Weight changes in obese adults 6-months after discontinuation of double-blind zonisamide or placebo treatment.

We evaluated weight changes in obese patients at 6-months after they ended participation in a 12-month randomised controlled trial in which they received daily placebo, zonisamide 200 mg or zonisamide 400 mg, in addition to lifestyle counselling. Of the originally randomised 225 patients, 218 completed month-12 when study interventions were discontinued. For the 154 patients who returned for 6-month follow-up off-treatment, weight changes between month-12 and month-18 for placebo (n = 53), zonisamide 200 mg (n = 49) and zonisamide 400 mg groups (n = 52) were 0.5 kg [95% confidence interval (CI), -0.8 to 1.8; 0.7%], 1.5 kg (0.2-2.8; 1.6%; p = 0.26 vs. placebo) and 2.4 kg (1.1-3.7; 2.6%; p = 0.04 vs. placebo), respectively. Our results suggest that although zonisamide 400 mg daily for 12-months resulted in greater weight loss than with placebo, weight regain after discontinuation of interventions was greater in the zonisamide 400 mg group than placebo group.

Phentermine/topiramate for weight reduction and treatment of adverse metabolic consequences in obesity.

Phentermine hydrochloride is a noradrenergic sympathetic amine approved for decades by the U.S. Food and Drug Administration (FDA) at doses as high as 37.5 mg/day for the short-term treatment of obesity. Topiramate is a sulfamate-substituted monosaccharide marketed since 1996, and approved by the FDA for seizure disorders at doses up to 400 mg/day and for the prevention of migraine headaches at doses up to 100 mg/day. Clinical trial data suggest topiramate promotes weight loss. The prescribing information of neither agent describes adverse drug interactions with the other. The controlled-release formulation of phentermine and topiramate at low, medium and full doses (with full dose containing 15 mg of phentermine hydrochloride and 92 mg of topiramate) promotes weight reduction, with clinical trial data supporting improvement in adiposopathic consequences leading to metabolic diseases. Reported adverse events with this combination agent are as expected, based upon knowledge of the individual components.

Atomoxetine for weight reduction in obese women: a preliminary randomised controlled trial.

BACKGROUND AND OBJECTIVE: Atomoxetine is a potent central norepinephrine uptake inhibitor, currently marketed for treatment of attention-deficit/hyperactivity disorder (ADHD). With the understanding that noradrenergic agents could be useful in assisting obese individuals to lose weight, we conducted this preliminary study to evaluate short-term efficacy and safety of atomoxetine in obese adults. DESIGN: At 12-week randomised, double-blind, placebo-controlled trial, conducted at Duke University Medical Centre, USA, from May 2004 to December 2004. PARTICIPANTS: A total of 30 obese women (mean (s.e.) body mass index of 36.1 (0.6) kg/m2). INTERVENTIONS: Participants were randomly assigned to receive atomoxetine (n=15) or placebo (n=15). All participants were advised to follow a balanced hypocaloric diet (500 kcal/day deficit). Atomoxetine therapy was started at 25 mg/day orally, with gradual increase to 100 mg/day over 1 week. Placebo dosing was identical. MEASUREMENTS: Body weight in kilograms was the primary outcome measure. Other measurements included waist circumference, blood pressure and heart rate, fasting plasma glucose and lipids, and depressive symptoms. RESULTS: Last-observation-carried-forward analysis of the available data for participants who had completed at least one post-randomisation assessment, demonstrated that the atomoxetine group (n=12) lost more body weight over the 12-week period than the placebo (n=14) group (mean (s.e.) -3.6 (1.0) kg (-3.7% loss) vs 0.1 (0.4) kg (0.2% gain); F (4,96)=11.9; P<0.0001). Three participants in the atomoxetine group and none in the placebo group lost >or=5% weight. Side effects were minimal. CONCLUSION: Atomoxetine demonstrated modest short-term weight loss efficacy relative to placebo in this preliminary study of obese women.

Bupropion for weight loss: an investigation of efficacy and tolerability in overweight and obese women.

OBJECTIVE: On the basis of the clinical observations that bupropion facilitated weight loss, we investigated the efficacy and tolerability of this drug in overweight and obese adult women. RESEARCH METHODS AND PROCEDURES: A total of 50 overweight and obese (body mass index: 28.0 to 52.6 kg/m(2)) women were included. The core component of the study was a randomized, double-blind, placebo-controlled comparison for 8 weeks. Bupropion or placebo was started at 100 mg/d with gradual dose increase to a maximum of 200 mg twice daily. All subjects were prescribed a 1600 kcal/d balanced diet and compliance was monitored with food diaries. Responders continued the same treatment in a double-blind manner for an additional 16 weeks to a total of 24 weeks. There was additional single-blind follow-up treatment for a total of 2 years. RESULTS: Subjects receiving bupropion achieved greater mean weight loss (last-observation-carried-forward analysis) over the first 8 weeks of the study (p = 0.0001): 4.9% +/- 3.4% (n = 25) for bupropion treatment compared with 1.3% +/- 2.4% (n = 25) for placebo treatment. For those who completed the 8 weeks, the comparison was 6.2% +/- 3.1% (n = 18) vs. 1.6% +/- 2.9% (n = 13), respectively(p = 0.0002), with 12 of 18 of the bupropion subjects (67%) losing over 5% of baseline body weight compared with 2 of 13 in the placebo group (15%; p = 0.0094). In the continuation phase, 14 bupropion responders who completed 24 weeks achieved weight loss of 12.9% +/- 5.6% with fat accounting for 73.5% +/- 3.7% of the weight lost and no change in bone mineral density as assessed by DXA. Bupropion was generally well-tolerated in this sample. DISCUSSION: Bupropion was more effective than placebo in achieving weight loss at 8 weeks in overweight and obese adult women in this preliminary study. Initial responders to bupropion benefited further in the continuation phase.

Central nervous system serotonin function and cardiovascular responses to stress.

OBJECTIVE: The objective of this study was to evaluate the impact of indices of central nervous system (CNS) serotonin function on cardiovascular reactivity to mental stress. METHODS: Lumbar puncture was performed on 54 healthy volunteers to obtain cerebrospinal fluid (CSF) for determination of 5-hydroxyindoleacetic acid (5HIAA) levels. Genotypes were determined with respect to a functional polymorphism of the serotonin transporter gene promoter region (5HTTLPR). Subjects then underwent mental stress testing. RESULTS: Persons with one or two long (l) 5HTTLPR alleles had CSF levels of the major serotonin metabolite, 5HIAA, that were 50% higher than those of persons with the s/s 5HTTLPR genotype. Persons with one or two l alleles or higher CSF 5HIAA levels also exhibited greater blood pressure and heart rate responses to a mental stress protocol. CONCLUSIONS: These findings suggest the 5HTTLPR polymorphism affects CNS serotonin function, and they are consistent with the general hypothesis that CNS serotonin function is involved in the regulation of potentially health-damaging biobehavioral characteristics. In particular, the l allele could contribute, through its association with increased cardiovascular reactivity to stress, to increased risk of cardiovascular disease.

Psychoneuroendocrinology and brain imaging in depression.

In the past three decades, psychoneuroendocrinologic investigations have generated a great volume of information, particularly in the field of affective disorders, which has formed the basis for designing studies with newer tools such as anatomic and functional imaging. In this article, the authors focus on endocrine imaging in psychiatry and attempt to relate morphometric findings to physiologic neuroendocrine dysfunction in depression.