Metabolic consequences of antipsychotic therapy: Preclinical and clinical perspectives on diabetes, diabetic ketoacidosis, and obesity

Handbook of Experimental Pharmacology

Volumn 212, Issue , 2012, Pages 135-164

  Heal, David J ^a   Gosden, Jane ^a   Jackson, Helen C ^a   Cheetham, Sharon C ^a   Smith, Sharon L ^a  

^a RenaSci Ltd   (United Kingdom)

Author keywords

Antipsychotics; Diabetes; Diabetic ketoacidosis; Metabolic dysfunction; Obesity; Weight gain

Indexed keywords

ANTIOBESITY AGENT; ARIPIPRAZOLE; CHLORPROMAZINE; CLOZAPINE; DEXFENFLURAMINE; FLUOXETINE; FLUPHENAZINE; HALOPERIDOL; INSULIN SENSITIZING AGENT; LIRAGLUTIDE; LOXAPINE; METFORMIN; MOLINDONE; NEUROLEPTIC AGENT; NORADRENALIN UPTAKE INHIBITOR; OLANZAPINE; PIMOZIDE; QUETIAPINE; RISPERIDONE; SERTINDOLE; SIBUTRAMINE; SULFONYLUREA; SULFONYLUREA DERIVATIVE; SULPIRIDE; TIOTIXENE; TOPIRAMATE; UNINDEXED DRUG; ZIPRASIDONE; ZONISAMIDE; ZOTEPINE;

ARTICLE; BODY WEIGHT; CARDIOVASCULAR RISK; CONTROLLED CLINICAL TRIAL (TOPIC); DIABETES MELLITUS; DIABETIC KETOACIDOSIS; DISEASE MODEL; DRUG FATALITY; DYSLIPIDEMIA; GLYCEMIC CONTROL; HUMAN; IMPAIRED GLUCOSE TOLERANCE; INSULIN RESISTANCE; META ANALYSIS (TOPIC); METABOLIC DISORDER; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; RISK FACTOR; SCHIZOPHRENIA; SIDE EFFECT; WEIGHT GAIN; ANIMAL; ANIMAL MODEL; CHEMICALLY INDUCED DISORDER; DRUG EFFECT; METABOLISM; REVIEW;

ANIMALS; ANTIPSYCHOTIC AGENTS; BODY WEIGHT; DIABETES MELLITUS; DIABETIC KETOACIDOSIS; HUMANS; INSULIN-SECRETING CELLS; MODELS, ANIMAL; OBESITY;

EID: 84870168532     PISSN: 01712004     EISSN: 18650325     Source Type: Book Series    
DOI: 10.1007/978-3-642-25761-2_6     Document Type: Article

References (129)

1. Abdul-Ghani MA, DeFronzo RA (2010) Pathogenesis of insulin resistance in skeletal muscle. J Biomed Biotechnol 2010:476279
2. Albaugh VL, Henry CR, Bello NT, Hajnal A, Lynch SL, Halle B et al (2006) Hormonal and metabolic effects of olanzapine and clozapine related to body weight in rodents. Obesity (Silver Spring) 14:36-51 (Pubitemid 46214773)
3. Allison DB, Fontaine KR, Heo M, Mentore JL, Cappelleri JC, Chandler LP et al (1999a) The distribution of body mass index among individuals with and without schizophrenia. J Clin Psychiatry 60:215-220 (Pubitemid 29193917)
4. Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC et al (1999b) Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 156:1686-1696 (Pubitemid 29517559)
5. Baptista T, Tenda L, Contreras Q, Albornoz MA, Paez X, de Quijada M et al (1998) Mechanism of the neuroleptic-induced obesity in rats. Prog Neuropsychopharmacol Biol Psychiatry 22:187-198
6. Baptista T, de Baptista EQ, Kin NMKNY, Beaulieu S, Walker D, Joober R et al (2002a) Comparative effects of the antipsychotic sulpiride or risperidone in rats. I: Bodyweight, food intake, body composition, hormones and glucose tolerance. Brain Res 957:144-151 (Pubitemid 35346582)
7. Baptista T, Lacrux A, Pàez X, Hernàndez L, Beaulieu S (2002b) The antipsychotic drug sulpiride does not affect bodyweight in male rats. Is insulin resistance involved? Eur J Pharmacol 447:91-98 (Pubitemid 34775226)
8. Beckman JA, Creager MA, Libby P (2002) Diabetes and atherosclerosis. Epidemiology, pathophysiology, and management. J Am Med Assoc 287:2570-2581 (Pubitemid 34517204)
9. Bhole V, deVera M, Rahman MM, Krisnan E, Choi H (2010) Epidemiology of gout in women: 52-year follow up of a prospective cohort. Arthritis Rheum 62:1069-1076
