The authors report no financial relationships relevant to this article.
Meta-analysis of 117 high-quality studies found that sertraline and escitalopram are superior to other “new-generation” antidepressants.1
CASE: A woman with diabetes who is fatigued but cannot sleep
Mrs. D., 45 years old, has been your patient for several years. She has type 2 diabetes. On her latest visit, she reports a loss of energy and difficulty sleeping, and wonders if these symptoms could be related to the diabetes.
As you explore further and question Mrs. D. about her symptoms, she becomes tearful, and tells you she has episodes of sadness and no longer enjoys things the way she used to. Although she has no history of depression, when you suggest that her symptoms may be an indication of depression, she readily agrees.
You discuss treatment options, including antidepressants and psychotherapy. Mrs. D. decides to try medication. But with so many antidepressants on the market, how do you choose one?
Major depression is the fourth leading cause of disease globally, according to the World Health Organization.2 Depression is common in the United States as well, and primary care physicians, including ObGyns, are often the ones who are diagnosing and treating it. In fact, the US Preventive Services Task Force recently expanded its recommendation that primary care providers screen adults for depression, to include adolescents 12 to 18 years old.3 When depression is diagnosed, physicians must help patients decide on an initial treatment plan.
Options for initial treatment of unipolar major depression include psychotherapy and the use of an antidepressant. For mild and moderate depression, psychotherapy alone is as effective as medication. Combined psychotherapy and antidepressants are more effective than either treatment alone for all degrees of depression.4
The ideal medication for depression would be a drug with a high level of effectiveness and a low side-effect profile; until now, however, there has been little evidence to support one antidepressant over another. Previous meta-analyses have concluded that there are no significant differences in either efficacy or acceptability among the various second-generation antidepressants on the market.5,6 Therefore, physicians have historically made initial monotherapy treatment decisions based on side effects and cost.7,8 The meta-analysis we report here tells a different story, providing strong evidence that some antidepressants are more effective and better tolerated than others.
Two “best” drugs revealed
Cipriani and colleagues1 conducted a systematic review and multiple-treatments meta-analysis of 117 prospective randomized, controlled trials (RCTs). Taken together, the RCTs evaluated the comparative efficacy and acceptability of 12 second-generation antidepressants: bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, mirtazapine, paroxetine, reboxetine, sertraline, and venlafaxine.
The methodology of this meta-analysis differed from that of traditional meta-analyses by allowing the integration of data from both direct and indirect comparisons. (An indirect comparison is one in which drugs from different trials are assessed by combining the results of their effectiveness and comparing the combined finding with the effectiveness of a drug that all the trials have in common.) Previous studies, based only on direct comparison, yielded inconsistent results.
The studies included in this meta-analysis were all RCTs in which one of these 12 antidepressants was tested against one, or several, other second-generation antidepressants as monotherapy for the acute treatment phase of unipolar major depression. The authors excluded placebo-controlled trials in order to evaluate efficacy and acceptability of the study medications relative to other commonly used antidepressants. They defined acute treatment as 8 weeks of antidepressant therapy, with a range of 6 to 12 weeks. The primary outcomes studied were response to treatment and dropout rate.
Response to treatment (efficacy) was constructed as a Yes or No variable; a positive response was defined as a reduction of ≥50% in symptom score on either the Hamilton Depression Rating Scale or the Montgomery-Asberg Rating Scale, or a rating of “improved” or “very much improved” on the Clinical Global Impression scale at 8 weeks. Efficacy was calculated on an intention-to-treat basis; if data were missing for a participant, that person was classified as a nonresponder.
Dropout rate was used to represent acceptability, because the authors believed it to be a more clinically meaningful measure than either side effects or symptom scores. Comparative efficacy and acceptability were analyzed. Fluoxetine—the first of the secondgeneration antidepressants—was used as the reference medication. The FIGURE shows the outcomes for nine of the antidepressants, compared with those of fluoxetine. The other two antidepressants, milnacipran and reboxetine, were omitted because they are not available in the United States.