Weight gain associated with atypical antipsychotic drugs: Mechanisms and management

Expert Review of Neurotherapeutics

Volumn 3, Issue 1, 2003, Pages 59-68

  Ananth, Jambur ^a   Venkatesh, Ravi ^a   Burgoyne, Karl ^a   Augustines, Davin ^a   Corpuz, Virginia ^b   Gunatilake, Sarath ^b  

^a HARBOR UCLA MEDICAL CENTER   (United States)

^b Metropolitan State Hospital   (United States)

Author keywords

Atypical antipsychotic drugs and weight gain; Management of obesity; Obesity; Pathophysiology of obesity; Schizophrenia and obesity

Indexed keywords

AMISULPRIDE; CLOZAPINE; DEXAMPHETAMINE; FENFLURAMINE; MAZINDOL; NEUROLEPTIC AGENT; OLANZAPINE; PHENMETRAZINE; PHENTERMINE; QUETIAPINE; RISPERIDONE; SIBUTRAMINE; ZIPRASIDONE;

APPETITE DISORDER; BODY MASS; BODY WEIGHT; CALORIC INTAKE; DRUG EFFECT; GENE LOCATION; HUMAN; MORBID OBESITY; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PATHOPHYSIOLOGY; REVIEW; SCHIZOPHRENIA; WEIGHT GAIN;

EID: 0037229813     PISSN: 14737175     EISSN: None     Source Type: Journal    
DOI: 10.1586/14737175.3.1.59     Document Type: Review

References (110)

