Safety and tolerability of antipsychotic co-treatment in patients with schizophrenia: results from a systematic review and meta-analysis of randomized controlled trials

References

• Falkai P, Wobrock T, Lieberman J, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 1: acute treatment of schizophrenia. World J Biol Psychiatry Off J World Fed Soc Biol Psychiatry. 2005;6(3):132–191.
   PubMed Web of Science ®Google Scholar
• Moore TA, Buchanan RW, Buckley PF, et al. The Texas medication algorithm project antipsychotic algorithm for schizophrenia: 2006 update. J Clin Psychiatry. 2007;68(11):1751–1762.
   PubMed Web of Science ®Google Scholar
• Buchanan RW, Kreyenbuhl J, Kelly DL, et al. The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophr Bull. 2010;36(1):71–93.
   PubMed Web of Science ®Google Scholar
• Lehman AF, Lieberman JA, Dixon LB, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004;161(2 Suppl):1–56.
   PubMed Web of Science ®Google Scholar
• Goodwin G, Fleischhacker W, Arango C, et al. Advantages and disadvantages of combination treatment with antipsychotics ECNP Consensus Meeting, March 2008, Nice. Eur Neuropsychopharmacol J Eur Coll Neuropsychopharmacol. 2009;19(7):520–532.
   PubMed Web of Science ®Google Scholar
• Ganguly R, Kotzan JA, Miller LS, et al. Prevalence, trends, and factors associated with antipsychotic polypharmacy among Medicaid-eligible schizophrenia patients, 1998-2000. J Clin Psychiatry. 2004;65(10):1377–1388.
   PubMed Web of Science ®Google Scholar
• Clark RE, Bartels SJ, Mellman TA, et al. Recent trends in antipsychotic combination therapy of schizophrenia and schizoaffective disorder: implications for state mental health policy. Schizophr Bull. 2002;28(1):75–84.
   PubMed Web of Science ®Google Scholar
• Gallego JA, Bonetti J, Zhang J, et al. Prevalence and correlates of antipsychotic polypharmacy: a systematic review and meta-regression of global and regional trends from the 1970s to 2009. Schizophr Res. 2012;138(1):18–28.
   PubMed Web of Science ®Google Scholar
• Correll CU, Gallego JA. Antipsychotic polypharmacy. Psychiatr Clin North Am. 2012;35(3):661–681.
   PubMed Web of Science ®Google Scholar
• Faries D, Ascher-Svanum H, Zhu B, et al. Antipsychotic monotherapy and polypharmacy in the naturalistic treatment of schizophrenia with atypical antipsychotics. BMC Psychiatry. 2005;5:26.
   PubMed Web of Science ®Google Scholar
• Tapp A, Wood AE, Secrest L, et al. Combination antipsychotic therapy in clinical practice. Psychiatr Serv Wash DC. 2003 Jan;54(1):55–59.
   PubMed Web of Science ®Google Scholar
• Correll CU, Shaikh L, Gallego JA, et al. Antipsychotic polypharmacy: a survey study of prescriber attitudes, knowledge and behavior. Schizophr Res. 2011 Sep;131(1–3):58–62.
   PubMed Web of Science ®Google Scholar
• Correll CU, Rummel-Kluge C, Corves C, et al. Antipsychotic combinations vs monotherapy in schizophrenia: a meta-analysis of randomized controlled trials. Schizophr Bull. 2009;35(2):443–457.
   PubMed Web of Science ®Google Scholar
• Barbui C, Signoretti A, Mulè S, et al. Does the addition of a second antipsychotic drug improve clozapine treatment? Schizophr Bull. 2009;35(2):458–468.
   PubMed Web of Science ®Google Scholar
• Gallego JA, Nielsen J, De Hert M, et al. Safety and tolerability of antipsychotic polypharmacy. Expert Opin Drug Saf. 2012;11(4):527–542.
   PubMed Web of Science ®Google Scholar
• Taylor DM, Smith L, Gee SH, et al. Augmentation of clozapine with a second antipsychotic - a meta-analysis. Acta Psychiatr Scand. 2012;125(1):15–24.
