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Polypharmacy in Psychiatry Practice, Volume I pp 75–105Cite as

Preclinical and Clinical Investigation of Antipsychotic Polypharmacy: What Is the Evidence?

Abstract

Antipsychotic polypharmacy is a common clinical practice whose implications have not been thoroughly assessed to date. There is a paucity of preclinical studies investigating the effects of antipsychotic combinations on animal models. These models are focusing on the effects of antipsychotic combinations on psychiatric and extrapyramidal symptoms’ simulations and on antipsychotic-induced metabolic abnormalities. Although most guidelines favour the use of antipsychotic monotherapy, clinical trials and meta-analyses examining the merits and disadvantages of polypharmacy are contradictory. A recent synthetic approach suggests that antipsychotic polypharmacy could be useful under conditions of acute symptoms’ exacerbation non-responsive to monotherapy but not so beneficial in chronic refractory illness. It also recommends that antipsychotic polypharmacy should always have a rational pharmacological basis. The role of antipsychotic combination strategies other than clozapine augmentation in treatment resistant patients needs to be clarified in future research. The specific effects of antipsychotic co-treatment in different symptoms dimensions, its interactions, adverse reactions and associations with medical morbidity and mortality remain to be further examined through rigorously designed clinical trials and prospective epidemiological studies.

Keywords

  • Antipsychotic
  • Polypharmacy
  • Preclinical
  • Clinical

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References

  1. Honer WG et al (2007) Conceptual and methodological issues in the design of clinical trials of antipsychotics for the treatment of schizophrenia. CNS Drugs 21(9):699–714

    PubMed  CAS  CrossRef  Google Scholar 

  2. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the treatment of schizophrenia and related disorders. (2005) Aust N Z J Psychiatry 39(1–2):1–30

    Google Scholar 

  3. The NICE guideline on core interventions in the treatment and management of schizophrenia in adulta in primary and secondary care (updated edition). (2010) National Collaborating Centre for Mental Health, N.C.C.f.M.H.G. Britain (ed), London

    Google Scholar 

  4. Taylor D, Paton C, Kapur S (eds) (2009) The Maudsley prescribing guidelines, 10th edn. Informa Healthcare, London

    Google Scholar 

  5. Gaebel W et al (2005) Schizophrenia practice guidelines: international survey and comparison. Br J Psychiatry 187:248–255

    PubMed  CrossRef  Google Scholar 

  6. Pandurangi AK, Dalkilic A (2008) Polypharmacy with second-generation antipsychotics: a review of evidence. J Psychiatr Pract 14(6):345–367

    PubMed  CrossRef  Google Scholar 

  7. Fleischhacker WW (2003) New developments in the pharmacotherapy of schizophrenia. J Neural Transm Suppl 64:105–117

    PubMed  CAS  Google Scholar 

  8. Tada M et al (2004) Combined treatment of quetiapine with haloperidol in animal models of antipsychotic effect and extrapyramidal side effects: comparison with risperidone and chlorpromazine. Psychopharmacology (Berl) 176(1):94–100

    CAS  CrossRef  Google Scholar 

  9. Egbe P et al (1990) Amperozide and conditioned behaviour in rats: potentiation by classical neuroleptics and alpha-methylparatyrosine. Pharmacol Toxicol 66(Suppl 1):18–21

    PubMed  CAS  CrossRef  Google Scholar 

  10. Leucht S et al (2009) Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet 373(9657):31–41

    PubMed  CAS  CrossRef  Google Scholar 

  11. Snigdha S et al (2008) Ziprasidone and aripiprazole attenuate olanzapine-induced hyperphagia in rats. J Psychopharmacol 22(5):567–571

    PubMed  CAS  CrossRef  Google Scholar 

  12. Wiker C et al (2008) Adjunctive galantamine, but not donepezil, enhances the antipsychotic-like effect of raclopride in rats. Int J Neuropsychopharmacol 11(6):845–850

