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Erschienen in: Drug Safety 4/2006

01.04.2006 | Review Article

Safety of Drug Therapies Used for Weight Loss and Treatment of Obesity

verfasst von: Dr Lisa L. Ioannides-Demos, Joseph Proietto, Andrew M. Tonkin, John J. McNeil

Erschienen in: Drug Safety | Ausgabe 4/2006

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Abstract

Some of the medications used for weight loss in the management of obesity have been associated with unacceptable morbidity and mortality. Safety concerns have led to the withdrawal of aminorex, followed by the fenfluramines in 1997, and phenylpropanolamine (norephedrine) in 2000. Aminorex was associated with an increased prevalence of primary pulmonary hypertension (PPH), fenfluramines with an increased prevalence of PPH and valvulopathy, and phenylpropanolamine with an increased risk of haemorrhagic stroke.
Several studies have investigated the safety of the fenfluramines, yet the benefit-risk profile has not been conclusively quantified. This is due to several deficiencies in the published studies, including a lack of data on the baseline prevalences of comorbid conditions in obese subjects, and potential confounders and biases in the study designs. Although several studies and systematic reviews support an increased risk of PPH and valvulopathy in patients who have taken fenfluramines, without knowledge of the background prevalence it is not possible to determine if the exposure preceded the outcome. The population at higher risk of these adverse effects includes those taking higher doses or with a longer duration of exposure to fenfluramines and those with pre-existing cardiac disease or a genetic predisposition. Patients exposed to fenfluramines continue to be monitored, with some follow-up studies indicating no overall worsening in valvulopathy over time.
There are limited efficacy and safety data for amfepramone (diethylpropion) and phentermine and their approval for the management of obesity is limited to short-term use. Orlistat and sibutramine are the only currently approved medications for long-term management of obesity. Although the benefit-risk profiles of sibutramine and orlistat appear positive, sibutramine continues to be monitored because of long-term safety concerns.
The safety and efficacy of currently approved drug therapies have not been evaluated in children and elderly patient populations and there is limited information in adolescents, whilst the long-term safety of current and potential new drug therapies in adults will require several years of postmarketing surveillance to fully elucidate their adverse effect profiles.
Fußnoten
1
The use of trade names is for product identification purposes only and does not imply endorsement.
 
Literatur
1.
Zurück zum Zitat Mokdad AH, Serdula MK, Dietz WH, et al. The spread of the obesity epidemic in the United States 1991-1998. JAMA 1999; 282: 1519–22PubMedCrossRef Mokdad AH, Serdula MK, Dietz WH, et al. The spread of the obesity epidemic in the United States 1991-1998. JAMA 1999; 282: 1519–22PubMedCrossRef
2.
Zurück zum Zitat Mokdad AH, Bowman BA, Ford ES, et al. The continuing epidemics of obesity and diabetes in the United States. JAMA 2001; 286: 1195–200PubMedCrossRef Mokdad AH, Bowman BA, Ford ES, et al. The continuing epidemics of obesity and diabetes in the United States. JAMA 2001; 286: 1195–200PubMedCrossRef
3.
Zurück zum Zitat Flegal KM, Carroll MD, Ogden CL, et al. Prevalence and trends in obesity amongst US adults, 1999-2000. JAMA 2002; 288: 1723–7PubMedCrossRef Flegal KM, Carroll MD, Ogden CL, et al. Prevalence and trends in obesity amongst US adults, 1999-2000. JAMA 2002; 288: 1723–7PubMedCrossRef
4.
Zurück zum Zitat University of York, NHS Centre for Reviews and Dissemination. A systematic review of the interventions for the prevention and treatment of obesity and the maintenance of weight loss. Tork: NHS Centre for Reviews and Dissemination, 1997 University of York, NHS Centre for Reviews and Dissemination. A systematic review of the interventions for the prevention and treatment of obesity and the maintenance of weight loss. Tork: NHS Centre for Reviews and Dissemination, 1997
5.
Zurück zum Zitat Eckersley RM. Losing the battle of the bulge: causes and consequences of increasing obesity. Med J Aust 2001; 174: 590–2PubMed Eckersley RM. Losing the battle of the bulge: causes and consequences of increasing obesity. Med J Aust 2001; 174: 590–2PubMed
6.
Zurück zum Zitat Baur LA. Obesity: definitely a growing concern. Med J Aust 2001; 174: 553–4PubMed Baur LA. Obesity: definitely a growing concern. Med J Aust 2001; 174: 553–4PubMed
7.
Zurück zum Zitat Spector TD, Hart DJ, Doyle D. Incidence and progression of osteoarthritis in women with unilateral knee disease in the general population: the effect of obesity. Ann Rheum Dis 1994; 53: 565–8PubMedCrossRef Spector TD, Hart DJ, Doyle D. Incidence and progression of osteoarthritis in women with unilateral knee disease in the general population: the effect of obesity. Ann Rheum Dis 1994; 53: 565–8PubMedCrossRef
8.
Zurück zum Zitat Seidel JC, Verschuren WM, Vanleer EM, et al. Overweight, underweight, and mortality: a prospective study of 48287 men and women. Arch Intern Med 1996; 156: 958–63CrossRef Seidel JC, Verschuren WM, Vanleer EM, et al. Overweight, underweight, and mortality: a prospective study of 48287 men and women. Arch Intern Med 1996; 156: 958–63CrossRef
9.
Zurück zum Zitat Calle EE, Thun NJ, Petrelli JM, et al. Body-mass index and mortality in a prospective cohort of US adults. N Engl J Med 1999; 341: 1097–105PubMedCrossRef Calle EE, Thun NJ, Petrelli JM, et al. Body-mass index and mortality in a prospective cohort of US adults. N Engl J Med 1999; 341: 1097–105PubMedCrossRef
10.
Zurück zum Zitat AACE/ACE position statement on the prevention, diagnosis and treatment of obesity (1998 revision). Endocr Pract 1998; 4: 297–330 AACE/ACE position statement on the prevention, diagnosis and treatment of obesity (1998 revision). Endocr Pract 1998; 4: 297–330
11.
Zurück zum Zitat Wilson PWF, D’Agostino RB, Sullivan L, et al. Overweight and obesity as determinants of cardiovascular risk. Arch Intern Med 2002; 162: 1867–72PubMedCrossRef Wilson PWF, D’Agostino RB, Sullivan L, et al. Overweight and obesity as determinants of cardiovascular risk. Arch Intern Med 2002; 162: 1867–72PubMedCrossRef
12.
Zurück zum Zitat Cerulli J, Malone M. Outcomes of pharmacological and surgical treatment for obesity. Pharmacoeconomics 1998; 14: 269–83PubMedCrossRef Cerulli J, Malone M. Outcomes of pharmacological and surgical treatment for obesity. Pharmacoeconomics 1998; 14: 269–83PubMedCrossRef
13.
Zurück zum Zitat Muls E, Kolanowski J, Scheen A, et al. The effects of orlistat on weight and on serum lipids in obese patients with hypercholesterolemia: a randomized, double-blind, placebo controlled, multicentre study. Int J Obes 2001; 25: 1713–21CrossRef Muls E, Kolanowski J, Scheen A, et al. The effects of orlistat on weight and on serum lipids in obese patients with hypercholesterolemia: a randomized, double-blind, placebo controlled, multicentre study. Int J Obes 2001; 25: 1713–21CrossRef
14.
Zurück zum Zitat Padwal R, Li SK. Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. Int J Obes Relat Metab Disord 2003; 27: 1437–46PubMedCrossRef Padwal R, Li SK. Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials. Int J Obes Relat Metab Disord 2003; 27: 1437–46PubMedCrossRef
15.
Zurück zum Zitat Halford JCG. Clinical pharmacotherapy for obesity: current drugs and those in advanced development. Curr Drugs Targets 2004; 5: 637–46CrossRef Halford JCG. Clinical pharmacotherapy for obesity: current drugs and those in advanced development. Curr Drugs Targets 2004; 5: 637–46CrossRef
16.
Zurück zum Zitat Torgerson JA, Hauptman J, Boldrin MN, et al. XENical in the prevention of Diabetes in Obese Subjects (XENDOS) study. Diabetes Care 2004; 27: 155–61PubMedCrossRef Torgerson JA, Hauptman J, Boldrin MN, et al. XENical in the prevention of Diabetes in Obese Subjects (XENDOS) study. Diabetes Care 2004; 27: 155–61PubMedCrossRef
17.
Zurück zum Zitat Glazer G. Long-term pharmacotherapy of obesity 2000: a review of efficacy and safety. Arch Intern Med 2001; 161: 1814–24PubMedCrossRef Glazer G. Long-term pharmacotherapy of obesity 2000: a review of efficacy and safety. Arch Intern Med 2001; 161: 1814–24PubMedCrossRef
18.
Zurück zum Zitat Weintraub M. Long-term weight control: the National Heart, Lung, and Blood Institute funded multimodal intervention study. Clin Pharmacol Ther 1992; 51Suppl.: 581–646PubMedCrossRef Weintraub M. Long-term weight control: the National Heart, Lung, and Blood Institute funded multimodal intervention study. Clin Pharmacol Ther 1992; 51Suppl.: 581–646PubMedCrossRef
19.
Zurück zum Zitat Weigle DS. Pharmacological therapy of obesity: past present and future. J Clin Endocrinol Metab 2003; 88: 2462–9PubMedCrossRef Weigle DS. Pharmacological therapy of obesity: past present and future. J Clin Endocrinol Metab 2003; 88: 2462–9PubMedCrossRef
20.
Zurück zum Zitat Krotkiewski M. Thyroid hormones and treatment of obesity. Internat J Obes 2000; 24 Suppl. 2: S116–9 Krotkiewski M. Thyroid hormones and treatment of obesity. Internat J Obes 2000; 24 Suppl. 2: S116–9
21.
Zurück zum Zitat Eliason BC, Doenier JA, Nuhlicek DN, et al. Desicated thyroid in a nutritional supplement. J Fam Pract 1994; 38: 287–8PubMed Eliason BC, Doenier JA, Nuhlicek DN, et al. Desicated thyroid in a nutritional supplement. J Fam Pract 1994; 38: 287–8PubMed
22.
Zurück zum Zitat Gwinup G, Poucher R. A controlled study of thyroid analogs in the therapy of obesity. Am J Med Sci 1967; 254: 416–20PubMedCrossRef Gwinup G, Poucher R. A controlled study of thyroid analogs in the therapy of obesity. Am J Med Sci 1967; 254: 416–20PubMedCrossRef
23.
Zurück zum Zitat Rivlin RS. Therapy of obesity with hormones. N Eng J Med 1975; 292: 26–9CrossRef Rivlin RS. Therapy of obesity with hormones. N Eng J Med 1975; 292: 26–9CrossRef
24.
Zurück zum Zitat Clapham JC. Treating obesity: pharmacology and energy expenditure. Curr Drug Targets 2004; 5: 309–23PubMedCrossRef Clapham JC. Treating obesity: pharmacology and energy expenditure. Curr Drug Targets 2004; 5: 309–23PubMedCrossRef
25.
Zurück zum Zitat Bray GA, Greenway FL. Pharmacological approaches to treating the obese patient. Clin Endocrinol Metab 1976; 5: 455–79PubMedCrossRef Bray GA, Greenway FL. Pharmacological approaches to treating the obese patient. Clin Endocrinol Metab 1976; 5: 455–79PubMedCrossRef
26.
Zurück zum Zitat Colman E. Anorectics on trial: a half century of federal regulation of prescription appetite suppressants. Ann Intern Med 2005; 143: 380–5PubMed Colman E. Anorectics on trial: a half century of federal regulation of prescription appetite suppressants. Ann Intern Med 2005; 143: 380–5PubMed
27.
Zurück zum Zitat Kosman ME, Unna KR. Effects of chronic administration of the amphetamines and other stimulants on behaviour. Clin Pharmacol Ther 1968; 9: 240–8PubMed Kosman ME, Unna KR. Effects of chronic administration of the amphetamines and other stimulants on behaviour. Clin Pharmacol Ther 1968; 9: 240–8PubMed
28.