   PubMed Web of Science ®Google Scholar
• Rupnow MFT, Greenspan A, Gharabawi GM, et al. Incidence and costs of polypharmacy: data from a randomized, double-blind, placebo-controlled study of risperidone and quetiapine in patients with schizophrenia or schizoaffective disorder. Curr Med Res Opin. 2007 Nov;23(11):2815–2822.
   PubMed Web of Science ®Google Scholar
• Zhu B, Ascher-Svanum H, Faries DE, et al. Cost of antipsychotic polypharmacy in the treatment of schizophrenia. BMC Psychiatry. 2008 Apr;4(8):19.
   Web of Science ®Google Scholar
• Baandrup L, Sørensen J, Lublin H, et al. Association of antipsychotic polypharmacy with health service cost: a register-based cost analysis. Eur J Health Econ. 2012;13(3):355–363.
   PubMed Web of Science ®Google Scholar
• De Hert M, Detraux J, van Winkel R, et al. Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat Rev Endocrinol. 2012 Feb;8(2):114–126.
   Web of Science ®Google Scholar
• De Hert M, Dobbelaere M, Sheridan EM, et al. Metabolic and endocrine adverse effects of second-generation antipsychotics in children and adolescents: a systematic review of randomized, placebo controlled trials and guidelines for clinical practice. Eur Psychiatry J Assoc Eur Psychiatr. 2011 Apr;26(3):144–158.
   PubMed Web of Science ®Google Scholar
• Correll CU. Balancing efficacy and safety in treatment with antipsychotics. CNS Spectr. 2007 Oct;12(10 Suppl 17):12–20, 35.
   PubMed Web of Science ®Google Scholar
• Misawa F, Shimizu K, Fujii Y, et al. Is antipsychotic polypharmacy associated with metabolic syndrome even after adjustment for lifestyle effects?: a cross-sectional study. BMC Psychiatry. 2011 Jul;26(11):118.
   Web of Science ®Google Scholar
• Shores LE. Normalization of risperidone-induced hyperprolactinemia with the addition of aripiprazole. Psychiatry Edgmont Pa Townsh. 2005 Mar;2(3):42–45.
   PubMedGoogle Scholar
• Henderson DC, Kunkel L, Nguyen DD, et al. An exploratory open-label trial of aripiprazole as an adjuvant to clozapine therapy in chronic schizophrenia. Acta Psychiatr Scand. 2006 Feb;113(2):142–147.
   PubMed Web of Science ®Google Scholar
• Shim J-C, Shin J-GK, Kelly DL, et al. Adjunctive treatment with a dopamine partial agonist, aripiprazole, for antipsychotic-induced hyperprolactinemia: a placebo-controlled trial. Am J Psychiatry. 2007;164(9):1404–1410.
   PubMed Web of Science ®Google Scholar
• Chang JS, Ahn YM, Park HJ, et al. Aripiprazole augmentation in clozapine-treated patients with refractory schizophrenia: an 8-week, randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2008 May;69(5):720–731.
   PubMed Web of Science ®Google Scholar
• Mir A, Shivakumar K, Williamson RJ, et al. Change in sexual dysfunction with aripiprazole: a switching or add-on study. J Psychopharmacol Oxf Engl. 2008 May;22(3):244–253.
   PubMed Web of Science ®Google Scholar
• Henderson DC, Fan X, Copeland PM, et al. Aripiprazole added to overweight and obese olanzapine-treated schizophrenia patients. J Clin Psychopharmacol. 2009 Apr;29(2):165–169.
   PubMed Web of Science ®Google Scholar
• Kane JM, Correll CU, Goff DC, et al. A multicenter, randomized, double-blind, placebo-controlled, 16-week study of adjunctive aripiprazole for schizophrenia or schizoaffective disorder inadequately treated with quetiapine or risperidone monotherapy. J Clin Psychiatry. 2009;70(10):1348–1357.
   PubMed Web of Science ®Google Scholar
• Chen C-K, Huang Y-S, Ree S-C, et al. Differential add-on effects of aripiprazole in resolving hyperprolactinemia induced by risperidone in comparison to benzamide antipsychotics. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Oct;34(8):1495–1499.