1. Flegal KM, Carroll MD, Kuczmarski RJ, Johnson CL. Overweight and obesity in the United States: prevalence and trends, 1960-1994. Int. J. Obes. Relat. Metab. Disord. 22(1), 39-47 (1998).
2. National Institutes of Health. Clinical guidelines on the identification, evaluation and treatment of overweight and obesity in adults: the evidence report. Obesity Res. 6(Suppl. 2) 50s-63s (1998).
3. Mokdad AH, Bowman BA, Ford ES, Vinicor F, Marks JS, Koplan JP. The continuing epidemic of obesity and diabetes in the United States. JAMA 286, 1195-1200(2001).
4. Gordon HL, Law A, Hohman KE. The problem of overweight in hospitalized psychotic patients. Psychiatry Q. 34, 69-82 (1960).
5. Allison DB, Fontaine KR, Moonseong H. The distribution of body mass index among individuals with and without schizophrenia. J. Clin. Psych. 60, 215-220 (1999).
6. Mukherjee S, Decina P, Bocola V. Diabetes mellitus in schizophrenic patients. Compr. Psych. 37, 68-73 (1996).
7. Tsuang MT, Perkins K, Simpson JC. Physical diseases in schizophrenia and affective disorder. J. Clin. Psych. 44(2), 42-46(1983).
8. Bernstein JG. Induction of obesity by psychotropic drugs. Ann. NY Acad Sci. 499, 203-215 (1987).
9. Baptista T. Bodyweight gain induced by antipsychotic drugs: Mechanisms and management. Acta Psych. Scand. 100, 3-16 (1999).
10. Ananth J, Venkatesh, R, Burgoyne K, Gunatilake S. Atypical antipsychotic drug use and diabetes. Submitted to Psychosomatics Psychotherapy (2001).
11. Klett CJ, Caffey EM Jr. Weight changes during treatment with phenothiazine derivatives. J. Neuropsych. 2, 102-108 (1960).
12. Holden JM, Holden UP. Weight changes with schizophrenic psychosis and psychotropic drug therapy. Psychosomatics 11(6), 551-561 (1970).
13. Branchey MH, Lee JH, Amin R, Simpson GM. High- and low-potency neuroleptics in elderly psychiatric patients. JAMA 239(18), 1860-1862 (1978).
14. Silverstone T, Smith G, Goodall E. Prevalence of obesity in patients receiving depot antipsychotics. Br. J. Psych. 153, 214-217 (1988).
15. Dufresne RL, Valentino D, Kass DJ. Thioridazine improves affective symptoms in schizophrenic patients. Psychopharm. Bull. 29(2), 249-255 (1993).
16. Doss FW. The effect of antipsychotic drugs on body weight: A retrospective review. J. Clin. Psych. 40, 528-530 (1979).
17. Bernstein JG. Psychotropic drug induced weight gain: mechanisms and management. Clin. Neuropharm 11 (Suppl. 1), s194-s2O6 (1988).
18. Rockwell WJ, Ellinwood EH Jr, Trader DW. Psychotropic drugs promoting weight gain: health risks and treatment implications. S. Med. Jour. 76(11), 1407-1412 (1983).
19. Brady KT. Weight gain associated with psychotropic drugs. S. Med Jour. 82, 611-617 (1989).
20. Bhavnani SM, Levin GM. Antipsychotic agents: A survey of the prevalence, severity and burden of side effects. Int. Clin. Psychopharm. 11(1), 1-12 (1996).
21. Allison DB, Casey DE. Antipsychotic-induced weight gain: A review of the Literature. J. Clin. Psych. 62(Suppl. 7), 22-31(2001).
22. Casey DE. The relationship of pharmacology to side effects. J. Clin. Psych. 58(Suppl. 10), 55-62 (1997).
23. Lieberman JA, Kane JM, Johns CA. Clozapine: guidelines for clinical management. J. Clin. Psych. 50, 329-338 (1989).
24. Naber D, Hippius H. The European experience with clozapine. Hosp. Comm. Psych. 41, 886-890 (1990).
25. Povlsen UJ, Noring U, Fog R, Gerlach J. Tolerability and therapeutic effect of dozapine: a retrospective investigation of 216 patients treated with dozapine for up to 12 years. Acta Psych. Scand. 71, 176-185 (1985).
26. Hummer M, Kemmler WC, Kurz M, Kurzthaler I, Oberbauer H, Fleischhacker WW. Weight gain induced by clozapine. Eur. Neuropsychopharm. 5(4), 437-440 (1995).
27. Wirshing DA, Wirshing WC, Kysar L et al. Novel antipsychotics: comparison of weight gain liabilities. J. Clin. Psych. 60(6), 358-363 (1999).
28. Tran PV, Hamilton SH, Kuntz AJ. Double-blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders. J. Clin. Psychopharm. 17, 407-418 (1997).
29. Tohen M, Zarate CA. Antipsychotic agents and bipolar disorder. J. Clin. Psych. 59(Suppl. 1), 38-48 (1998).
30. Guille C, Sachs GS, Ghaemi SN. A naturalistic comparison of clozapine, risperidone and olanzapine in the treatment of bipolar disorder. J. Clin. Psych. 61(9), 638-642 (2000).
31. Frankenburg FR, Zanarini MC, Kando J, Centorrino F. Clozapine and body mass change. Biol. Psych. 43, 520-524 (1998).
