 20, 2005, issue of the Annals of Internal Medicine, also concluded that the available research did not suggest a clinically important difference in efficacy between these antidepressants.
The current review reexamines newer antidepressants in both efficacy and acceptability to patients.
Study Highlights
- Researchers focused on randomized controlled trials of treatment of unipolar depression in adults with the following antidepressants: bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, mirtazapine, paroxetine, reboxetine, sertraline, and venlafaxine.
- The main outcomes of the study were treatment response and treatment discontinuation during the first 8 weeks of antidepressant therapy. A treatment response was defined as a 50% improvement in standard rating scales for depression or a score of much improved or very much improved on the clinical global impression.
- A multiple-treatment meta-analysis was used to compare the efficacy of the included antidepressants.
- Study investigators used 117 trials completed between 1991 and 2007 for analysis. These trials included a total of 25,928 adults.
- 64% of participants were women. The mean duration of the studies was 8.1 weeks. Only 14 studies had a follow-up period that exceeded 12 weeks.
- Escitalopram, mirtazapine, sertraline, and venlafaxine were significantly more efficacious vs duloxetine, fluoxetine, fluvoxamine, paroxetine, and reboxetine.
- Reboxetine was significantly less efficacious vs the other 11 antidepressants.
- In acceptability, sertraline and escitalopram were superior to duloxetine, fluvoxamine, paroxetine, and reboxetine. Escitalopram was also better tolerated vs venlafaxine.
- Bupropion and citalopram were also well tolerated vs other antidepressants.
- Overall, the researchers recommend sertraline and escitalopram as offering the best combination of efficacy and acceptability for the acute treatment of depression.
- Researchers also note that sertraline is offered at a lower price vs escitalopram in most countries, and this additional advantage may make sertraline the treatment of choice for the acute management of depression.
Pearls for Practice
- A previous review suggested that newer antidepressants are relatively similar in regard to their efficacy in treating major depression, although the body of original research into this subject is limited.
- In the current review, sertraline is the most recommended newer antidepressant for the acute management of depression.
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