Zurück zum Zitat Thomas SHL, Butt AY, Corris PA, et al. Appetite suppressants and primary pulmonary hypertension in the United Kingdom. Br Heart J 1995; 74: 660–3PubMedCrossRef Thomas SHL, Butt AY, Corris PA, et al. Appetite suppressants and primary pulmonary hypertension in the United Kingdom. Br Heart J 1995; 74: 660–3PubMedCrossRef
29.
Zurück zum Zitat Lake CR, Gallan S, Masso E, et al. Adverse drug effects attributed to phenylpropanolamine: a review of 142 case reports. Am J Med 1990; 89: 195–208PubMedCrossRef Lake CR, Gallan S, Masso E, et al. Adverse drug effects attributed to phenylpropanolamine: a review of 142 case reports. Am J Med 1990; 89: 195–208PubMedCrossRef
30.
Zurück zum Zitat Langleben D, Walker AM, Korelitz JJ, et al. Temporal trends in the number of reported cases of pulmonary hypertension and use of anorexigens, antidepressants, and amphetamines, 1998-2001 [abstract]. Am J Respir Crit Care Med 2004; 169: A171 Langleben D, Walker AM, Korelitz JJ, et al. Temporal trends in the number of reported cases of pulmonary hypertension and use of anorexigens, antidepressants, and amphetamines, 1998-2001 [abstract]. Am J Respir Crit Care Med 2004; 169: A171
31.
32.
Zurück zum Zitat Stroe AE, Hall J, Amin F. Psychotic episode related to phenylpropanolamine and amantadine in a healthy female [letter]. Gen Hosp Psychiatry 1995; 17: 457–8PubMedCrossRef Stroe AE, Hall J, Amin F. Psychotic episode related to phenylpropanolamine and amantadine in a healthy female [letter]. Gen Hosp Psychiatry 1995; 17: 457–8PubMedCrossRef
33.
Zurück zum Zitat Goodhue A, Bartel RL, Smith NB. Exacerbation of psychosis by phenylpropanolamine [letter]. Am J Psychiatry 2000; 157: 1021–2PubMedCrossRef Goodhue A, Bartel RL, Smith NB. Exacerbation of psychosis by phenylpropanolamine [letter]. Am J Psychiatry 2000; 157: 1021–2PubMedCrossRef
34.
Zurück zum Zitat Douglas A, Douglas JG, Robertson CE, et al. Plasma phentermine levels, weight loss and side-effects. Internat J Obes 1983; 7: 591–5 Douglas A, Douglas JG, Robertson CE, et al. Plasma phentermine levels, weight loss and side-effects. Internat J Obes 1983; 7: 591–5
35.
Zurück zum Zitat Munro JF, MacCuish AC, Wilson EM, et al. Comparison of continuous and intermittent anorectic therapy in obesity. Br Med J 1968; 1: 352–4PubMedCrossRef Munro JF, MacCuish AC, Wilson EM, et al. Comparison of continuous and intermittent anorectic therapy in obesity. Br Med J 1968; 1: 352–4PubMedCrossRef
36.
Zurück zum Zitat Truant AP, Olon LP, Cobb S. Phentermine resin as an adjunct in medical weight reduction: a controlled randomized double-blind prospective study. Curr Ther Res Clin Exp 1972; 14: 726–38PubMed Truant AP, Olon LP, Cobb S. Phentermine resin as an adjunct in medical weight reduction: a controlled randomized double-blind prospective study. Curr Ther Res Clin Exp 1972; 14: 726–38PubMed
37.
Zurück zum Zitat Kaplan LM. Pharmacological therapies for obesity. Gastroenterol Clin North Am 2005; 34: 91–104PubMedCrossRef Kaplan LM. Pharmacological therapies for obesity. Gastroenterol Clin North Am 2005; 34: 91–104PubMedCrossRef
38.
Zurück zum Zitat National Task Force on the Prevention and Treatment of Obesity. Long-term pharmacotherapy in the management of obesity. JAMA 1996; 276: 1907–15 National Task Force on the Prevention and Treatment of Obesity. Long-term pharmacotherapy in the management of obesity. JAMA 1996; 276: 1907–15
39.
Zurück zum Zitat Weiser M, Frishman WH, Michaelson MD, et al. The pharmacological approach to the treatment of obesity. J Clin Pharmacol 1997; 37: 453–73PubMed Weiser M, Frishman WH, Michaelson MD, et al. The pharmacological approach to the treatment of obesity. J Clin Pharmacol 1997; 37: 453–73PubMed
40.
41.
Zurück zum Zitat Malchow-Moller A, Larsen S, Hey H, et al. Ephedrine as an anorectic: the story of the ‘Elisinore pill’. Internat J Obes 1981; 5: 183–7 Malchow-Moller A, Larsen S, Hey H, et al. Ephedrine as an anorectic: the story of the ‘Elisinore pill’. Internat J Obes 1981; 5: 183–7
42.
43.
Zurück zum Zitat Brooke D, Kerwin R, Lloyd K. Diethylpropion hydrochlorideinduced psychosis. Br J Psychiatry 1988; 152: 572–3PubMed Brooke D, Kerwin R, Lloyd K. Diethylpropion hydrochlorideinduced psychosis. Br J Psychiatry 1988; 152: 572–3PubMed
45.
Zurück zum Zitat Little JD, Romans SE. Psychosis following readministration of diethylproprion: a possible role for kindling? Int Clin Psychopharmacol 1993; 8: 67–70PubMedCrossRef Little JD, Romans SE. Psychosis following readministration of diethylproprion: a possible role for kindling? Int Clin Psychopharmacol 1993; 8: 67–70PubMedCrossRef
46.
47.
Zurück zum Zitat Kramer MS, Lane DA. Pharmacoepidemiology report. Aminorex, dexfenfluramine and primary pulmonary hypertension. J Clin Epidemiol 1998; 51: 361–4PubMedCrossRef Kramer MS, Lane DA. Pharmacoepidemiology report. Aminorex, dexfenfluramine and primary pulmonary hypertension. J Clin Epidemiol 1998; 51: 361–4PubMedCrossRef
48.
Zurück zum Zitat Inoue S. Clinical studies with mazindol. Obes Res 1995; 3(Suppl. 4): 549–52 Inoue S. Clinical studies with mazindol. Obes Res 1995; 3(Suppl. 4): 549–52
49.
Zurück zum Zitat Bradley MH, Blum NJ, Scheib RJ. Mazindol in obesity with known cardiac disease: a clinical evaluation. J Intern Med Res 1976; 2: 347–9 Bradley MH, Blum NJ, Scheib RJ. Mazindol in obesity with known cardiac disease: a clinical evaluation. J Intern Med Res 1976; 2: 347–9
50.
Zurück zum Zitat Inoue S, Egawa M, Satoh S, et al. Clinical and basic aspects of an anorexiant mazindol as an antiobesity agent in Japan. Am J Clin Nutr 1992; 55: 199S–202SPubMed Inoue S, Egawa M, Satoh S, et al. Clinical and basic aspects of an anorexiant mazindol as an antiobesity agent in Japan. Am J Clin Nutr 1992; 55: 199S–202SPubMed
51.
Zurück zum Zitat Hagiwara M, Tsuchida A, Hyakkoku M, et al. Delayed onset of pulmonary hypertension associated with an appetite suppressant, mazindol: a case report. Jpn Circ J 2000; 64: 218–21PubMedCrossRef Hagiwara M, Tsuchida A, Hyakkoku M, et al. Delayed onset of pulmonary hypertension associated with an appetite suppressant, mazindol: a case report. Jpn Circ J 2000; 64: 218–21PubMedCrossRef
52.
Zurück zum Zitat Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000; 343: 1833–8PubMedCrossRef Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000; 343: 1833–8PubMedCrossRef
53.
Zurück zum Zitat Shekelle PG, Hardy ML, Morton SC, et al. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA 2003; 289: 1537–45PubMedCrossRef Shekelle PG, Hardy ML, Morton SC, et al. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA 2003; 289: 1537–45PubMedCrossRef
54.
Zurück zum Zitat Greenway FL. The safety and efficacy of pharmaceutical and herbal caffiene and ephedrine use as a weight loss agent. Obes Rev 2001; 2: 199–211PubMedCrossRef Greenway FL. The safety and efficacy of pharmaceutical and herbal caffiene and ephedrine use as a weight loss agent. Obes Rev 2001; 2: 199–211PubMedCrossRef
55.
Zurück zum Zitat McCann UD, Eligulashvili V, Ricaurte GA. Adverse neuropsychiatric events associated with dexfenfluramine and fenfluramine. Prog Neuropsychopharmacol Biol Psychiatry 1998; 22: 1987–102CrossRef McCann UD, Eligulashvili V, Ricaurte GA. Adverse neuropsychiatric events associated with dexfenfluramine and fenfluramine. Prog Neuropsychopharmacol Biol Psychiatry 1998; 22: 1987–102CrossRef
56.
Zurück zum Zitat Connolly HM, McGoon MD. Obesity drugs and the heart. Curr Probl Cardiol 1999; 24: 747–92CrossRef Connolly HM, McGoon MD. Obesity drugs and the heart. Curr Probl Cardiol 1999; 24: 747–92CrossRef
57.
Zurück zum Zitat Goldstein DJ, Potvin JH. Long-term weight loss: the effect of pharmacologic agents. Am J Clin Nutr 1994: 60: 647–57PubMed Goldstein DJ, Potvin JH. Long-term weight loss: the effect of pharmacologic agents. Am J Clin Nutr 1994: 60: 647–57PubMed
58.
Zurück zum Zitat Pinder RM, Brogden RN, Sawyer PR, et al. Fenfluramine: a review of its pharmacological properties and therapeutic efficacy in obesity. Drugs 1975; 10: 241–323PubMedCrossRef Pinder RM, Brogden RN, Sawyer PR, et al. Fenfluramine: a review of its pharmacological properties and therapeutic efficacy in obesity. Drugs 1975; 10: 241–323PubMedCrossRef
59.
Zurück zum Zitat Bever KA, Perry PJ. Dexfenfluramine hydrochloride: an anorexigenic agent. Am J Heath Syst Pharm 1997; 54: 2059–72 Bever KA, Perry PJ. Dexfenfluramine hydrochloride: an anorexigenic agent. Am J Heath Syst Pharm 1997; 54: 2059–72
60.
Zurück zum Zitat Davis R, Faulds D. Dexfenfluramine: an updated review of its therapeutic use in the management of obesity. Drugs 1996; 52: 696–724PubMedCrossRef Davis R, Faulds D. Dexfenfluramine: an updated review of its therapeutic use in the management of obesity. Drugs 1996; 52: 696–724PubMedCrossRef
61.
Zurück zum Zitat Mathus-Vliegen EMH, Van de Voorde K, Kok AME, et al. Dexfenfluramine in the treatment of severe obesity: a placebocontrolled investigation of the effects on weight loss, cardiovascular risk factors, food intake and eating behaviour. J Intern Med 1992; 232: 199–27CrossRef Mathus-Vliegen EMH, Van de Voorde K, Kok AME, et al. Dexfenfluramine in the treatment of severe obesity: a placebocontrolled investigation of the effects on weight loss, cardiovascular risk factors, food intake and eating behaviour. J Intern Med 1992; 232: 199–27CrossRef
62.
Zurück zum Zitat Preval H, Pakyurek AM. Psychotic episode associated with dexfenfluramine [letter]. Am J Psychiatry 1997; 154: 1624–5PubMed Preval H, Pakyurek AM. Psychotic episode associated with dexfenfluramine [letter]. Am J Psychiatry 1997; 154: 1624–5PubMed
63.
Zurück zum Zitat Li Z, Maglione M, Tu W, et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med 2005; 142: 532–46PubMed Li Z, Maglione M, Tu W, et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med 2005; 142: 532–46PubMed
64.
