Atypical antipsychotics-induced metabolic syndrome and nonalcoholic fatty liver disease: a critical review

References

• Turner T. Chlorpromazine: unlocking psychosis. BMJ. 2007;334(Suppl 1):S7. doi:10.1136/bmj.39034.609074.9417204765
   PubMedGoogle Scholar
• Maric NP, Jovicic MJ, Mihaljevic M, Miljevic C. Improving current treatments for schizophrenia. Drug Dev Res. 2016;77:357–367. doi:10.1002/ddr.2133727633376
   PubMed Web of Science ®Google Scholar
• Warnez S, Alessi-Severini S. Clozapine: a review of clinical practice guidelines and prescribing trends. BMC Psychiatry. 2014;14:102. doi:10.1186/1471-244X-14-10224708834
   PubMed Web of Science ®Google Scholar
• McDonagh M, Peterson K, Carson S, Fu R, Thakurta S. Drug Class Review. A typical antipsychotic drugs: final update 3 report. Drug Class Rev. 2010.
   Google Scholar
• Hermann RC, Yang D, Ettner SL, Marcus SC, Yoon C, Abraham M. Prescription of antipsychotic drugs by office-based physicians in the United States, 1989–1997. Psychiatr Serv. 2002;53:425–430. doi:10.1176/appi.ps.53.4.42511919355
   PubMed Web of Science ®Google Scholar
• Carbon M, Hsieh C-H, Kane JM, Correll CU. Tardive dyskinesia prevalence in the period of second-generation antipsychotic use: a meta-analysis. J Clin Psychiatry. 2017;78:e264–e278. doi:10.4088/JCP.16r1083228146614
   PubMed Web of Science ®Google Scholar
• Zhang JP, Gallego JA, Robinson DG, Malhotra AK, Kane JM, Correll CU. Efficacy and safety of individual second-generation vs. first-generation antipsychotics in first-episode psychosis: a systematic review and meta-analysis. Int J Neuropsychopharmacol. 2013;16:1205–1218. doi:10.1017/S146114571200127723199972
   PubMed Web of Science ®Google Scholar
• Mitchell AJ, Vancampfort D, Sweers K, van Winkel R, Yu W, De Hert M. Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders–a systematic review and meta-analysis. Schizophr Bull. 2013;39:306–318. doi:10.1093/schbul/sbr14822207632
   PubMed Web of Science ®Google Scholar
• De Hert M, Yu W, Detraux J, Sweers K, van Winkel R, Correll CU. Body weight and metabolic adverse effects of asenapine, iloperidone, lurasidone and paliperidone in the treatment of schizophrenia and bipolar disorder: a systematic review and exploratory meta-analysis. CNS Drugs. 2012;26:733–759. doi:10.2165/11634500-000000000-0000022900950
   PubMed Web of Science ®Google Scholar
• Hasnain M, Fredrickson SK, Vieweg WV, Pandurangi AK. Metabolic syndrome associated with schizophrenia and atypical antipsychotics. Curr Diab Rep. 2010;10:209–216. doi:10.1007/s11892-010-0112-820425584
   PubMed Web of Science ®Google Scholar
• Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs. 2005;19(Suppl 1):1–93. doi:10.2165/00023210-200519001-00001
   PubMed Web of Science ®Google Scholar
• Newcomer JW. Antipsychotic medications: metabolic and cardiovascular risk. J Clin Psychiatry. 2007;68(Suppl 4):8–13.
   PubMed Web of Science ®Google Scholar
• Rummel-Kluge C, Komossa K, Schwarz S, et al. 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. 2010;123:225–233. doi:10.1016/j.schres.2010.07.01220692814
   PubMed Web of Science ®Google Scholar
• Galassi A, Reynolds K, He J. Metabolic syndrome and risk of cardiovascular disease: a meta-analysis. Am J Med. 2006;119:812–819. doi:10.1016/j.amjmed.2006.02.03117000207
   PubMed Web of Science ®Google Scholar
• Gami AS, Witt BJ, Howard DE, et al. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol. 2007;49:403–414. doi:10.1016/j.jacc.2006.09.03217258085
   PubMed Web of Science ®Google Scholar
• Mottillo S, Filion KB, Genest J, et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol. 2010;56:1113–1132. doi:10.1016/j.jacc.2010.05.03420863953
   PubMed Web of Science ®Google Scholar
• Eckel RH, Alberti KG, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2010;375:181–183. doi:10.1016/S0140-6736(09)61794-320109902
   PubMed Web of Science ®Google Scholar
• Massart J, Begriche K, Moreau C, Fromenty B. Role of nonalcoholic fatty liver disease as risk factor for drug-induced hepatotoxicity. J Clin Transl Res. 2017;3:212–232. doi:10.18053/jctres.03.2017S1.00628691103
   PubMedGoogle Scholar
• Tarantino G, Conca P, Basile V, et al. A prospective study of acute drug-induced liver injury in patients suffering from non-alcoholic fatty liver disease. Hepatol Res. 2007;37:410–415. doi:10.1111/j.1872-034X.2007.00072.x17539815
   PubMed Web of Science ®Google Scholar
• Slim M, Medina-Caliz I, Gonzalez-Jimenez A, et al. Hepatic safety of atypical antipsychotics: current evidence and future directions. Drug Saf. 2016;39:925–943. doi:10.1007/s40264-016-0436-727449495
   PubMed Web of Science ®Google Scholar