32. George TP, Sernyak MJ, Ziedonis DM, Woods SW. Effects of clozapine on smoking in chronic schizophrenic out-patients. J. Clin. Psych. 156, 344-346 (1995).
33. Grunberg NE. Smoking cessation and weight gain. N. Engl. J. Med. 324, 768-769 (1991).
34. Leadbetter R, Shutty M, Pavalonis D, Vieweg V, Higgins P, Downs M. Clozapine induced weight gain: prevalence and clinical relevance. Am. J. Psych. 149, 68-72 (1992).
35. Bai YM, Lin CC, Chen JY, Lin CY. Weight gain among patients on dozapine. Psych. Ser. 50(5), 704-705 (1999).
36. Marder SR, Meibach RC. Risperidone in the treatment of schizophrenia. Am. J. Psych. 151(6), 825-835 (1994).
37. Csernansky JG, Mahmoud R, Brenner R. A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. N. Engl. J. Med. 348, 16-22 (2002).
38. Conley RR, Mahmoud R and Risperidone Study Group. Risperidone versus olanzapine in patients with schizophrenia and schizoaffective disorder. Presented at the annual meeting of the American College of Neuropsychopharmacology, Acapulco, Mexico, Dec 12-16 (1999).
39. Peuskens JA on behalf of Risperdione Study Group. Risperidone in the treatment of patients with chronic schizophrenia: a multinational multicenter double-blind parallel group study versus haloperidol. Br. J. Psych. 166, 712-726 (1995).
40. Hoyberg OJ, Fensbo C, Remvig J, Lingjaerde O, Sloth-Nielsen M, Slavesen I. Risperidone versus perphenazine in the treatment of chronic schizophrenic patients with acute exacerbations Acta Psychiatr. Scand. 88, 395-402 (1993).
41. Csemansky J, Okamoto A. Risperidone versus haloperidol in the prevention of relapse in chronic schizophrenia and schizoaffective disorders: a long-term double-blind comparison. Eur. Neuropsychopharm. 9(Suppl. 5), s268 (1999).
42. Cohen S, Glazewski R, Khan S, Khan A. Weight gain with risperidone among patients with mental retardation: effect of calorie restriction. Clin. Psych. 62, 114-116 (2001).
43. Arvanitis LA, Miller BG. Multiple fixed doses of'seroquel' (quetiapine) in patients with acute exacerbation of schizophrenia: A comparison with haloperidol and placebo. The Seroquel Trial 13 Study Group. Bio. Psych. 42(4), 233-246(1997).
44. Peuskens JA. Comparison of quetiapine and chlorpromazine in the treatment of schizophrenia. Acta Pych. Scand. 96, 265-273(1997).
45. Small JG, Hirsch SR, Arvanitis LA. Quetiapine in patients with schizophrenia. Arch. Gen. Psych. 54, 549-557 (1997).
46. Tandon R, Harrigan E, Zorn S. Ziprasidone: A novel antipsychotic with unique pharmacology and therapeutic potential. J. Serotonin Res. 4, 159-177 (1997).
47. Daniel DG, Zimbroff DL, Potkin SG, Reeves KR, Harrigan EP, Lakshminarayanan M. Ziprasidone 80 mg/day and 160 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a six week placebo-controlled trial. Neuropsychopharmacology 20(5), 491-505 (1999).
48. Keck P Jr, Buffenstein A, Ferguson J et al. Ziprasidone 40 and 120 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 4 week placebo-controlled trial. Psychopharmacology 140(2), 173-184 (1998).
49. Weiden P, Simpson G, Kramer T. Switching from olanzapine to ziprasidone: clinical effects. Eur. Neuropsychopharm. 9(Suppl. 5), s264 (1999).
50. Simpson G, Potkin S, Switch Study Group. Switching from risperidone to ziprasidone. Eur. Neuropsychopharm 9(Suppl. 5), s265 (1999).
51. Arato MO, O'Connor R, Meltzer H. Ziprasidone investigators Study Group. Ziprasidone: efficacy in the prevention of relapse and in the long-term treatment of negative symptoms of chronic schizophrenia. Eur. Neuropsychopharm. 7(Suppl. 2), S214 (1997).
52. Beasley CM Jr, Tollefson GD, Tran PV Safety of olanzapine. J. Clin. Psych. 58(Suppl. 10), 13-17 (1997).
53. Zyprexa PDR. Physician's Desk Reference. Montvale, NJ, USA, 1641-1645 (1999).
54. Martinez JM, Russell JM, Mackell JA. Average dose and weight gain: olanzapine versus risperidone. In: New research program and abstracts of the 152nd annual meeting of the American Psychiatric Association, Abstract NR136, Washington DC, USA, May 15-20, (1999).
55. Sachs GS, Guille C. Weight gain associated with use of psychotropic medications. J. Clin. Psych. 60(Suppl. 21), 16-19 (1999).
56. Conley RR, Meltzer HY. Adverse events related to olanzapine. J. Clin. Psych. 61(Suppl. 8), 26-29, discussion 30 (2000).
57. Gupta, S, Droney T, Al-Samarrai S, Keller P, Frank B. Olanzapine induced weight gain. Ann. Clin. Psych. 10, 39 (1999).