Zurück zum Zitat Leung WYS, ai]Thomas GN, Chan JCN, et al. Weight management and current options in pharmacotherapy: orlistat and sibutramine. Clin Ther 2003; 25: 58–80PubMedCrossRef Leung WYS, ai]Thomas GN, Chan JCN, et al. Weight management and current options in pharmacotherapy: orlistat and sibutramine. Clin Ther 2003; 25: 58–80PubMedCrossRef
65.
Zurück zum Zitat McNeely W, Goa KL. Sibutramine: a review of its contribution to the management of obesity. Drugs 1998; 56: 1093–124PubMedCrossRef McNeely W, Goa KL. Sibutramine: a review of its contribution to the management of obesity. Drugs 1998; 56: 1093–124PubMedCrossRef
66.
Zurück zum Zitat Nisoli E, Carruba MO. A benefit-risk assessment of sibutramine in the management of obesity. Drug Saf 2003; 26: 1027–48PubMedCrossRef Nisoli E, Carruba MO. A benefit-risk assessment of sibutramine in the management of obesity. Drug Saf 2003; 26: 1027–48PubMedCrossRef
67.
Zurück zum Zitat McMahon FG, Fujiok K, Singh BN, et al. Efficacy and safety of sibutramine in obese white and African-American patients with hypertension: a 1-year, double-blind, placebo-controlled, multicentre trial. Arch Intern Med 2000; 160: 2185–91PubMedCrossRef McMahon FG, Fujiok K, Singh BN, et al. Efficacy and safety of sibutramine in obese white and African-American patients with hypertension: a 1-year, double-blind, placebo-controlled, multicentre trial. Arch Intern Med 2000; 160: 2185–91PubMedCrossRef
68.
Zurück zum Zitat Bray GA, Blackburn GL, Ferguson JM, et al. Sibutramine produces dose-related weight loss. Obes Res 1999; 7: 189–98PubMedCrossRef Bray GA, Blackburn GL, Ferguson JM, et al. Sibutramine produces dose-related weight loss. Obes Res 1999; 7: 189–98PubMedCrossRef
69.
Zurück zum Zitat Apfelbaum M, Vague P, Ziegler O, et al. Long-term maintenance of weight loss after very-low-calorie diet: Efficacy and tolerability of sibutramine. Am J Med 1999; 106: 179–84PubMedCrossRef Apfelbaum M, Vague P, Ziegler O, et al. Long-term maintenance of weight loss after very-low-calorie diet: Efficacy and tolerability of sibutramine. Am J Med 1999; 106: 179–84PubMedCrossRef
70.
71.
Zurück zum Zitat Haddock CK, Poston WSC, Dill PL, et al. Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomised clinical trials. Int J Obes 2002; 26: 262–73CrossRef Haddock CK, Poston WSC, Dill PL, et al. Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomised clinical trials. Int J Obes 2002; 26: 262–73CrossRef
72.
Zurück zum Zitat Ioannides-Demos LL, Proietto J, McNeil JJ. Pharmacotherapy for obesity. Drugs 2005; 65: 1391–418PubMedCrossRef Ioannides-Demos LL, Proietto J, McNeil JJ. Pharmacotherapy for obesity. Drugs 2005; 65: 1391–418PubMedCrossRef
73.
Zurück zum Zitat Guy-Grand B, Crepaldi G, Lefebvre P, et al. International trial of long-term dexfenfluramine in obesity. Lancet 1989; II: 1142–4CrossRef Guy-Grand B, Crepaldi G, Lefebvre P, et al. International trial of long-term dexfenfluramine in obesity. Lancet 1989; II: 1142–4CrossRef
74.
Zurück zum Zitat Goldstein DJ, Rampey AH, Enas GG, et al. Fluoxetine: a randomised clinical trial in the treatment of obesity. Int J Obes Relat Metab Disord 1994; 18: 129–35PubMed Goldstein DJ, Rampey AH, Enas GG, et al. Fluoxetine: a randomised clinical trial in the treatment of obesity. Int J Obes Relat Metab Disord 1994; 18: 129–35PubMed
75.
Zurück zum Zitat James WPT, Astrup A, Finer N, et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. Lancet 2000; 356: 2119–25PubMedCrossRef James WPT, Astrup A, Finer N, et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. Lancet 2000; 356: 2119–25PubMedCrossRef
76.
Zurück zum Zitat Wirth A, Krause J. Long-term weight loss with sibutramine: a randomized controlled trial. JAMA 2001; 286: 1331–9PubMedCrossRef Wirth A, Krause J. Long-term weight loss with sibutramine: a randomized controlled trial. JAMA 2001; 286: 1331–9PubMedCrossRef
77.
Zurück zum Zitat Davidson MH, Hauptman J, DiGirolamo M, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomised controlled trial. JAMA 1999; 281: 235–42PubMedCrossRef Davidson MH, Hauptman J, DiGirolamo M, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomised controlled trial. JAMA 1999; 281: 235–42PubMedCrossRef
78.
Zurück zum Zitat Sjöström L, Rissanen A, Anderson T, et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group. Lancet 1998; 352: 167–73PubMedCrossRef Sjöström L, Rissanen A, Anderson T, et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group. Lancet 1998; 352: 167–73PubMedCrossRef
79.
Zurück zum Zitat Rossner S, Sjostrom L, Noack R, et al. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. European Orlistat Obesity Study Group. Obes Res 2000; 8: 49–61CrossRef Rossner S, Sjostrom L, Noack R, et al. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. European Orlistat Obesity Study Group. Obes Res 2000; 8: 49–61CrossRef
80.
Zurück zum Zitat Bays H, Dujovne C. Pharmacotherapy of obesity: currently marketed and upcoming agents. Am J Cardiovasc Drugs 2002; 2: 245–53PubMedCrossRef Bays H, Dujovne C. Pharmacotherapy of obesity: currently marketed and upcoming agents. Am J Cardiovasc Drugs 2002; 2: 245–53PubMedCrossRef
81.
Zurück zum Zitat Wooltorton E, Sibbald B. Ephedra/ephedrine: cardiovascular and CNS effects. Can Med Assoc J 2002; 166: 633 Wooltorton E, Sibbald B. Ephedra/ephedrine: cardiovascular and CNS effects. Can Med Assoc J 2002; 166: 633
82.
83.
Zurück zum Zitat Figueras A, Laporte JR. Regulatory decisions in a globalised world: the domino effect of phenylpropanolamine withdrawal in Latin America. Drug Saf 2002; 25(10): 689–93PubMedCrossRef Figueras A, Laporte JR. Regulatory decisions in a globalised world: the domino effect of phenylpropanolamine withdrawal in Latin America. Drug Saf 2002; 25(10): 689–93PubMedCrossRef
84.
Zurück zum Zitat Kim SH, Lee YM, Jee SH, et al. Effect of sibutramine on weight loss and blood pressure: a meta-analysis of controlled trials. Obes Res 2003; 11: 1116–23PubMedCrossRef Kim SH, Lee YM, Jee SH, et al. Effect of sibutramine on weight loss and blood pressure: a meta-analysis of controlled trials. Obes Res 2003; 11: 1116–23PubMedCrossRef
85.
Zurück zum Zitat Wooltorton E. Obesity drug sibutramine (Meridia): hypertension and cardiac arrhythmias. CMAJ 2002; 166: 1307–8PubMed Wooltorton E. Obesity drug sibutramine (Meridia): hypertension and cardiac arrhythmias. CMAJ 2002; 166: 1307–8PubMed
86.
Zurück zum Zitat European Agency for the Evaluation of Medicinal Products. Committee for Propriety Medicinal Products Meeting of 25–27 June 2002. Press release [online]. Available from URL: http://www.emea.eu.int/ [Accessed 2003 Dec 1] European Agency for the Evaluation of Medicinal Products. Committee for Propriety Medicinal Products Meeting of 25–27 June 2002. Press release [online]. Available from URL: http://​www.​emea.​eu.​int/​ [Accessed 2003 Dec 1]
87.
Zurück zum Zitat Abenhaim L, Moride Y, Brenot S, et al. Appetite-suppressant drugs and the risk of pulmonary hypertension. International Primary Pulmonary Hypertension Study Group. N Engl J Med 1996; 335: 609–16PubMedCrossRef Abenhaim L, Moride Y, Brenot S, et al. Appetite-suppressant drugs and the risk of pulmonary hypertension. International Primary Pulmonary Hypertension Study Group. N Engl J Med 1996; 335: 609–16PubMedCrossRef
89.
90.
Zurück zum Zitat Michelakis ED, Weir EK. Anorectic drugs and pulmonary hypertension from the bedside to the bench. Am J Med Sci 2001; 321: 292–9PubMedCrossRef Michelakis ED, Weir EK. Anorectic drugs and pulmonary hypertension from the bedside to the bench. Am J Med Sci 2001; 321: 292–9PubMedCrossRef
91.
Zurück zum Zitat Gurtner HP. Aminorex and pulmonary hypertension. Cor Vasa 1985; 27: 60–171 Gurtner HP. Aminorex and pulmonary hypertension. Cor Vasa 1985; 27: 60–171
92.
Zurück zum Zitat Langleben D. Relearning the lessons of history: anorexigens and pulmonary hypertension. Chest 1998; 114: 55S–7SPubMedCrossRef Langleben D. Relearning the lessons of history: anorexigens and pulmonary hypertension. Chest 1998; 114: 55S–7SPubMedCrossRef
93.
Zurück zum Zitat Kramer MS, Lane DA. Aminorex, dexfenfluramine, and primary pulmonary hypertension. J Clin Epidemiol 1998; 51: 361–4PubMedCrossRef Kramer MS, Lane DA. Aminorex, dexfenfluramine, and primary pulmonary hypertension. J Clin Epidemiol 1998; 51: 361–4PubMedCrossRef
94.
Zurück zum Zitat Douglas JD, Munro JF, Kitchin AH, et al. Pulmonary hypertension and fenfluramine. BMJ 1981; 283: 881–3PubMedCrossRef Douglas JD, Munro JF, Kitchin AH, et al. Pulmonary hypertension and fenfluramine. BMJ 1981; 283: 881–3PubMedCrossRef
95.
Zurück zum Zitat Tellier P. Fenfluramines, idiopathic pulmonary primary hypertension and cardiac valve disorders: facts and artifacts. Ann Med Intern 2001; 152: 429–36 Tellier P. Fenfluramines, idiopathic pulmonary primary hypertension and cardiac valve disorders: facts and artifacts. Ann Med Intern 2001; 152: 429–36
96.
Zurück zum Zitat Loogen F, Worth H, Schwan G, et al. Long-term follow-up of pulmonary hypertension in patients with and without anorectic drug intake. Cor Vasa 1985; 27: 111–24PubMed Loogen F, Worth H, Schwan G, et al. Long-term follow-up of pulmonary hypertension in patients with and without anorectic drug intake. Cor Vasa 1985; 27: 111–24PubMed
97.
Zurück zum Zitat McMurray J, Bloomfield P, Miller HC. Irreversible pulmonary hypertension after treatment with fenfluramine [letter]. BMJ 1986; 292: 239–40PubMedCrossRef McMurray J, Bloomfield P, Miller HC. Irreversible pulmonary hypertension after treatment with fenfluramine [letter]. BMJ 1986; 292: 239–40PubMedCrossRef
98.
Zurück zum Zitat Mark EJ, Patalas ED, Chang HT, et al. Brief report: fatal pulmonary hypertension associated with short-term use of fenfluramine and phentermine. N Engl J Med 1997; 337: 602–6PubMedCrossRef Mark EJ, Patalas ED, Chang HT, et al. Brief report: fatal pulmonary hypertension associated with short-term use of fenfluramine and phentermine. N Engl J Med 1997; 337: 602–6PubMedCrossRef
99.
Zurück zum Zitat Atanassoff PG, Weiss BM, Schmid ER, et al. Pulmonary hypertension and dexfenfluramine [letter]. Lancet 1992; 339: 436PubMedCrossRef Atanassoff PG, Weiss BM, Schmid ER, et al. Pulmonary hypertension and dexfenfluramine [letter]. Lancet 1992; 339: 436PubMedCrossRef
100.
