Patrick M. O'Neil

Randomized Placebo‐Controlled Clinical Trial of Lorcaserin for Weight Loss in Type 2 Diabetes Mellitus: The BLOOM‐DM Study

The BLOOM‐DM (Behavioral Modification and Lorcaserin for Obesity and Overweight Management in Diabetes Mellitus) study evaluated efficacy and safety of lorcaserin for weight loss in patients with type 2 diabetes. Secondary objectives included evaluations of glycemic control, lipids, blood pressure, and quality of life. This 1‐year, randomized, placebo‐controlled trial enrolled 604 patients 1:1:1 to placebo, lorcaserin 10 mg once daily (QD) or lorcaserin 10 mg twice daily (BID). Patients were treated with metformin, a sulfonylurea (SFU) or both; had glycated hemoglobin (HbA1c) 7–10%; were 18–65 years old; and had BMI 27–45 kg/m2. Patients received diet and exercise counseling. Safety monitoring included serial echocardiograms. Mean (± SD) age was 52.7 ± 8.7; 54.2% were women; 60.5% were white, 20.9% were African American, and 13.8% were Hispanic. Mean (± SD) weight was 103.6 ± 17.8 kg; BMI was 36.0 ± 4.5 kg/m2. Most patients (91.7%) took metformin; 50.2% took a SFU. More patients lost ≥5% body weight with lorcaserin BID (37.5%; P < 0.001) or lorcaserin QD (44.7%; P < 0.001) vs. placebo (16.1%; modified intent to treat (MITT)/last observation carried forward (LOCF)). Least square mean (± SEM) weight change was −4.5 ± 0.35% with lorcaserin BID and −5.0 ± 0.5% with lorcaserin QD vs. −1.5 ± 0.36% with placebo (P < 0.001 for each). HbA1c decreased 0.9 ± 0.06 with lorcaserin BID, 1.0 ± 0.09 with lorcaserin QD, and 0.4 ± 0.06 with placebo (P < 0.001 for each); fasting glucose decreased 27.4 ± 2.5 mg/dl, −28.4 ± 3.8 mg/dl, and 11.9 ± 2.5 mg/dl, respectively (P < 0.001 for each). Symptomatic hypoglycemia occurred in 7.4% of patients on lorcaserin BID, 10.5% on lorcaserin QD, and 6.3% on placebo. Common adverse events were headache, back pain, nasopharyngitis, and nausea. Lorcaserin was associated with significant weight loss and improvement in glycemic control in patients with type 2 diabetes.

Clinical Practice as Natural Laboratory for Psychotherapy Research: A Guide to Case-Based Time-Series Analysis.

Both researchers and practitioners need to know more about how laboratory treatment protocols translate to real-world practice settings and how clinical innovations can be systematically tested and communicated to a skeptical scientific community. The single-case time-series study is well suited to opening a productive discourse between practice and laboratory. The appeal of case-based time-series studies, with multiple observations both before and after treatment, is that they enrich our design palette by providing the discipline another way to expand its empirical reach to practice settings and its subject matter to the contingencies of individual change. This article is a users guide to conducting empirically respectable case-based time-series studies in a clinical practice or laboratory setting.

Weight Loss With Naltrexone SR/Bupropion SR Combination Therapy as an Adjunct to Behavior Modification: The COR-BMOD Trial

