Table III.

Non-randomized studies of efficacy of naltrexone for weight loss in adult patients

Author (year), journal, title	Quality	No. of patients	Inclusion criteria	Intervention comparator	Active N Age % female	Primary outcome	Efficacy assessment Effect size − ES (95% CI)	Safety
Mason AE et al. (2015) Journal: Eating Behaviors Title: Putting the brakes on the “drive to eat”: Pilot effects of naltrexone and reward-based eating on food cravings among obese women	IF: 2.23 (2015) Category of evidence: IIa Jadad: 0/5	N = 44	Female sex, overweight status (30 ≤ body mass index [BMI] ≤ 40 kg/m2), and age of 20–45 years	Placebo 50 mg naltrexone 25 mg naltrexone 1:00 PM (after lunch) on days 1 (placebo), 4 (25 mg naltrexone), 7 (placebo), 10 (50 mg naltrexone), and 4 weeks after day 10 (50 mg naltrexone)	N = 44 Age: 32.7 ±7.6 Female: 100%	Reward-Based Eating Drive (RED) scale	Significant positive associations between RED and craving intensity on each placebo day (p = 0.017, p = 0.034) and non-significant associations on naltrexone days	Adverse event: nausea
						Food-craving intensity	Placebo, 25 mg, and 50 mg doses did not differentially impact craving intensity Revealed a dose RED interaction such that the association between RED and craving intensity differed between the placebo and 50 mg doses [b = –0.06, SE(b) = 0.02, 95% CI: –0.099, –0.012, p = 0.012] The association between RED and craving intensity did not significantly differ between the placebo and 25 mg doses
Daubenmier J et al. (2014) Journal: Appetite Title: A new biomarker of hedonic eating? A preliminary investigation of cortisol and nausea responses to acute opioid blockade	IF: 0.34 (2014) Category of evidence: IIa Jadad: 0/5	N = 33	Female with BMI between 25 and 40 kg/m2; pre-menopausal; no history of diabetes or cardiovascular disease, or active endocrinologic disorder	Naltrexone (50 mg)	N = 33 Age = 40.9 ±8.0 Female = 100%	Cortisol responses to naltrexone	Cortisol decreased by 3.6 ±2.2 nmol/l between 1 PM and 4 PM on the control days (95% CI: 2.8–4.4; t(32) = 9.4, p < 0.001) and increased on the naltrexone day by 8.0 ±17.4 nmol/l (95% CI: 1.5–14.5; t(29) = 2.53, p = 0.02) between 1 PM and 4 PM	Adverse event: nausea
						Nausea responses to naltrexone	The mean level of nausea severity was 1.23 ±1.3
Wilcox CS et al. (2010) Journal: Addict Behav Title: An open-label study of naltrexone and bupropion combination therapy for smoking cessation in overweight and obese subjects	IF: 3.13 (2010) Category of evidence: IIb Jadad: 0/5	N = 30	18 to 65 years of age; BMI ≥ 27 and ≤ 45 kg/m2; smoking an average of ≥ 10 cigarettes/day in the preceding year with < 3 months of total abstinence; an expired CO concentration > 10 ppm; self-reported motivation to stop smoking of ≥ 7 on a scale of 1 to 10, with 10 defined as highest motivation; at least moderate concern about gaining weight after quitting smoking (on a scale of 1–10, where a score of 5 indicates moderate weight gain is defined as at least 10 lbs); systolic blood pressure ≤ 140 mmHg; diastolic blood pressure ≤ 90 mmHg (a stable regimen of antihypertensive medications was allowed)	Naltrexone SR (8 mg)/bupropion SR (90 mg), with final daily doses of 32 mg/day naltrexone SR and 360 mg/day bupropion SR	N = 30 Age = 42.5 ±11.3 Female = 53.3%	As a secondary endpoint: percent change from baseline in body weight	Body weight did not significantly change in the entire population (0.4 ±3.0%, p = 0.555), but increased slightly in continuous abstainers (1.3 ±3.3%, p = 0.148)	Treatment-emergent adverse events with frequency ≥ 10% The combination of naltrexone and bupropion was generally well tolerated; the most common adverse events were nausea, insomnia, and constipation