Zurück zum Zitat Roche N, Labrune S, Braun J-M, et al. Pulmonary hypertension and dexfenfluramine [letter]. Lancet 1992; 339: 436–7PubMedCrossRef Roche N, Labrune S, Braun J-M, et al. Pulmonary hypertension and dexfenfluramine [letter]. Lancet 1992; 339: 436–7PubMedCrossRef
101.
Zurück zum Zitat Cacoub P, Dorent R, Nataf P, et al. Piette JC. Godeau P, Gandjbakhch I. Pulmonary hypertension and dexfenfluramine. Eur J Clin Pharmacol 1995; 48: 81–3PubMedCrossRef Cacoub P, Dorent R, Nataf P, et al. Piette JC. Godeau P, Gandjbakhch I. Pulmonary hypertension and dexfenfluramine. Eur J Clin Pharmacol 1995; 48: 81–3PubMedCrossRef
102.
Zurück zum Zitat Brenot F, Herve P, Petitpretz P, et al. Primary pulmonary hypertension and fenfluramine use. Br Heart J 1993; 70: 537–41PubMedCrossRef Brenot F, Herve P, Petitpretz P, et al. Primary pulmonary hypertension and fenfluramine use. Br Heart J 1993; 70: 537–41PubMedCrossRef
104.
Zurück zum Zitat Delcroix M, Kurz X, Walckiers D, et al. High incidence of primary pulmonary hypertension associated with appetite suppressants in Belgium. Eur Respir J 1998; 12: 271–6PubMedCrossRef Delcroix M, Kurz X, Walckiers D, et al. High incidence of primary pulmonary hypertension associated with appetite suppressants in Belgium. Eur Respir J 1998; 12: 271–6PubMedCrossRef
105.
Zurück zum Zitat Rich S, Rubin L, Walker AM, et al. Anorexigens and pulmonary hypertension in the United States: results from the surveillance of North American Pulmonary Hypertension. Chest 2000; 117: 870–4PubMedCrossRef Rich S, Rubin L, Walker AM, et al. Anorexigens and pulmonary hypertension in the United States: results from the surveillance of North American Pulmonary Hypertension. Chest 2000; 117: 870–4PubMedCrossRef
106.
Zurück zum Zitat Teramae CY, Connolly HM, Grogan M, et al. Diet drug-related cardiac valve disease: the Mayo Clinic echocardiographic laboratory experience. Mayo Clin Proc 2000; 75: 456–61PubMed Teramae CY, Connolly HM, Grogan M, et al. Diet drug-related cardiac valve disease: the Mayo Clinic echocardiographic laboratory experience. Mayo Clin Proc 2000; 75: 456–61PubMed
107.
Zurück zum Zitat Louis WJ. Primary pulmonary hypertension and anorectic drugs [letter]. N Engl J Med 1999; 340: 480–2PubMedCrossRef Louis WJ. Primary pulmonary hypertension and anorectic drugs [letter]. N Engl J Med 1999; 340: 480–2PubMedCrossRef
108.
Zurück zum Zitat Abenhaim L, Rich S, Benichou J, et al. Primary pulmonary hypertension and anorectic drugs [letter]. N Engl J Med 1999; 340: 481–2 Abenhaim L, Rich S, Benichou J, et al. Primary pulmonary hypertension and anorectic drugs [letter]. N Engl J Med 1999; 340: 481–2
109.
Zurück zum Zitat Lilienfield DE, Rubin LJ. Mortality from primary pulmonary hypertension in the United States, 1979-1996. Chest 2000; 117: 796–800CrossRef Lilienfield DE, Rubin LJ. Mortality from primary pulmonary hypertension in the United States, 1979-1996. Chest 2000; 117: 796–800CrossRef
110.
Zurück zum Zitat Rothman RB. The age-adjusted mortality rate from primary pulmonary hypertension, in age range 20 to 54 years, did not increase during the years of peak ‘phen-fen’ use [letter]. Chest 2000; 118: 1516–7PubMedCrossRef Rothman RB. The age-adjusted mortality rate from primary pulmonary hypertension, in age range 20 to 54 years, did not increase during the years of peak ‘phen-fen’ use [letter]. Chest 2000; 118: 1516–7PubMedCrossRef
111.
Zurück zum Zitat Manson JE, Faich GA. Pharmacotherapy for obesity- do the benefits outweigh the risk? N Engl J Med 1996; 335: 659–60PubMedCrossRef Manson JE, Faich GA. Pharmacotherapy for obesity- do the benefits outweigh the risk? N Engl J Med 1996; 335: 659–60PubMedCrossRef
112.
Zurück zum Zitat Herve P, Launay JM, Scrbohaci ML, et al. Increased plasma serotonin in primary pulmonary hypertension. Am J Med 1995; 99: 249–54PubMedCrossRef Herve P, Launay JM, Scrbohaci ML, et al. Increased plasma serotonin in primary pulmonary hypertension. Am J Med 1995; 99: 249–54PubMedCrossRef
113.
Zurück zum Zitat Weir EK, Reeve HL, Johnson G, et al. A role for potassium channels in smooth muscle cells and platelets in the etiology of primary pulmonary hypertension. Chest 1998; 114(3 Suppl.): 200S–4SPubMedCrossRef Weir EK, Reeve HL, Johnson G, et al. A role for potassium channels in smooth muscle cells and platelets in the etiology of primary pulmonary hypertension. Chest 1998; 114(3 Suppl.): 200S–4SPubMedCrossRef
114.
Zurück zum Zitat Anchors M. Fluoxetine is a safer alternative to fenfluramine in the medical treatment of obesity. Arch Intern Med 1997; 157: 1270PubMedCrossRef Anchors M. Fluoxetine is a safer alternative to fenfluramine in the medical treatment of obesity. Arch Intern Med 1997; 157: 1270PubMedCrossRef
115.
Zurück zum Zitat Rothman RB, Ayestas MA, Dersch CM, et al. Aminorex, fenfluramine and chlorphentermine are serotonin transporter substrates: implication for primary pulmonary hypertension. Circulation 1999; 100: 869–75PubMedCrossRef Rothman RB, Ayestas MA, Dersch CM, et al. Aminorex, fenfluramine and chlorphentermine are serotonin transporter substrates: implication for primary pulmonary hypertension. Circulation 1999; 100: 869–75PubMedCrossRef
116.
Zurück zum Zitat Guven A, Koksal N, Cetinkaya A, et al. Effects of the sibutramine therapy on pulmonary artery pressure in obese patients. Diabetes Obes Metab 2004; 6: 50–5PubMedCrossRef Guven A, Koksal N, Cetinkaya A, et al. Effects of the sibutramine therapy on pulmonary artery pressure in obese patients. Diabetes Obes Metab 2004; 6: 50–5PubMedCrossRef
117.
Zurück zum Zitat Abramowicz MJ, Van Haecke P, Demedts M, et al. Primary pulmonary hypertension after amfepramone (diethylpropion) with BMPR2 mutation. Eur Respir J 2003; 22: 560–2PubMedCrossRef Abramowicz MJ, Van Haecke P, Demedts M, et al. Primary pulmonary hypertension after amfepramone (diethylpropion) with BMPR2 mutation. Eur Respir J 2003; 22: 560–2PubMedCrossRef
118.
Zurück zum Zitat Archer SL, Djaballah K, Humbert M, et al. Nitric oxide deficiency in fenfluramine- and dexfenfluramine- induced pulmonary hypertension. Am J Respir Crit Care Med 1998; 158: 1061–7PubMed Archer SL, Djaballah K, Humbert M, et al. Nitric oxide deficiency in fenfluramine- and dexfenfluramine- induced pulmonary hypertension. Am J Respir Crit Care Med 1998; 158: 1061–7PubMed
119.
Zurück zum Zitat Blanpain C, Le Poul E, Parma J, et al. Serotonin 5-HT(2B) receptor loss of function mutation in a patient with fenfluramine- associated primary pulmonary hypertension. Cardiovasc Res 2003; 60: 518–28PubMedCrossRef Blanpain C, Le Poul E, Parma J, et al. Serotonin 5-HT(2B) receptor loss of function mutation in a patient with fenfluramine- associated primary pulmonary hypertension. Cardiovasc Res 2003; 60: 518–28PubMedCrossRef
120.
Zurück zum Zitat Connolly HM, Crary JL, McGoon MD, et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 1997; 337: 581–8PubMedCrossRef Connolly HM, Crary JL, McGoon MD, et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 1997; 337: 581–8PubMedCrossRef
121.
Zurück zum Zitat Reid CL, Gardin JM, Yunis C, et al. Prevalence and clinical correlates of aortic and mitral regurgitation in a young adult population: the CARDIA study [abstract]. Circulation 1994; 90: 1520 Reid CL, Gardin JM, Yunis C, et al. Prevalence and clinical correlates of aortic and mitral regurgitation in a young adult population: the CARDIA study [abstract]. Circulation 1994; 90: 1520
122.
Zurück zum Zitat Weissman NJ. Appetite suppressants and valvular heart disease. Am J Med Sci 2001; 321: 285–91PubMedCrossRef Weissman NJ. Appetite suppressants and valvular heart disease. Am J Med Sci 2001; 321: 285–91PubMedCrossRef
123.
Zurück zum Zitat Bowen R, Glicklich A, Khan K, et al. Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine. US Department of Health and Human Services Interim Public Health Recommendations. November 1997. MMWR Morb Mortal Wkly Rep 1997; 46: 1061–6 Bowen R, Glicklich A, Khan K, et al. Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine. US Department of Health and Human Services Interim Public Health Recommendations. November 1997. MMWR Morb Mortal Wkly Rep 1997; 46: 1061–6
124.
Zurück zum Zitat Graham DJ, Green L. Further cases of valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 1997; 337: 635PubMedCrossRef Graham DJ, Green L. Further cases of valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 1997; 337: 635PubMedCrossRef
125.
Zurück zum Zitat Cannistra LB, Davis SM, Bauman AG. Valvular heart disease associated with dexfenfluramine. N Engl J Med 1997; 337: 636PubMedCrossRef Cannistra LB, Davis SM, Bauman AG. Valvular heart disease associated with dexfenfluramine. N Engl J Med 1997; 337: 636PubMedCrossRef
126.
Zurück zum Zitat Griffen L, Anchors M. Asymptomatic mitral and aortic valve disease is seen in half of the patients taking ‘Phen-Fen’. Arch Intern Med 1998; 158: 102PubMedCrossRef Griffen L, Anchors M. Asymptomatic mitral and aortic valve disease is seen in half of the patients taking ‘Phen-Fen’. Arch Intern Med 1998; 158: 102PubMedCrossRef
127.
Zurück zum Zitat Rasmussen S, Corya BC, Glassman RD. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 1997; 337: 1772–6CrossRef Rasmussen S, Corya BC, Glassman RD. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 1997; 337: 1772–6CrossRef
128.
Zurück zum Zitat Cannistra LB, Cannistra AJ. Regression of multivalvular regurgitation after the cessation of fenfluramine and phentermine treatment. N Engl J Med 1998; 339: 771PubMedCrossRef Cannistra LB, Cannistra AJ. Regression of multivalvular regurgitation after the cessation of fenfluramine and phentermine treatment. N Engl J Med 1998; 339: 771PubMedCrossRef
129.
Zurück zum Zitat Khan MA, Herzog CA, St Peter JV, et al. The prevalence of cardiac valvular insufficiency assessed by transthoracic echocardiography in obese patients treated with appetite-suppressant drugs. N Engl J Med 1998; 339: 713–8PubMedCrossRef Khan MA, Herzog CA, St Peter JV, et al. The prevalence of cardiac valvular insufficiency assessed by transthoracic echocardiography in obese patients treated with appetite-suppressant drugs. N Engl J Med 1998; 339: 713–8PubMedCrossRef
130.
