A double-blind comparison of nefazodone and fluoxetine in the treatment of depressed outpatients

Background Nefazodone is a recently released antidepressant that has shown similar efficacy in clinical trials when compared to tricyclic antidepressants and to some serotonin selective reuptake inhibitors (SSRI'S). It has also demonstrated to be better tolerated than tricyclics and with an equivalent tolerance with respect to SSRI'S. However comparisons with fluoxetine have not been reported. Being fluoxetine a worldwide highly prescribed antidepressant, a comparative trial of both drugs would be of interest. Method A total of 74 outpatients with a major depressive episode (DSM-III-R) entered into an 8-week trial to compare the efficacy and tolerance of nefazodone and fluoxetine in a double-blind, randomized parallel group design. Evaluations were performed at weekly intervals using the Hamilton scales for depression and anxiety (HAM-D and HAM-A), as well as the Clinical Global Impression (CGI) and Patient Global Assessment (PGA) scales to compare efficacy. Tolerance and safety were compared using reports of adverse events. Results analyses were performed both on the Last Observation Carried Forward (LOCF) and visitwise data sets, with an analysis of Variance (ANOVA) model to test for differences between treatments from baseline and within the different study weeks. Results Thirty seven patients received fluoxetine (mean dose 24.0 mgs/day), and 37 received nefazodone (mean dose 400.0 mgs/day). However one patient in the nefazodone group did not have at least one eficacy evaluation during treatment and was excluded from the analysis. Demographic and clinical characteristics did not differ between the groups. At the end of week 8, the 17-item HAM-D total score (LOCF data set) mean change was -12.4 for fluoxetine and -12.3 for nefazodone, showing a comparable antidepressant response. No differences between groups were also observed when comparing several individual depressive items, as well as the remaining scales. Anxiety symptoms were reduced comparatively according to the mean change from baseline in the total HAM-A scores (-10.0 in both groups). In general both drugs were well tolerated generating moderate side-effects tha did not interfere with treatment outcome. Safety assessment revealed no evidence that nefazodone administration resultad in any medically serious adverse events or in organic toxicity based on physical examination findings and significant abnormal laboratory values. Conclusions The results of the study indicate that both nefazodone and fluoxetine are of equivalent efficacy for treating moderate to severe major depression. Nefazodone was found to be safe and well tolerated, without any important differences with respect to fluoxetine. Further studies are needed to characterize the efficacy of nefazodone in other forms of depression and also to evaluate its efficacy and effects over longer periods of treatment.