10. Bobes J, Rejas J, Garcia-Garcia M, Rico-Villademoros F, Garcia-Portilla MP, Fernandiz I et al (2003) Weight gain in patients with schizophrenia treated with risperidone, olanzapine, quetiepine or haloperidol: results of the EIRE study. Schizophr Res 62:77-82
11. Brown S, Birtwistle J, Roe L, Thompson C (1999) The unhealthy lifestyle of people with schizophrenia. Psychol Med 29:697-701 (Pubitemid 29261358)
12. Chintoh AF, Mann SW, Lam TKT, Giacca A, Remington G (2008) Insulin resistance following continuous, chronic olanzapine treatment: an animal model. Schizophr Res 104:23-30
13. Chintoh AF, Mann SW, Lam L, Giacca A, Fletcher P, Nobrega J et al (2009) Insulin resistance and secretion in vivo: effects of different antipsychotics in an animal model. Schizophr Res 108:127-133
14. Chiu CC, Chen KP, Liu HC, Lu ML (2006) The early effect of olanzapine and risperidone on insulin secretion in atypical-naïve schizophrenic patients. J Clin Psychopharmacol 26:504-507
15. Chrzanowski WK, Marcus RN, Torbeyns A, Nyilas M, McQuade RD (2006) Effectiveness of long-term aripiprazole therapy in patients with acutely relapsing or chronic, stable schizophrenia: a 52-week, open-label comparison with olanzapine. Psychopharmacology (Berl) 189:259-266 (Pubitemid 44691547)
16. Church CO, Stevens DL, Fugate SE (2005) Diabetic ketoacidosis associated with aripiprazole. Diabet Med 22:1440-1443 (Pubitemid 41391324)
17. Coccurello R, Brina D, Caprioli A, Conti R, Ghirardi O, Schepis F et al (2009) 30 Days of continuous olanzapine infusion determines energy imbalance, glucose intolerance, insulin resistance, and dyslipidemia in mice. J Clin Psychopharmacol 29:576-583
18. Cohen D (2004) Atypical antipsychotics and new onset diabetes mellitus. An overview of the literature. Pharmacopsychiatry 37:1-11 (Pubitemid 38230734)
19. Cohen S, Chiles J, MacNaughton A (1990) Weight gain associated with clozapine. Am J Psychiatry 147:503-504 (Pubitemid 20107121)
20. Cohn TA, Remington G, Zipursky RB, Azad A, Connolly P, Wolever TM (2006) Insulin resistance and adiponectin levels in drug-free patients with schizophrenia: a preliminary report. Can J Psychiatry 51:382-386, (Pubitemid 43854472)
21. Erratum in: Can J Psychiatr 2006 51:552
22. Cooper GD, Pickvance LC, Wilding JPH, Halford JCG, Goudie AJ (2005) A parametric analysis of olanzapine-induced weight gain in female rats. Psychopharmacology 181:80-89 (Pubitemid 41440918)
23. Cooper GD, Pickvance LC, Wilding JPH, Harrold JA, Halford JCG, Goudie AJ (2007) Effects of olanzapine in male rats: enhanced adiposity in the absence of hyperphagia, weight gain or metabolic abnormalities. J Psychopharmacol 21:405-413 (Pubitemid 47077303)
24. Cooper GD, Harrold JA, Halford JC, Goudie AJ (2008) Chronic clozapine treatment in female rats does not induce weight gain or metabolic abnormalities but enhances adiposity: implications for animal models of antipsychotic-induced weight gain. Prog Neuropsychopharmacol Biol Psychiatry 32:428-436 (Pubitemid 351178959)
25. Cope MB, Nagy TR, Fernández JR, Geary N, Casey DE, Allison DB (2005) Antipsychotic drug-induced weight gain: development of an animal model. Int J Obes 29:607-614 (Pubitemid 40769482)
26. Cope MB, Li X, Jumbo-Lucioni P, DiCostanzo CA, Jamison WG, Kesterson RA et al (2009) Risperidone alters food intake, core body temperature, and locomotor activity in mice. Physiol Behav 96:457-463
27. Correll CU, Manu P, Olshanskiy V, Napolitano B, Kane JM, Malhotra AK (2009) Cardiometabolic risk of second-generation antipsychotic medications during first-time use in children and adolescents. J Am Med Assoc 302:1765-1773