Zurück zum Zitat Weissman NJ, Tighe JF, Gottdiener JS, et al. An assessment of heart-valve abnormalities in obese patients taking dexfenfluramine, sustained-release dexfenfluramine, or placebo. Sustained-release Dexfenfluramine Study Group. N Engl J Med 1998; 339: 725–32PubMedCrossRef Weissman NJ, Tighe JF, Gottdiener JS, et al. An assessment of heart-valve abnormalities in obese patients taking dexfenfluramine, sustained-release dexfenfluramine, or placebo. Sustained-release Dexfenfluramine Study Group. N Engl J Med 1998; 339: 725–32PubMedCrossRef
131.
Zurück zum Zitat Jollis JG, Landolfo CK, Kisslo J, et al. Fenfluramine and phentermine and cardiovascular findings: effect of treatment duration on prevalence of valve abnormalities. Circulation 2000; 101: 2071–7PubMedCrossRef Jollis JG, Landolfo CK, Kisslo J, et al. Fenfluramine and phentermine and cardiovascular findings: effect of treatment duration on prevalence of valve abnormalities. Circulation 2000; 101: 2071–7PubMedCrossRef
132.
Zurück zum Zitat Weissman NJ, Gottdiener JS, Gwynne JT. Appetite suppressant drugs and heart disease [letter]. N Engl J Med 1999; 340: 479 Weissman NJ, Gottdiener JS, Gwynne JT. Appetite suppressant drugs and heart disease [letter]. N Engl J Med 1999; 340: 479
133.
Zurück zum Zitat Singl JP, Evans J, Levy D, et al. Framingham Heart Study [abstract]. Circulation 1997; 96: 1541 Singl JP, Evans J, Levy D, et al. Framingham Heart Study [abstract]. Circulation 1997; 96: 1541
134.
Zurück zum Zitat Wadden TA, Berkowitz RI, Silvestr F, et al. The fen-phen finale: a study of weight loss and valvular disease. Obes Res 1998; 6: 278–84PubMedCrossRef Wadden TA, Berkowitz RI, Silvestr F, et al. The fen-phen finale: a study of weight loss and valvular disease. Obes Res 1998; 6: 278–84PubMedCrossRef
135.
Zurück zum Zitat Wee CC, Phillips RS, Aurigemma G, et al. Risk for valvular heart disease among users of fenfluramine and dexfenfluramine who underwent echocardiography before use of medication. Ann Intern Med 1998; 129: 870–4PubMed Wee CC, Phillips RS, Aurigemma G, et al. Risk for valvular heart disease among users of fenfluramine and dexfenfluramine who underwent echocardiography before use of medication. Ann Intern Med 1998; 129: 870–4PubMed
136.
Zurück zum Zitat Ryan DH, Bray GA, Helmcke F, et al. Serial echocardiographic and clinical evaluation of valvular regurgitation before, during and after treatment with fenfluramine or dexfenfluramine and mazindol or phentermine. Obes Res 1999; 7: 313–22PubMedCrossRef Ryan DH, Bray GA, Helmcke F, et al. Serial echocardiographic and clinical evaluation of valvular regurgitation before, during and after treatment with fenfluramine or dexfenfluramine and mazindol or phentermine. Obes Res 1999; 7: 313–22PubMedCrossRef
137.
Zurück zum Zitat Burger AJ, Sherman HB, Charlamb MJ, et al. Low prevalence of valvular heart disease in 226 phentermine-fenfluramine protocol subjects prospectively followed for up to 30 months. J Am Coll Cardiol 1999; 34: 1153–8PubMedCrossRef Burger AJ, Sherman HB, Charlamb MJ, et al. Low prevalence of valvular heart disease in 226 phentermine-fenfluramine protocol subjects prospectively followed for up to 30 months. J Am Coll Cardiol 1999; 34: 1153–8PubMedCrossRef
138.
Zurück zum Zitat Kancherla MK, Salti HI, Mulderink TA, et al. Echocardiographic prevalence of mitral and/or aortic regurgitation in patients exposed to either fenfluramine-phentermine combination or to dexfenfluramine. Am J Cardiol 1999; 84: 1335–8PubMedCrossRef Kancherla MK, Salti HI, Mulderink TA, et al. Echocardiographic prevalence of mitral and/or aortic regurgitation in patients exposed to either fenfluramine-phentermine combination or to dexfenfluramine. Am J Cardiol 1999; 84: 1335–8PubMedCrossRef
139.
Zurück zum Zitat Lepor NE, Gross SB, Daley WL, et al. Dose and duration of fenfluramine-phentermine therapy impacts the risk of significant valvular heart disease. Am J Cardiol 2000; 86: 107–10PubMedCrossRef Lepor NE, Gross SB, Daley WL, et al. Dose and duration of fenfluramine-phentermine therapy impacts the risk of significant valvular heart disease. Am J Cardiol 2000; 86: 107–10PubMedCrossRef
140.
Zurück zum Zitat Burger AJ, Charlamb MJ, Singh S, et al. Low risk of significant echocardiographic valvulopathy in patients treated with anorectic drugs. Int J Cardiol 2001; 79: 159–65PubMedCrossRef Burger AJ, Charlamb MJ, Singh S, et al. Low risk of significant echocardiographic valvulopathy in patients treated with anorectic drugs. Int J Cardiol 2001; 79: 159–65PubMedCrossRef
141.
Zurück zum Zitat Weissman NJ, Tighe JF, Gottdiener JS, et al. Prevalence of valvular-regurgitation associated with dexfenfluramine three to five months after discontinuation of treatment. J Am Coll Cardiol 1999; 34: 2088–95PubMedCrossRef Weissman NJ, Tighe JF, Gottdiener JS, et al. Prevalence of valvular-regurgitation associated with dexfenfluramine three to five months after discontinuation of treatment. J Am Coll Cardiol 1999; 34: 2088–95PubMedCrossRef
142.
Zurück zum Zitat Shively BK, Roldan CA, Gill EA, et al. Prevalence and determinants of valvulopathy in patients treated with dexfenfluramine. Circulation 1999; 100: 2161–7PubMedCrossRef Shively BK, Roldan CA, Gill EA, et al. Prevalence and determinants of valvulopathy in patients treated with dexfenfluramine. Circulation 1999; 100: 2161–7PubMedCrossRef
143.
Zurück zum Zitat Hensrud DD, Conolly HM, Grogan M, et al. Echocardiographic improvement over time after cessation of use of fenfluramine and phentermine. Mayo Clin Proc 1999; 74: 1191–7PubMedCrossRef Hensrud DD, Conolly HM, Grogan M, et al. Echocardiographic improvement over time after cessation of use of fenfluramine and phentermine. Mayo Clin Proc 1999; 74: 1191–7PubMedCrossRef
144.
Zurück zum Zitat Gardin JM, Schumacher D, Constantine G, et al. Valvular abnormalities and cardiovascular status following exposure to dexfenfluramine or phentermine/fenfluramine. JAMA 2000; 283: 1703–9PubMedCrossRef Gardin JM, Schumacher D, Constantine G, et al. Valvular abnormalities and cardiovascular status following exposure to dexfenfluramine or phentermine/fenfluramine. JAMA 2000; 283: 1703–9PubMedCrossRef
145.
Zurück zum Zitat Davidoff R, McTiernan A, Constantine G, et al. Echocardiographic examination of women previously treated with fenfluramine. Long-term follow-up of a randomised, double blind, placebo-controlled trial. Arch Intern Med 2001; 161: 1429–36PubMedCrossRef Davidoff R, McTiernan A, Constantine G, et al. Echocardiographic examination of women previously treated with fenfluramine. Long-term follow-up of a randomised, double blind, placebo-controlled trial. Arch Intern Med 2001; 161: 1429–36PubMedCrossRef
146.
Zurück zum Zitat Jick H, Vasilakis C, Weinrauch LA, et al. A population based study of appetite suppressant drugs and the risk of cardiacvalve regurgitation. N Engl J Med 1998; 339: 719–24PubMedCrossRef Jick H, Vasilakis C, Weinrauch LA, et al. A population based study of appetite suppressant drugs and the risk of cardiacvalve regurgitation. N Engl J Med 1998; 339: 719–24PubMedCrossRef
147.
Zurück zum Zitat Klein AL, Burstow DJ, Tajik AJ, et al. Age-related prevalence of valvular regurgitation in normal suibjects. J AM Soc Echocardiogr 1990; 3: 54–63PubMed Klein AL, Burstow DJ, Tajik AJ, et al. Age-related prevalence of valvular regurgitation in normal suibjects. J AM Soc Echocardiogr 1990; 3: 54–63PubMed
148.
Zurück zum Zitat Shively B, Roldan C, Gurule F, et al. Age-related changes in cardiac function by color Doppler echocardiography. J AM Coll Cardiol 1990; 15: 187ACrossRef Shively B, Roldan C, Gurule F, et al. Age-related changes in cardiac function by color Doppler echocardiography. J AM Coll Cardiol 1990; 15: 187ACrossRef
149.
Zurück zum Zitat Weissman NJ, Panza JA, Tighe JF, et al. Natural history of valvular regurgitation 1 year after discontinuation of dexfenfluramine therapy: a randomised, double-blind, placebo-controlled trial. Ann Intern Med 2001; 134: 267–73PubMed Weissman NJ, Panza JA, Tighe JF, et al. Natural history of valvular regurgitation 1 year after discontinuation of dexfenfluramine therapy: a randomised, double-blind, placebo-controlled trial. Ann Intern Med 2001; 134: 267–73PubMed
150.
Zurück zum Zitat Gardin JM, Weissman NJ, Leung C, et al. Clinical and echocardiographic follow-up of patients previously treated with dexfenfluramine or phentermine/fenfluramine. JAMA 2001; 286: 2011–4PubMedCrossRef Gardin JM, Weissman NJ, Leung C, et al. Clinical and echocardiographic follow-up of patients previously treated with dexfenfluramine or phentermine/fenfluramine. JAMA 2001; 286: 2011–4PubMedCrossRef
151.
Zurück zum Zitat Mast ST, Jollis JG, Ryan T, et al. The progression of fenfluramine-associated valvular heart disease assessed by echocardiography. Ann Intern Med 2001; 134: 261–6PubMed Mast ST, Jollis JG, Ryan T, et al. The progression of fenfluramine-associated valvular heart disease assessed by echocardiography. Ann Intern Med 2001; 134: 261–6PubMed
152.
Zurück zum Zitat Dahl CF, Allen MR. Regression and progression of valvulopathy associated with fenfluramine and phentermine. Ann Intern Med 2002; 136: 489PubMed Dahl CF, Allen MR. Regression and progression of valvulopathy associated with fenfluramine and phentermine. Ann Intern Med 2002; 136: 489PubMed
153.
Zurück zum Zitat Unger P, Nortier J, Martinez MM, et al. High prevalence of fenfluramine-related aortic regurgitation in women with endstage renal disease secondary to Chinese herb nephropathy. Nephrol Dial Transpl 2003; 18: 906–10CrossRef Unger P, Nortier J, Martinez MM, et al. High prevalence of fenfluramine-related aortic regurgitation in women with endstage renal disease secondary to Chinese herb nephropathy. Nephrol Dial Transpl 2003; 18: 906–10CrossRef
154.
Zurück zum Zitat Li R, Serdula MK, Williamson DF, et al. Dose-effect of fenfluramine use on the severity of valvular heart disease among fen-phen patients with valvulopathy. Int J Obes Relat Metab Disord 1999; 23: 926–8PubMedCrossRef Li R, Serdula MK, Williamson DF, et al. Dose-effect of fenfluramine use on the severity of valvular heart disease among fen-phen patients with valvulopathy. Int J Obes Relat Metab Disord 1999; 23: 926–8PubMedCrossRef
155.
Zurück zum Zitat Parisi AF. Diet-drug debacle. Ann Intern Med 1998; 129: 903–5PubMed Parisi AF. Diet-drug debacle. Ann Intern Med 1998; 129: 903–5PubMed
156.
