Which antidepressants is safer and more effective?

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American Family Physician > Jan 15, 2006 > Article > Print friendly

No difference among new antidepressants by F. Shaughnessy,

American Family Physician > Jan 2006

Clinical Question: Which of the newer antidepressants 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unsuccessfully, to obtain unpublished data filed with the U.S. Food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)

ALLEN F. SHAUGHNESSY, PHARM.D.

Study Reference: Hansen RA, et al. Efficacy and safety of second-

generation antidepressants in the treatment of major depressive

disorder. Ann Intern Med September 20, 2005;143:415-26.