   PubMed Web of Science ®Google Scholar
• Fleischhacker WW, Heikkinen ME, Olié J-P, et al. Effects of adjunctive treatment with aripiprazole on body weight and clinical efficacy in schizophrenia patients treated with clozapine: a randomized, double-blind, placebo-controlled trial. Int J Neuropsychopharmacol. 2010 Sep;13(8):1115–1125.
   PubMed Web of Science ®Google Scholar
• Yasui-Furukori N, Kaneda A, Sugawara N, et al. Effect of adjunctive treatment with aripiprazole to atypical antipsychotics on cognitive function in schizophrenia patients. J Psychopharmacol (Oxf). 2012 Jan 1;26(6):806–812.
   PubMed Web of Science ®Google Scholar
• Fan X, Borba CPC, Copeland P, et al. Metabolic effects of adjunctive aripiprazole in clozapine-treated patients with schizophrenia. Acta Psychiatr Scand. 2013 Mar;127(3):217–226.
   PubMed Web of Science ®Google Scholar
• Lee BJ, Lee SJ, Kim MK, et al. Effect of aripiprazole on cognitive function and hyperprolactinemia in patients with schizophrenia treated with risperidone. Clin Psychopharmacol Neurosci. 2013 Aug;11(2):60–66.
   PubMed Web of Science ®Google Scholar
• Chen J-X, Su Y-A, Bian Q-T, et al. Adjunctive aripiprazole in the treatment of risperidone-induced hyperprolactinemia: a randomized, double-blind, placebo-controlled, dose-response study. Psychoneuroendocrinology. 2015 Apr;24(58):130–140.
   Web of Science ®Google Scholar
• DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986 Sep;7(3):177–188.
   PubMedGoogle Scholar
• Correll CU. From receptor pharmacology to improved outcomes: individualising the selection, dosing, and switching of antipsychotics. Eur Psychiatry. 2010 Jun;25(Suppl 2):S12–21.
   PubMed Web of Science ®Google Scholar
• Stahl SM. Stahl’s essential psychopharmacology: neuroscientific basis and practical applications. Cambridge: Cambridge University Press; 2013. p. 1181.
   Google Scholar
• Gardner DM, Murphy AL, O’Donnell H, et al. International consensus study of antipsychotic dosing. Am J Psychiatry. 2010 Jun;167(6):686–693.
   PubMed Web of Science ®Google Scholar
• Duval S, Tweedie R. A nonparametric “Trim and Fill” method of accounting for publication bias in meta-analysis. J Am Stat Assoc. 2000 Mar 1;95(449):89–98.
   Web of Science ®Google Scholar
• Zhang L, Xu Y. A comparison study on treatment effect of clozapine, chlorpromazine and the combination of clozapine and chlorpromazine in schizophrenia. Chin J Nerv Ment Dis. 1989;5(5):306–308.
   Google Scholar
• Liu YD, Huang WF, Huang SJ. A control study of clozapine combined with fluphenazine in refractory schizophrenia (in Chinese). Med J Chin People´s Health. 2008;20:1274.
   Google Scholar
• Friedman JI, Lindenmayer J-P, Alcantara F, et al. Pimozide augmentation of clozapine inpatients with schizophrenia and schizoaffective disorder unresponsive to clozapine monotherapy. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2011 May;36(6):1289–1295.
   PubMed Web of Science ®Google Scholar
• Gunduz-Bruce H, Oliver S, Gueorguieva R, et al. Efficacy of pimozide augmentation for clozapine partial responders with schizophrenia. Schizophr Res. 2013 Feb;143(2–3):344–347.
   PubMed Web of Science ®Google Scholar
• Yi J, Hu Y, Wan Q. Efficacy and safety of amisupride combined with clozapine treatment in refractory schizophrenia. (in Chinese). J Psychiatry. 2014;27(4):278–280.
   Google Scholar
• Ren L, Sun JS. A control study of aripiprazole combined with clozapine in schizophrenia (in Chinese). Mod J Integr Tradit Chin West Med. 2008;17:11601.
   Google Scholar
• Sun HJ. A control study of clozapine plus aripiprazole in the treatment of male treatment-resistant schizophrenia (in Chinese). J Clin Psychosom Dis. 2010;16:510–512.
   Google Scholar
• Wang FJ, Zhou ZP. The clinical research of aripiprazole combined with clozapine in chronic schizophrenia (in Chinese). Med J Chin Peoples Health. 2012;24:2822–2835.
