Atypical Antipsychotics Induced Metabolic Syndrome

Year 2015, Volume: 7 Issue: 1, 81 - 97, 01.03.2015

Ayşegül Demirel Ömer Demirel Müfit Uğur

https://doi.org/10.5455/cap.20140527123634

Abstract

The use of atypical antipsychotics in patients with schizophrenia is tightly related to the metabolic abnormalities like weight gain, diabetes, dyslipidemia and/or hypertension. Beside of having unique receptor binding features, their heterogeneous receptor binding properties ara also involved in the occurence of the metabolic side effects caused by atypical antipsychotics. It is striking that atypical antipschotics related metabolic side effects have the potential to influence each other in a negative way. Metabolic abnormalities related to atypical antipschotics do not only lead to increase in mortality, but also worsen clinical course and functionality of patients with schizophrenia. Thus, patients treated with atypical antipsychotics should be evaluated routinely with respect to their metabolic states. In this article, metabolic side effects of atypical antipsychotics and their mechanisms were investigated on pharmacological basis.

Keywords

Schizophrenia, metabolic syndrome, atypical antipsychotics

Atipik Antipsikotiklere Bağlı Metabolik Sendrom

Abstract

Şizofreni hastalarında atipik antipsikotik ilaçların kullanımının kilo alımı, diyabet, dislipidemi ve/veya hipertansiyon gibi metabolik anormalliklerle sıkı sıkıya ilişkili olduğu bilinmektedir. Metabolik yan etkiler atipik antipsikotiklerin sadece kendilerine has reseptör bağlama özelliklerinin olmasının dışında bu ilaçların heterojen reseptör bağlama özellikleriyle de ilişkili bulunmuştur. Ayrıca bu ajanlarla ortaya çıkan metabolik yan etkilerin birbirlerini tetikleme potansiyelinin olması dikkati çekmektedir. Metabolik bozukluklarla ilişkili olarak hastalarda sadece mortalitenin artmadığı, aynı zamanda kliniğin kötüleştiği ve işlevselliğin azaldığı da gözlemlenmektedir. Bu nedenlerle atipik antipsikotiklerle tedavi edilen hastaların rutin olarak metabolik durumunun gözden geçirilmesi gereklidir. Bu derlemede atipik antipsikotiklerin metabolik yan etkileri ve mekanizmaları farmakolojik boyutta incelenmiştir.