• Said MA, Sulaiman AH, Habil MH, et al. Metabolic syndrome and cardiovascular risk among patients with schizophrenia receiving antipsychotics in Malaysia. Singapore Med J. 2012;53:801–807.23268153
   PubMed Web of Science ®Google Scholar
• Bou KR. Atypical antipsychotic drugs, schizophrenia, and metabolic syndrome in non-Euro- American societies. Clin Neuropharmacol. 2012;35:141–147. doi:10.1097/WNF.0b013e31824d528822592510
   PubMed Web of Science ®Google Scholar
• McEvoy JP, Meyer JM, Goff DC, et al. 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. 2005;80:19–32. doi:10.1016/j.schres.2005.07.01416137860
   PubMed Web of Science ®Google Scholar
• Vanuzzo D, Lo NC, Pilotto L, et al. Cardiovascular epidemiologic observatory 2008–2011: preliminary results. G Ital Cardiol (Rome). 2010;11:25S–30S.20879475
   PubMedGoogle Scholar
• Zhang Y, Chen M, Chen J, et al. Metabolic syndrome in patients taking clozapine: prevalence and influence of catechol-O-methyltransferase genotype. Psycho- Pharmacology (berl). 2014;231:2211–2218. doi:10.1007/s00213-013-3410-4
   Web of Science ®Google Scholar
• Baptista T. Body weight gain induced by antipsychotic drugs: mechanisms and management. Acta Psychiatr Scand. 1999;100:3–16.10442434
   PubMed Web of Science ®Google Scholar
• Leadbetter R, Shutty M, Pavalonis D, Vieweg V, Higgins P, Downs M. Clozapine-induced weight gain: prevalence and clinical relevance. Am J Psychiatry. 1992;149:68–72. doi:10.1176/ajp.149.1.681728188
   PubMed Web of Science ®Google Scholar
• Kumra S, Herion D, Jacobsen LK, Briguglia C, Grothe D. Case study: risperidone-induced hepatotoxicity in pediatric patients. J Am Acad Child Adolesc Psychiatry. 1997;36:701–705. doi:10.1097/00004583-199705000-000229136506
   PubMed Web of Science ®Google Scholar
• Kemner C, Willemsen-Swinkels SH, de Jonge M, Tuynman-Qua H, van Engeland H. Open-label study of olanzapine in children with pervasive developmental disorder. J Clin Psychopharmacol. 2002;22:455–460.12352267
   PubMed Web of Science ®Google Scholar
• Gagliano A, Germanò E, Pustorino G, et al. Risperidone treatment of children with autistic disorder: effectiveness, tolerability, and pharmacokinetic implications. J Child Adolesc Psychopharmacol. 2004;14:39–47. doi:10.1089/10445460477384047215142390
   PubMed Web of Science ®Google Scholar
• Madhusoodanan S, Suresh P, Brenner R, Pillai R. Experience with the atypical antipsychotics risperidone and olanzapine in the elderly. Ann Clin Psychiatry. 1999;11:113–118.10482120
   PubMedGoogle Scholar
• Street JS, Clark WS, Gannon KS, et al. Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer disease in nursing care facilities: a double-blind, randomized, placebo-controlled trial. The HGEU study group. Arch Gen Psychiatry. 2000;57:968–976.11015815
   PubMed Web of Science ®Google Scholar
• Barahal HS, Freeman N. Sudden graying of hair, alopecia, and diabetes mellitus of psychogenic origin. Psychiatr Q. 1946;20:31–38.21018012
   PubMed Web of Science ®Google Scholar
• Gury C. Schizophrenia, diabetes mellitus and antipsychotics. Encephale. 2004;30:382–391.15538314
   PubMed Web of Science ®Google Scholar
• Haupt DW, Newcomer JW. Hyperglycemia and antipsychotic medications. J Clin Psychiatry. 2001;62(Suppl 27):15–26; discussion 40–41.
   Google Scholar
• Colli A, Cocciolo M, Francobandiera F, Rogantin F, Cattalini N. Diabetic ketoacidosis associated with clozapine treatment. Diabetes Care. 1999;22:176–177. doi:10.2337/diacare.22.1.176a
   PubMed Web of Science ®Google Scholar
• Newcomer JW, Haupt DW, Fucetola R, et al. Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry. 2002;59:337–345.11926934
   PubMed Web of Science ®Google Scholar
• Wetterling T, Schneider B, Weber B. Dyslipidemia and schizophrenia. Psychiatr Prax. 2007;34:223–229. doi:10.1055/s-2006-94005617160750
   PubMed Web of Science ®Google Scholar
• Galling B, Roldán A, Nielsen RE, et al. Type 2 diabetes mellitus in youth exposed to antipsychotics: a systematic review and meta-analysis. JAMA Psychiatry. 2016;73:247–259. doi:10.1001/jamapsychiatry.2015.292326792761
   PubMed Web of Science ®Google Scholar
• Atmaca M, Kuloglu M, Tezcan E, Ustundag B. Serum leptin and triglyceride levels in patients on treatment with atypical antipsychotics. J Clin Psychiatry. 2003;64:598–604.12755665
   PubMed Web of Science ®Google Scholar
• Meyer JM, Koro CE. The effects of antipsychotic therapy on serum lipids: a comprehensive review. Schizophr Res. 2004;70:1–17. doi:10.1016/j.schres.2004.01.01415246458
   PubMed Web of Science ®Google Scholar
• Wirshing DA, Boyd JA, Meng LR, Ballon JS, Marder SR, Wirshing WC. The effects of novel antipsychotics on glucose and lipid levels. J Clin Psychiatry. 2002;63:856–865.12416594
   PubMed Web of Science ®Google Scholar
