Bupropion SR vs. Placebo for Weight Loss in Obese Patients with Depressive Symptoms

Abstract

Objective: This randomized, double‐blind, placebocontrolled study evaluated the efficacy and tolerability of bupropion sustained‐release (bupropion SR) in reducing weight and depressive symptoms in obese adults. Research Methods and Procedures: Obese adults (body mass index, 30 to 44 kg/m2) not currently meeting criteria for major depression but with depressive symptoms (Beck Depression Inventory score 10–30) received bupropion SR 300 mg/d or placebo for 26 weeks with a 500 kcal/d‐deficit diet. Patients who lost <5% of baseline weight at week 12 had bupropion SR dosage or placebo increased to 400 mg/d in a blinded fashion. Results: The bupropion SR group (n = 193) lost an average of 4.4 kg (4.6% of baseline weight) vs. 1.7 kg (1.8% of baseline weight) on placebo (n = 191, p < 0.001, last‐observation‐carried‐forward analysis). More patients in the bupropion SR group than in the placebo group (40% vs. 16% of intent‐to‐treat sample, 50% vs. 28% of completers, respectively) lost at least 5% of baseline weight (p < 0.05 at week 4, p < 0.001 at weeks 6 to 26). The percentage of patients reporting ≥50% decrease in depressive symptoms did not differ between groups, but depressive symptoms improved more with bupropion SR than with placebo among patients with a history of major depression (p < 0.05, weeks 4 to 26). In the sample as a whole, improvement in depressive symptoms was related to weight loss of ≥5% regardless of treatment (p < 0.0001). Bupropion SR was well‐tolerated. Discussion: Bupropion SR in combination with a 500 kcal/d‐deficit diet facilitated weight loss. Weight loss of ≥5% may improve mood in obese patients with depressive symptoms.

Inhibition of Dopamine and Norepinephrine Reuptake Produces Additive Effects on Energy Balance in Lean and Obese Mice

“…However, these changes do not appear to reduce the hypophagic effects of catecholamine reuptake inhibitorsFour results indicate that BUP, GBR, and NIS all cause dose-dependent hypophagia in obese mice. These findings are supported by the efficacy of BUP in reducing body weight in obese humans (Gadde et al, 2001;Anderson et al, 2002;Jain et al, 2002) and validate the need for further research on the effects of catecholamine reuptake inhibitors on energy balance in both lean and obese animal models.…”

“…BUP has also recently been demonstrated to produce a significant 5-8% weight loss in clinical trials with obese patients (Gadde et al, 2001;Anderson et al, 2002;Jain et al, 2002); however, the mechanism of BUP-induced weight loss is unknown.…”

Randomized Controlled Trials of the D1/D5 Antagonist Ecopipam for Weight Loss in Obese Subjects

“…Larger weight losses after Lap-Band surgery are associated with greater improvements in Beck Depression Inventory scores. If weight loss typically results in improvements in mood across methods of weight loss (37,38), a treatment that results in sustained weight loss would be expected to improve instead of worsen the mood of the participants. Previous human studies of ecopipam in cocaine-abusing patients did not report any psychiatric adverse effects including depression or suicidality (22,23,39); however, these studies were all of short duration and do not offer sufficient assurance that depression may not occur with the more extended treatment that would be required to treat obesity.…”

Psychological Functioning of Obese Individuals

“…79 These benefits appear to result whether the weight was lost with diet and exercise, 80 verylow-calorie diets, 81 pharmacotherapy, 82 or bariatric surgery.…”