    PubMed  CAS  CrossRef  Google Scholar 

  13. Eltayb A et al (2005) Topiramate augments the antipsychotic-like effect and cortical dopamine output of raclopride. Naunyn Schmiedebergs Arch Pharmacol 372(3):195–202

    PubMed  CAS  CrossRef  Google Scholar 

  14. Wadenberg MG et al (2001) Antagonism at 5-HT(2A) receptors potentiates the effect of haloperidol in a conditioned avoidance response task in rats. Pharmacol Biochem Behav 68(3):363–370

    PubMed  CAS  CrossRef  Google Scholar 

  15. Liegeois JF, Ichikawa J, Meltzer HY (2002) 5-HT(2A) receptor antagonism potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and inhibits that in the nucleus accumbens in a dose-dependent manner. Brain Res 947(2):157–165

    PubMed  CAS  CrossRef  Google Scholar 

  16. Ichikawa J et al (2005) Valproic acid potentiates both typical and atypical antipsychotic-induced prefrontal cortical dopamine release. Brain Res 1052(1):56–62

    PubMed  CAS  CrossRef  Google Scholar 

  17. Ago Y et al (2005) Sulpiride in combination with fluvoxamine increases in vivo dopamine release selectively in rat prefrontal cortex. Neuropsychopharmacology 30(1):43–51

    PubMed  CAS  CrossRef  Google Scholar 

  18. Honer WG et al (2009) A translational research approach to poor treatment response in patients with schizophrenia: clozapine-antipsychotic polypharmacy. J Psychiatry Neurosci 34(6):433–442

    PubMed  Google Scholar 

  19. Advokat C et al (2004) Comparison of risperidone and olanzapine as used under “real-world” conditions in a state psychiatric hospital. Prog Neuropsychopharmacol Biol Psychiatry 28(3):487–495

    PubMed  CAS  CrossRef  Google Scholar 

  20. Faries D et al (2005) Antipsychotic monotherapy and polypharmacy in the naturalistic treatment of schizophrenia with atypical antipsychotics. BMC Psychiatry 5:26

    PubMed  CrossRef  Google Scholar 

  21. Ganguly R et al (2004) Prevalence, trends, and factors associated with antipsychotic polypharmacy among Medicaid-eligible schizophrenia patients, 1998–2000. J Clin Psychiatry 65(10):1377–1388

    PubMed  CrossRef  Google Scholar 

  22. Jaffe AB, Levine J (2003) Antipsychotic medication coprescribing in a large state hospital system. Pharmacoepidemiol Drug Saf 12(1):41–48

    PubMed  CrossRef  Google Scholar 

  23. Kreyenbuhl J et al (2006) Long-term combination antipsychotic treatment in VA patients with schizophrenia. Schizophr Res 84(1):90–99

    PubMed  CrossRef  Google Scholar 

  24. Lunsky Y, Elserafi J (2012) Antipsychotic medication prescription patterns in adults with developmental disabilities who have experienced psychiatric crisis. Res Dev Disabil 33(1):32–38

    PubMed  CrossRef  Google Scholar 

  25. Procyshyn RM et al (2001) Antipsychotic polypharmacy: a survey of discharge prescriptions from a tertiary care psychiatric institution. Can J Psychiatry 46(4):334–339

    PubMed  CAS  Google Scholar 

  26. Dosreis S et al (2011) Antipsychotic treatment among youth in foster care. Pediatrics 128(6):e1459–e1466

    PubMed  CrossRef  Google Scholar 

  27. Bingefors K, Isacson D, Lindstrom E (2003) Dosage patterns of antipsychotic drugs for the treatment of schizophrenia in Swedish ambulatory clinical practice—a highly individualized therapy. Nord J Psychiatry 57(4):263–269