• Meyer JM. A retrospective comparison of weight, lipid, and glucose changes between risperidone- and olanzapine-treated inpatients: metabolic outcomes after 1 year. J Clin Psychiatry. 2002;63:425–433.12019668
   PubMed Web of Science ®Google Scholar
• Olfson M, Marcus SC, Corey-Lisle P, Tuomari AV, Hines P, L’Italien GJ. Hyperlipidemia following treatment with antipsychotic medications. Am J Psychiatry. 2006;163:1821–1825. doi:10.1176/ajp.2006.163.10.182117012695
   PubMed Web of Science ®Google Scholar
• Weiden PJ, Daniel DG, Simpson G, Romano SJ. Improvement in indices of health status in outpatients with schizophrenia switched to ziprasidone. J Clin Psychopharmacol. 2003;23:595–600. doi:10.1097/01.jcp.0000095347.32154.0814624190
   PubMed Web of Science ®Google Scholar
• Doucette DE, Grenier JP, Robertson PS. Olanzapine-induced acute pancreatitis. Ann Pharmacother. 2000;34:1128–1131. doi:10.1345/aph.1939011054978
   PubMed Web of Science ®Google Scholar
• Gupta A, Dadheech G, Yadav D, Sharma P, Gautam S. Metabolic issues in schizophrenic patients receiving antipsychotic treatment. Indian J Clin Biochem. 2014;29:196–201. doi:10.1007/s12291-013-0415-z24757302
   PubMedGoogle Scholar
• Kerr TA, Jonnalagadda S, Prakash C, Azar R. Pancreatitis following olanzapine therapy: a report of three cases. Case Rep Gastroenterol. 2007;1:15–20. doi:10.1159/00010422221487466
   PubMedGoogle Scholar
• Rizos E, Tournikioti K, Alevyzakis E, et al. Acute necrotizing pancreatitis following olanzapine treatment and 759C/T polymorphism of HTR2C gene: a case report. In Vivo. 2015;29:529–531.26359410
   PubMed Web of Science ®Google Scholar
• Rossor AM, Leech N, Neely RD. Olanzapine-induced chylomicronemia presenting as acute pancreatitis. J Clin Psychopharmacol. 2007;27:395–396. doi:10.1097/01.jcp.0000264988.55603.bb17632226
   PubMed Web of Science ®Google Scholar
• Targher G, Bertolini L, Padovani R, et al. Prevalence of non-alcoholic fatty liver disease and its association with cardiovascular disease in patients with type 1 diabetes. J Hepatol. 2010;53:713–718. doi:10.1016/j.jhep.2010.04.03020619918
   PubMed Web of Science ®Google Scholar
• Carney CP, Jones L, Woolson RF. Medical comorbidity in women and men with schizophrenia: a population-based controlled study. J Gen Intern Med. 2006;21:1133–1137. doi:10.1111/j.1525-1497.2006.00563.x17026726
   PubMed Web of Science ®Google Scholar
• Fuller BE, Rodriguez VL, Linke A, Sikirica M, Dirani R, Hauser P. Prevalence of liver disease in veterans with bipolar disorder or schizophrenia. Gen Hosp Psychiatry. 2011;33:232–237. doi:10.1016/j.genhosppsych.2011.03.00621601719
   PubMed Web of Science ®Google Scholar
• Sokal J, Messias E, Dickerson FB, et al. Comorbidity of medical illnesses among adults with serious mental illness who are receiving community psychiatric services. J Nerv Ment Dis. 2004;192:421–427.15167405
   PubMed Web of Science ®Google Scholar
• Hsu JH, Chien IC, Lin CH, Chou YJ, Chou P. Increased risk of chronic liver disease in patients with schizophrenia: a population-based cohort study. Psychosomatics. 2014;55:163–171. doi:10.1016/j.psym.2013.06.00123932529
   PubMed Web of Science ®Google Scholar
• Morlán-Coarasa MJ, Arias-Loste MT, de la Foz VO, et al. Incidence of non-alcoholic fatty liver disease and metabolic dysfunction in first episode schizophrenia and related psychotic disorders: a 3-year prospective randomized interventional study. Psychopharmacology (Berl). 2016;233:3947–3952. doi:10.1007/s00213-016-4422-727620899
   PubMed Web of Science ®Google Scholar
• Liu H, Lu HY. Nonalcoholic fatty liver disease and cardiovascular disease. World J Gastroenterol. 2014;20:8407–8415. doi:10.3748/wjg.v20.i26.840725024598
   PubMed Web of Science ®Google Scholar
• Moore N, Hall G, Sturkenboom M, Mann R, Lagnaoui R, Begaud B. Biases affecting the proportional reporting ratio (PPR) in spontaneous reports pharmacovigilance databases: the example of sertindole. Pharmacoepidemiol Drug Saf. 2003;12:271–281. doi:10.1002/pds.84812812006
   PubMed Web of Science ®Google Scholar
• Hale AS. A review of the safety and tolerability of sertindole. Int Clin Psychopharmacol. 1998;13(Suppl 3):S65–S70.9690973
   PubMed Web of Science ®Google Scholar
• Haddad PM, Anderson IM. Antipsychotic-related QTc prolongation, torsade de pointes and sudden death. Drugs. 2002;62:1649–1671. doi:10.2165/00003495-200262110-0000612109926
   PubMed Web of Science ®Google Scholar
• Azorin JM, Strub N, Loft H. A double-blind, controlled study of sertindole versus risperidone in the treatment of moderate-to-severe schizophrenia. Int Clin Psychopharmacol. 2006;21:49–56.16317317
   PubMed Web of Science ®Google Scholar
• Daniel DG, Wozniak P, Mack RJ, McCarthy BG. Long-term efficacy and safety comparison of sertindole and haloperidol in the treatment of schizophrenia. The Sertindole Study Group. Psychopharmacol Bull. 1998;34:61–69.9564200