Keywords

Şizofreni, metabolik sendrom, atipik antipsikotikler

References

• Aktepe E (2011) Çocuk ve ergenlerde psikotrop ilaçların endokrin ve metabolik yan etkileri. TSK Koruyucu Hekimlik Bülteni, 10:741-750.
• Alberti KG, Zimmel PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of WHO consultation. Diabet Med, 15:539-553.
• Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC et al. (1999) Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry, 156:1686-1696.
• Almeras N, Despres JP, Villeneuve J, Demers MF, Roy MA, Cadrin C et al. (2004) Development of atherogenic metabolic risk factor profile associated with the use of atypical antipsychotics. J Clin Psychiatry, 65:557-564.
• Assie MB, Carilla-Durand E, Bardin L, Maraval M, Aliaga M, Malfetes N et al. (2008) The antipsychotics clozapine and olanzapine increase plasma glucose and corticosterone levels in rats: comparison with aripiprazole, ziprasidone, bifeprunox and F15063. Eur J Pharmacol, 592:160-166.
• Baker GF, Rogers HJ (1972) Effects of psychotropic drugs on the erythrocyte permeability to glucose and ethylidene glucose. Biochem Pharmacol, 21:1871-1878.
• Baptista T, Hernandez L, Hoebel BG (1990) Systemic sulpiride increases dopamine metabolites in the lateral hypothalamus. Pharmacol Biochem Behav, 37:227-229.
• Baptista T, Kin NM, Beaulieu S, De Baptista EA (2002) Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management and research perspectives. Pharmacopsychiatry, 35:205-219.
• Basson BR, Kinon BJ, Taylor CC, Szymanski KA, Gilmore JA, Tollefson GD (2001) Factors influencing acute weight change in patients with schizophrenia treated with olanzapine, haloperidol, or risperidone. J Clin Psychiatry, 62:231-238.
• Bat-Pitault F, Delorme R (2009) Aripiprazole and hypertension in adolescents. J Child Adolesc Psychopharmacol, 19:601-602.
• Biswas PN, Wilton LV, Pearcel GL, Freemantle S, Shakir SA (2001) The pharmacovigilance of olanzapine: results of a post- marketing surveillance study on 8858 patients in England. J Psychopharmacol, 15:265-271.
• Borras L, Constant EL, Eytan A, Huguelet P (2005) Hypertension and aripiprazole. Am J Psychiatry, 162:2392.
• Buchholz S, Morrow AF, Coleman PL (2008) Atypical antipsychotic-induced diabetes mellitus: an update on epidemiology and postulated mechanisms. Intern Med J, 38:602-606.
• Buse JB, Cavazzoni P, Hornbuckle K, Hutchings D, Breier A, Jovanovic L (2003) A retrospective cohort study of diabetes mellitus and antipsychotic treatment in the United States. J Clin Epidemiol, 56:164-170.
• Casey DE, Zorn SH (2001) The pharmacology of weight gain with antipsychotics. J Clin Psychiatry, 62(Suppl. 7):S4-S10.
• Casey DE (2005) Metabolic issues and cardiovascular disease in patients with psychiatric disorders. Am J Med, 118:15S-22S.
• 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.
• Cohen RM, Nordahl TE, Semple WE, Andreason P, Litman RE, Pickar D (1997) The brain metabolic patterns of clozapine and fluphenazine-treated patients with schizophrenia during a continuous performance task. Arch Gen Psychiatry, 54:481-486.
• Corey-Lisle PK, Kolotkin RL, Crosby RD, Tuomari VV, Carson WH, Newcomer JW (2005) Schizophrenia: relationship between body mass index and quality of life. Abstract presented at the Annual Meeting of the American Psychiatric Association, Atlanta, GA.
• Coulter D. (2003) Atypical antipsychotics may cause hypertension. Prescriber Update, 24(1):4.
• De Hert M, Mittoux A, He Y, Peuskens J (2011) Metabolic parameters in the short- and long-term treatment of schizophrenia with sertindole or risperidone. Eur Arch Psychiatry Clin Neurosci, 261:231-239.
• De Hert M, Schreurs V, Vancampfort D, Winkel RV (2009). Metabolic syndrome in people with schizophrenia: a review. World Psychiatry, 8:15-22.
