# Treatment of SSRI-Resistant Depression: Use of non-SSRI medications



## David Baxter PhD (Oct 11, 2007)

Treatment of SSRI-Resistant Depression: A Meta-Analysis Comparing Within- Versus Across-Class Switches
George I. Papakostasa, Maurizio Favaa, Michael E. Thasebc
3 May 2007

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.

_*Admin Summary*
Patients with major depression who do not respond to SSRI medication may do better by switching to one of the SNRI or other non-SSRI antidepressants than trying a different SSRI._


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