Background: Evidence suggests that the newerantidepressant drugs may differ with respect to their effects onbody weight, especially during long-term treatment. However, thepublished data about treatment-emergent weight change with thenewer antidepressants are limited. Most reports of unexpectedselective serotonin reuptake inhibitor (SSRI)-associated weightgain are anecdotal or from small controlled trials. To determineif differences exist among the newer antidepressants, the authorsretrospectively analyzed data from clinical trials comparingnefazodone with SSRIs and with imipramine.
Method: Weight change data supplied byBristol-Myers Squibb from 6 completed clinical trials comparingthe antidepressant nefazodone (N = 523) with 3 SSRIs, fluoxetine,sertraline, and paroxetine (N = 513), as well as 3 trialscomparing nefazodone (N = 225) with the tricyclic antidepressantimipramine (N = 224) were analyzed. In all studies, nefazodonewas found to be equal in efficacy to the comparatorantidepressants. Studies that included both acute and long-termtreatment phases were included in the analysis. Acute phases ofthe trials lasted either 6 or 8 weeks, and long-term phasesvaried in duration from 16 to 46 weeks. The analysis includedsummarizing the number and percentage of patients in each groupwith a >= 7% change in body weight from baseline at any pointin the long-term and acute phases, at endpoint, and at week 16 ofthe long-term phases.
Results: Using 7% or greater weight change asthe measure of clinical significance, 4.3% of SSRI-treatedpatients had lost weight at any point in the acute phase versus1.7% of those treated with nefazodone (p = .017). However, at anypoint during the long-term phase, significantly more SSRI-treatedpatients than nefazodone-treated patients showed a significantincrease in body weight (17.9% vs. 8.3%; p = .003). At any pointin the acute phase, significantly more imipramine-treatedpatients than nefazodone-treated patients had a 7% or greaterincrease in body weight (4.9% vs. 0.9%; p = .027), and for thelong-term phase the comparison yielded 24.5% versus 9.5%. Thedifference during the long-term phase was statisticallysignificant in women (p = .017), but not in men (p = .078) due tothe small numbers of men in each group.
Conclusion: SSRIs caused more weight loss duringshort-term treatment but more weight gain during long-termtreatment. These results lend support to the observation thatsome antidepressants have a greater expected risk of weight gainthan others during long-term therapy.