Fluoxetine Treatment of Patients With Major Depressive Disorder Who Failed Initial Treatment With Sertraline

Background: This study was conducted to determine if patients with major depressive disorder who had previously failed treatment with one serotonin selective reuptake inhibitor (SSRI) would respond to a different SSRI.

Method: Adult outpatients (N=106) with DSM-III-R major depressive disorder and a history of either intolerance (N=34) or nonresponse (N=72) to treatment with sertraline were treated with fluoxetine (mean dose=37.2 mg/day) in a standardized, open-label, 6-week clinical trial. Outcome was assessed at each visit using the Hamilton Rating Scale for Depression (HAM-D), the Clinical Global Impressions (CGI-Improvement and CGI-Severity) scales, and the Patient’s Global Improvement (PGI) scale.

Results: Ninety-one patients (86%) completed the study. Sixty-seven patients (63%) responded to fluoxetine (i.e., experienced ž50% reduction in HAM-D₂₈ total score at endpoint versus baseline). In addition, clinically and statistically significant improvements were noted on all measures of depressive symptoms and global functioning. There was a nonsignificant trend for patients with a history of less vigorous sertraline trials to respond more favorably to fluoxetine. Fluoxetine therapy was generally well tolerated, and there were only slight differences in adverse events reported by patients who had been intolerant to sertraline versus those who were nonresponders.

Conclusion: These findings indicate that fluoxetine and sertraline, two widely used SSRIs, are not interchangeable. Patients who either have had trouble tolerating or have not responded to sertraline may do well on fluoxetine treatment.