This 56‐week, randomized, placebo‐controlled trial examined the efficacy and safety of naltrexone plus bupropion as an adjunct to intensive behavior modification (BMOD). A total of 793 participants (BMI = 36.5 ± 4.2 kg/m2) was randomly assigned in a 1:3 ratio to: (i) placebo + BMOD (N = 202); or (ii) naltrexone sustained‐release (SR, 32 mg/day), combined with bupropion SR (360 mg/day) plus BMOD (i.e., NB32 + BMOD; N = 591). Both groups were prescribed an energy‐reduced diet and 28 group BMOD sessions. Co‐primary end points were percentage change in weight and the proportion of participants who lost ≥5% weight at week 56. Efficacy analyses were performed on a modified intent‐to‐treat population (ITT; i.e., participants with ≥1 postbaseline weight while taking study drug (placebo + BMOD, N = 193; NB32 + BMOD, N = 482)). Missing data were replaced with the last observation obtained on study drug. At week 56, weight loss was 5.1 ± 0.6% with placebo + BMOD vs. 9.3 ± 0.4% with NB32 + BMOD (P < 0.001). A completers analysis revealed weight losses of 7.3 ± 0.9% (N = 106) vs. 11.5 ± 0.6% (N = 301), respectively (P < 0.001). A third analysis, which included all randomized participants, yielded losses of 4.9 ± 0.6 vs. 7.8 ± 0.4%, respectively (P < 0.001). Significantly more NB32 + BMOD‐ vs. placebo + BMOD‐treated participants lost ≥5 and ≥10% of initial weight, and the former had significantly greater improvements in markers of cardiometabolic disease risk. NB32 + BMOD was generally well tolerated, although associated with more reports of nausea than placebo + BMOD. The present findings support the efficacy of combined naltrexone/bupropion therapy as an adjunct to intensive BMOD for obesity.

Rational design of a combination medication for the treatment of obesity.

Existing obesity therapies are limited by safety concerns and modest efficacy reflecting a weight loss plateau. Here, we explore combination therapy with bupropion (BUP), a putative stimulator of melanocortin pathways, and an opioid antagonist, naltrexone (NAL), to antagonize an inhibitory feedback loop that limits sustained weight reduction. In vitro electrophysiologic experiments were conducted to determine the extent to which BUP+NAL stimulated hypothalamic pro‐opiomelanocortin (POMC) neurons in mouse brain. A subsequent study further characterized the effect of combination BUP+NAL treatment on food intake in lean and obese mice. Finally, a randomized, blinded, placebo‐controlled trial in obese adult subjects was conducted. Randomization included: BUP (300 mg) + NAL (50 mg), BUP (300 mg) + placebo (P), NAL (50 mg) + P or P+P for up to 24 weeks. BUP+NAL stimulated murine POMC neurons in vitro and caused a greater reduction in acute food intake than either monotherapy, an effect consistent with synergism. Combined BUP+NAL provided sustained weight loss without evidence of an efficacy plateau through 24 weeks of treatment. BUP+NAL completers diverged from NAL+P (P < 0.01) and P+P (P < 0.001) at week 16 and from BUP+P by week 24 (P < 0.05). The combination was also well tolerated. Translational studies indicated that BUP+NAL therapy produced synergistic weight loss which exceeded either BUP or NAL alone. These results supported the hypothesis that NAL, through blockade of β‐endorphin mediated POMC autoinhibition, prevents the classic weight loss plateau observed with monotherapies such as BUP. This novel treatment approach (BUP+NAL) holds promise for the treatment of obesity.

The National Women's Study: relationship of victimization and posttraumatic stress disorder to bulimia nervosa.

OBJECTIVE In recent years there has been increased interest regarding the role of crime victimization in the development and/or maintenance of eating disorders, particularly bulimia nervosa. METHOD To examine the relationship among assault, bulimia nervosa, and binge eating disorder, a national, representative sample of 3,006 women completed structured telephone interviews. RESULTS Lifetime prevalence of completed, forcible rape for respondents with bulimia nervosa was 26.6%, as compared with 11.5% for respondents with binge eating disorder and 13.3% for respondents without bulimia nervosa or binge eating disorder. Compared to respondents without bulimia nervosa or binge eating disorder, aggravated assault history was significantly more prevalent in women with bulimia nervosa (26.8%), as was a lifetime history of posttraumatic stress disorder (36.9%). Characteristics of sexual assault experiences were not associated with dysfunctional eating patterns. Specific types of disordered eating such as compensatory behaviors in bulimia nervosa were associated with higher rates of victimization. CONCLUSIONS In sum, the significantly higher rates of both sexual and aggravated assault among women with bulimia nervosa compared with women without such a diagnosis support the hypothesis that victimization may contribute to the development and/or maintenance of bulimia nervosa.