58. Wildocher D, Allilaire JF, Guerard des Lauriers A, Lacubrier V. Amisulpiride neuroleptic and antinegative action. Encephale 16, 159-163 (1990).
59. Leucht S, Pitschel-Walz G, Engel RR, Kissling W. Amisulpiride, an unusual 'atypical' antipsychotic: a metaanalysis of randomized controlled trials. Am. J. Psychiatry 159, 177-179 (2002).
60. Baptista T, Alastre T, Contreras Q et al Effects of the antipsychotic drug, amisulpiride, on reproductive system hormones in healthy men: Relationship with body weight regulation. Pharmacopsychiatry 30, 256-262 (1997).
61. Peuskens J, Bech P, Moller HJ, Bale R Fleuret G, Rein W. Amisulpiride vs. Risperidone in the treatment of acute exacerbations of schizophrenia. Amisulpiride Study group. Psychiatry Res. 88, 107-117 (1999).
62. Rein W, Turjanski S, Favennec-Meidinger C. Amisulpiride, an atypical antipsychotic-safety profile. Poster presented at Xth WPA Congress, Madrid, Spain, August 23-28, (1996).
63. Robinson RG, McHugh PR, Folstein MF. Measurement of appetite disturbances in psychiatric disorders. J. Psych. Res. 12, 59-68 (1975).
64. Amdisen A. Drug produced obesity. Experiences with chlorpromazine, perphenazine and clopenthixol. Dan. Med. Bull. 11, 182-189 (1964).
65. Johnson DAW, Breen M. Weight changes with depot neuroleptic maintenance therapy. Acta Psych. Scand. 59, 525-528 (1979).
66. Umbricht DSG, Pollack S, Kane JM. Clozapine and weight gain. J. Clin. Psych. 55(Suppl. B), 157-160 (1994).
67. Stanton JM. Weight gain associated with neuroleptic medication: a review. Schiz. Bull. 21, 463-472 (1995).
68. Kinon B, Basson B, Gilmore JA, Tollefson GD. Long-term olanzapine treatment: weight change and weight related health factors in schizophrenia. J. Clin. Psych. 62, 92-100 (2001).
69. Henderson D, Cagliero E, Gray C et al. Clozapine, diabetes mellitus, weight gain and lipid abnormalities: A five year naturalistic study. Am. J. Psych. 57(6), 975-981 (2000).
70. Goldstein JM. The new generation of antipsychotic drugs: how atypical are they? Int. J. Neuropsychopharmacol. 3(4), 339-349 (2000).
71. 2c serotonin receptors. Nature 374(6522), 542-546 (1995).
72. Casey DE, Zorn SH. The pharmacology of weight gain with antipsychotics. J. Clin. Psych. 62(Suppl. 7), 4-10 (2001).
73. Campfield LA, Smith FJ, Guisez Y, Devos R, Bum P. Recombinant mouse OB protein: Evidence for a peripheral signal linking adiposity and central neural networks. Science 269(5223), 546-549 (1995).
74. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 22, 763-770 (1998).
75. Melkersson KI, Hulting AL, Brismar KE. Elevated levels of insulin, lepin and blood lipids in olanzapine treated patients with schizophrenia or related pychoses. J. Clin. Psych. 61(10), 742-749 (2000).
76. Kraus T, Haack M, Schuld A et al. Body weight and leptin plasma levels during treatment with antipsychotic drugs. Am. J. Psych. 156(2), 312-314 (1999).
77. Ahren B, Larsson H, Wilhelmsson C, Nasman B, Olsson T. Regulation of circulating leptin in humans. Endocrine 7(1), 1-8 (1997).
78. Yamaguchi T, Kamon J, Waki H et al. The fat derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat. Med. 7, 941-946(2001).
79. Pollmacher T, Hinze-Selch D, Mullington J. Effects of clozapine on plasma cytokine and soluble cytokine receptor levels. J. Clin. Psychopharm. 16(5), 403-409 (1996).
80. Hinze-Selch D, Deuschle M, Weber B, Heuser I, Pollmacher T. Effect of co-administration of clozapine and fluvoxamine versus clozapine monotherapy on blood cell counts plasma levels of cytokines and bodyweight. Psychopharmacology 149, 163-169 (2000).
81. Argiles JM, Lopez-Soriano J, Busquets S, Lopez-Soriano FJ. Journey from Cachexia to obesity by TNF. FASEB J. 11, 743-751 (1997).
82. Auwerx J, Staels B. Leptin. Lancet 351, 737-742 (1998).
83. Fontaine KR, Heo M, Harrigan EP et al. Estimating the consequences of antipsychotic induced weight gain on health and mortality rate. Psych. Res. 101(3), 277-288 (2001).
84. Hauner H. The impact of pharmacotherapy on weight management in Type 2 diabetes. Int. J. Obes. 23(Suppl. 7), S12-S17 (1999).
85. Winkelman JW. Schizophrenia obesity and obstructive sleep apnea. J. Clin. Psych. 62, 8-11 (20O1).
86. Rankinen T, Perusse L, Weisnagel SJ, Snyder EE, Chagon YC, Bouchard C. The human obesity gene map: the 2001 update. Obes. Res. 10(3), 196-243 (2002).