   Google Scholar
• Sun YS, Sun JZ. Effect of combined low-dose clozapine and ziprasidone on treatment of refractory schizophrenia (in Chinese). J Hainan Med Univ. 2012;18:551–553.
   Google Scholar
• Li X. The clinical efficiency of aripiprazole with clozapine for the female refractory schizophrenia (in Chinese). Chin J Gen Pract. 2013;11(10):1573–1577.
   Google Scholar
• Liang Y, Liu MD. Effects of aripiprazole combined with low doses of clozapine on the negative symptoms and cognitive function of schizophrenia patients (in Chinese). Intern Med China. 2013;8(2):118–119.
   Google Scholar
• Gao YF, Comparative A. Study of clozapine combined with quetiapine in the treatment of refractory schizophrenia (in Chinese). Med Innov China. 2013;10(17):28–29.
   Google Scholar
• Peng H, Kuang Y, Huang X. A control study of risperidone in combination with clozapine in treating refractory schizophrenia. J Mod Clin Med Bioeng. 2001;7(2):100–102.
   Google Scholar
• Anil Yağcioğlu AE, Kivircik Akdede BB, Turgut TI, et al. A double-blind controlled study of adjunctive treatment with risperidone in schizophrenic patients partially responsive to clozapine: efficacy and safety. J Clin Psychiatry. 2005 Jan;66(1):63–72.
   PubMed Web of Science ®Google Scholar
• Honer WG, Thornton AE, Chen EYH, et al. Clozapine alone versus clozapine and risperidone with refractory schizophrenia. N Engl J Med. 2006 Feb 2;354(5):472–482.
   PubMed Web of Science ®Google Scholar
• Josiassen RC, Joseph A, Kohegyi E, et al. Clozapine augmented with risperidone in the treatment of schizophrenia: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry. 2005 Jan;162(1):130–136.
   PubMed Web of Science ®Google Scholar
• Freudenreich O, Henderson DC, Walsh JP, et al. Risperidone augmentation for schizophrenia partially responsive to clozapine: a double-blind, placebo-controlled trial. Schizophr Res. 2007 May;92(1–3):90–94.
   PubMed Web of Science ®Google Scholar
• Ou GP. A control study on risperidone combined with clozapine in the treatment of schizophrenia with aggressed behavior. (in Chinese). J Clin Psychosom Dis. 2007;13:117–119.
   Google Scholar
• Meng YF, Liu MH. A control study of risperidone combined with clozapine in the treatment of treatment-resistant schizophrenia (in Chinese). J Clin Psychosom Dis. 2010;16:129–131.
   Google Scholar
• Liu JM, Sun DN. Risperidone and low dose clozapine combination for the treatment of male refractory schizophrenia (in Chinese). Strait Pharm J. 2011;23:101–103.
   Google Scholar
• Weiner E, Conley RR, Ball MP, et al. Adjunctive risperidone for partially responsive people with schizophrenia treated with clozapine. Neuropsychopharmacology. 2010 Oct;35(11):2274–2283.
   PubMed Web of Science ®Google Scholar
• Nielsen J, Emborg C, Gydesen S, et al. Augmenting clozapine with sertindole: a double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol. 2012 Apr;32(2):173–178.
   PubMed Web of Science ®Google Scholar
• Wang CH, Qin TF, Lin YL, et al. A clinical effect and following-up study about sulpiride and clozapine for 105 cases of the schizophrenia type. J Xinxiang Med Coll. 1994;11(2):148–151.
   Google Scholar
• Liu Q, Li X, Zhang Y. The treatment effect of combined clozapine and sulpiride on negative symptoms of schizophrenia. Chin J Psychiatry. 1996;5(29):87–90.
   Google Scholar
• Shiloh R, Zemishlany Z, Aizenberg D, et al. Sulpiride augmentation in people with schizophrenia partially responsive to clozapine. A double-blind, placebo-controlled study. Br J Psychiatry J Ment Sci. 1997 Dec;171:569–573.
   PubMed Web of Science ®Google Scholar
• Zhu Y, Zhang S, Zhang D. A controlled trial comparing chlorimipramine and sulpiride as adjunct to clozapine in the treatment of negative symptoms of schizophrenia. J Clin Psychol Med. 1999;9(4):204–205.
