Effects of nefazodone on body weight: A pooled analysis of selective serotonin reuptake inhibitor- and imipramine-controlled trials

Background: Evidence suggests that the newer antidepressant drugs may diffe r with respect to their effects on body weight, especially during long-term treatment. However, the published data about treatment-emergent weight cha nge with the newer antidepressants are limited. Most reports of unexpected selective serotonin reuptake inhibitor (SSRI)-associated weight gain are an ecdotal or from small controlled trials. To determine if differences exist among the newer antidepressants, the authors retrospectively analyzed data from clinical trials comparing nefazodone with SSRIs and with imipramine. Method: Weight change data supplied by Bristol-Myers Squibb from 6 complete d clinical trials comparing the antidepressant nefazodone (N = 523) with 3 SSRIs, fluoxetine, sertraline, and paroxetine (N = 513), as well as 3 trial s comparing nefazodone (N = 225) with the tricyclic antidepressant imiprami ne (N = 224) were analyzed. In all studies, nefazodone was found to be equa l in efficacy to the comparator antidepressants. Studies that included both acute and long-term treatment phases were included in the analysis. Acute phases of the trials lasted either 6 or 8 weeks, and long-term phases varie d in duration from 16 to 46 weeks. The analysis included summarizing the nu mber and percentage of patients in each group with a greater than or equal to 7% change in body weight from baseline at any point in the long-term and acute phases, at endpoint, and at week 16 of the long-term phases. Results: Using 7% or greater weight change as the measure of clinical signi ficance, 4.3% of SSRI-treated patients had lost weight at any point in the acute phase versus 1.7% of those treated with nefazodone (p = .017). Howeve r, at any point during the long-term phase, significantly more SSRI-treated patients than nefazodone-treated patients showed a significant increase in body weight (17.9% vs. 8.3%; p = .003). At any point in the acute phase, s ignificantly more imipramine-treated patients than nefazodone-treated patie nts had a 7% or greater increase in body weight (4.9% vs. 0.9%; p = .027), and for the long-term phase the comparison yielded 24.5% versus 9.5%. The d ifference during the long-term phase was statistically significant in women (p = .017), but not in men (p = .078) due to the small numbers of men in e ach group. Conclusion: SSRIs caused more weight loss during short-term treatment but m ore weight gain during longterm treatment. These results lend support to th e observation that some antidepressants have a greater expected risk of wei ght gain than others during long-term therapy.