28. Daniel DG, Wozniak P, Mack RJ, McCarthy BG (1998) Long-term efficacy and safety comparison of sertindole and haloperidol in the treatment of schizophrenia. The sertindole study group. Psychopharmacol Bull 34:61-69 (Pubitemid 28176303)
29. De Hert M, Hanssens L, van Winkel R, Wampers M, Van Eyck D, Scheen A et al (2007) A case series: evaluation of the metabolic safety of aripiprazole. Schizophr Bull 33:823-830 (Pubitemid 47343707)
30. De Hert M, Schreurs V, Sweers K, Van Eyck D, Hanssens L, Inko S et al (2008) Typical and atypical antipsychotics differentially affect long-term incidence rates of the metabolic syndrome in first-episode patients with schizophrenia: a retrospective chart review. Schizophr Res 101:295-303
31. De Hert M, Dobbelaere M, Sheridan EM, Cohen D, Correll CU (2011a) Metabolic and endocrine adverse effects of second-generation antipsychotics in children and adolescents: a systematic review of randomised, placebo controlled trials and guidelines for clinical practice. Eur Psychiatry 26:144-158
32. De Hert M, Mittoux A, he Peuskens JY (2011b) Metabolic parameters in the short- and long-term treatment of schizophrenia with sertindole and risperidone. Eur Arch Psychiatry Clin Neurosci 261:231-239
33. De Hert M, Detraux J, van Winkel R, Yu W, Correll CU (2011c) Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat Rev Endocrinol 8(2):114-126
34. DeFronzo RA (2010) Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard lecture 2009. Diabetologia 53:1270-1287
35. Editorial: Drugs causing weight gain (1974) [No authors listed] Br Med J 1:168.
36. Eledrisi MS, Alshanti MS, Shah MF, Brolosy B, Jaha N (2006) Overview of the diagnosis and management of diabetic ketoacidosis. Am J Med Sci 331:243-251 (Pubitemid 43804601)
37. Fell MJ, Marshall KM, Williams J, Neill JC (2004a) Effects of the atypical antipsychotic olanzapine on reproductive function and weight gain in female rats. J Psychopharmacol 18:149-155 (Pubitemid 38954901)
38. Fell MJ, Neill JC, Marshall KM (2004b) Effects of the classical antipsychotic haloperidol and atypical antipsychotic risperidone on weight gain, the oestrous cycle and uterine weight in female rats. Eur Neuropsychopharmacol 14(5):385-392 (Pubitemid 39141681)
39. Fell MJ, Gibson R, McDermott E, Sisodia G, Marshall KM, Neill JC (2005a) Investigation into the effects of the novel antipsychotic ziprasidone on weight gain and reproductive function in female rats. Behav Brain Res 160:338-343 (Pubitemid 40603530)
40. Fell MJ, Neill JC, Rao C, Marshall KM (2005b) Effects of sub-chronic antipsychotic drug treatment on body weight and reproductive function in juvenile female rats. Psychopharmacology (Berl) 182:499-507 (Pubitemid 41464631)
41. Fell MJ, Anjum N, Dickinson K, Marshall KM, Peltola LM, Vickers S et al (2007) The distinct effects of subchronic antipsychotic drug treatment on macronutrient selection, body weight, adiposity, and metabolism in female rats. Psychopharmacology (Berl) 194:221-231 (Pubitemid 47457949)
42. Fell MJ, Neill JC, Anjum N, Peltola LM, Marshall KM (2008) Investigation into the influence of a high fat diet on antipsychotic-induced weight gain in female rats. J Psychopharmacol 22:182-186 (Pubitemid 351322855)
43. Felson DT (1996) Weight and osteoarthritis. Am J Clin Nutr 63(3 Suppl):430S-432S (Pubitemid 26075825)