   Google Scholar
• Ren L, Zhu YP, Sun JS. A study of ziprasidone combined wtih clozapine in 30 refractory schizophrenia (in Chinese). Her Med. 2009;28:414–416.
   Google Scholar
• Qu YZ. The treatment efficacy of clozapine combined with ziprasidone in schizophrenia (in Chinese). Lin Chuangyushijian. 2012;10:14–15.
   Google Scholar
• Sun WH, Chen Y, Wang KY. The study of combining clozapine and aripiprazole for the treatment of negative symptoms of schizophrenia (in Chinese). Med J Chin Peoples Health. 2012;24:2592–2594.
   Google Scholar
• Muscatello MRA, Pandolfo G, Micò U, et al. Augmentation of clozapine with ziprasidone in refractory schizophrenia: a double-blind, placebo-controlled study. J Clin Psychopharmacol. 2014 Feb;34(1):129–133.
   PubMed Web of Science ®Google Scholar
• Higashima M, Takeda T, Nagasawa T, et al. Combined therapy with low-potency neuroleptic levomepromazine as an adjunct to haloperidol for agitated patients with acute exacerbation of schizophrenia. Eur Psychiatry J Assoc Eur Psychiatr. 2004 Sep;19(6):380–381.
   PubMed Web of Science ®Google Scholar
• Yagi G. A double-blind controlled study on the usefulness of carpipramine-chlorpromazine combination in the pharmacotherapy of chronic schizophrenic patients. Clin Eval. 1976;4(3):351–403.
   Google Scholar
• Barrett WW, Elsworth RB, Clark LD, et al. Study of the differential behavioral effects of reserpine, chlorpromazine, and a combination of these drugs in chronic schizophrenic patients. Dis Nerv Syst. 1957;18(6):209–215.
   Google Scholar
• Talbot DR. Are tranquilizer combinations more effective than a single tranquilizer? Am J Psychiatry. 1964 Dec;121:597–600.
   PubMed Web of Science ®Google Scholar
• Gong G, Zhao L. A control study of quetiapine combined with chlorpromazine in the treatment of acute schizophrenia (in Chinese). J ClinPsychosom Dis. 2007;13:508–916.
   Google Scholar
• Lin C-H, Kuo -C-C, Chou L-S, et al. A randomized, double-blind comparison of risperidone versus low-dose risperidone plus low-dose haloperidol in treating schizophrenia. J Clin Psychopharmacol. 2010 Oct;30(5):518–525.
   PubMed Web of Science ®Google Scholar
• Tang YM, Liu YM, Sun XB. A control study of olanzapine only and combined with low-dose perphenazine in patients with schizophrenia (in Chinese). Guide China Med. 2013;11(9):557–558.
   Google Scholar
• Xie J, Li Y. The treatment efficacy of chlorpromazine combined with quetiapine in delayed schizophrenia (in Chinese). Med J Chin Peoples Health. 2012;24:1342–1343.
   Google Scholar
• Shen Y, Xie GP, Liu SH. Effects of risperidone combined with low doses of amisulpride on the social function of schizophrenia patients (in Chinese). J GanNan Med Univ. 2013;33(6):851–853.
   Google Scholar
• Wang J. Clinical study of refractory auditory hallucination in schizophrenia patients treated with olanzapine and amisupride. Chin J Pract Nerv Dis. 2015 Apr;18(9):8–10.
   Google Scholar
• Wang LL, Xun ZY. A control study on female schizophrenia treated with risperidone combined with low dose aripiprazole (in Chinese). Taijin Pharm. 2010;22:40–42.
   Google Scholar
• Liu L, Qi SG, Dong XH, et al. A placebo-controlled trail of adjunctive treatment with aripiprazole for risperidone-induced hyperprolactinemia (in Chinese). China J Health Psychol. 2011;19:1288–1290.
   Google Scholar
• Chen JH, Wu YF, Liao XZ. The treatment efficacy of olanzapine combined with aripiprazole in female first-episode schizophrenia (in Chinese). Guide China Med. 2012;10:145–146.
   Google Scholar
• Shu G. A case-control study of risperidone and risperidone combined with low doses of aripiprazole in treatment of schizophrenia (in Chinese). Med J Chin Peoples Health. 2012;24:2085–20086.