Zurück zum Zitat Sachdev M, Miller WC, Ryan T, et al. Effect of fenfluramine-derivative diet pills on cardiac valves: a meta-analysis of observational studies. Am Heart J 2002; 144: 1065–73PubMedCrossRef Sachdev M, Miller WC, Ryan T, et al. Effect of fenfluramine-derivative diet pills on cardiac valves: a meta-analysis of observational studies. Am Heart J 2002; 144: 1065–73PubMedCrossRef
158.
Zurück zum Zitat Klein AL, Griffin BP, Grimm RA, et al. Natural history of valvular regurgitation using side-by-side echocardiographic analysis in anorexigen-treated subjects. Am J Cardiol 2005; 96: 1711–7PubMedCrossRef Klein AL, Griffin BP, Grimm RA, et al. Natural history of valvular regurgitation using side-by-side echocardiographic analysis in anorexigen-treated subjects. Am J Cardiol 2005; 96: 1711–7PubMedCrossRef
159.
Zurück zum Zitat Roldan CA, Decker PJ, Gelgand EA, et al. Transesophageal echocardiography in phentermine-fenfluramine users suggests frequent misdiagnosis of valvular heart disease by transthoracic echocardiography [abstract]. J Am Coll Cardiol 1999; 33: 549ACrossRef Roldan CA, Decker PJ, Gelgand EA, et al. Transesophageal echocardiography in phentermine-fenfluramine users suggests frequent misdiagnosis of valvular heart disease by transthoracic echocardiography [abstract]. J Am Coll Cardiol 1999; 33: 549ACrossRef
160.
Zurück zum Zitat Kimmel SE, Keane MG, Crary JL, et al. Detailed examination of fenfluramine-phentermine users with valve abnormalities identified in Fargo, North Dakota. Am J Cardiol 1999; 84: 304–8PubMedCrossRef Kimmel SE, Keane MG, Crary JL, et al. Detailed examination of fenfluramine-phentermine users with valve abnormalities identified in Fargo, North Dakota. Am J Cardiol 1999; 84: 304–8PubMedCrossRef
161.
Zurück zum Zitat Maher TJ, Ulus IH, Wurtman RJ. Phentermine and other monoamine-oxidase inhibitors may increase plasma serotonin when given with fenfluramines. Lancet 1999; 353: 38PubMedCrossRef Maher TJ, Ulus IH, Wurtman RJ. Phentermine and other monoamine-oxidase inhibitors may increase plasma serotonin when given with fenfluramines. Lancet 1999; 353: 38PubMedCrossRef
163.
Zurück zum Zitat Bana DS, MacNeal PS, LeCompte PM, et al. Cardiac murmurs and endocardial fibrosis associated with methysergide therapy. Am Heart J 1974; 88: 640–55PubMedCrossRef Bana DS, MacNeal PS, LeCompte PM, et al. Cardiac murmurs and endocardial fibrosis associated with methysergide therapy. Am Heart J 1974; 88: 640–55PubMedCrossRef
164.
Zurück zum Zitat Redfield MM, Nicholson WJ, Edwards WD, et al. Valve disease associated with ergot alkaloid use: echocardiographic and pathologic correlations. Ann Intern Med 1992; 117: 50–2PubMed Redfield MM, Nicholson WJ, Edwards WD, et al. Valve disease associated with ergot alkaloid use: echocardiographic and pathologic correlations. Ann Intern Med 1992; 117: 50–2PubMed
165.
Zurück zum Zitat Hauck AJ, Edwards WD, Danielson GK, et al. Mitral and aortic valve disease associated with ergotamine therapy for migraine. Report of two cases and review of literature. Arch Pathol Lab Med 1990; 114: 62–4PubMed Hauck AJ, Edwards WD, Danielson GK, et al. Mitral and aortic valve disease associated with ergotamine therapy for migraine. Report of two cases and review of literature. Arch Pathol Lab Med 1990; 114: 62–4PubMed
166.
Zurück zum Zitat Pritchett AM, Morrison JF, Edwards WD, et al. Valvular heart disease in patients taking pergolide. Mayo Clin Proc 2002; 77: 1280–6PubMedCrossRef Pritchett AM, Morrison JF, Edwards WD, et al. Valvular heart disease in patients taking pergolide. Mayo Clin Proc 2002; 77: 1280–6PubMedCrossRef
167.
Zurück zum Zitat Horvath J, Fross RD, Kleiner-Fisman G, et al. Severe multivalvular heart disease: a new complication of the ergot derivative dopamine agonists. Mov Disord 2004; 19: 656–62PubMedCrossRef Horvath J, Fross RD, Kleiner-Fisman G, et al. Severe multivalvular heart disease: a new complication of the ergot derivative dopamine agonists. Mov Disord 2004; 19: 656–62PubMedCrossRef
168.
169.
Zurück zum Zitat Griffen L, Anchors M. The ‘Phen-Pro’ diet drug combination is not associated with valvular heart disease. Arch Intern Med 1998; 158: 1278–9PubMedCrossRef Griffen L, Anchors M. The ‘Phen-Pro’ diet drug combination is not associated with valvular heart disease. Arch Intern Med 1998; 158: 1278–9PubMedCrossRef
170.
Zurück zum Zitat Mast ST, Gersing KR, Anstrom KJ, et al. Association between selective serotonin-reuptake inhibitor therapy and heart valve regurgitation. Am J Cardiol 2001; 87: 989–93PubMedCrossRef Mast ST, Gersing KR, Anstrom KJ, et al. Association between selective serotonin-reuptake inhibitor therapy and heart valve regurgitation. Am J Cardiol 2001; 87: 989–93PubMedCrossRef
171.
Zurück zum Zitat Halpern A, Leite CC, Herszkowicz N, et al. Evaluation of efficacy, reliability, and tolerability of sibutramine in obese patients with an echocardiographic study. Rev Hosp Clin Fac Med Sao Paulo 2002; 57: 98–102PubMedCrossRef Halpern A, Leite CC, Herszkowicz N, et al. Evaluation of efficacy, reliability, and tolerability of sibutramine in obese patients with an echocardiographic study. Rev Hosp Clin Fac Med Sao Paulo 2002; 57: 98–102PubMedCrossRef
172.
Zurück zum Zitat Zannad F, Gille B, Grentzinger A, et al. Effects of sibutramine on ventricular dimensions and heart valves in obese patients during weight reduction. Am Heart J 2002; 144: 508–15PubMedCrossRef Zannad F, Gille B, Grentzinger A, et al. Effects of sibutramine on ventricular dimensions and heart valves in obese patients during weight reduction. Am Heart J 2002; 144: 508–15PubMedCrossRef
173.
Zurück zum Zitat Bach DS, Rissanen AM, Mendel CM, et al. Absence of cardiac valve dysfunction in obese patients treated with sibutramine. Obes Res 1999; 7: 363–9PubMedCrossRef Bach DS, Rissanen AM, Mendel CM, et al. Absence of cardiac valve dysfunction in obese patients treated with sibutramine. Obes Res 1999; 7: 363–9PubMedCrossRef
174.
Zurück zum Zitat Fowles RE, Cloward TV, Yowell RL. Endocardial fibrosis associated with fenfluramine-phentermine. N Engl J Med 1998; 338: 1316PubMedCrossRef Fowles RE, Cloward TV, Yowell RL. Endocardial fibrosis associated with fenfluramine-phentermine. N Engl J Med 1998; 338: 1316PubMedCrossRef
175.
Zurück zum Zitat Schembre DB, Boynton KK. Appetite-suppressant drugs and pulmonary hypertension [letter]. N Engl J Med 1997; 336: 510–1PubMedCrossRef Schembre DB, Boynton KK. Appetite-suppressant drugs and pulmonary hypertension [letter]. N Engl J Med 1997; 336: 510–1PubMedCrossRef
176.
Zurück zum Zitat Wen PY, Feske SK, Teoh SK, et al. Cerebral haemorrhage in patient taking fenfluramine and phentermine for obesity. Neurology 1997; 49: 632–3PubMedCrossRef Wen PY, Feske SK, Teoh SK, et al. Cerebral haemorrhage in patient taking fenfluramine and phentermine for obesity. Neurology 1997; 49: 632–3PubMedCrossRef
177.
Zurück zum Zitat Pentel PR, Aaron C, Paya C. Therapeutic doses of phenylpropanolamine increase supine systolic blood pressure. Int J Obes 1985; 9: 115–9PubMed Pentel PR, Aaron C, Paya C. Therapeutic doses of phenylpropanolamine increase supine systolic blood pressure. Int J Obes 1985; 9: 115–9PubMed
178.
Zurück zum Zitat Lake CR, Gallant S, Masson E, et al. Adverse drug effects attributed to phenylpropanolamine: a review of 142 case reports. Am J Med 1990; 89: 195–208PubMedCrossRef Lake CR, Gallant S, Masson E, et al. Adverse drug effects attributed to phenylpropanolamine: a review of 142 case reports. Am J Med 1990; 89: 195–208PubMedCrossRef
179.
Zurück zum Zitat Leo PJ, Hollander JE, Shih RD, et al. Phenylpropanolamine and associated myocardial injury. Ann Emerg Med 1996; 28: 359–62PubMedCrossRef Leo PJ, Hollander JE, Shih RD, et al. Phenylpropanolamine and associated myocardial injury. Ann Emerg Med 1996; 28: 359–62PubMedCrossRef
180.
Zurück zum Zitat Pilsczek FH, Karcic AA, Freeman I. Case report: Dexatrim (Phenylpropanolamine) as a cause of myocardial infarction. Heart Lung 2003; 32: 100–4PubMedCrossRef Pilsczek FH, Karcic AA, Freeman I. Case report: Dexatrim (Phenylpropanolamine) as a cause of myocardial infarction. Heart Lung 2003; 32: 100–4PubMedCrossRef
181.
Zurück zum Zitat Kokkinos J, Levine SR. Possible association of ischemic stroke with phentermine. Stroke 1993; 24: 310–3PubMedCrossRef Kokkinos J, Levine SR. Possible association of ischemic stroke with phentermine. Stroke 1993; 24: 310–3PubMedCrossRef
182.
Zurück zum Zitat Crol R, Dierckx R, Saerens J, et al. Transient ischemic attacks associated with amfepramone therapy: a case report. Functional Neurol 1993; 8: 351–4 Crol R, Dierckx R, Saerens J, et al. Transient ischemic attacks associated with amfepramone therapy: a case report. Functional Neurol 1993; 8: 351–4
183.
Zurück zum Zitat Hanotin C, Thomas F, Jones SP, et al. A comparison of sibutramine and dexfenfluramine in the treatment of obesity. Obes Res 1998; 6: 285–91PubMedCrossRef Hanotin C, Thomas F, Jones SP, et al. A comparison of sibutramine and dexfenfluramine in the treatment of obesity. Obes Res 1998; 6: 285–91PubMedCrossRef
184.
Zurück zum Zitat McMahon FG, Weinstein SP, Rowe E, et al. Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors. J Hum Hypertens 2002; 16: 5–11PubMedCrossRef McMahon FG, Weinstein SP, Rowe E, et al. Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors. J Hum Hypertens 2002; 16: 5–11PubMedCrossRef
185.
Zurück zum Zitat Birkenfeld AL, Schroeder C, Boschmann M, et al. Paradoxical effect of sibutramine on autonomic cardiovascular regulation. Circulation 2002; 106: 2459–65PubMedCrossRef Birkenfeld AL, Schroeder C, Boschmann M, et al. Paradoxical effect of sibutramine on autonomic cardiovascular regulation. Circulation 2002; 106: 2459–65PubMedCrossRef
186.
187.
Zurück zum Zitat Sayin T, Guldal M. Sibutramine: possible cause of a reversible cardiomyopathy [letter]. Int J Cardiol 2005; 99: 481–2PubMedCrossRef Sayin T, Guldal M. Sibutramine: possible cause of a reversible cardiomyopathy [letter]. Int J Cardiol 2005; 99: 481–2PubMedCrossRef
188.