    PubMed  CrossRef  Google Scholar 

  28. Broekema WJ, de Groot IW, van Harten PN (2007) Simultaneous prescribing of atypical antipsychotics, conventional antipsychotics and anticholinergics—a European study. Pharm World Sci 29(3):126–130

    PubMed  CAS  CrossRef  Google Scholar 

  29. Ghio L et al (2011) Antipsychotic utilisation and polypharmacy in Italian residential facilities: a survey. Epidemiol Psychiatr Sci 20(2):171–179

    PubMed  CAS  CrossRef  Google Scholar 

  30. Grohmann R et al (2004) Psychotropic drug use in psychiatric inpatients: recent trends and changes over time—data from the AMSP study. Pharmacopsychiatry 37(Suppl 1):S27–S38

    PubMed  Google Scholar 

  31. Magliano L et al (2004) Prescription of psychotropic drugs to patients with schizophrenia: an Italian national survey. Eur J Clin Pharmacol 60(7):513–522

    PubMed  CrossRef  Google Scholar 

  32. Tibaldi G et al (1997) Utilization of neuroleptic drugs in Italian mental health services: a survey in Piedmont. Psychiatr Serv 48(2):213–217

    PubMed  CAS  Google Scholar 

  33. Renkel S, Rasmussen K (2006) Antipsychotic medication and length of stay at a psychiatric maximum-security unit in Norway (1987–2000). Nord J Psychiatry 60(2):132–136

    PubMed  CrossRef  Google Scholar 

  34. Burns T et al (2006) Maintenance antipsychotic medication patterns in outpatient schizophrenia patients: a naturalistic cohort study. Acta Psychiatr Scand 113(2):126–134

    PubMed  CAS  CrossRef  Google Scholar 

  35. Lerma-Carrillo I et al (2008) Antipsychotic polypharmacy in patients with schizophrenia in a brief hospitalization unit. Clin Neuropharmacol 31(6):319–332

    PubMed  CAS  CrossRef  Google Scholar 

  36. Kroken RA et al (2009) Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study. BMC Psychiatry 9:24

    PubMed  CrossRef  CAS  Google Scholar 

  37. Paton C et al (2003) Patterns of antipsychotic and anticholinergic prescribing for hospital inpatients. J Psychopharmacol 17(2):223–229

    PubMed  CrossRef  Google Scholar 

  38. Muijen M, Silverstone T (1987) A comparative hospital survey of psychotropic drug prescribing. Br J Psychiatry 150:501–504

    PubMed  CAS  CrossRef  Google Scholar 

  39. Santone G et al (2010) Patient characteristics and process factors associated with antipsychotic polypharmacy in a nationwide sample of psychiatric inpatients in Italy. Pharmacoepidemiol Drug Saf 20:441–449

    PubMed  CrossRef  Google Scholar 

  40. Hamann J et al (2003) Antipsychotic prescribing patterns in Germany: a retrospective analysis using a large outpatient prescription database. Int Clin Psychopharmacol 18(4):237–242

    PubMed  CrossRef  Google Scholar 

  41. Chong MY et al (2004) Antipsychotic drug prescription for schizophrenia in East Asia: rationale for change. Psychiatry Clin Neurosci 58(1):61–67

    PubMed  CrossRef  Google Scholar 

  42. Koen L et al (2008) Antipsychotic prescription patterns in Xhosa patients with schizophrenia or schizoaffective disorder. Afr J Psychiatry (Johannesbg) 11(4):287–290

    CAS  Google Scholar 

  43. McKean A, Vella-Brincat J (2009) Audit of antipsychotic polypharmacy in Christchurch. Australas Psychiatry 17(4):336–337

    PubMed  CrossRef  Google Scholar 

  44. Chakos MH et al (2006) Baseline use of concomitant psychotropic medications to treat schizophrenia in the CATIE trial. Psychiatr Serv 57(8):1094–1101