   Google Scholar
• Li WJ, Liu HX. A control study of aripiprazole combined with low-dose olanzapine in the treatment of schizophrenia (in Chinese). J Clin Psychiatry. 2013;23(1):72.
   Google Scholar
• Zhao YQ. A control study on aripiprazole reduces risperidone-induced weight gain and increase of prolactin in patients with schizophrenia (in Chinese). Sichuan Ment Health. 2013;26(2):122–123.
   Google Scholar
• Wang W, Wang J, Luo X, et al. Controlled clinical research on treatment of schizophrenia by risperidone combined with low-dose aripiprazole (in Chinese). China J Health Psychol. 2014;22(7):964–966.
   Google Scholar
• Zhou P, Liu LQ, Hao JF, et al. The study of aripiprazole on preventing the hyperprolactinemia induced by antipsychotics on female (in Chinese). J Int Psychiatry. 2014;41(2):69–72.
   Google Scholar
• Xie C, Ni XL. The compared study of treating schizophrenia with risperidone combining clozapine. J Prev Med Inf. 2001;17(4):245.
   Google Scholar
• Zhang XZ, Gan QT, Yuan JA. A control study of ziprasidone combined with clozapine in treatment of schizophrenia (in Chinese). Med J Chin Peoples Health. 2010;22:568–569.
   Google Scholar
• Gao YJ, An HW, Jin HQ. Comparative study on risperidone combined with clozapine and risperidone in the treatment of refractory schizophrenia (in Chinese). Med Recapitulate. 2011;17:3342–3343.
   Google Scholar
• Yao YH, Chen JL, Shen JH. A clinical control study on effects of clozapine with risperidone on refractory schizophrenia (in Chinese). Chines J Gen Pract. 2012;10:1526–1527.
   Google Scholar
• Liang Y, Liu MD. A control study of aripiprazole combined with low-dose clozapine in female schizophrenia (in Chinese). J Clin Psychosom Disearses. 2013;10(4):3.
   Google Scholar
• Lu DQ, Xiao G. A controlled study between aripiprazole combined with low-dose of clozapine and single aripiprazole in the treatment of female chronic schizophrenia (in Chinese). Yiyao Qianyan. 2014;3:9–10.
   Google Scholar
• Kotler M, Strous RD, Reznik I, et al. Sulpiride augmentation of olanzapine in the management of treatment-resistant chronic schizophrenia: evidence for improvement of mood symptomatology. Int Clin Psychopharmacol. 2004 Jan;19(1):23–26.
   PubMed Web of Science ®Google Scholar
• Yang LS, Ma HL, Li YX, et al. Comparative study on combining olanzapine with dogmatil in the treatment of resistant schizophrenia (in Chinese). China J Health Psychol. 2012;20:484–486.
   Google Scholar
• Jiang T, Jiang XF. Clinical controlled study of olanzapine combined with sulpiride therapy for refractory schizophrenia (in Chinese). Chin J Pract Nerv Dis. 2013;16:24.
   Google Scholar
• Lin C-H, Wang F-C, Lin S-C, et al. Antipsychotic combination using low-dose antipsychotics is as efficacious and safe as, but cheaper, than optimal-dose monotherapy in the treatment of schizophrenia: a randomized, double-blind study. Int Clin Psychopharmacol. 2013 Sep;28(5):267–274.
   PubMed Web of Science ®Google Scholar
• Zhang C, Zhu LB, Ren JP. Clinical observation of olanzapine combined with sulpiride in refractory schizophrenia (in Chinese). Clin J Clin Ration Drug Use. 2013;3:21–22.
   Google Scholar
• Liu L, Sun J, Wang W. Small dose of ziprasidone intervention on olanzapine-induced metablic disorder in schizophrenia patients (in Chinese). China J Health Psychol. 2014;22(8):1124–1127.
   Google Scholar
• Correll CU, Frederickson AM, Kane JM, et al. Does antipsychotic polypharmacy increase the risk for metabolic syndrome? Schizophr Res. 2007 Jan;89(1–3):91–100.
   PubMed Web of Science ®Google Scholar
• Wood L, Egger M, Gluud LL, et al. Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study. BMJ. 2008 Mar 15;336(7644):601–605.