• De Hert M, van Winkel R, Van Eyck D, Hanssens L,Wampers M, Scheen A et al. (2006) Prevalence of diabetes, metabolic syndrome and metabolic abnormalities in schizophrenia over the course of the illness: a cross-sectional study. Clin Pract Epidemiol Ment Health, 2:14.
• de Leon J, Diaz FJ (2007) Planning for the optimal design of studies to personalize antipsychotic prescriptions in the post-CATIE era: the clinical and pharmacoepidemiological data suggest that pursuing the pharmacogenetics of metabolic syndrome complications (hypertension, diabetes mellitus and hyperlipidemia) may be a reasonable strategy. Schizophr Res, 96:185-197.
• DeQuardo JR, Tandon R (1998) Do atypical antipsychotic medications favorably alter the long-term course of schizophrenia? J Psychiatric Res, 32:229-242.
• Dixon L, Weiden P, Delahanty J, Goldberg R, Postrado L, Lucksted A et al. (2000) Prevalence and correlates of diabetes in national schizophrenia samples. Schizophr Bull, 26:903-912.
• Dixon L, Postrado L, Delahanty J, Fischer PJ, Lehman A (1999) The association of medical comorbidity in schizophrenia with poor physical and mental health. J Nerv Ment Dis, 187:496–502.
• Dwyer DS, Liu Y, Bradley RJ (1999a) Dopamine receptor antagonists modulate glucose uptake in rat pheochromocytoma (PC12) cells. Neurosci Lett, 274:151-154.
• Dwyer DS, Pinkofsky HB, Liu Y, Bradley RJ (1999b) Antipsychotic drugs affect glucose uptake and the expression of glucose transporters in PC12 cells. Prog Neuropsychopharmacol Biol Psychiatry, 23:69-80.
• Elman I, Borsook D, Lukas SE (2006) Food intake and reward mechanisms in patients with schizophrenia: implications for metabolic disturbances and treatment with second-generation antipsychotic agents. Neuropsychopharmacology, 31:2091- 2120.
• Engl J, Hanusch-Enserer U, Prager R, Patsch JR, Ebenbichler C (2005) The metabolic syndrome: effects of a pronounced weight loss induced by bariatric surgery. Wien Klin Wochenschr, 117:243-254.
• Fadel J, Bubser M, Deutch AY (2002) Differential activation of orexin neurons by antipsychotic drugs associated with weight gain. J Neuroscience, 22: 6742-6746.
• Feldman PD, Hay LK, Deberdt W, Kennedy JS, Hutchins DS, Hay DP et al. (2004) Retrospective cohort study of diabetes mellitus and antipsychotic treatment in a geriatric population in the United States. J Am Med Dir Assoc, 5:38-46.
• Ford ES, Giles WH, Dietz WH (2002) Prevalence of metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA, 287:356-359.
• George TP, Winther LC (1996) Hypertension after initiation of clozapine. Am J Psychiatry, 153:1368-1369.
• Gianfrancesco F, Grogg A, Mahmoud R, Wang RH, Meletiche D (2003) Differential effects of antipsychotic agents on the risk of development of type 2 diabetes mellitus in patients with mood disorders. Clin Ther, 25:1150-1171.
• Gilles M, Wilke A, Kopf D, Nonell A, Lehner H, Deuschle M. (2005) Antagonism of the serotonin (5-HT)-2 receptor and insulin sensitivity: implications for atypical antipsychotics. Psychosom Med, 67:748-51.
• Goodpaster BH, Kelley DE, Wing RR, Meier A, Thaete FL (1999) Effects of weight loss on regional fat distribution and insulin sensitivity in obesity. Diabetes, 8:839-847.
• Gough SCL, O’Donovan MC (2005) Clustering of metabolic comorbidity in schizophrenia: a genetic contribution? J Psychopharmacol, 19(suppl. 6):47-55.
• Green AI, Patel JK, Goisman RM, Allison DB, Blackburn G (2000) Weight gain from novel antipsychotic drugs: need for action. Gen Hosp Psychiatry, 22:224-235.
• Griffin ME, Marcucci MJ, Cline GW, Bell K, Barucci N, Lee D et al. (1999) Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signalling cascade. Diabetes, 48:1270-1274.
• Hagg S, Joelsson L, Mjorndal T, Spigset O, Oja G, Dahlqvist R (1998) Prevalence of diabetes and impaired glucose tolerance in patients treated with Clozapine compared with patients treated with conventional depot neuroleptic medications. J Clin Psychiatry, 59:294-299.
