brand logo

Am Fam Physician. 2006;73(2):311-312

Clinical Question: Which of the newer anti-depressants is safer and more effective?

Setting: Various (meta-analysis)

Study Design: Meta-analysis (randomized controlled trials)

Synopsis: The researchers who performed this systematic review and meta-analysis of the safety, tolerability, and effectiveness of the newer antidepressants used six databases to find all randomized controlled studies of one antidepressant versus another of at least 12 weeks’ duration. They also searched reference lists of review articles; contacted pharmaceutical manufacturers; and tried, unsuccessfully, to obtain unpublished data filed with the U.S. Food and Drug Administration. Two researchers independently reviewed the articles for eligibility, and the data were abstracted from the selected studies by trained reviewers and then evaluated by another researcher. The 46 studies, 85 percent of which were sponsored by pharmaceutical companies, were of varying quality. The quality of most of the effectiveness studies (21 of 22) was fair, and one study was rated as good. Twenty of these trials found no difference between the two antidepressants they evaluated. Two trials found a difference in at least one outcome: escitalopram (Lexapro) produced improved depression scores versus citalopram (Celexa) in one study but not another, and paroxetine (Paxil) was found to be more effective than fluoxetine (Prozac) in one of eight studies comparing the two drugs. In the meta-analysis, combining the results of six studies found no difference between fluoxetine and paroxetine. In five studies (total of 1,190 patients), sertraline (Zoloft) was slightly more effective than fluoxetine (relative benefit = 1.1; 95% confidence interval [CI], 1.01 to 1.20). Venlafaxine (Effexor) also was slightly more effective than fluoxetine in six studies of more than 1,300 patients (relative benefit = 1.12; 95% CI, 1.02 to 1.23). Faster onset of action was not identified consistently for any specific drug. Similarly, quality of life was not significantly different with any of the drugs. The overall incidence of adverse effects and discontinuation rates was similar among the antidepressants, although specific adverse effects were significantly different. Nausea and vomiting rates were consistently higher for venlafaxine than for other antidepressants. Sexual side effects were less common with bupropion (Wellbutrin) than with sertraline and fluoxetine, and were more common with paroxetine, sertraline, and mirtazapine (Remeron). Weight gain was not systematically compared but seemed to be highest in the patients receiving mirtazapine and lowest in those receiving fluoxetine.

Bottom Line: When it comes to the new nontricyclic antidepressants, the medical literature does not provide clear guidance as to which one is more effective, of faster onset, safer, or better tolerated. Sexual side effects are lower with bupropion, and nausea seems to occur more often with venlafaxine. Other research has shown these new drugs to be no more effective or better tolerated than tricyclic antidepressants. For now, patients should be started on an antidepressant with the realization that most patients will need to switch to another drug at least once. (Level of Evidence: 1a)

POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see Copyright Wiley-Blackwell. Used with permission.

For definitions of levels of evidence used in POEMs, see

To subscribe to a free podcast of these and other POEMs that appear in AFP, search in iTunes for “POEM of the Week” or go to

This series is coordinated by Natasha J. Pyzocha, DO, contributing editor.

A collection of POEMs published in AFP is available at

Continue Reading

More in AFP

Copyright © 2006 by the American Academy of Family Physicians.

This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.  See permissions for copyright questions and/or permission requests.