The overall meta-analysis included 25,928 individuals, with 24,595 in the efficacy analysis and 24,693 in the acceptability analysis. Nearly two thirds (64%) of the participants were women. The mean duration of follow-up was 8.1 weeks. The mean sample size per study was 110.
Studies of women with postpartum depression were excluded.
Escitalopram and sertraline stand out. Overall, escitalopram, mirtazapine, sertraline, and venlafaxine were significantly more efficacious than fluoxetine or the other medications. Bupropion, citalopram, escitalopram, and sertraline were better tolerated than the other antidepressants. Escitalopram and sertraline were found to have the best combination of efficacy and acceptability.
Efficacy results. Fifty-nine percent of participants responded to sertraline, versus a 52% response rate for fluoxetine (number needed to treat [NNT]=14). Similarly, 52% of participants responded to escitalopram, compared with 47% of those taking fluoxetine (NNT=20).
Acceptability results. In terms of the dropout rate, 28% of participants discontinued fluoxetine, versus 24% of patients taking sertraline. This means that 25 patients would need to be treated with sertraline, rather than fluoxetine, to avoid one discontinuation. In the comparison of fluoxetine versus escitalopram, 25% discontinued fluoxetine, compared with 24% who discontinued escitalopram.
The efficacy and acceptability of sertraline and escitalopram compared with other second-generation antidepressant medications follow similar trends.
Generic advantage. The investigators recommend sertraline as the best choice for an initial antidepressant because it is available in generic form and is therefore lower in cost. They further recommend that sertraline, instead of fluoxetine or placebo, be the new standard against which other antidepressants are compared.
FIGURE Sertraline and escitalopram come out on top in acceptability and efficacy
Researchers analyzed a number of second-generation antidepressants, using fluoxetine as the reference medication. Sertraline and escitalopram provided the best combination of efficacy and acceptability.1
Choice is now evidence-based
We now have solid evidence for choosing sertraline or escitalopram as the first medication to use when treating a patient with newly diagnosed depression. This represents a practice change because antidepressants that are less effective and less acceptable have been chosen more frequently than either of these medications. That conclusion is based on our analysis of the National Ambulatory Medical Care Survey database for outpatient and ambulatory clinic visits in 2005-2006 (the most recent data available). We conducted this analysis to determine which of the second-generation antidepressants were prescribed more often for initial monotherapy of major depression.
Our finding? An estimated 4 million patients 18 years and older given a diagnosis of depression in the course of the study year received new prescriptions for a single antidepressant. Six medications accounted for 90% of prescriptions, in this order:
- fluoxetine (Prozac)
- duloxetine (Cymbalta)
- escitalopram (Lexapro)
- paroxetine (Paxil)
- venlafaxine (Effexor)
- sertraline (Zoloft).
Sertraline and escitalopram, the drugs shown to be most effective and acceptable in the Cipriani meta-analysis, accounted for 11.8% and 14.5% of the prescriptions, respectively.
Caveats
This meta-analysis looked at the acute phase of treatment only
The results of this study are limited to initial therapy as measured at 8 weeks. Few long-term outcome data are available; response to initial therapy may not be a predictor of full remission or long-term success. Current guidelines suggest maintenance of the initial successful therapy, often with increasing intervals between visits, to prevent relapse.9
This study does not add new insight into long-term response rates. Nor does it deal with choice of a replacement or second antidepressant for nonresponders or those who cannot tolerate the initial drug.
What’s more, the study covers drug treatment alone, which may not be the best initial treatment for depression. Psychotherapy, in the form of cognitive behavioral therapy or interpersonal therapy, when available, is equally effective, has fewer potential physiologic side effects, and may produce longer-lasting results.10,11
Little is known about study design
The authors of this study had access only to limited information about inclusion criteria and the composition of initial study populations or settings. There is a difference between a trial designed to evaluate the “efficacy” of an intervention (i.e., “the beneficial and harmful effects of an intervention under controlled circumstances”) and the “effectiveness” of an intervention (i.e., the “beneficial and harmful effects of the intervention under usual circumstances”).12 It is not clear which of the 117 studies were efficacy studies and which were effectiveness studies. This may limit the overall generalizability of the study results to a primary care population.
Studies included in this meta-analysis were selected exclusively from published literature. There is some evidence of a bias toward the publication of studies that have yielded positive results, which may have the effect of overstating the effectiveness of a given antidepressant.13 However, we have no reason to believe that this bias would favor any particular drug.