87. Froguel P, Boutin P. Genetics of pathways regulating body weight in the development of obesity in humans. Exp. Biol. Med. (Maywood) 226(11), 991-996 (2001).
88. Steppan CM, Lazar MA. Resistin and obesity-associated insulin resistance. Trends Endocrinol. Metab. 13(1), 18-23 (2002).
89. Boelsterli UA, Bedoucha M. Toxicological consequences of altered peroxisome proliferator-activated receptor gamma (PPAR gamma) expression in the liver: insights from models of obesity and Type 2 diabetes. Biochem. Pharmacol. 63(1), 1-10 (2002).
90. Reinstein MJ, Sirotovskaya LA, Jones LE, Mohan S, Chasanov M. Effect of dozapine-quetiapine combination therapy on weight and glycaemic control: Preliminary findings. Clin. Drug Inves. 18, 99-104 (1999).
91. Jimerson DC, Lesem MD, Kaye WH, Hegg AP, Brewerron TD. Eating disorders and depression: is there a serotonin connection? Biol. Psych. 28(5), 443-454 (1991).
92. Grinspoon S, Gulick T, Askari H et al. Serum leptin levels in women with anorexia nervosa. J. Clin. Endocrin. Metabol. 81, 3861-3863 (1996).
93. Kaye WH, Gwirtsman HE, George DT, Ebert MH. Altered serotonin activity in anorexia nervosa after long-term weight restoration. Does elevated cerebrospinal fluid 5-hydroxyindoleacetic acid level correlate with rigid and obsessive behavior? Arch. Gen. Psych. 48(6), 556-562 (1991).
94. Sullivan PF. Mortality in anorexia nervosa. Am. J. Psych. 152, 1073-1074 (1995).
95. Rigotti NA, Neer RM, Skates SJ, Herzog DB, Nussbaum SR. The clinical course of osteoporosis in anorexia nervosa. JAMA 265(9), 1133-1138 (1990).
96. Klibanski A, Biller BMK, Schoenfeld D, Herzog DB, Saxe V. The effects of estrogen administration on trabecular bone loss in young women with anorexia nervosa. J. Clin. Endocrin. Met. 80(3), 898-904 (1995).
97. Garattini S, Mennini T, Samain R. Reduction of food intake by manipulation of central nervous serotonin: current experimental results. Br. J. Psych. 155(Suppl. 8), 41-51 (1989).
98. Goodall E, Oxtoby C, Richards R, Watkinson G, Brown D, Silverstone T. A Clinical trial of the efficacy and acceptability of d-fenfluramine in the treatment of neuroleptic induced obesity. Br. J. Psych. 153, 208-213 (1988).
99. Wirth A. Long-term weight loss with sibutramine: A randomized controlled trial. JAMA 286, 1331-1339 (2001).
100. Angelescu I, Klawe C, Benkert O. Orlistat in the treatment of psychopharmacologically induced weight gain. J. Clin. Psychopharm. 20, 716-717 (2000).
101. Cortingham EM. Metformin leads to weight loss in adolescents who gained weight on psychiatric drugs. American Psychiatric Association, Chicago, IL, USA (2000).
102. Kusumakar V, Yatham LN, O' Donovan C, Kutcher SP. Topiramate augmentation: a preliminary open study of its effectiveness in women with refractory rapid cycling bipolar disorder and significant weight gain from previous treatment. Poster presented at the Third International Conference in Bipolar Disorder, Pittsburgh, PA, USA, June 17-19 (1999).
103. Dursun SM, Devarajan S. Clozapine weight gain, plus topiramate weight loss. Can. J. Psych. 45(2), 198 (2000).
104. Correa N, Opler LA, Kay SR, Birmaher B. Amantadine in the treatment of neuroendorine side effects of neuroleptics. J. Clin. Psychopharm. 7, 91-95 (1987).
105. Deberdt W, Floris M, Lejeunne J. Effect of amantadine on weight gain during olanzapine treatment. Poster presentation at the US Psychiatric and Mental Health Congress, Nov 16-19 (2000).
106. Wilcox JA, Tsuang J. Psychological effects of amantadine on psychotic subjects. Neuropsychobiology 23, 144-146 (1990).
107. Brier A, Tanaka Y, Roychowdahury Clark S. Nazitidine for the Prevention of Olanzapine associated weight gain in schizophrenia and related disorders: A Randomized Controlled Double-blind Study. Presented at College of Psychiatric and Neurologic Pharmacisits, San Antonio, TX, USA, March 26-28 (2001).
108. Stoa-Birketvedt G, Waldum HL, Vonen B, Florholmen J. Effect of cimetidine on basal and postprandial plasma concentrations of cholecystokinin and gastrin in humans. Acta Physiol. Scand. 159(4), 321-325 (1997).
109. Stoa-Birketvedt G, Paus PN, Gnass R. Cimetidine reduces weight gain and improves metabolic control in overweight patients with Type 2 diabetes. J. Obes. Relat. Metab. Disord. 22, 1041-1045 (1998).
110. Cowan GSM Jr, Frank A. Medical management of obesity. CME Medscape (2001).