title: Treatment of SSRI-resistant depression: a meta-analysis comparing within- versus across-class switches.
abstract: 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.
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. gpapakostas@partners.org
authors.forename: George I
authors.initials: GI
authors.lastname: Papakostas
authors.forename: Maurizio
authors.initials: M
authors.lastname: Fava
authors.forename: Michael E
authors.initials: ME
authors.lastname: Thase
mesh_terms: D016642:Bupropion / Q000627:therapeutic use; D003511:Cyclohexanols / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004351:Drug Resistance; D006801:Humans; D008803:Mianserin / Q000031:analogs & derivatives / Q000627:therapeutic use; D000078785:Mirtazapine; D016032:Randomized Controlled Trials as Topic; D017367:Selective Serotonin Reuptake Inhibitors / Q000145:classification* / Q000627:therapeutic use*; D000069470:Venlafaxine Hydrochloride
chemical_list: D016642:Bupropion; D003511:Cyclohexanols; D008803:Mianserin; D000078785:Mirtazapine; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride