Changes in Symptoms of Depression with Weight Loss: Results of a Randomized Trial

A recent meta-analysis concluded that the weight loss medication rimonabant was associated with an increased risk of adverse psychiatric events (1). In June 2007 a U.S. Food and Drug Administration panel expressed concern about the drug’s association with suicidal ideation and behavior (2); and in November 2008 rimonabant’s manufacturer decided to discontinue development of the medication. The mechanisms by which rimonabant may increase the risk of adverse emotional responses are not well understood. Moreover, studies to date have not isolated the potentially separate effects on mood of medication versus weight loss. Numerous studies reported that weight loss, achieved with diet and exercise (i.e., lifestyle modification), was associated with mean improvements in symptoms of depression, when mood was measured before and after weight reduction using standardized measures such as the Beck Depression Inventory (BDI) (3-7). Similarly positive findings were reported when weight loss was induced by lifestyle modification in combination with medications including sibutramine (8-11), orlistat (11, 12), and fenfluramine (13, 14). None of these studies, however, reported changes in mood at more frequent intervals. Furthermore, none described potentially adverse changes in psychosocial functioning in individual participants, which may have been overlooked by examining only mean values. The present study investigated changes in symptoms of depression in obese individuals who participated in a 1-year randomized weight loss trial, described previously (15), which compared the efficacy of lifestyle modification alone, sibutramine alone, and the combination of the two approaches. Mood was assessed seven times during the year using the BDI-II (16), which includes an item on suicidal ideation. The study provided an opportunity to determine whether different weight-loss approaches (i.e. lifestyle modification versus sibutramine) are associated with differential changes in mood and whether some participants experience negative emotional responses to weight loss that are not captured by traditional before- and after-treatment assessments.