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Among new-generation antidepressants, sertraline (Zoloft and others) may be the best first-line medication.
To receive the imprimatur of the U.S. Food and Drug Administration or the regulatory agencies of other countries, a pharmaceutical compound must be safe and efficacious. However, it is difficult to assess relative efficacy and tolerability among compounds prescribed for the same indication. Antidepressant drugs are a case in point. Recently, Cipriani and coauthors used a new method—multiple-treatments meta-analysis—to examine 117 head-to-head, randomized trials of 12 new-generation antidepressants for major depressive disorder (MDD) in almost 26,000 patients.1 The authors conducted two types of analyses: of efficacy, defined as at least a 50% symptom reduction at week 8, and of acceptability, determined by dropout rates for any reason during the first 8 weeks of treatment. The authors report no funding for this work.
Escitalopram (Lexapro), mirtazapine (Remeron and others), sertraline (Zoloft and others), and venlafaxine (Effexor and others) were significantly more efficacious than duloxetine (Cymbalta), fluoxetine (Prozac and others), fluvoxamine (Luvox and others), paroxetine (Paxil and others), and reboxetine.* Reboxetine was significantly less efficacious than all the other 11 antidepressants.
In terms of acceptability, duloxetine and paroxetine were less well tolerated than escitalopram and sertraline. Fluvoxamine was less well tolerated than citalopram (Celexa and others), escitalopram, and sertraline. Venlafaxine was less well tolerated than escitalopram. Escitalopram and sertraline were better tolerated than duloxetine, fluvoxamine, paroxetine, and reboxetine.
Mirtazapine, escitalopram, venlafaxine, and sertraline were among the most efficacious treatments, and all were more efficacious than fluoxetine. Escitalopram, sertraline, bupropion (Wellbutrin and others), and citalopram were better tolerated than the other antidepressants.
Examining their findings in the aggregate, the authors observe that two of the most efficacious treatments, mirtazapine and venlafaxine, may not be the best for overall acceptability. By contrast, escitalopram and sertraline appear preferable as a starting treatment for moderate to severe MDD, since they have the best balance between efficacy and acceptability. Of the 12 antidepressants studied, only escitalopram and duloxetine retain patent protection in the United States and Europe. Because sertraline is off patent and less expensive, it may be a better all-around choice. Reboxetine, fluvoxamine, paroxetine, and duloxetine were the least efficacious and least acceptable drugs, which makes them less favorable options for the acute treatment of MDD. Reboxetine was the least tolerated agent. The authors suggest that reboxetine not be used as routine first-line acute treatment for MDD.
In an accompanying comment, Parikh applauds the finding from the Cipriani et al. analysis, calling it highly relevant to practicing psychiatrists and other physicians.2 He points out, however, that 8-week data may not be generalizable to the longer periods that antidepressants are usually prescribed and hopes for similar meta-analyses to address long-term treatment of MDD.
Clinicians have many reasonable choices for first-line treatment for MDD. The data from this excellent analysis, combining clinically relevant measures of efficacy and tolerability, can provide guidance. Cipriani et al. suggest that, when cost is taken into account, sertraline may be the best first-line medication.
*Reboxetine is a selective norepinephrine reuptake inhibitor not available in the United States.
1Cipriani A, Furukawa TA, Salanti G, Geddes JR, Higgins JPT, Churchill R, Watanabe N, Nakagawa A, Omori IM, McGuire H, Tansella M, Barbui C: Comparative efficacy and acceptability of 12 new-generation antidepressants: A multiple-treatments meta-analysis. Lancet 2009;373:746-758.
2Parikh SV: Antidepressants are not all created equal. Lancet 2009;373:700-701.