44. Flack JM, Peters R, Shafi T, Alrefai H, Nasser SA, Crook E (2003) Prevention of hypertension and its complications: theoretical basis and guidelines for treatment. J Am Soc Nephrol 14(Suppl 2):S92-S98 (Pubitemid 36750500)
45. Fleischhaker C, Heiser P, Hennighausen K, Herpertz-Dahlmann B, Holtkamp K, Mehler-Wex C et al (2008) Weight gain in children and adolescents during 45 weeks treatment with clozapine, olanzapine and risperidone. J Neural Transm 115:1599-1608
46. Gentile S (2006) Long-term treatment with atypical antipsychotics and the risk of weight gain: a literature analysis. Drug Saf 29:303-319
47. Goudie AJ, Smith JA, Halford JC (2002) Characterization of olanzapine-induced weight gain in rats. J Psychopharmacol 16:291-296 (Pubitemid 35470572)
48. Graham KA, Cho H, Brownley KA, Harp JB (2008) Early treatment-related changes in diabetes and cardiovascular disease risk markers in first episode psychosis subjects. Schizophr Res 101:1-3
49. Haddad P (2005) Weight change with atypical antipsychotics in the treatment of schizophrenia. J Psychopharmacol 19:16-27 (Pubitemid 44567855)
50. Haupt DW, Fahnestock PA, Flavin KA, Schweiger JA, Steves A, Hessler MJ et al (2007) Adiposity and insulin sensitivity derived from intravenous glucose tolerance tests in antipsychotic-treated patients. Neuropsychopharmacology 32:2561-2569 (Pubitemid 350126844)
51. 6 agonist, E-6837. Society for Neurosciences Meeting, Abstract No. 584.12/RR85
52. Henderson DC (2001) Clinical experience with insulin resistance, diabetic ketoacidosis, and type 2 diabetes mellitus in patients treated with atypical antipsychotic agents. J Clin Psychiatry 62(Suppl 27):10-14, discussion 40-1 (Pubitemid 34052252)
53. Henderson DC, Cagliero E, Copeland PM, Borba CP, Evins E, Hayden D et al (2005a) Glucose metabolism in patients with schizophrenia treated with atypical antipsychotic agents: a frequently sampled intravenous glucose tolerance test and minimal model analysis. Arch Gen Psychiatry 62:19-28 (Pubitemid 40096067)
54. Henderson DC, Copeland PM, Daley TB, Borba CP, Cather C, Nguyen DD et al (2005b) A doubleblind, placebo-controlled trial of sibutramine for olanzapine-associated weight gain. Am J Psychiatry 162:954-962 (Pubitemid 40676209)
55. Herman MA, Kahn BB (2006) Glucose transport and sensing in the maintenance of glucose homeostasis and metabolic harmony. J Clin Invest 116:1767-1775 (Pubitemid 44033296)
56. Heshka S, Heymsfield S (2001) Obesity and gallstones. In: Bjorntorp P (ed) International textbook of obesity. Wiley, Chichester, pp 399-409
57. Hoffmann VP, Case M, Stauffer VL, Jacobson JG, Conley RR (2010) Predictive value of early changes in triglycerides and weight for longer-term changes in metabolic measures during olanzapine, ziprasidone or aripiprazole treatment for schizophrenia and schizoaffective disorder post hoc analyses of 3 randomized, controlled clinical trials. J Clin Psychopharmacol 30:656-660
58. Houseknecht KL, Robertson AS, Zavadoski W, Gibbs EM, Johnson DE, Rollema H (2007) Acute effects of atypical antipsychotics on whole-body insulin resistance in rats: implications for adverse metabolic effects. Neuropsychopharmacology 32:289-297 (Pubitemid 46106936)
59. International Obesity Task Force [IOTF] (2010). http://www.iotf.org
60. Jackson HC, Bearham MS, Hutchins LJ, Mazurkiewicz SE, Needham AM, Heal DJ (1997) Investigation of the mechanisms underlying the hypophagic effects of 5-HT and noradrenaline reuptake inhibitor, sibutramine, in the rat. Br J Pharmacol 121:1613-1618 (Pubitemid 27343387)
