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

J Clin Psychiatry. 2001 Apr;62(4):256-60.


Background: Evidence suggests that the newer antidepressant drugs may differ with respect to their effects on body weight, especially during long-term treatment. However, the published data about treatment-emergent weight change with the newer antidepressants are limited. Most reports of unexpected selective serotonin reuptake inhibitor (SSRI)-associated weight gain are anecdotal 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 completed clinical trials comparing the antidepressant nefazodone (N = 523) with 3 SSRIs, fluoxetine, sertraline, and paroxetine (N = 513), as well as 3 trials comparing nefazodone (N = 225) with the tricyclic antidepressant imipramine (N = 224) were analyzed. In all studies, nefazodone was found to be equal 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 varied in duration from 16 to 46 weeks. The analysis included summarizing the number and percentage of patients in each group with a > or = 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 significance, 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). However, 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, significantly more imipramine-treated patients than nefazodone-treated patients 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 difference 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 each group.

Conclusion: SSRIs caused more weight loss during short-term treatment but more weight gain during long-term treatment. These results lend support to the observation that some antidepressants have a greater expected risk of weight gain than others during long-term therapy.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents, Second-Generation / adverse effects
  • Antidepressive Agents, Second-Generation / pharmacology
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Antidepressive Agents, Tricyclic / adverse effects
  • Antidepressive Agents, Tricyclic / pharmacology
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Body Weight / drug effects*
  • Controlled Clinical Trials as Topic
  • Depressive Disorder / drug therapy*
  • Female
  • Humans
  • Imipramine / adverse effects
  • Imipramine / pharmacology
  • Imipramine / therapeutic use*
  • Male
  • Piperazines
  • Serotonin Uptake Inhibitors / adverse effects
  • Serotonin Uptake Inhibitors / pharmacology
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Sex Factors
  • Treatment Outcome
  • Triazoles / adverse effects
  • Triazoles / pharmacology
  • Triazoles / therapeutic use*
  • Weight Gain / drug effects


  • Antidepressive Agents, Second-Generation
  • Antidepressive Agents, Tricyclic
  • Piperazines
  • Serotonin Uptake Inhibitors
  • Triazoles
  • nefazodone
  • Imipramine