Second-generation antidepressants similar in efficacy

December 1, 2008

Second-generation antidepressants generally have equivalent efficacy, according to a review published in the Annals of Internal Medicine. Although these agents demonstrate similar response rates, differences in onset of action or side effects may affect prescribing decisions.

Second-generation antidepressants generally have equivalent efficacy, according to a review published in the Annals of Internal Medicine. Although these agents demonstrate similar response rates, differences in onset of action or side effects may affect prescribing decisions.

For this review, the investigators searched Medline, EMBASE, Psych-Lit, the Cochrane Central Register of Controlled Trials, and International Pharmaceutical Abstracts from 1980 through April 2007. The authors also accessed the Center for Drug Evaluation and Research (CDER) database to search for unpublished data that had been submitted to FDA. The analysis included head-to-head controlled trials lasting ≥6 weeks (used to assess efficacy or effectiveness), placebo-controlled trials (used for indirect comparison models), observational studies with ≥100 patients and with ≥12 weeks of follow up (used to assess adverse events), and meta-analyses (if relevant to key questions and of good/fair methodological quality). The antidepressants under consideration in this study were bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, trazodone, and venlafaxine.

Investigators identified 2,318 relevant citations; 203 were included in the final analysis. The majority of these studies (n=140) were supported by pharmaceutical companies.

In 7 studies, mirtazapine was reported to have a significantly faster onset of action compared with citalopram, fluoxetine, paroxetine, and sertraline after 1 to 2 weeks of treatment; after 4 weeks of treatment, the response rates were similar among agents. Mirtazapine and venlafaxine had a similar speed of action.

In 4 head-to-head trials, relapse or recurrence prevention rates were similar between fluoxetine and sertraline, fluvoxamine and sertraline, duloxetine and paroxetine, and trazodone and venlafaxine. Across all trials, 38% of patients did not demonstrate a treatment response, and 54% did not achieve remission.

In assessments of symptom clusters that typically accompany depression, the antidepressants generally had similar effects on anxiety, insomnia, and pain, although comparative data for these outcomes were limited.

The investigators evaluated adverse event data from 80 head-to-head trials and 42 additional studies. Overall, the antidepressants demonstrated similar adverse event profiles. In efficacy trials, 61% of patients on average experienced ≥1 adverse event. Several studies offered evidence that bupropion is associated with a significantly lower rate of sexual adverse events compared with fluoxetine and sertraline. Other studies demonstrated that paroxetine is associated with a higher rate of sexual dysfunction compared with fluoxetine, fluvoxamine, nefazodone, and sertraline. Suicidality rates were similar among the agents; however, the authors pointed out that confounding by indication may have skewed these results.

The investigators discussed several limitations of their study, including the possibility of publication bias, a lack of power resulting in wide confidence intervals, and the possibility that these studies in highly selected populations may not be applicable to the average patient with MDD. They pointed out that little is known about the appropriate duration of antidepressant therapy for the maintenance of response, the effect of various antidepressant formulations on treatment adherence, and the association between drug dose and relapse risk. They stated that "current evidence is insufficient to identify patient factors that can reliably predict response or nonresponse to an individual drug." As such, they suggested, "An emphasis on providing treatment trials of adequate dose and duration . . . seems at least as important as the choice of specific drug."

SOURCE

Gartlehner G, Gaynes BN, Hansen RA, et al. Comparative benefits and harms of second-generation antidepressants: Background paper for the American College of Physicians. Ann Intern Med. 2008;149:734–750.