61. Jin H, Meyer JM, Jeste DV (2002) Phenomenology of and risk factors for new-onset diabetes mellitus and diabetic ketoacidosis associated with atypical antipsychotics: an analysis of 45 published cases. Ann Clin Psychiatry 14:59-64 (Pubitemid 34538833)
62. Johnson DA, Breen M (1979) Weight gain with depot neuroleptic maintenance therapy. Acta Psychiatr Scand 59:525-528 (Pubitemid 9191722)
63. Johnson DE, Yamazaki H, Ward KM, Schmidt AW, Lebel WS, Treadway JL et al (2005) Inhibitory effects of antipsychotics on carbachol-enhanced insulin secretion from perfused rat islets. Diabetes 54:1552-1558
64. Kalinichev M, Rourke C, Jones DN (2006) Body weights and plasma prolactin levels in female rats treated subchronically with ziprasidone versus olanzapine. Behav Pharmacol 17:289-292
65. Kane JM, Osuntokun O, Kryzhanovskaya LA, Xu W, Stauffer VL, Watson SB et al (2009) A 28-week, randomised, double-blind study of olanzapine versus aripiprazole in the treatment of schizophrenia. J Clin Psychiatry 70:572-581
66. Keck PE Jr, Calabrese JR, McQuade RD, Carson WH, Carlson BX, Rollin LM et al (2006) A randomised, double-blind, placebo-controlled 26-week trial of aripiprazole in recently manic patients with bipolar I disorder. J Clin Psychiatry 67:626-637 (Pubitemid 43764240)
67. Keck PE Jr, Calabrese JR, McIntyre RS, McQuade RD, Carson WH, Eudicone JM et al (2007) Aripiprazole monotherapy for maintenance therapy in bipolar I disorder: a 100-week, doubleblind study versus placebo. J Clin Psychiatry 68:1480-1491 (Pubitemid 350073394)
68. Kim SH, Nikolics L, Abbasi F, Lamendola C, Link J, Reaven GM et al (2010) Relationship between body mass and insulin resistance in patients treated with second generation antipsychotic agents. J Psychiatr Res 44:493-498
69. Lambert BL, Cunningham FE, Miller DR, Dalack GW, Hur K (2006) Diabetes risk associated with use of olanzapine, quetiapine, and risperidone in veterans health administration patients with schizophrenia. Am J Epidemiol 164:672-681 (Pubitemid 44453496)
70. Law M, Wald N, Morris J (2003) Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy. Health Technol Assess 7:1-94
71. Leadbetter R, Shutty M, Pavalonis D, Vieweg V, Higgins P, Downs M (1992) Clozapine-induced weight gain: prevalence and clinical relevance. Am J Psychiatry 149:68-72
72. Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenbeck RA, Perkins DO, Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators et al (2005) Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 353:1209-1223 (Pubitemid 41345943)
73. Lykkegaard K, Larsen PJ, Vrang N, Bock C, Bock T, Knudsen LB (2008) The once-daily human GLP-1 analog, liraglutide, reduces olanzapine-induced weight gain and glucose intolerance. Schizophr Res 103:94-103
74. Maayan L, Vakhrusheva J, Correll CU (2010) Effectiveness of medications used to attenuate antipsychotic-related weight gain and metabolic abnormalities: a systematic review and meta-analysis. Neuropsychopharmacology 35:1520-1530
75. McQuade RD, Stock E, Marcus R, Jody D, Gharbia NA, Vanveggel S et al (2004) A comparison of weight change during treatment with olanzapine or aripiprazole: results from a randomised, double-blind study. J Clin Psychiatry 65:47-56
76. Melkersson K, Jansson E (2005) The atypical antipsychotics quetiapine, risperidone and ziprasidone do not increase insulin release in vitro. Neuro Endocrinol Lett 26:205-208 (Pubitemid 40975097)
77. Meltzer HY (1989) Clinical studies on the mechanism of action of clozapine: the dopamineserotonin hypothesis of schizophrenia. Psychopharmacology (Berl) 99:S18-S27 (Pubitemid 19244134)
