[Weight gain during treatment with antipsychotics: clinical relevance, pathophysiology, and therapeutical strategies]

[Article in German]

Himmerich H, Schuld A, Pollmacher T.

Max-Planck-Institut fur Psychiatrie, Munchen.

The clinical relevance of drug-induced weight changes is due to the development of obesity, increased rates of morbidity and reduced treatment compliance, even if the psychopharmacological treatment is effective. Possible underlying causes of weight gain in patients treated with antipsychotic drugs are the psychiatric disorder itself, and changes in the neurotransmitter, cytokine and hormone systems. Clinical management of psychopharmacologically induced weight gain includes diet, behavioral and pharmacological therapy. Possible add-on strategies - based on case reports and small studies - are ephedrine, sibutramine, orlistat, topiramate, nizatidine, naltrexone, metformin, amantadine, and reboxetine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15586316&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Effects of different weight loss protocols on serum leptin levels in obese females.

Ozcelik O, Dogan H, Celik H, Ayar A, Serhatlioglu S, Kelestimur H.

Firat University Faculty of Medicine, Department of Physiology; Elazig, Turkey. oozcelik firat.edu.tr.

We comparatively investigated the effects of different weight loss protocols on leptin levels in obese females with the aim of addressing the leptin resistance which have been determined to be an aggravating factor in obesity. Twenty-four obese females enrolled to one of the three 12 week weight loss protocols: orlistat-induced weight loss (OWL, n=8), exercise-induced weight loss (EWL, n=8) and orlistat plus exercise-induced weight loss (OEWL, n=8). Serum leptin levels were measured in duplicate by radioimmunoassay. There were significant reductions in body weight and fat mass after the 12 week period in all groups: -11.4+/-0.5 kg (P=0.01) and -9.8+/-0.5 kg (OEWL), -8.3+/-0.8 kg (P=0.01) and -5.7+/-0.9 kg (OWL), -8.9+/-1.2 kg (P=0.01) and -7.4+/-1.2 kg (EWL), respectively. Serum leptin levels were also decreased markedly in all groups: -59.2% (OEWL, P=0.01), -37.8% (OWL, P=0.01) and -48.6% (EWL, P=0.01). In addition, there were marked decreases in leptin levels for each kilogram of fat mass after the 12 week period: -48.2+/-7.2% (OEWL P=0.01), -27.8+/-4.8% (OWL, P=0.01) and -39.3+/-4.3% (EWL, P=0.01). Decreases in serum leptin levels expressed per kilogram of fat mass were significantly higher in OEWL group compared to OWL (P= 0.03). Consequently, in obesity treatment, an exercise training program in adjunct to pharmacotherapy provides higher amount of weight reduction and fat mass loss, and importantly seem to have further beneficial effects on leptin resistance, as indicated by decreases in leptin levels expressed per kilogram of fat mass.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15588160&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Efficacy of sibutramine, orlistat and combination therapy on short-term weight management in obese patients.

Kaya A, Aydin N, Topsever P, Filiz M, Ozturk A, Dagar A, Kilinc E, Ekmekcioglu C.

Haydarpasa Numune Training and Research Hospital, 5th Department of Internal Medicine, Istanbul, Turkey.