   PubMed Web of Science ®Google Scholar
• Schulz KF, Chalmers I, Hayes RJ, et al. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA. 1995 Feb 1;273(5):408–412.
   PubMed Web of Science ®Google Scholar
• Schulz KF, Grimes DA. Blinding in randomised trials: hiding who got what. Lancet Lond Engl. 2002 Feb 23;359(9307):696–700.
   PubMed Web of Science ®Google Scholar
• Correll CU, Skuban A, Ouyang J, et al. Efficacy and safety of brexpiprazole for the treatment of acute schizophrenia: a 6-week randomized, double-blind, placebo-controlled trial. Am J Psychiatry. 2015 Sep 1;172(9):870–880.
   PubMed Web of Science ®Google Scholar
• Kane JM, Skuban A, Ouyang J, et al. A multicenter, randomized, double-blind, controlled phase 3 trial of fixed-dose brexpiprazole for the treatment of adults with acute schizophrenia. Schizophr Res. 2015 May;164(1–3):127–135.
   PubMed Web of Science ®Google Scholar
• Kane JM, Zukin S, Wang Y, et al. Efficacy and safety of cariprazine in acute exacerbation of schizophrenia: results from an international, phase III clinical trial. J Clin Psychopharmacol. 2015 Aug;35(4):367–373.
   PubMed Web of Science ®Google Scholar
• Durgam S, Cutler AJ, Lu K, et al. Cariprazine in acute exacerbation of schizophrenia: a fixed-dose, phase 3, randomized, double-blind, placebo- and active-controlled trial. J Clin Psychiatry. 2015 Dec;76(12):e1574–82.
   PubMed Web of Science ®Google Scholar
• Joukamaa M, Heliövaara M, Knekt P, et al. Schizophrenia, neuroleptic medication and mortality. Br J Psychiatry J Ment Sci. 2006;188:122–127.
   PubMed Web of Science ®Google Scholar
• Waddington JL, Youssef HA, Kinsella A. Mortality in schizophrenia. Antipsychotic polypharmacy and absence of adjunctive anticholinergics over the course of a 10-year prospective study. Br J Psychiatry J Ment Sci. 1998 Oct;173:325–329.
   PubMed Web of Science ®Google Scholar
• Tiihonen J, Lönnqvist J, Wahlbeck K, et al. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet Lond Engl. 2009 Aug 22;374(9690):620–627.
   PubMed Web of Science ®Google Scholar
• Katona L, Czobor P, Bitter I. Real-world effectiveness of antipsychotic monotherapy vs. polypharmacy in schizophrenia: to switch or to combine? A nationwide study in Hungary. Schizophr Res. 2014 Jan;152(1):246–254.
   PubMed Web of Science ®Google Scholar
• Tiihonen J, Suokas JT, Suvisaari JM, et al. Polypharmacy with antipsychotics, antidepressants, or benzodiazepines and mortality in schizophrenia. Arch Gen Psychiatry. 2012 May;69(5):476–483.
   PubMed Web of Science ®Google Scholar
• Baandrup L, Gasse C, Jensen VD, et al. Antipsychotic polypharmacy and risk of death from natural causes in patients with schizophrenia: a population-based nested case-control study. J Clin Psychiatry. 2010 Feb;71(2):103–108.
   PubMed Web of Science ®Google Scholar
• Essock SM, Schooler NR, Stroup TS, et al. Effectiveness of switching from antipsychotic polypharmacy to monotherapy. Am J Psychiatry. 2011 Jul;168(7):702–708.
   PubMed Web of Science ®Google Scholar
• Constantine RJ, Andel R, McPherson M, et al. The risks and benefits of switching patients with schizophrenia or schizoaffective disorder from two to one antipsychotic medication: a randomized controlled trial. Schizophr Res. 2015 Aug;166(1–3):194–200.
   PubMed Web of Science ®Google Scholar
• Hori H, Yoshimura R, Katsuki A, et al. Switching to antipsychotic monotherapy can improve attention and processing speed, and social activity in chronic schizophrenia patients. J Psychiatr Res. 2013 Dec;47(12):1843–1848.
   PubMed Web of Science ®Google Scholar