Night eating syndrome: effects of brief relaxation training on stress, mood, hunger, and eating patterns

BACKGROUND: Night eating syndrome (NES) is characterized by a lack of appetite in the morning, consumption of 50% or more of daily food intake after 6:00 p.m., and difficulty falling and/or staying asleep. It has been associated with stress and with poor results at attempts to lose weight.OBJECTIVE: The purpose of this study was to determine whether a relaxation intervention (Abbreviated Progressive Muscle Relaxation Therapy, APRT) that has been shown to significantly reduce stress levels in normal, healthy adults would also benefit an NES sample.RESEARCH METHODS AND PROCEDURES: A total of 20 adults with NES were randomly assigned to either a relaxation training (APRT) or a Control (quietly sitting for the same amount of time) group, and all subjects attended two laboratory sessions 1 week apart. Pre- and postsession indices of stress, anxiety, relaxation, and salivary cortisol were obtained, as well as Day 1 and Day 8 indices of mood. Food diaries and hunger ratings were also obtained.RESULTS: The results indicated that 20 min of a muscle relaxation exercise significantly reduced stress, anxiety, and salivary cortisol immediately postsession. After practicing these exercises daily for a week, subjects exhibited lowered stress, anxiety, fatigue, anger, and depression on Day 8. APRT was also associated with significantly higher a.m. and lower p.m. ratings of hunger, and a trend of both more breakfast and less night-time eating.DISCUSSION: These data support the role of stress and anxiety in NES and suggest that practicing relaxation may be an important component of treatment for this condition.

Development and validation of the Eating Behavior Inventory

The Eating Behavior Inventory (EBI) is a self-report instrument for assessing behaviors that have been theoretically implicated in weight loss, e.g., self-monitoring of food intake and of weight, refusing offers of food, eating at only one place, shopping from a list, eating in response to emotions. Thirty items were constructed in the form of first-person statements, e.g., “I eat in the middle of the night.” Each item was to be rated with a 5-point scale according to how often it was true for the respondent. Items were scored such that higher scores always reflected more “appropriate” (theoretically facilitative of weight control) eating patterns. Validity of individual items and total score was assessed in four studies. Twenty-six of the original items appeared valid and were retained. The resulting total score demonstrated validity in these studies and in two cross-validational comparisons. Internal consistency as measured by split-half reliability and correlations of item scores with total score was acceptable. One month test-retest reliability of item and total scores was satisfactory. Clinical and research applications of the EBI are discussed.

Changes in Food Cravings during Low-Calorie and Very-Low-Calorie Diets

Objective: This study examined food cravings during a primarily food‐based low‐calorie diet (LCD) and a supplement‐based very‐LCD (VLCD).

Effect of NPY5R antagonist MK-0557 on weight regain after very-low-calorie diet-induced weight loss

Objective: To evaluate whether MK‐0557, a highly selective, orally administered neuropeptide Y Y5 receptor antagonist, could limit weight regain after very‐low‐calorie diet (VLCD)‐induced weight loss.

Weighing the evidence: benefits of regular weight monitoring for weight control.

We address the assertion that weighing obese patients in weight loss programs can be a source of distress and can lead to unfavorable outcomes. Examination of the relevant literature suggests that there is no evidence that weighing by weight loss participants is a cause of negative mood or of body dissatisfaction. Further, there is little evidence that negative mood states or body dissatisfaction lead to a poor outcome in weight loss programs. To the contrary, a number of studies consistently show that more frequent weighing is associated with better weight loss and maintenance. We offer suggestions for dealing with this issue in clinical practice.