OBJECTIVES: To compare changes in anthropometric measures [body mass index (BMI), body weight] of obese patients treated with diet and exercise alone or additionally sibutramine, orlistat or the combination of both drugs, respectively. To describe encountered adverse effects. METHODS: Short-term (12 weeks), randomized, open-labeled trial. A total of 86 patients (18.6% male, age 41.1 +/- 8.7 years, BMI: 36.11 +/- 4.34 kg/m(2)) were randomized to (1) sibutramine group (10 mg/d, n = 22), or (2) orlistat group (3 x 120 mg/d, n = 25), or (3) combination group (10 mg sibutramine/d + 3 x 120 mg orlistat/d, n = 20), or (4) diet group (n = 19). The primary outcome parameter was a decrease in BMI. Additionally patient-reported adverse effects were reported. RESULTS: The four interventional groups displayed decreases in BMI as follows: (1) -4.41 +/- 1.26 kg/m(2); (2) -3.64 +/- 0.97 kg/m(2); (3) -5.12 +/- 1.44 kg/m(2) and (4) -2.52 +/- 1.36 kg/m(2); with the diet group showing the significantly lowest decrease in BMI compared to the orlistat (P = 0.004), sibutramine (P < 0.001) or the combination groups (P < 0.001), respectively. Decreases in BMI did not statistically differed between the sibutramine group and the combination therapy group (P = 0.072). However, both treatment groups were significantly more efficient in decreasing BMI than the orlistat group (P < 0.001). In addition to well-known side effects, such as gastrointestinal disturbances, headache and dry mouth, newly described adverse effects were self-reported hypermenorrhea (13.6%, n = 3) with sibutramine and forgetfulness with orlistat (24%, n = 6). CONCLUSION: In our study pharmacotherapy showed significant better results in the short-term management of obesity than dietary regimens alone. Sibutramine and sibutramine in combination with orlistat seemed to be equally effective in terms of weight reduction compared to orlistat monotherapy. Attention should be paid to the possibility of adverse effects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15589067&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Orlistat for obesity: benefits beyond weight loss.

Hsieh CJ, Wang PW, Liu RT, Tung SC, Chien WY, Chen JF, Chen CH, Kuo MC, Hu YH.

Division of Edocrinology and Metabolosm, Department of Internal Medicine, Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung Hsien 83305, Taiwan. c2607c ms56.hinet.net

Orlistat lowers lipids and improves insulin sensitivity, but its effect on other metabolic syndrome related parameters is not known. To assess its influence on adiponectin, high sensitive C-reactive protein (hs-CRP) and other metabolic syndrome related parameters, this study enrolled 106 participants in a weight-reduction program and categorized them into a group of 51 who had been treated with orlistat 360 mg/day for one year and a group of 55 age and sex and body mass index (BMI) matched controls. The orlistat group had greater changes in BMI, % body fat (% BF), waist circumference, and insulin resistance, hs-CRP, leptin and adiponectin levels after one year on the program than the controls. After adjusting for % BF and waist circumference, change of serum leptin and adiponectin levels remained significantly different. It was found that orlistat could effectively manage obesity related co-morbidities, especially insulin resistance and atherosclerosis risk. It decreases leptin and increases adiponectin independent of % BF and waist circumference. Therefore, orlistat appears to have anti-diabetic and anti-atherogenic properties and may help prevent metabolic syndrome in the overweight people.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15620437&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)


Reduction of body weight and co-morbidities by orlistat: The XXL--Primary Health Care Trial.

Wirth A.

Teutoburger-Wald-Klinik, D-49214 Bad Rothenfelde, Germany. alfred.wirth lva-hannover.de

AIM: The aim of this postmarketing surveillance (PMS) study was to investigate the effect of an orlistat therapy under the everyday conditions of our health care system. METHODS: 11 131 women and 4418 men from Germany [mean age 48 years, mean body mass index (BMI) 34.7 kg/m(2) and mean duration of obesity 13.7 years] were included. The patients were predominantly cared for by general practitioners. Four fifths of the patients reported having obesity-associated co-morbidities. All patients were advised to take orlistat 120 mg three times daily. RESULTS: After a mean treatment duration of 7.1 months, both women and men lost 10.7% of their baseline weight (87% lost > 5% weight and 51% lost > 10% weight). All cardiovascular risk factors improved markedly, and the intake of concomitant medications was either reduced or discontinued. Compared with baseline, 65% of the patients assessed their general state of health to have improved. For more than 90% of their patients, physicians described the success of the treatment as satisfactory, and most patients (62%) were willing to continue with the treatment. CONCLUSIONS: The results obtained in this naturalistic PMS study were comparable with the results of randomised and placebo-controlled studies, which were performed predominantly in special care centres. Therefore, without any risk of adversely affecting the quality of treatment provided, the treatment of obese patients with orlistat may be transferred to general practitioners.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15642072&dopt=Abstract orlistat Xenical online refs
xenical (orlistat)