• Hajduch E, Rencurel F, Balendran A, Batty IH, Downes CP, Hun HS (1999) Serotonin (5-hydroxytryptamine), a novel regulator of glucose transport in rat skeletal muscle. J Biol Chem, 274:13563-13568.
• Hatemi H, Yumuk VD, Turan N, Arik N(2003) Prevalence of overweight and obesity in Turkey. Metab Syndr Relat Disord, 1:285- 290.
• Heiskanen T, Niskanen L, Lyytikainen R, Saarinen PI, Hinttikka J (2003) Metabolic syndrome in patients with schizophrenia. J Clin Psychiatry, 64:575-579.
• Henderson DC, Daley TB, Kunkel L, Rodrigues-Scott M, Koul P, Hayden D (2004) Clozapine and hypertension: a chart review of 82 patients. J Clin Psychiatry, 65:686-689.
• Hennekens CH, Hennekens AR, Hollar D, Casey DE (2005) Schizophrenia and increased risks of cardiovascular disease. Am Heart J, 150:1115-1121.
• Hofer A, Kemmler G, Eder U, Edlinger M, Hummer M, Fleischhacker WW (2004) Quality of life in schizophrenia: the impact of psychopathology, attitude toward medication, and side effects. J Clin Psychiatry, 65:932-939.
• Holt RI, Peveler RC, Byrne CD (2004) Schizophrenia, the metabolic syndrome and diabetes. Diabetic Med, 21:515-523.
• Inoue K, Nakazawa K, Watano T, Ohara-Imaızumı M, Fujımorl K, Takanaka A (1992) Dopamine receptor agonists and antagonists enhance ATP-activated currents. Eur J Pharmacol, 215:321-324.
• Jafari S, Fernandez-Enright F, Huang X-F (2012) Structural contributions of antipsychotic drugs to their therapeutic profiles and metabolic side effects. J Neurochem, 120:371–384.
• Jassim G, Skrede S, Vázquez MJ, Wergedal H, Vik-Mo AO, Lunder N et al. (2012) Acute effects of orexigenic antipsychotic drugs on lipid and carbohydrate metabolism in rat. Psychopharmacology (Berl), 219:783-94.
• Jibson MD, Tandon R (1998) New atypical antipsychotic medications. J Psychiatr Res, 32:215-228.
• Jibson MD, Tandon R (2000) Treatment of schizophrenia. Psychiatr Clin North Am, 7:83-113.
• 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.
• Johnson DE, Yamazaki H, Ward KM Schmidt AW, Lebel WS, Treadway JL (2005) Inhibitory effects of antipsychotics on carbachol- enhanced insulin secretion from perifused rat islets: role of muscarinic antagonism in antipsychotic-induced diabetes and hyperglycemia. Diabetes, 54:1552-1558.
• Jones M, Jones A (2008) The effect of antipsychotic medication on metabolic syndrome. Nurs Stand, 22:43-48.
• Juruena MF, Sena EP, Oliveira IR (2011) Sertindole in the management of schizophrenia. J Cent Nerv Syst Dis, 3:75-85.
• Kane J, Honigfeld G, Singer J, Meltzer H (1988) Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlorpromazine. Arch Gen Psychiatry, 45:789-796.
• Kannel WB (2005) Risk stratification of dyslipidemia: insights from the Framingham Study. Curr Med Chem Cardiovasc Hematol Agents, 3:187-193.
• Kapur S, Remington G (2001) Atypical antipsychotics: new directions and new challenges in the treatment of schizophrenia. Annu Rev Med, 52:503-517.
• Koeller EA, Cross JT, Doralswamy PM, Schneider BS. (2003) Risperidone-associated diabetes mellitus: a pharmacovigilance study. Pharmacotherapy, 23:735-744.
• Koller EA, Schneider B, Bennett K, Dubitsky G. (2001) Clozapine-associated diabetes. Am J Med, 111:716-723.
• Koro CE, Fedder DO, L’Italien GJ, Weiss SS, Magder LS, Kreyenbuhl J et al. (2002) An assessment of the independent effects of olanzapine and risperidone exposure on the risk of hyperlipidemia in schizophrenic patients. Arch Gen Psychiatry, 59:1021- 1026.
• Lamberti JS, Bellnier T, Schwarzkopf SB (1992) Weight gain among schizophrenic patients treated with clozapine. Am J Psychiatry, 149:689-690.
• Lee DW, Fowler R, Kadlubek P, Haberman M (2002) No significant difference in the risk of diabetes mellitus during treatment with typical versus atypical antipsychotics: results from a large observational study. Drug Benefit Trends, 14:46-52.
• Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO et al. (2005) Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med, 353:1209-1223.
