Abstract
Background/objectivesProlonged-release (PR) naltrexone 32 mg/bupropion 360 mg (NB) is approved for chronic weight management as an adjunct to reduced-calorie diet and increased physical activity. Central nervous system-active medications have the potential to affect mood; therefore, post hoc analysis of clinical trial data was conducted to evaluate psychiatric adverse events (PAEs) and effects on mood of NB therapy versus placebo.Subjects/methodsData were pooled from 5 prospective, double-blind, randomized, placebo-controlled clinical trials (duration range, 24–56 weeks) of NB in subjects with overweight or obesity. PAEs were collected via AE preferred terms, organized into major subtopics (e.g., anxiety, depression, sleep disorders), and divided into category terms (e.g., anxiety, potential anxiety symptoms). Additionally, the Inventory of Depressive Symptomatology Self Report (IDS-SR; score range 0–84) and the Columbia Classification Algorithm of Suicide Assessment (C-CASA) evaluated treatment-emergent depressive/anxiety symptoms and suicidal behavior/ideation, respectively.ResultsBaseline characteristics and comorbidities were comparable for placebo (n = 1515) and NB (n = 2545). Most common PAEs in the NB group (using category grouping; NB vs placebo) were sleep disorders (12.7 vs 7.9%, P < 0.001), anxiety (5.4 vs 3.3%, P = 0.029), and depression (1.8 vs 2.7%, P = 0.014); PAEs were more frequent during dose escalation and generally mild or moderate. Mean (SD) changes in IDS-SR total score from baseline to endpoint were small in both groups: 0.13 (5.83) for NB and −0.45 (5.65) for placebo. Retrospective AE categorization via C-CASA confirmed no completed suicides, suicide attempts, or preparatory acts toward imminent suicidal behavior.ConclusionsThis large pooled analysis of 5 clinical trials provides additional safety information about the NB PAE profile. Anxiety and sleep disorder-related PAEs were more frequent with NB versus placebo but were mostly mild to moderate and generally occurred early. Depression-related PAEs were less common with NB than placebo, and NB was not associated with suicidal ideation or behavior in this patient population.
Highlights
Excess body weight is a risk factor for many serious illnesses, and minor weight loss may reduce risk
Among individuals with obesity (BMI > 30 kg/ m2) or with type 2 diabetes and overweight, weight loss of 5–10% is associated with clinically relevant improvements in many cardiometabolic risk factors as well as improvement in measures of quality of life, mobility, depression, sexual dysfunction, and urinary stress incontinence [2, 4]
Combined data from phase 3 clinical trials showed that NB therapy was associated with significantly greater weight loss compared with diet and exercise alone (7.0 vs 2.3%; P < 0.001) [9]
Summary
Excess body weight is a risk factor for many serious illnesses, and minor weight loss may reduce risk. Among individuals with obesity (BMI > 30 kg/ m2) or with type 2 diabetes and overweight (body mass index [BMI] ≥ 25 kg/m2), weight loss of 5–10% is associated with clinically relevant improvements in many cardiometabolic risk factors as well as improvement in measures of quality of life, mobility, depression, sexual dysfunction, and urinary stress incontinence [2, 4]. The combination of prolonged-release (PR) naltrexone 32 mg plus PR bupropion 360 mg (NB) is approved worldwide for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity in adults with an initial BMI of ≥30 kg/m2 or ≥27 kg/m2 and ≥1 weight-related comorbidity (e.g., dyslipidemia, controlled hypertension, type 2 diabetes mellitus) [5, 6]. The most common adverse events (AEs) associated with NB in clinical trials were nausea, constipation, and headache, which were generally transient [9,10,11,12,13]
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