   PubMed Web of Science ®Google Scholar
• Zimbroff DL, Kane JM, Tamminga CA, et al. Controlled, dose-response study of sertindole and haloperidol in the treatment of schizophrenia. Sertindole study group. Am J Psychiatry. 1997;154:782–791. doi:10.1176/ajp.154.6.7829167505
   PubMed Web of Science ®Google Scholar
• Gallhofer B, Jaanson P, Mittoux A, Tanghøj P, Lis S, Krieger S. Course of recovery of cognitive impairment in patients with schizophrenia: a randomised double-blind study comparing sertindole and haloperidol. Pharmacopsychiatry. 2007;40:275–286. doi:10.1055/s-2007-99029118030652
   PubMed Web of Science ®Google Scholar
• Idris N, Neill J, Grayson B, et al. Sertindole improves sub-chronic PCP-induced reversal learning and episodic memory deficits in rodents: involvement of 5-HT(6) and 5-HT (2A) receptor mechanisms. Psychopharmacology (Berl). 2010;208:23–36. doi:10.1007/s00213-009-1702-519851757
   PubMed Web of Science ®Google Scholar
• Rodefer JS, Nguyen TN, Karlsson JJ, Arnt J. Reversal of subchronic PCP-induced deficits in attentional set shifting in rats by sertindole and a 5-HT6 receptor antagonist: comparison among antipsychotics. Neuropsychopharmacology. 2008;33:2657–2666. doi:10.1038/sj.npp.130165418094666
   PubMed Web of Science ®Google Scholar
• Karamatskos E, Lambert M, Mulert C, Naber D. Drug safety and efficacy evaluation of sertindole for schizophrenia. Expert Opin Drug Saf. 2012;11:1047–1062. doi:10.1517/14740338.2012.72698422992213
   PubMed Web of Science ®Google Scholar
• De Hert M, Mittoux A, He Y, Peuskens J. Metabolic parameters in the short- and long-term treatment of schizophrenia with sertindole or risperidone. Eur Arch Psychiatry Clin Neurosci. 2011;261:231–239. doi:10.1007/s00406-010-0142-x20820795
   PubMed Web of Science ®Google Scholar
• Boyda HN, Tse L, Procyshyn RM, Honer WG, Barr AM. Preclinical models of antipsychotic drug-induced metabolic side effects. Trends Pharmacol Sci. 2010;31:484–497. doi:10.1016/j.tips.2010.07.00220674990
   PubMed Web of Science ®Google Scholar
• Baptista T, de Baptista EA, Ying KNM, et al. Comparative effects of the antipsychotics sulpiride or risperidone in rats. I: bodyweight, food intake, body composition, hormones and glucose tolerance. Brain Res. 2002;957:144–151. doi:10.1016/s0006-8993(02)03616-812443990
   PubMed Web of Science ®Google Scholar
• Goudie AJ, Smith JA, Halford JC. Characterization of olanzapine-induced weight gain in rats. J Psychopharmacol. 2002;16:291–296. doi:10.1177/02698811020160040212503827
   PubMed Web of Science ®Google Scholar
• Cooper GD, Pickavance LC, Wilding JP, Harrold JA, Halford JC, Goudie AJ. Effects of olanzapine in male rats: enhanced adiposity in the absence of hyperphagia, weight gain or metabolic abnormalities. J Psychopharmacol. 2007;21:405–413. doi:10.1177/026988110606963717050655
   PubMed Web of Science ®Google Scholar
• Pouzet B, Mow T, Kreilgaard M, Velschow S. Chronic treatment with antipsychotics in rats as a model for antipsychotic-induced weight gain in human. Pharmacol Biochem Behav. 2003;75:133–140. doi:10.1016/S0091-3057(03)00042-X12759121
   PubMed Web of Science ®Google Scholar
• Cooper GD, Harrold JA, Halford JC, Goudie AJ. 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. 2008;32:428–436. doi:10.1016/j.pnpbp.2007.09.01217933447
   PubMed Web of Science ®Google Scholar
• Tulipano G, Rizzetti C, Bianchi I, Fanzani A, Spano P, Cocchi D. Clozapine-induced alteration of glucose homeostasis in the rat: the contribution of hypothalamic-pituitary-adrenal axis activation. Neuroendocrinology. 2007;85:61–70. doi:10.1159/00010098117374945
   PubMed Web of Science ®Google Scholar
• Victoriano M, Hermier D, Even PC, et al. Early perturbation in feeding behaviour and energy homeostasy in olanzapine-treated rats. Psychopharmacology (Berl). 2009;206:167–176. doi:10.1007/s00213-009-1593-519572122
   PubMed Web of Science ®Google Scholar
• Smith GC, Chaussade C, Vickers M, Jensen J, Shepherd PR. Atypical antipsychotic drugs induce derangements in glucose homeostasis by acutely increasing glucagon secretion and hepatic glucose output in the rat. Diabetologia. 2008;51:2309–2317. doi:10.1007/s00125-008-1152-318843478
   PubMed Web of Science ®Google Scholar
• Smith GC, Vickers MH, Cognard E, Shepherd PR. Clozapine and quetiapine acutely reduce glucagon-like peptide-1 production and increase glucagon release in obese rats: implications for glucose metabolism and food choice behaviour. Schizophr Res. 2009;115:30–40. doi:10.1016/j.schres.2009.07.01119679451
   PubMed Web of Science ®Google Scholar