78. Meltzer HY, Matsubara S, Lee JC (1989) The ratios of serotonin2 and dopamine2 affinities differentiate atypical and typical antipsychotic drugs. Psychopharmacol Bull 25:390-392 (Pubitemid 20260244)
79. Meyer JM, Davis VG, Goff DC, McEvoy JP, Nasrallah HA, Davis SM et al (2008) Change in metabolic syndrome parameters with antipsychotic treatment in the CATIE schizophrenia trial: prospective data from phase 1. Schizophr Res 101:273-286
80. Minet-Ringuet J, Even PC, Lacroix M, Tomé D, de Beaurepaire R (2006) A model for antipsychotic-induced obesity in the male rat. Psychopharmacology (Berl) 187:447-454 (Pubitemid 44200516)
81. Minet-Ringuet J, Even PC, Valet P, Carpéné C, Visentin V, Prévot D et al (2007) Alterations of lipid metabolism and gene expression in rat adipocytes during chronic olanzapine treatment. Mol Psychiatry 12:562-571 (Pubitemid 46816768)
82. Mokdad AH, Bowman BA, Ford ES, Vinicor F, Marks JS, Koplan JP (2001) The continuing epidemics of obesity and diabetes in the United States. J Am Med Assoc 286:1195-1200 (Pubitemid 33015548)
83. Montani J-P, Antic V, Yang Z, Dulloo A (2002) Pathways from obesity to hypertension: from the perspective of a vicious triangle. Int J Obes 26(suppl 2):S28-S38 (Pubitemid 35034485)
84. Mortensen PB, Juel K (1993) Mortality and causes of death in first admitted schizophrenic patients. Br J Psychiatry 163:183-189 (Pubitemid 23233086)
85. Newcomer JW (2005) Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs 19(Suppl 1):1-93 (Pubitemid 40677047)
86. Newcomer JW (2007a) Metabolic considerations in the use of antipsychotic medications: a review of recent evidence. J Clin Psychiatry 68(Suppl 1):20-27
87. Newcomer JW (2007b) Antipsychotic medications: metabolic and cardiovascular risk. J Clin Psychiatry 68(Suppl 4):8-13 (Pubitemid 46762118)
88. Nielsen J, Skadhede S, Correll CU (2010) Antipsychotics associated with the development of type 2 diabetes in antipsychotic-naïve schizophrenia patients. Neuropsychopharmacology 35:1997-2004
89. Osborn DP, Levy G, Nazareth I, Petersen I, Islam A, King MB (2007) Relative risk of cardiovascular and cancer mortality in people with severe mental illness from the United Kingdom's general practice research database. Arch Gen Psychiatry 64:242-249 (Pubitemid 46220782)
90. Penzner JB, Dudas M, Saito E, Olshanskiy V, Parikh UH, Kapoor S et al (2009) Lack of effect of stimulant combination with second-generation antipsychotics on weight gain, metabolic changes, prolactin levels, and sedation in youth with clinically relevant aggression or oppositionality. J Child Adolesc Psychopharmacol 19:563-573
91. Peroutka SJ, U'Prichard DC, Greenberg DA, Snyder SH (1977) Neuroleptic drug interactions with norepinephrine alpha receptor binding sites in rat brain. Neuropharmacology 16:549-556 (Pubitemid 8176063)
92. Perrone JA, Chabla JM, Hallas BH, Horowitz JM, Torres G (2004) Weight loss dynamics during combined fluoxetine and olanzapine treatment. BMC Pharmacol 4:27
93. Pi-Sunyer X (2002) The obesity epidemic: pathophysiology and consequences of obesity. Obes Res 10(suppl 2):97S-104S
94. Pouzet B, Mow T, Kreilgaard M, Velschow S (2003) Chronic treatment with antipsychotics in rats as a model for antipsychotic-induced weight gain in human. Pharmacol Biochem Behav 75:133-140 (Pubitemid 36577588)
95. Rashid P, Leonardi-Bee J, Bath P (2003) Blood pressure reduction and secondary prevention of stroke and other vascular events: a systematic review. Stroke 34:2741-2749
96. Ratzoni G, Gothelf D, Brand-Gothelf A, Reidman J, Kikinzon L, Gai G et al (2002) Weight gain associated with olanzapine and risperidone in adolescent patients: a comparative prospective study. J Am Acad Child Adolesc Psychiatry 41:337-343 (Pubitemid 38338156)
97. Reddymasu S, Bahta E, Levine S, Manas K, Slay LE (2006) Elevated lipase and diabetic ketoacidosis associated with aripiprazole. JOP 7:303-305
98. Reist C, Mintz J, Albers LJ, Jamal MM, Szabo S, Ozdemir V (2007) Second-generation antipsychotic exposure and metabolic-related disorders in patients with schizophrenia: an observational pharmacoepidemiology study from 1988 to 2002. J Clin Psychopharmacol 27:46-51 (Pubitemid 46105762)
99. Reynolds GP, Kirk SL (2010) Metabolic side effects of antipsychotic drug treatment: pharmacological mechanisms. Pharmacol Ther 125:169-179
100. Ryan MC, Collins P, Thakore JH (2003) Impaired fasting glucose tolerance in first-episode, drugnaive patients with schizophrenia. Am J Psychiatry 160:284-289 (Pubitemid 41110453)
101. Ryan MC, Flanagan S, Kinsella U, Keeling F, Thakore JH (2004) The effects of atypical antipsychotics on visceral fat distribution in first episode, drug-naïve patients with schizophrenia. Life Sci 74:1999-2008, (Pubitemid 38210353)
102. Erratum in: Life Sci. 2004 75:2851
103. Sacher J, Mossaheb N, Spindelegger C, Klein N, Geiss-Granadia T, Sauermann R et al (2008) Effects of olanzapine and ziprasidone on glucose tolerance in healthy volunteers. Neuropharmacology 33:1633-1641 (Pubitemid 351684708)
104. Saddichha S, Manjunatha N, Ameen S, Akhtar S (2008) Diabetes and schizophrenia - effect of disease or drug? Results from a randomized, double-blind, controlled prospective study in firstepisode schizophrenia. Acta Psychiatr Scand 117:342-347 (Pubitemid 351502438)
105. Savoy YE, Ashton MA, Miller MW, Nedza FM, Spracklin DK, Hawthorn MH (2010) Differential effects of various typical and atypical antipsychotics on plasma glucose and insulin levels in the mouse: evidence for the involvement of sympathetic regulation. Schizophr Bull 36:410-418
106. Scheen AJ, de Hert MA (2007) Abnormal glucose metabolism in patients treated with antipsychotics. Diabetes Metab 33:169-175 (Pubitemid 46876639)
107. Shobo M, Yamada H, Koakutsu A, Hamada N, Fujii M, Harada K et al (2011a) Chronic treatment with olanzapine via a novel infusion pump induces adiposity in male rats. Life Sci 88:761-765
108. Shobo M, Yamada H, Mihara T, Kondo Y, Irie M, Harada K et al (2011b) Two models for weight gain and hyperphagia as side effects of atypical antipsychotics in male rats: validation with olanzapine and ziprasidone. Behav Brain Res 216:561-568
109. Silverstone T, Smith G, Goodall E (1988) Prevalence of obesity in patients receiving depot antipsychotics. Br J Psychiatry 153:214-217
110. Simpson GM, Weiden P, Pigott T, Murray S, Siu CO, Romano SJ (2005) Six-month, blinded, multicenter continuation study of ziprasidone versus olanzapine in schizophrenia. Am J Psychiatry 162:1535-1538 (Pubitemid 41105572)
111. Smith GC, Chaussade C, Vickers M, Jensen J, Shepherd PR (2008a) Atypical antipsychotic drugs induce derangements in glucose homeostasis by acutely increasing glucagon secretion and hepatic glucose output in the rat. Diabetologia 51:2309-2317
112. Smith M, Hopkins D, Peveler RC, Holt RIG, Woodward M, Ismail K (2008b) First-v. second-generation antipsychotics and risk for diabetes in schizophrenia: systematic review and meta-analysis. Brit J Psychiatry 192:406-411 (Pubitemid 351809892)