    PubMed  CrossRef  Google Scholar 

  45. Constantine RJ, Boaz T, Tandon R (2010) Antipsychotic polypharmacy in the treatment of children and adolescents in the fee-for-service component of a large state Medicaid program. Clin Ther 32(5):949–959

    PubMed  CrossRef  Google Scholar 

  46. Hanssens L et al (2006) Pharmacological treatment of ambulatory schizophrenic patients in Belgium. Clin Pract Epidemiol Ment Health 2:11

    PubMed  CAS  CrossRef  Google Scholar 

  47. Heresco-Levy U et al (1989) Prescribing patterns of neuroactive drugs in 98 schizophrenic patients. Isr J Psychiatry Relat Sci 26(3):157–163

    PubMed  CAS  Google Scholar 

  48. Humberstone V, Wheeler A, Lambert T (2004) An audit of outpatient antipsychotic usage in the three health sectors of Auckland, New Zealand. Aust N Z J Psychiatry 38(4):240–245

    PubMed  CrossRef  Google Scholar 

  49. Lass J, Mannik A, Bell JS (2008) Pharmacotherapy of first episode psychosis in Estonia: comparison with national and international treatment guidelines. J Clin Pharm Ther 33(2):165–173

    PubMed  CAS  CrossRef  Google Scholar 

  50. Lee B, Walker V (2008) Polypharmacy as the initial second-generation antipsychotic treatment. Psychiatr Serv 59(7):717

    PubMed  CrossRef  Google Scholar 

  51. Leslie DL, Rosenheck RA (2003) Benchmarking the quality of schizophrenia pharmacotherapy: a comparison of the Department of Veterans Affairs and the private sector. J Ment Health Policy Econ 6(3):113–121

    PubMed  Google Scholar 

  52. Morrato EH et al (2007) Prevalence, utilization patterns, and predictors of antipsychotic polypharmacy: experience in a multistate Medicaid population, 1998–2003. Clin Ther 29(1):183–195

    PubMed  CAS  CrossRef  Google Scholar 

  53. Leslie DL, Rosenheck RA (2001) Use of pharmacy data to assess quality of pharmacotherapy for schizophrenia in a national health care system: individual and facility predictors. Med Care 39(9):923–933

    PubMed  CAS  CrossRef  Google Scholar 

  54. Botts S, Hines H, Littrell R (2003) Antipsychotic polypharmacy in the ambulatory care setting, 1993–2000. Psychiatr Serv 54(8):1086

    PubMed  CrossRef  Google Scholar 

  55. Divac N et al (2007) Antipsychotic polypharmacy at the University Psychiatric Hospital in Serbia. Pharmacoepidemiol Drug Saf 16(11):1250–1251

    PubMed  CrossRef  Google Scholar 

  56. Chong SA et al (2000) Contrasting clozapine prescribing patterns in the east and west? Ann Acad Med Singapore 29(1):75–78

    PubMed  CAS  Google Scholar 

  57. Kiivet RA et al (1995) Patterns of drug treatment of schizophrenic patients in Estonia, Spain and Sweden. Br J Clin Pharmacol 40(5):467–476

    PubMed  CAS  CrossRef  Google Scholar 

  58. Andersen SE, Johansson M, Manniche C (2008) The prescribing pattern of a new antipsychotic: a descriptive study of aripiprazole for psychiatric in-patients. Basic Clin Pharmacol Toxicol 103(1):75–81

    PubMed  CAS  CrossRef  Google Scholar 

  59. Molina JD et al (2009) Combined treatment with amisulpride in patients with schizophrenia discharged from a short-term hospitalization unit: a 1-year retrospective study. Clin Neuropharmacol 32(1):10–15

    PubMed  CAS  Google Scholar 

  60. Boaz TL et al (2011) Risperidone long-acting therapy prescribing patterns and their impact on early discontinuation of treatment in a large Medicaid population. J Clin Psychiatry 72(8):1079–1085