• Houseknecht KL, Robertson AS, Zavadoski W, Gibbs EM, Johnson DE, Rollema H. Acute effects of atypical antipsychotics on whole-body insulin resistance in rats: implications for adverse metabolic effects. Neuropsychopharmacology. 2007;32:289–297. doi:10.1038/sj.npp.130120917035934
   PubMed Web of Science ®Google Scholar
• Chintoh AF, Mann SW, Lam L, et al. Insulin resistance and decreased glucose-stimulated insulin secretion after acute olanzapine administration. J Clin Psychopharmacol. 2008;28:494–499. doi:10.1097/JCP.0b013e318184b4c518794643
   PubMed Web of Science ®Google Scholar
• Chintoh AF, Mann SW, Lam L, et al. Insulin resistance and secretion in vivo: effects of different antipsychotics in an animal model. Schizophr Res. 2009;108:127–133. doi:10.1016/j.schres.2008.12.01219157785
   PubMed Web of Science ®Google Scholar
• Vestri HS, Maianu L, Moellering DR, Garvey WT. Atypical antipsychotic drugs directly impair insulin action in adipocytes: effects on glucose transport, lipogenesis, and antilipolysis. Neuropsychopharmacology. 2007;32:765–772. doi:10.1038/sj.npp.130114216823387
   PubMed Web of Science ®Google Scholar
• Yang LH, Chen TM, Yu ST, Chen YH. Olanzapine induces SREBP-1-related adipogenesis in 3T3-L1 cells. Pharmacol Res. 2007;56:202–208. doi:10.1016/j.phrs.2007.05.00717651982
   PubMed Web of Science ®Google Scholar
• Minet-Ringuet J, Even PC, Valet P, et al. Alterations of lipid metabolism and gene expression in rat adipocytes during chronic olanzapine treatment. Mol Psychiatry. 2007;12:562–571. doi:10.1038/sj.mp.400194817211438
   PubMed Web of Science ®Google Scholar
• Fernø J, Vik-Mo AO, Jassim G, et al. Acute clozapine exposure in vivo induces lipid accumulation and marked sequential changes in the expression of SREBP, PPAR, and LXR target genes in rat liver. Psychopharmacology (Berl). 2009;203:73–84. doi:10.1007/s00213-008-1370-x18989661
   PubMed Web of Science ®Google Scholar
• Raeder MB, Fernø J, Vik-Mo AO, Steen VM. SREBP activation by antipsychotic- and antidepressant-drugs in cultured human liver cells: relevance for metabolic side-effects. Mol Cell Biochem. 2006;289:167–173. doi:10.1007/s11010-006-9160-416718372
   PubMed Web of Science ®Google Scholar
• Monteiro S, Dias P, Madeira S, et al. Metabolic syndrome in dyslipidemia consultations. Rev Port Cardiol. 2006;25:821–831.17100172
   PubMedGoogle Scholar
• Yang Z, Yin JY, Gong ZC, et al. Evidence for an effect of clozapine on the regulation of fat-cell derived factors. Clin Chim Acta. 2009;408:98–104. doi:10.1016/j.cca.2009.07.02119682446
   PubMed Web of Science ®Google Scholar
• Hemmrich K, Gummersbach C, Pallua N, Luckhaus C, Fehsel K. Clozapine enhances differentiation of adipocyte progenitor cells. Mol Psychiatry. 2006;11:980–981. doi:10.1038/sj.mp.400189217063181
   PubMed Web of Science ®Google Scholar
• Hemmrich K, Kappel BA, Paul NE, et al. Antipsychotic drugs increase adipose stem cell differentiation–implications for treatment with antipsychotic drugs. J Clin Psychopharmacol. 2011;31:663–665. doi:10.1097/JCP.0b013e31822bf0a521881453
   PubMed Web of Science ®Google Scholar
• Sertié AL, Suzuki AM, Sertié RA, et al. Effects of antipsychotics with different weight gain liabilities on human in vitro models of adipose tissue differentiation and metabolism. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35:1884–1890. doi:10.1016/j.pnpbp.2011.07.01721840366
   PubMed Web of Science ®Google Scholar
• Bulua AC, Simon A, Maddipati R, et al. Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS). J Exp Med. 2011;208:519–533. doi:10.1084/jem.2010204921282379
   PubMed Web of Science ®Google Scholar
• Pillai A, Parikh V, Terry AV, Mahadik SP. Long-term antipsychotic treatments and crossover studies in rats: differential effects of typical and atypical agents on the expression of antioxidant enzymes and membrane lipid peroxidation in rat brain. J Psychiatr Res. 2007;41:372–386. doi:10.1016/j.jpsychires.2006.01.01116564057
   PubMed Web of Science ®Google Scholar
• Polydoro M, Schröder N, Lima MN, et al. Haloperidol- and clozapine-induced oxidative stress in the rat brain. Pharmacol Biochem Behav. 2004;78:751–756. doi:10.1016/j.pbb.2004.05.01815301931
   PubMed Web of Science ®Google Scholar
• Schaffer LF, de Freitas CM, Chiapinotto CAP, et al. Harpagophytum procumbens ethyl acetate fraction reduces fluphenazine-induced vacuous chewing movements and oxidative stress in rat brain. Neurochem Res. 2016;41:1170–1184. doi:10.1007/s11064-015-1811-y26732278
   PubMed Web of Science ®Google Scholar
• Lauressergues E, Martin F, Helleboid A, et al. Overweight induced by chronic risperidone exposure is correlated with overexpression of the SREBP-1c and FAS genes in mouse liver. Naunyn Schmiedebergs Arch Pharmacol. 2011;383:423–436. doi:10.1007/s00210-010-0597-321336545
   PubMed Web of Science ®Google Scholar
• Lauressergues E, Staels B, Valeille K, et al. Antipsychotic drug action on SREBPs-related lipogenesis and cholesterogenesis in primary rat hepatocytes. Naunyn Schmiedebergs Arch Pharmacol. 2010;381:427–439. doi:10.1007/s00210-010-0499-420333360
   PubMed Web of Science ®Google Scholar
• Canfrán-Duque A, Casado ME, Pastor O, et al. Atypical antipsychotics alter cholesterol and fatty acid metabolism in vitro. J Lipid Res. 2013;54:310–324. doi:10.1194/jlr.M02694823175778
   PubMed Web of Science ®Google Scholar
• Soliman HM, Wagih HM, Algaidi SA, Hafiz AH. Histological evaluation of the role of atypical antipsychotic drugs in inducing non-alcoholic fatty liver disease in adult male albino rats (light and electron microscopic study). Folia Biol (Praha). 2013;59:173–180.24280139
   PubMed Web of Science ®Google Scholar
• Bilgic S, Tastemir KD, Azirak S, Guvenc AN, Kocaman N, Ozer MK. The protective effect of thymoquinone over olanzapine-induced side effects in liver, and metabolic side effects. Bratisl Lek Listy. 2017;118:618–625. doi:10.4149/BLL_2017_11929198130
   PubMed Web of Science ®Google Scholar
• Li Y, Su R, Xu S, Huang Q, Xu H. Artesunate prevents rats from the clozapine-induced hepatic steatosis and elevation in plasma triglycerides. Neuropsychiatr Dis Treat. 2017;13:2477–2487. doi:10.2147/NDT.S14506929026311
   PubMed Web of Science ®Google Scholar
• Coccurello R, Moles A. Potential mechanisms of atypical antipsychotic-induced metabolic derangement: clues for understanding obesity and novel drug design. Pharmacol Ther. 2010;127:210–251. doi:10.1016/j.pharmthera.2010.04.00820493213
   PubMed Web of Science ®Google Scholar
• Balt SL, Galloway GP, Baggott MJ, Schwartz Z, Mendelson J. Mechanisms and genetics of antipsychotic-associated weight gain. Clin Pharmacol Ther. 2011;90:179–183. doi:10.1038/clpt.2011.9721633343
   PubMed Web of Science ®Google Scholar
• Correll CU, Malhotra AK. Pharmacogenetics of antipsychotic-induced weight gain. Psychopharmacology (Berl). 2004;174:477–489. doi:10.1007/s00213-004-1949-915243737
   PubMed Web of Science ®Google Scholar
• Field BC, Chaudhri OB, Bloom SR. Obesity treatment: novel peripheral targets. Br J Clin Pharmacol. 2009;68:830–843. doi:10.1111/j.1365-2125.2009.03522.x20002077
   PubMed Web of Science ®Google Scholar
• Gil-Campos M, Cañete RR, Gil A. Adiponectin, the missing link in insulin resistance and obesity. Clin Nutr. 2004;23:963–974. doi:10.1016/j.clnu.2004.04.01015380884
   PubMed Web of Science ®Google Scholar
• Li S, Shin HJ, Ding EL, van Dam RM. Adiponectin levels and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2009;302:179–188. doi:10.1001/jama.2009.97619584347
   PubMed Web of Science ®Google Scholar
• Sapra M, Lawson D, Iranmanesh A, Varma A. Adiposity-independent hypoadiponectinemia as a potential marker of insulin resistance and inflammation in schizophrenia patients treated with second generation antipsychotics. Schizophr Res. 2016;174:132–136. doi:10.1016/j.schres.2016.04.05127211515
   PubMed Web of Science ®Google Scholar
• Bartoli F, Crocamo C, Clerici M, Carrà G. Second-generation antipsychotics and adiponectin evels in schizophrenia: a comparative meta-analysis. Eur Neuropsychopharmacol. 2015;25:1767–1774. doi:10.1016/j.euroneuro.2015.06.01126164075
   PubMed Web of Science ®Google Scholar
• Tagami K, Kashiwase Y, Yokoyama A, et al. The atypical antipsychotic, olanzapine, potentiates ghrelin-induced receptor signaling: an in vitro study with cells expressing cloned human growth hormone secretagogue receptor. Neuropeptides. 2016;58:93–101. doi:10.1016/j.npep.2015.12.01026775231
   PubMed Web of Science ®Google Scholar
• Hegedűs C, Kovács D, Kiss R, et al. Effect of long-term olanzapine treatment on meal-induced insulin sensitization and on gastrointestinal peptides in female Sprague-Dawley rats. J Psychopharmacol. 2015;29:1271–1279. doi:10.1177/026988111560295226349558
   PubMed Web of Science ®Google Scholar
• Virkkunen M, Wahlbeck K, Rissanen A, Naukkarinen H, Franssila-Kallunki A. Decrease of energy expenditure causes weight increase in olanzapine treatment - a case study. Pharmacopsychiatry. 2002;35:124–126. doi:10.1055/s-2002-3152112107860
   PubMed Web of Science ®Google Scholar
• Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112:1796–1808. doi:10.1172/JCI1924614679176
   PubMed Web of Science ®Google Scholar
• Van Gaal LF. Long-term health considerations in schizophrenia: metabolic effects and the role of abdominal adiposity. Eur Neuropsychopharmacol. 2006;16(Suppl 3):S142–S148. doi:10.1016/j.euroneuro.2006.06.00516863690
   PubMed Web of Science ®Google Scholar
• Victoriano M, de Beaurepaire R, Naour N, et al. Olanzapine-induced accumulation of adipose tissue is associated with an inflammatory state. Brain Res. 2010;1350:167–175. doi:10.1016/j.brainres.2010.05.06020570665
   PubMed Web of Science ®Google Scholar
• Devlin MJ, Yanovski SZ, Wilson GT. Obesity: what mental health professionals need to know. Am J Psychiatry. 2000;157:854–866. doi:10.1176/appi.ajp.157.6.85410831462
   PubMed Web of Science ®Google Scholar
• Monji A, Kato T, Kanba S. Cytokines and schizophrenia: microglia hypothesis of schizophrenia. Psychiatry Clin Neurosci. 2009;63:257–265.19579286
   PubMed Web of Science ®Google Scholar
• O’Connell KE, Thakore J, Dev KK. Pro-inflammatory cytokine levels are raised in female schizophrenia patients treated with clozapine. Schizophr Res. 2014;156:1–8. doi:10.1016/j.schres.2014.03.02024742875
   PubMed Web of Science ®Google Scholar
• Sobiś J, Rykaczewska-Czerwińska M, Świętochowska E, Gorczyca P. Therapeutic effect of aripiprazole in chronic schizophrenia is accompanied by anti-inflammatory activity. Pharmacol Rep. 2015;67:353–359. doi:10.1016/j.pharep.2014.09.00725712663
   PubMed Web of Science ®Google Scholar
• Hatziagelaki E, Tsiavou A, Gerasimou C, et al. Effects of olanzapine on cytokine profile and brain-derived neurotrophic factor in drug-naive subjects with first-episode psychosis. Exp Ther Med. 2019;17:3071–3076. doi:10.3892/etm.2019.728530906479
   PubMed Web of Science ®Google Scholar
• Drzyzga L, Obuchowicz E, Marcinowska A, Herman ZS. Cytokines in schizophrenia and the effects of antipsychotic drugs. Brain Behav Immun. 2006;20:532–545. doi:10.1016/j.bbi.2006.02.00216580814
   PubMed Web of Science ®Google Scholar
• Baker GF, Rogers HJ. Effects of psychotropic drugs on the erythrocyte permeability to glucose and ethylidene glucose. Biochem Pharmacol. 1972;21:1871–1878. doi:10.1016/0006-2952(72)90183-94646186
   PubMed Web of Science ®Google Scholar
• Ardizzone TD, Bradley RJ, Freeman AM, Dwyer DS. Inhibition of glucose transport in PC12 cells by the atypical antipsychotic drugs risperidone and clozapine, and structural analogs of clozapine. Brain Res. 2001;923:82–90. doi:10.1016/s0006-8993(01)03026-811743975
   PubMed Web of Science ®Google Scholar
• Dwyer DS, Liu Y, Bradley RJ. Dopamine receptor antagonists modulate glucose uptake in rat pheochromocytoma (PC12) cells. Neurosci Lett. 1999;274:151–154. doi:10.1016/s0304-3940(99)00712-010548412
   PubMed Web of Science ®Google Scholar
• Dwyer DS, Pinkofsky HB, Liu Y, Bradley RJ. Antipsychotic drugs affect glucose uptake and the expression of glucose transporters in PC12 cells. Prog Neuropsychopharmacol Biol Psychiatry. 1999;23:69–80.10368857
   PubMed Web of Science ®Google Scholar
• Dwyer DS, Donohoe D. Induction of hyperglycemia in mice with atypical antipsychotic drugs that inhibit glucose uptake. Pharmacol Biochem Behav. 2003;75:255–260.12873613
   PubMed Web of Science ®Google Scholar
• Jassim G, Skrede S, Vázquez MJ, et al. Acute effects of orexigenic antipsychotic drugs on lipid and carbohydrate metabolism in rat. Psychopharmacology (Berl). 2012;219:783–794. doi:10.1007/s00213-011-2397-y21748251
   PubMed Web of Science ®Google Scholar
• Hou JC, Pessin JE. Ins (endocytosis) and outs (exocytosis) of GLUT4 trafficking. Curr Opin Cell Biol. 2007;19:466–473. doi:10.1016/j.ceb.2007.04.01817644329
   PubMed Web of Science ®Google Scholar
• Beaulieu JM, Sotnikova TD, Marion S, Lefkowitz RJ, Gainetdinov RR, Caron MG. An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic neurotransmission and behavior. Cell. 2005;122:261–273. doi:10.1016/j.cell.2005.05.01216051150
   PubMed Web of Science ®Google Scholar
• Girault JA, Greengard P. The neurobiology of dopamine signaling. Arch Neurol. 2004;61:641–644. doi:10.1001/archneur.61.5.64115148138
   PubMed Web of Science ®Google Scholar
• Martínez JA. Mitochondrial oxidative stress and inflammation: an slalom to obesity and insulin resistance. J Physiol Biochem. 2006;62:303–306.17615956
   PubMed Web of Science ®Google Scholar
• Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010;72:219–246. doi:10.1146/annurev-physiol-021909-13584620148674
   PubMed Web of Science ®Google Scholar
• Baig MR, Navaira E, Escamilla MA, Raventos H, Walss-Bass C. Clozapine treatment causes oxidation of proteins involved in energy metabolism in lymphoblastoid cells: a possible mechanism for antipsychotic-induced metabolic alterations. J Psychiatr Pract. 2010;16:325–333.20859109
   PubMed Web of Science ®Google Scholar
• Casademont J, Garrabou G, Miró O, et al. Neuroleptic treatment effect on mitochondrial electron transport chain: peripheral blood mononuclear cells analysis in psychotic patients. J Clin Psychopharmacol. 2007;27:284–288. doi:10.1097/JCP.0b013e318054753e17502776
   PubMed Web of Science ®Google Scholar