Zurück zum Zitat Faria AN, Ribeiro Filho FF, Kohlmann NE, et al. Effects of sibutramine on abdominal fat mass, insulin resistance and blood pressure in obese hypertensive patients. Diabetes Obes Metab 2005; 7: 246–53PubMedCrossRef Faria AN, Ribeiro Filho FF, Kohlmann NE, et al. Effects of sibutramine on abdominal fat mass, insulin resistance and blood pressure in obese hypertensive patients. Diabetes Obes Metab 2005; 7: 246–53PubMedCrossRef
189.
Zurück zum Zitat Glick R, Hoying J, Cerullo L, et al. Phenylpropanolamine: an over-the-counter drug causing central nervous system vasculitis and intracerebral hemorrhage: case report and review. Neurosurgery 1987; 20: 969–74PubMedCrossRef Glick R, Hoying J, Cerullo L, et al. Phenylpropanolamine: an over-the-counter drug causing central nervous system vasculitis and intracerebral hemorrhage: case report and review. Neurosurgery 1987; 20: 969–74PubMedCrossRef
190.
Zurück zum Zitat Kase CS, Foster TE, Reed JE, et al. Intracerebral hemorrhage and phenylpropanolamine use. Neurology 1987; 37: 399–404PubMedCrossRef Kase CS, Foster TE, Reed JE, et al. Intracerebral hemorrhage and phenylpropanolamine use. Neurology 1987; 37: 399–404PubMedCrossRef
191.
Zurück zum Zitat Mueller SM, Muller J, Asdell SM. Cerebral hemorrhage associated with phenylpropanolamine in combination with caffeine. Stroke 1984; 15: 119–23PubMedCrossRef Mueller SM, Muller J, Asdell SM. Cerebral hemorrhage associated with phenylpropanolamine in combination with caffeine. Stroke 1984; 15: 119–23PubMedCrossRef
192.
Zurück zum Zitat Johnson DA, Etter HS, Reeves DM. Stroke and phenylpropanolamine use. Lancet 1983; II: 970CrossRef Johnson DA, Etter HS, Reeves DM. Stroke and phenylpropanolamine use. Lancet 1983; II: 970CrossRef
193.
Zurück zum Zitat Kernan WN, Viscoli CM, Brass LM, et al. Phenylpropanolamine and risk of hemorrhagic stroke. N Engl J Med 2000; 343: 1826–32PubMedCrossRef Kernan WN, Viscoli CM, Brass LM, et al. Phenylpropanolamine and risk of hemorrhagic stroke. N Engl J Med 2000; 343: 1826–32PubMedCrossRef
194.
Zurück zum Zitat McCann UD, Seiden LS, Rubin LJ, et al. Brain serotonin neurotoxicity and primary pulmonary hypertension from fenfluramine and dexfenfluramine: a systematic review of the evidence. JAMA 1997; 278: 666–72PubMedCrossRef McCann UD, Seiden LS, Rubin LJ, et al. Brain serotonin neurotoxicity and primary pulmonary hypertension from fenfluramine and dexfenfluramine: a systematic review of the evidence. JAMA 1997; 278: 666–72PubMedCrossRef
195.
Zurück zum Zitat Angrist B, Sathananthan G, Wilk S, et al. Amphetamine psychosis: behavioral and biochemical aspects. J Psychiatr Res 1974; 11: 13–23PubMedCrossRef Angrist B, Sathananthan G, Wilk S, et al. Amphetamine psychosis: behavioral and biochemical aspects. J Psychiatr Res 1974; 11: 13–23PubMedCrossRef
196.
Zurück zum Zitat Groves PM, Rebec GV. Biochemistry and behavior: some central actions of amphetamine and antipsychotic drugs. Annu Rev Psychol 1976; 27: 91–127PubMedCrossRef Groves PM, Rebec GV. Biochemistry and behavior: some central actions of amphetamine and antipsychotic drugs. Annu Rev Psychol 1976; 27: 91–127PubMedCrossRef
197.
Zurück zum Zitat Janowsky DS, Risch C. Amphetamine psychosis and psychotic symptoms. Psychopharmacology (Berl) 1979; 65: 73–7CrossRef Janowsky DS, Risch C. Amphetamine psychosis and psychotic symptoms. Psychopharmacology (Berl) 1979; 65: 73–7CrossRef
198.
Zurück zum Zitat Taflinski T, Chojnacka J. Sibutramine-associated psychotic episode [letter]. Am J Psychiatry 2000; 157: 2057–8PubMedCrossRef Taflinski T, Chojnacka J. Sibutramine-associated psychotic episode [letter]. Am J Psychiatry 2000; 157: 2057–8PubMedCrossRef
199.
Zurück zum Zitat Clark DWJ, Harrison-Woolrych M. Sibutramine may be associated with memory impairment. BMJ 2004; 329: 1316PubMedCrossRef Clark DWJ, Harrison-Woolrych M. Sibutramine may be associated with memory impairment. BMJ 2004; 329: 1316PubMedCrossRef
200.
Zurück zum Zitat Goh BK, Ng PP, Giam YC. Severe bullous drug eruption due to sibutramine (Reductil®). Br J Dermatol 2003; 149: 193–227CrossRef Goh BK, Ng PP, Giam YC. Severe bullous drug eruption due to sibutramine (Reductil®). Br J Dermatol 2003; 149: 193–227CrossRef
201.
Zurück zum Zitat Curran MP, Scott LJ. Orlistat: a review of its use in the management of patients with obesity. Drugs 2004; 64: 2845–64PubMedCrossRef Curran MP, Scott LJ. Orlistat: a review of its use in the management of patients with obesity. Drugs 2004; 64: 2845–64PubMedCrossRef
202.
Zurück zum Zitat Hollander PA, Elbein SC, Hirsch IB, et al. Role of orlistat in the treatment of obese patients with type 2 diabetes. Diabetes Care 1998; 21: 1288–94PubMedCrossRef Hollander PA, Elbein SC, Hirsch IB, et al. Role of orlistat in the treatment of obese patients with type 2 diabetes. Diabetes Care 1998; 21: 1288–94PubMedCrossRef
203.
Zurück zum Zitat Finer N, James WP, Kopelman PG, et al. One-year treatment of obesity: a randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor. Int J Obes Relat Metab Disord 2000; 24: 306–13PubMedCrossRef Finer N, James WP, Kopelman PG, et al. One-year treatment of obesity: a randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor. Int J Obes Relat Metab Disord 2000; 24: 306–13PubMedCrossRef
204.
Zurück zum Zitat James WPT, Avenell A, Broom J, et al. A one-year trial to assess the value of orlistat in the management of obesity. Int J Obes 1997; 21Suppl. 3: 24–30 James WPT, Avenell A, Broom J, et al. A one-year trial to assess the value of orlistat in the management of obesity. Int J Obes 1997; 21Suppl. 3: 24–30
205.
Zurück zum Zitat Hauptman J, Lucas C, Boldrin MN, et al. Orlistat in the long-term treatment of obesity in primary care settings, for the Orlistat Primary Care Study Group. Arch Fam Med 2000; 9: 160–7PubMedCrossRef Hauptman J, Lucas C, Boldrin MN, et al. Orlistat in the long-term treatment of obesity in primary care settings, for the Orlistat Primary Care Study Group. Arch Fam Med 2000; 9: 160–7PubMedCrossRef
206.
Zurück zum Zitat Melia AT, Koss-Twardy SG, Zhi J. The effect of orlistat, an inhibitor of dietary fat absorption, on the absorption of vitamins A and E in healthy volunteers. J Clin Pharmacol 1996; 36: 647–53PubMed Melia AT, Koss-Twardy SG, Zhi J. The effect of orlistat, an inhibitor of dietary fat absorption, on the absorption of vitamins A and E in healthy volunteers. J Clin Pharmacol 1996; 36: 647–53PubMed
207.
Zurück zum Zitat Wadden TA, Berkowitz RI, Womble LG, et al. Effects of sibutramine plus orlistat in obese women following 1 year of treatment by sibutramine alone: a placebo-controlled trial. Obes Res 2000; 6: 431–7CrossRef Wadden TA, Berkowitz RI, Womble LG, et al. Effects of sibutramine plus orlistat in obese women following 1 year of treatment by sibutramine alone: a placebo-controlled trial. Obes Res 2000; 6: 431–7CrossRef
209.
Zurück zum Zitat Valsecia ME, Malgor LA, Farias EF, et al. Interaction between orlistat and antihypertensive drugs [letter]. Ann Pharmacother 2001; 35: 1495–6CrossRef Valsecia ME, Malgor LA, Farias EF, et al. Interaction between orlistat and antihypertensive drugs [letter]. Ann Pharmacother 2001; 35: 1495–6CrossRef
210.
Zurück zum Zitat Sobel RM. Ruptured retroperitoneal aneurysm in a patient taking phentermine hydrochloride. Am J Emerg Med 1999; 17: 102–3PubMedCrossRef Sobel RM. Ruptured retroperitoneal aneurysm in a patient taking phentermine hydrochloride. Am J Emerg Med 1999; 17: 102–3PubMedCrossRef
211.
Zurück zum Zitat Comay D, Ramsay J, Irvine EJ. Ischaemic colitis after weightloss medication. Can J Gastroenterol 2003; 17: 719–21PubMed Comay D, Ramsay J, Irvine EJ. Ischaemic colitis after weightloss medication. Can J Gastroenterol 2003; 17: 719–21PubMed
212.
Zurück zum Zitat Markowitz GS, Tartini A, D’Agati VD. Acute interstital nephritis following treatment with anoretic agents phentermine and phendimetrazine. Clin Nephrol 1998; 50: 252–4PubMed Markowitz GS, Tartini A, D’Agati VD. Acute interstital nephritis following treatment with anoretic agents phentermine and phendimetrazine. Clin Nephrol 1998; 50: 252–4PubMed
213.
Zurück zum Zitat Chounta A, Tsiodras S, Zouridakis S, et al. Sibutramine use associated with reversible hepatotoxicity. Annals Intern Med 2005; 143: 763–4 Chounta A, Tsiodras S, Zouridakis S, et al. Sibutramine use associated with reversible hepatotoxicity. Annals Intern Med 2005; 143: 763–4
214.
Zurück zum Zitat Gurley BJ, Gardner SF, Hubbard MA. Content versus label claims in ephedra-containing dietary supplements. Am J Health Syst Pharm 2000; 57: 963–9PubMed Gurley BJ, Gardner SF, Hubbard MA. Content versus label claims in ephedra-containing dietary supplements. Am J Health Syst Pharm 2000; 57: 963–9PubMed
215.
Zurück zum Zitat Chen C, Biller J, Willing SJ, et al. Ischemic stroke after using over the counter products containing ephedra. J Neurol Sci 2004; 217: 55–60PubMedCrossRef Chen C, Biller J, Willing SJ, et al. Ischemic stroke after using over the counter products containing ephedra. J Neurol Sci 2004; 217: 55–60PubMedCrossRef
216.
Zurück zum Zitat Boozer CN, Daly PA, Homel P, et al. Herbal ephedra/caffeine for weight loss: a 6-month randomized safety and efficacy trial. Int J Obes 2002; 26: 593–604CrossRef Boozer CN, Daly PA, Homel P, et al. Herbal ephedra/caffeine for weight loss: a 6-month randomized safety and efficacy trial. Int J Obes 2002; 26: 593–604CrossRef
217.
Zurück zum Zitat Bruno A, Nolte KB, Chapin J. Stroke associated with ephedrine use. Neurol 1993; 43: 1313–6 Bruno A, Nolte KB, Chapin J. Stroke associated with ephedrine use. Neurol 1993; 43: 1313–6
218.
Zurück zum Zitat Morgenstern LB, Viscoli CM, Kernan WN, et al. Use of Ephedra-containing products and risk for hemorrhagic stroke. Neurol 2003; 60: 132–5 Morgenstern LB, Viscoli CM, Kernan WN, et al. Use of Ephedra-containing products and risk for hemorrhagic stroke. Neurol 2003; 60: 132–5
219.