    PubMed  CrossRef  Google Scholar 

  61. Rupnow MF et al (2007) 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 23(11):2815–2822

    PubMed  CrossRef  Google Scholar 

  62. Johnson DA, Wright NF (1990) Drug prescribing for schizophrenic out-patients on depot injections. Repeat surveys over 18 years. Br J Psychiatry 156:827–834

    PubMed  CAS  CrossRef  Google Scholar 

  63. Phillips MR, Lu SH, Wang RW (1997) Economic reforms and the acute inpatient care of patients with schizophrenia: the Chinese experience. Am J Psychiatry 154(9):1228–1234

    PubMed  CAS  Google Scholar 

  64. Edlinger M et al (2005) Trends in the pharmacological treatment of patients with schizophrenia over a 12 year observation period. Schizophr Res 77(1):25–34

    PubMed  CrossRef  Google Scholar 

  65. Gilmer TP et al (2007) Antipsychotic polypharmacy trends among Medicaid beneficiaries with schizophrenia in San Diego County, 1999–2004. Psychiatr Serv 58(7):1007–1010

    PubMed  CrossRef  Google Scholar 

  66. McCue RE, Waheed R, Urcuyo L (2003) Polypharmacy in patients with schizophrenia. J Clin Psychiatry 64(9):984–989

    PubMed  CrossRef  Google Scholar 

  67. Mojtabai R, Olfson M (2010) National trends in psychotropic medication polypharmacy in office-based psychiatry. Arch Gen Psychiatry 67(1):26–36

    PubMed  CrossRef  Google Scholar 

  68. Nielsen J et al (2010) 10-year trends in the treatment and outcomes of patients with first-episode schizophrenia. Acta Psychiatr Scand 122(5):356–366

    PubMed  CrossRef  Google Scholar 

  69. Kreyenbuhl JA et al (2007) Long-term antipsychotic polypharmacy in the VA health system: patient characteristics and treatment patterns. Psychiatr Serv 58(4):489–495

    PubMed  CrossRef  Google Scholar 

  70. Biancosino B et al (2005) Determinants of antipsychotic polypharmacy in psychiatric inpatients: a prospective study. Int Clin Psychopharmacol 20(6):305–309

    PubMed  CrossRef  Google Scholar 

  71. Ito H, Koyama A, Higuchi T (2005) Polypharmacy and excessive dosing: psychiatrists’ perceptions of antipsychotic drug prescription. Br J Psychiatry 187:243–247

    PubMed  CrossRef  Google Scholar 

  72. Karagianis J et al (2009) Antipsychotic switching: results from a one-year prospective, observational study of patients with schizophrenia. Curr Med Res Opin 25(9):2121–2132

    PubMed  CrossRef  Google Scholar 

  73. Bredski J et al (2011) The prediction of discharge from in-patient psychiatric rehabilitation: a case-control study. BMC Psychiatry 11:149

    PubMed  CrossRef  Google Scholar 

  74. Ahn J et al (2008) Classifying patients by antipsychotic adherence patterns using latent class analysis: characteristics of nonadherent groups in the California Medicaid (Medi-Cal) program. Value Health 11(1):48–56

    PubMed  CrossRef  Google Scholar 

  75. Ananth J, Parameswaran S, Gunatilake S (2004) Antipsychotic polypharmacy. Curr Pharm Des 10(18):2231–2238

    PubMed  CAS  CrossRef  Google Scholar 

  76. Covell NH et al (2002) Antipsychotic prescribing practices in Connecticut’s public mental health system: rates of changing medications and prescribing styles. Schizophr Bull 28(1):17–29

    PubMed  CrossRef  Google Scholar 

  77. Connolly A, Taylor D (2008) Ethnicity and quality of antipsychotic prescribing among in-patients in south London. Br J Psychiatry 193(2):161–162

    PubMed  CrossRef  Google Scholar 

  78. Connolly A, