Elsevier

Biological Psychiatry

Volume 63, Issue 7, 1 April 2008, Pages 699-704
Biological Psychiatry

Original Article
Treatment of SSRI-Resistant Depression: A Meta-Analysis Comparing Within- Versus Across-Class Switches

https://doi.org/10.1016/j.biopsych.2007.08.010Get rights and content

Background

Two broad treatment options exist for switching antidepressants for depressed patients who fail to respond to a selective serotonin reuptake inhibitor (SSRI): either a second course of SSRI therapy or a different class of antidepressants. The goal of the present work was to conduct a meta-analysis of studies comparing these two switch strategies.

Methods

Several sources were searched for randomized clinical trials comparing these two switch strategies.

Results

Data from four clinical trials (n = 1496) were combined using a random-effects model. Patients randomized to switch to a non-SSRI antidepressant (bupropion, mirtazapine, venlafaxine) were more likely to experience remission than patients switched to a second SSRI (risk ratio = 1.29, p = .007). Pooled remission rates were 28% (for non-SSRIs) and 23.5% (for SSRIs). There was also a nonsignificant trend (p = .1) in the rate of discontinuation due to intolerance favoring the within-class switch strategy (risk ratio = 1.23). There was no difference in response rates between the two treatment groups.

Conclusions

These results suggest a modest yet statistically significant advantage in remission rates when switching patients with SSRI-resistant depression to a non-SSRI rather than an SSRI antidepressant. With the number needed to treat (NNT) statistic as one indicator of clinical significance, nearly 22 SSRI nonresponders would need to be switched to a non-SSRI rather than a second SSRI antidepressant to obtain one additional remitter. This difference falls well below the mark of NNT = 10 suggested by the United Kingdom’s National Institute of Clinical Excellence but nonetheless might be of public health relevance given the large number of SSRI-resistant patients switched to an SSRI versus a non-SSRI antidepressant.

Section snippets

Data Sources and Search Strategy

Six search strategies were employed to help identify studies for inclusion in the meta-analysis.

  • Studies were first identified using searches of PubMed/MEDLINE. Searches were conducted by first cross-referencing the term resistant and then the term switching with each of the six following terms: fluoxetine, sertraline, paroxetine, citalopram, escitalopram, and fluvoxamine. The search was limited to randomized controlled trials.

  • These searches were then repeated using EMBASE.

  • We also obtained the

Results

Initially, 75 abstracts were identified with the use of PubMed/MEDLINE. Of these, 72 did not meet the inclusion criteria (review articles, other topics). The remaining three abstracts described clinical trials comparing switching to different classes of antidepressants for SSRI-resistant depression (10, 11, 16). These three articles were obtained and reviewed thoroughly. Two of these articles met criteria for inclusion in the meta-analysis (10, 11). The third article was excluded because it

Discussion

In this meta-analysis of randomized clinical trials examining the efficacy of switching to a second SSRI versus a non-SSRI antidepressant for patients with MDD who had not responded to an initial course of SSRI therapy, we found evidence supporting a switch to a non-SSRI rather than an SSRI. Specifically, across studies, there was a modest relative advantage in remission rates for patients switched to the non-SSRI antidepressants compared with those who were switched to a second trial within

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