• Ji B, La Y, Gao L, et al. A comparative proteomics analysis of rat mitochondria from the cerebral cortex and hippocampus in response to antipsychotic medications. J Proteome Res. 2009;8:3633–3641. doi:10.1021/pr800876z19441803
   PubMed Web of Science ®Google Scholar
• Kotzka J, Müller-Wieland D. Sterol regulatory element-binding protein (SREBP)-1: gene regulatory target for insulin resistance. Expert Opin Ther Targets. 2004;8:141–149. doi:10.1517/14728222.8.2.14115102555
   PubMed Web of Science ®Google Scholar
• Shimano H. Sterol regulatory element-binding proteins (SREBPs): transcriptional regulators of lipid synthetic genes. Prog Lipid Res. 2001;40:439–452.11591434
   PubMed Web of Science ®Google Scholar
• Fernø J, Raeder MB, Vik-Mo AO, et al. Antipsychotic drugs activate SREBP-regulated expression of lipid biosynthetic genes in cultured human glioma cells: a novel mechanism of action. Pharmacogenomics J. 2005;5:298–304. doi:10.1038/sj.tpj.650032316027736
   PubMed Web of Science ®Google Scholar
• Cai HL, Tan QY, Jiang P, et al. A potential mechanism underlying atypical antipsychotics-induced lipid disturbances. Transl Psychiatry. 2015;5:e661. doi:10.1038/tp.2015.16126485545
   PubMed Web of Science ®Google Scholar
• McKenney JM, Sica D. Prescription omega-3 fatty acids for the treatment of hypertriglyceridemia. Am J Health Syst Pharm. 2007;64:595–605. doi:10.2146/ajhp06016417353568
   PubMed Web of Science ®Google Scholar
• Hassanali Z, Ametaj BN, Field CJ, Proctor SD, Vine DF. Dietary supplementation of n-3 PUFA reduces weight gain and improves postprandial lipaemia and the associated inflammatory response in the obese JCR:LA-cp rat. Diabetes Obes Metab. 2010;12:139–147. doi:10.1111/j.1463-1326.2009.01130.x19917068
   PubMed Web of Science ®Google Scholar
• Pachikian BD, Neyrinck AM, Cani PD, et al. Hepatic steatosis in n-3 fatty acid depleted mice: focus on metabolic alterations related to tissue fatty acid composition. BMC Physiol. 2008;8:21. doi:10.1186/1472-6793-8-2119046413
   PubMedGoogle Scholar
• Pachikian BD, Essaghir A, Demoulin JB, et al. Hepatic n-3 polyunsaturated fatty acid depletion promotes steatosis and insulin resistance in mice: genomic analysis of cellular targets. PLoS One. 2011;6:e23365. doi:10.1371/journal.pone.002336521853118
   PubMed Web of Science ®Google Scholar
• Qi K, Fan C, Jiang J, et al. Omega-3 fatty acid containing diets decrease plasma triglyceride concentrations in mice by reducing endogenous triglyceride synthesis and enhancing the blood clearance of triglyceride-rich particles. Clin Nutr. 2008;27:424–430. doi:10.1016/j.clnu.2008.02.00118362042
   PubMed Web of Science ®Google Scholar
• Araya J, Rodrigo R, Videla LA, et al. Increase in long-chain polyunsaturated fatty acid n - 6/n - 3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease. Clin Sci (Lond). 2004;106:635–643. doi:10.1042/CS2003032614720121
   PubMed Web of Science ®Google Scholar
• Burrows T, Collins CE, Garg ML. Omega-3 index, obesity and insulin resistance in children. Int J Pediatr Obes. 2011;6:e532–e539. doi:10.3109/17477166.2010.54948921226540
   PubMed Web of Science ®Google Scholar
• Evans DR, Parikh VV, Khan MM, Coussons C, Buckley PF, Mahadik SP. Red blood cell membrane essential fatty acid metabolism in early psychotic patients following antipsychotic drug treatment. Prostaglandins Leukot Essent Fatty Acids. 2003;69:393–399.14623492
   PubMed Web of Science ®Google Scholar
• Ranjekar PK, Hinge A, Hegde MV, et al. Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenic and bipolar mood disorder patients. Psychiatry Res. 2003;121:109–122.14656446
   PubMed Web of Science ®Google Scholar
• Reddy RD, Keshavan MS, Yao JK. Reduced red blood cell membrane essential polyunsaturated fatty acids in first episode schizophrenia at neuroleptic-naive baseline. Schizophr Bull. 2004;30:901–911. doi:10.1093/oxfordjournals.schbul.a00714015957200
   PubMed Web of Science ®Google Scholar
• Caniato RN, Alvarenga ME, Garcia-Alcaraz MA. Effect of omega-3 fatty acids on the lipid profile of patients taking clozapine. Aust N Z J Psychiatry. 2006;40:691–697. doi:10.1080/j.1440-1614.2006.01869.x16866765
   PubMed Web of Science ®Google Scholar
• Peet M, Horrobin DF. A dose-ranging exploratory study of the effects of ethyl- eicosapentaenoate in patients with persistent schizophrenic symptoms. J Psychiatr Res. 2002;36:7–18.11755456
   PubMed Web of Science ®Google Scholar
• McNamara RK, Magrisso IJ, Hofacer R, et al. Omega-3 fatty acid deficiency augments risperidone-induced hepatic steatosis in rats: positive association with stearoyl-CoA desaturase. Pharmacol Res. 2012;66:283–291. doi:10.1016/j.phrs.2012.06.01022750665
   PubMed Web of Science ®Google Scholar