Zurück zum Zitat McBride BF, Karapanos AK, Krudysz A, et al. Electrocardiographic and hemodynamic effects of a multicomponent dietary supplement containing ephedra and caffeine: a randomized controlled trial. JAMA 2004; 291: 216–21PubMedCrossRef McBride BF, Karapanos AK, Krudysz A, et al. Electrocardiographic and hemodynamic effects of a multicomponent dietary supplement containing ephedra and caffeine: a randomized controlled trial. JAMA 2004; 291: 216–21PubMedCrossRef
220.
Zurück zum Zitat United States General Accounting Office. Report to the chairman subcommittee wellness and human rights committee on government reform, House of Representatives. Dietary supplements. Review of health-related call records for users of Metabolite 356 [online]. 2003 Mar. Available from URL: http://www.gao.gov/new.items/d03494.pdf [Accessed 2005 Aug 3] United States General Accounting Office. Report to the chairman subcommittee wellness and human rights committee on government reform, House of Representatives. Dietary supplements. Review of health-related call records for users of Metabolite 356 [online]. 2003 Mar. Available from URL: http://​www.​gao.​gov/​new.​items/​d03494.​pdf [Accessed 2005 Aug 3]
221.
Zurück zum Zitat LoVecchio F, Eckholdt PA. Transient ischaemic attack associated with Metabolite 356 use. Am J Emerg Med 2005; 23: 199–200PubMedCrossRef LoVecchio F, Eckholdt PA. Transient ischaemic attack associated with Metabolite 356 use. Am J Emerg Med 2005; 23: 199–200PubMedCrossRef
222.
Zurück zum Zitat Kawata K, Takehira Y, Kobayashi Y, et al. Three cases of liver injury caused by Sennomotokounou, a Chinese dietary supplement for weight loss. Intern Med 2003; 42: 1188–92PubMedCrossRef Kawata K, Takehira Y, Kobayashi Y, et al. Three cases of liver injury caused by Sennomotokounou, a Chinese dietary supplement for weight loss. Intern Med 2003; 42: 1188–92PubMedCrossRef
223.
Zurück zum Zitat Adachi M, Saito H, Kobayashi H, et al. Hepatic injury in 12 patients taking the herbal weight loss AIDS Chaso or Onshido. Ann Intern Med 2003; 139: 488–92PubMed Adachi M, Saito H, Kobayashi H, et al. Hepatic injury in 12 patients taking the herbal weight loss AIDS Chaso or Onshido. Ann Intern Med 2003; 139: 488–92PubMed
224.
Zurück zum Zitat Stevens T, Qadri A, Zein NN. Two patients with acute liver injury associated with use of the herbal weight-loss supplement hydroxycut. Ann Intern Med 2005; 142: 477–8PubMed Stevens T, Qadri A, Zein NN. Two patients with acute liver injury associated with use of the herbal weight-loss supplement hydroxycut. Ann Intern Med 2005; 142: 477–8PubMed
225.
Zurück zum Zitat Favreau JT, Ryu ML, Braunstein G, et al. Severe hepatotoxicity associated with the dietary supplement LipoKinetix. Ann Intern Med 2002; 136: 590–5PubMed Favreau JT, Ryu ML, Braunstein G, et al. Severe hepatotoxicity associated with the dietary supplement LipoKinetix. Ann Intern Med 2002; 136: 590–5PubMed
226.
Zurück zum Zitat Nasir JM, Durning SJ, Ferguson M, et al. Exercise-induced syncope associated with QT prolongation and ephedrine-free xenadrine. Mayo Clin Proc 2004; 79: 1059–62PubMedCrossRef Nasir JM, Durning SJ, Ferguson M, et al. Exercise-induced syncope associated with QT prolongation and ephedrine-free xenadrine. Mayo Clin Proc 2004; 79: 1059–62PubMedCrossRef
227.
Zurück zum Zitat Mansi IA, Huang J. Rhabdomyolysis in response to weight-loss herbal medicine. Am J Med Sci 2004; 327: 356–7PubMedCrossRef Mansi IA, Huang J. Rhabdomyolysis in response to weight-loss herbal medicine. Am J Med Sci 2004; 327: 356–7PubMedCrossRef
228.
Zurück zum Zitat Nortier JL, Martinez MC, Schmeiser HH, et al. Urothelialcarcinoma associated with the use of a Chinese herb (Aristochiafanchi). N Engl J Med 2000; 342: 1686–92PubMedCrossRef Nortier JL, Martinez MC, Schmeiser HH, et al. Urothelialcarcinoma associated with the use of a Chinese herb (Aristochiafanchi). N Engl J Med 2000; 342: 1686–92PubMedCrossRef
229.
Zurück zum Zitat Ioset J-R, Raoelison GE, Hostettmann K. Detection of aristolochic acid in Chinese phytomedicines and dietary supplements used as slimming regimens. Food Chem Toxicol 2003; 41: 29–36PubMedCrossRef Ioset J-R, Raoelison GE, Hostettmann K. Detection of aristolochic acid in Chinese phytomedicines and dietary supplements used as slimming regimens. Food Chem Toxicol 2003; 41: 29–36PubMedCrossRef
230.
Zurück zum Zitat Cosyns JP. Aristochic acid and ‘Chinese herbs nephropathy’: a review of the evidence to date. Drug Saf 2003; 26: 33–48PubMedCrossRef Cosyns JP. Aristochic acid and ‘Chinese herbs nephropathy’: a review of the evidence to date. Drug Saf 2003; 26: 33–48PubMedCrossRef
231.
Zurück zum Zitat Bray GA, Hollander P, Klein S, et al. A 6-month randomized, placebo-controlled dose-ranging trial of topiramate for weight loss in obesity. Obes Res 2003; 11: 722–33PubMedCrossRef Bray GA, Hollander P, Klein S, et al. A 6-month randomized, placebo-controlled dose-ranging trial of topiramate for weight loss in obesity. Obes Res 2003; 11: 722–33PubMedCrossRef
232.
Zurück zum Zitat Wilding J, Van Gaal L, Rissanen A, et al. A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects. Int J Obes 2004; 28: 1399–410CrossRef Wilding J, Van Gaal L, Rissanen A, et al. A randomized double-blind placebo-controlled study of the long-term efficacy and safety of topiramate in the treatment of obese subjects. Int J Obes 2004; 28: 1399–410CrossRef
233.
Zurück zum Zitat Astrup A, Caterson I, Zelissen P, et al. Topiramate: long-term maintenance of weight loss induced by a low-calorie diet in obese subjects. Obes Res 2004; 12: 1658–69PubMedCrossRef Astrup A, Caterson I, Zelissen P, et al. Topiramate: long-term maintenance of weight loss induced by a low-calorie diet in obese subjects. Obes Res 2004; 12: 1658–69PubMedCrossRef
234.
Zurück zum Zitat Astrup A, Toubro S. Topiramate: a new potential pharmacological treatment for obesity. Obes Res 2004; 12Suppl.: 167S–73SPubMedCrossRef Astrup A, Toubro S. Topiramate: a new potential pharmacological treatment for obesity. Obes Res 2004; 12Suppl.: 167S–73SPubMedCrossRef
235.
Zurück zum Zitat Tonstad S, Tykarski A, Weissgarten J, et al. Efficacy and safety of topiramate in the treatment of obese subjects with essential hypertension. Am J Cardiol 2005; 96: 243–51PubMedCrossRef Tonstad S, Tykarski A, Weissgarten J, et al. Efficacy and safety of topiramate in the treatment of obese subjects with essential hypertension. Am J Cardiol 2005; 96: 243–51PubMedCrossRef
236.
Zurück zum Zitat Van Gaal LF, Rissanen AM, Scheen AJ, et al. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patient: 1-year experience from the RIO-Europe study. Lancet 2005; 365: 1389–97PubMedCrossRef Van Gaal LF, Rissanen AM, Scheen AJ, et al. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patient: 1-year experience from the RIO-Europe study. Lancet 2005; 365: 1389–97PubMedCrossRef
237.
Zurück zum Zitat Pi-Sunyer FX, Aronne LJ, Heshmati HM, et al for the RIO-North America Study Group. Effect of rimonabant a cannabinoid-1 receptor blocker on weight and cardiometabolic risk factors in overweight or obese patients. RIO-North America: a randomized controlled trial. JAMA 2006; 295: 761–75PubMedCrossRef Pi-Sunyer FX, Aronne LJ, Heshmati HM, et al for the RIO-North America Study Group. Effect of rimonabant a cannabinoid-1 receptor blocker on weight and cardiometabolic risk factors in overweight or obese patients. RIO-North America: a randomized controlled trial. JAMA 2006; 295: 761–75PubMedCrossRef
238.
239.
Zurück zum Zitat Ettinger MP, Littlejohn TW, Schwartz SL, et al. Recombinant variant of ciliary neurotrophic factor for weight loss in obese adults: a randomized dose-ranging study. JAMA 2003; 289: 1826–32PubMedCrossRef Ettinger MP, Littlejohn TW, Schwartz SL, et al. Recombinant variant of ciliary neurotrophic factor for weight loss in obese adults: a randomized dose-ranging study. JAMA 2003; 289: 1826–32PubMedCrossRef
240.
Zurück zum Zitat Blanck HM, Khan LK, Serdula MK. Prescription weight loss pill use among Americans: patterns of pill use and lessons learned from the fen-phen market withdrawal. Prev Med 2004; 39: 1243–8PubMedCrossRef Blanck HM, Khan LK, Serdula MK. Prescription weight loss pill use among Americans: patterns of pill use and lessons learned from the fen-phen market withdrawal. Prev Med 2004; 39: 1243–8PubMedCrossRef
241.
Zurück zum Zitat Berkowitz RI, Wadden TA, Tershakovec AM, et al. Behavior therapy and sibutramine for the treatment of adolescent obesity: a randomized controlled trial. JAMA 2003; 289: 1805–12PubMedCrossRef Berkowitz RI, Wadden TA, Tershakovec AM, et al. Behavior therapy and sibutramine for the treatment of adolescent obesity: a randomized controlled trial. JAMA 2003; 289: 1805–12PubMedCrossRef
242.
Zurück zum Zitat McDuffie JR, Calis KA, Uwaifo GI, et al. Three-month tolerability of orlistat in adolescents with obesity-related comorbid conditions. Obes Res 2002; 10: 642–50PubMedCrossRef McDuffie JR, Calis KA, Uwaifo GI, et al. Three-month tolerability of orlistat in adolescents with obesity-related comorbid conditions. Obes Res 2002; 10: 642–50PubMedCrossRef
243.
Zurück zum Zitat Godoy-Matos A, Carraro L, Vieira A, et al. Treatment of obese adolescents with sibutramine: a randomised double-blind controlled study. J Clin Endocrinol Metab 2005; 90: 1460–5PubMedCrossRef Godoy-Matos A, Carraro L, Vieira A, et al. Treatment of obese adolescents with sibutramine: a randomised double-blind controlled study. J Clin Endocrinol Metab 2005; 90: 1460–5PubMedCrossRef
244.
Zurück zum Zitat Chanoine J-P, Hampl S, Jensen C, et al. Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial. JAMA 2005; 293: 2873–83PubMedCrossRef Chanoine J-P, Hampl S, Jensen C, et al. Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial. JAMA 2005; 293: 2873–83PubMedCrossRef
Metadaten
Titel
Safety of Drug Therapies Used for Weight Loss and Treatment of Obesity
verfasst von
Dr Lisa L. Ioannides-Demos
Joseph Proietto
Andrew M. Tonkin
John J. McNeil
Publikationsdatum
01.04.2006
Verlag
Springer International Publishing
Erschienen in
Drug Safety / Ausgabe 4/2006
Print ISSN: 0114-5916
Elektronische ISSN: 1179-1942
DOI
https://doi.org/10.2165/00002018-200629040-00001

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