Naltrexone/Bupropion combination therapy in overweight or obese patients with major depressive disorder: results of a pilot study

Abstract

Objective: To evaluate the effect of 32-mg/d naltrexone sustained release and 360-mg/d bupropion sustained release (NB32) in overweight and obese patients with major depressive disorder (MDD).

Method: Twenty-five female patients with a DSM-IV diagnosis of MDD, an Inventory of Depressive Symptomatology-Self-Report score > 26, and a body mass index ≥ 27 and ≤ 43 kg/m(2) received up to 24 weeks of open-label treatment with NB32 with dietary and behavioral counseling (data collection: March 2008-July 2009). The primary endpoint was change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score at 12 weeks; secondary endpoints included MADRS total score at week 24, change in weight, and Clinical Global Impressions-Improvement scale responder status (CGI-I score ≤ 2) at weeks 12 and 24 (modified intent-to-treat [mITT]: patients with ≥ 1 postbaseline MADRS total score on study drug; N = 23).

Results: MADRS scores showed significant reductions at weeks 12 and 24 (mITT-last observation carried forward [LOCF]: -13.1 ± 7.1 and -15.3 ± 8.1, respectively, P < .001 vs baseline for all). Mean ± SD weight loss was -4.0% ± 4.6% (mITT-LOCF) and -6.1% ± 4.7% (observed cases) at week 12 and -5.3% ± 6.5% (mITT-LOCF) and -9.2% ± 6.2% (observed cases) at week 24 (P < .001 vs baseline for all). By week 24, 95% of patients (mITT-LOCF) were responders (CGI-I score ≤ 2) and 70% were in remission (CGI-I score = 1). The safety/tolerability profile of NB32 was consistent with its individual components; the most common adverse events were nausea, constipation, headache, and insomnia, with no serious adverse events attributed to NB32.

Conclusion: Twenty-four weeks of open-label NB32 therapy with dietary and behavioral counseling was associated with improvement in depressive symptoms and reduced body weight in overweight/obese women with MDD.

Trial registration: ClinicalTrials.gov Identifier: NCT00624858.

Figures

Figure 1

Depression and Weight Loss Outcomesa,b aObserved cases; data represent mean ± SD. bP value is based on a t test for a within-group change from baseline. *P < .001. **P <.01. Abbreviation: NB32 = naltrexone sustained-release 32 mg/bupropion sustained-release 360 mg.

Figure 2

Improvement in Selected Eating and Food Craving Items on the Control of Eating Questionnaire After 12 and 24 Weeks of Treatment With NB32a,b aModified intent-to-treat–last observation carried forward; data represent mean ± SD. Responses reflect experiences during the previous 7 days. bP values are based on a t test that assesses if mean change from baseline is significantly different from zero. *P < .001. **P < .01. Abbreviation: NB32 = naltrexone sustained-release 32 mg/bupropion sustained-release 360 mg.

Figure 3

Improvement in Selected Control of Eating Questionnaire Items Relating to Mood After 12 and 24 Weeks of Treatment With NB32a,b aModified intent-to-treat–last observation carried forward; data represent mean ± SD. Responses reflect experiences during the previous 7 days. bP values are based on a t test that assesses if mean change from baseline is significantly different from zero. *P < .001, **P = .03. Abbreviation: NB32 = naltrexone sustained-release 32 mg/bupropion sustained-release 360 mg.