113. Smith GC, Vickers MH, Cognard E, Shepherd PR (2009) Clozapine and quetiepine acutely reduce glucagon-like peptide-1 production and increase glucagon release in obese rats: implications for glucose metabolism and food choice behaviour. Schizophr Res 115:30-40
114. Sowell MO, Mukhopadhyay N, Cavazzoni P, Shankar S, Steinberg HO, Breier A et al (2002) Hyperglycemic clamp assessment of insulin secretory responses in normal subjects treated with olanzapine, risperidone, or placebo. J Clin Endocrinol Metab 87:2918-2923 (Pubitemid 34655364)
115. Sowell MO, Mukhopadhyay N, Cavazzoni P, Carlson C, Mudaliar S, Chinnapongse S et al (2003) Evaluation of insulin sensitivity in healthy volunteers treated with olanzapine, risperidone, or placebo: a prospective, randomized study using the two-step hyperinsulinemic, euglycemic clamp. J Clin Endocrinol Metab 88:5875-5880 (Pubitemid 38033066)
116. Spelman LM, Walsh PI, Sharifi N, Collins P, Thakore JH (2007) Impaired glucose tolerance in first-episode drug-naïve patients with schizophrenia. Diabet Med 24:481-485 (Pubitemid 46669314)
117. Stanton JM (1995) Weight gain associated with neuroleptic medication: a review. Schizophr Bull 21:463-472
118. Stefanidis A, Verty AN, Allen AM, Owens NC, Cowley MA, Oldfield BJ (2009) The role of thermogenesis in antipsychotic drug-induced weight gain. Obesity 17:16-24
119. Svensson TH (2003) Alpha-adrenoceptor modulation hypothesis of antipsychotic atypicality. Prog Neuropsychopharmacol Biol Psychiatry 27:1145-1158 (Pubitemid 37464959)
120. van den Oever IA, Raterman HG, Nurmohamed MT, Simsek S (2010) Endothelial dysfunction, inflammation, and apoptosis in diabetes mellitus. Mediators Inflamm 2010:792393
121. Vestri HS, Maianu L, Moellering DR, Garvey WT (2007) Atypical antipsychotic drugs directly impair insulin action in adipocytes: effects on glucose transport, lipogenesis, and antilipolysis. Neuropsychopharmacology 32:765-772 (Pubitemid 46426168)
122. Vidarsdottir S, de Leeuw van Weenen JE, Frölich M, Roelfsema F, Romijn JA, Pijl H (2010) Effects of olanzapine and haloperidol on the metabolic status of healthy men. J Clin Endocrinol Metab 95:118-125
123. Wallingford NM, Sinnayah P, Bymaster FP, Gadde KM, Krishnan RK, McKinney AA, Landbloom RP et al (2008) Zonisamide prevents olanzapine-associated hyperphagia, weight gain, and elevated blood glucose in rats. Neuropsychopharmacology 33:2922-2933
124. Wetterling T (2001) Bodyweight gain with atypical antipsychotics. Drug Saf 24:59-73
125. Wilson DR, D'Souza L, Sarkar N, Newton M, Hammond C (2003) New-onset diabetes and ketoacidosis with atypical antipsychotics. Schizophr Res 59:1-6 (Pubitemid 35284487)
126. Wirshing DA, Boyd JA, Meng LR, Ballon JS, Marder SR, Wirshing WC (2002) The effects of novel antipsychotics on glucose and lipid levels. J Clin Psychiatry 63:856-865 (Pubitemid 35231725)
127. Wolk R, Shamsuzzaman AS, Somers VK (2003) Obesity, sleep apnoea and hypertension. Hypertension 42:1067-1074
128. Wu R-R, Zhao J-P, Jin H, Shao P, Fang M-S, Guo X-F et al (2008) Lifestyle intervention and metformin for treatment of antipsychotic-induced weight gain. A randomized controlled trial. J Am Med Assoc 299:185-193
129. Yood MU, deLorenze G, Quesenberry CP Jr, Oliveria SA, Tsai A-L, Willey VJ et al (2009) The incidence of diabetes in atypical antipsychotic users differs according to agent - results from a multisite epidemiologic study. Pharmacoepidemiol Drug Saf 18:791-799