• Lindenmayer JP, Cozobor P, Volavka J, Citrome L, Sheitman B, McEvoy JP et al. (2003) Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics. Am J Psychiatry,160:290-296.
• Mathews M, Muzina DJ (2007) Atypical antipsychotics: new drugs, new challenges. Cleve Clin J Med, 74:597-606.
• McEvoy JP, Meyer JM, Goff DC, Nasrallah HA, Davis SM, Sullivan L et al. (2005) Prevalence of the metabolic syndrome in patients with schizophrenia: baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophr Res, 80:19-32.
• McQuade R, Kostic D, Marcus R, Carson W, Iwamoto T, Torbeyns A et al. (2004) Aripiprazole versus olanzapine in schizophrenia: a 52 week open label extension study. American College of Neuropsychopharmacology 43rd annual meeting; San Juan, Puerto Rico.
• McQuade RD, Stock E, Marcus RAC (2004) Comparasion of weight change during treatment with olanzapine or aripiprazole: results from a randomized, double-blind study. J Clin Psychiatry, 65:7–56.
• Megna JL, Schwartz TL, Siddiqui UA, Rojas MH (2011) Obesity in adults with serious and persistent mental illness: A review of postulated mechanisms and current interventions. Ann Clin Psychiatry, 23:131-140.
• Melkerson KI, Hulting AL, Brismar KE (2000) Elevated levels of insulin, leptin, and blood lipids in olanzapine-treated patients with schizophrenia or related psychoses. J Clin Psychiatry, 61:742-749.
• Melkersson KI, Dahl M (2003) Relationship between levels of insulin or triglycerides and serum concentrations of the atypical antipsychotics clozapine and olanzapine in patients on treatment with therapeutic doses. Psychopharmacology, 170:157-166.
• Melkersson KI, Hulting AL, Brismar KE (1999) Different influences of classical antipsychotics and clozapine on glucose–insulin homeostasis in patients with schizophrenia or related psychoses. J Clin Psychiatry, 60:783-791.
• Meyer JM, Koro CE (2004) The effects of antipsychotic therapy on serum lipids: a comprehensive review. Schizophr Res, 70:1-17.
• Milano W, De Rosa M, Capasso A (2013) Antipsychotic drugs opposite to metabolic risk: neurotransmitters, neurohormonal and pharmacogenetic mechanisms underlying with weight gain and metabolic syndrome. Open Neurol J, 7:23-31.
• Paton C, Esop R, Young C, Taylor D (2004) Obesity, dyslipidaemias and smoking in an inpatient population treated with antipsychotic drugs. Acta Psychiatr Scand, 110:299-305.
• Pigott TA, Carson WH, Saha AR, Torbeyns AF, Stock E, Ingenito GG (2003) Aripiprazole for the prevention of relapse in stabilized patients with chronic schizophrenia: a placebo-controlled 26-week study. J Clin Psychiatry, 64:1048-1056.
• Pouliot MC, Després JP, Lemieux S, Moorjani S, Bouchard C, Tremblay A (1994) Waist circumference and abdominal sagittal diameter: best simple anthropometric indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women. Am J Cardiol, 73:460-468.
• Rege S (2008) Antipsychotic induced weight gain in schizophrenia: mechanisms and management. Aust N Z J Psychiatry, 42:369- 381.
• Robertson GS, Matsumura H, Fibiger HC (1994) Induction patterns of Fos-like immunoreactivity in the forebrain as predictors of atypical antipsychotic activity. J Pharmacol Exp Ther, 271:1058-1066.
• Robinson DG, Woerner MG, Alvir JM, Bilder RM, Hinrichsen GA, Lieberman JA (2002) Predictors of medication discontinuation by patients with first-episode schizophrenia and schizoaffective disorder. Schizophr Res, 57:209-219.
• Rosack IJ (2003) New-generation antipsychotic effective for treating mania. Psychiatric News, 38 (19) 31.
• Rummel-Kluge C, Komossa K, Schwarz S, Hunger H, Schmid F, Lobos CA et al. (2010) Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr Res, 123:225-233.
• Ryan MC, Collins P, Thakore JH (2003) Impaired fasting glucose tolerance in first-episode, drug-naive patients with schizophrenia. Am J Psychiatry, 160:284-289.
• Savoy YE, Ashton MA, Miller MW, Nedza FM, Spracklin DK, Hawthorn M (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.
• Schaffhauser AO, Madiehe AM, Braymer HD, Bray GA, York DA (2002) Effects of a high-fat diet and strain on hypothalamic gene expression in rats. Obes Res, 10:1188-1196.
• Schaffhauser R, Macdonald E, Blacklock C, Tilak SD, Wiles D, Halliday J et al. (1998) Dietary intake of schizophrenic patients in Nithsdale, Scotland: case-control study. BMJ, 317:784-785.
• Sernyak MJ, Leslie DL, Alarcon RD, Losonczy MF, Rosenheck R (2002) Association of diabetes mellitus with the use of atypical neuroleptics in the treatment of schizophrenia. Am J Psychiatry, 159:561-566.
• Sinha MK, Opentanova I, Ohannesian JP, Kolaczynski JW, Heiman ML, Hale J et al. (1996) Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting. J Clin Invest, 98:1277-1282.
• 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, 87:2918–2969.
• Sönmez EÖ, Kaya N (2011) Atipik antipsikotiklere bağlı kilo artışının önlenmesinde metformin kullanımı. Psikiyatride Güncel Yaklaşımlar, 3:309-320.
• Spelman LM, Walsh PI., Sharifi N, Collins P, Thakore JH (2007) Impaired glucose tolerance in first-episode drug-naive patients with schizophrenia. Diabet Med, 24:481-485.
• Stahl S, Mignon L, Meyer JM (2009) Which comes first: atypical treatment or cardiometabolic risk? Acta Psychiatr Scand, 119:171- 179.
• Tandon R, Jibson MD (2003) Efficacy of newer generation antipsychotics in the treatment of schizophrenia. Psychoneuroendocrinology, 28:9-26.
• Tandon R, Milner K, Jibson MD (1999) Antipsychotics from theory to practice: integrating clinical and basic data. J Clin Psychiatry, 60(Suppl. 8):S21-S28.
• Tandon R (2001) Industry-sponsored Phase IV clinical trials: promises and pitfalls, information and misinformation. Journal of Psychotic Disorders, 5:14-15.
• Tanrıverdi MH, Çelepkolu T, Aslanhan H (2013) Diyabet ve birinci basamak sağlık hizmetleri. Journal of Clinical and Experimental Investigations, 4:562-567.
• Tecott LH, Sun LM, Akana SF, Strack AM, Lowenstein DH, Dallman MF et al. (1995) Eating disorders and epilepsy in mice lacking 5- HT2c serotonin receptors. Nature, 374:542-546.
• Torrent C, Amann B, Sanchez-Moreno J, Colom F, Feinares M, Comes M et al. (2008) Weight gain in bipolar disorder: pharmacological treatment as a contributing factor. Acta Psychiatr Scand, 118:4-18.
• Van Gaal LF (2006) Long-term health considerations in schizophrenia: Metabolic effects and the role of abdominal adiposity. Eur Neuropsychopharmacol, 16:142-148.
• van Winkel R, De Hert M, Wampers M, Van Eyck D, Hanssens L, Scheen A et al. (2008) Major changes in glucose metabolism including new-onset diabetes within 3 months after initiation or switch of atypical antipsychotic medication in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry, 69:472-479.
• Venkatasubramanian G, Chittiprol S, Neelakantachar N, Naveen MN, Thirthall J, Gangadhar BN et al. (2007) Insulin and insulin- like growth factor-1 abnormalities in antipsychotic-naive schizophrenia. Am J Psychiatry, 164:1557-1560.
• Villanueva N, Markham-Abedi C, McNeely C, Diaz FJ, de Leon J (2006) Probable association between ziprasidone and worsening hypertension. Pharmacotherapy, 26:1352-1357.
• Wetterling T (2001) Bodyweight gain with atypical antipsychotics. a comparative review. Drug Saf, 24:59-73.
• Wirshing DA, Wirshing WC, Kysar L, Berisford MA, Goldstein D, Pashdag J et al. (1999) Novel antipsychotics: comparison of weight gain liabilities. J Clin Psychiatry, 60:358-363.
• Woo YS, Kim W, Chae CH, Yoon BH, Bahk W (2009) Blood pressure changes during clozapine or olanzapine treatment in Korean schizophrenic patients. World J Biol Psychiatry, 10(4):420-425.
• Yasui-Furukori N, Fujii A (2013) Worsened hypertension control induced by aripiprazole. Neuropschiatr Dis Treat, 9:505-507.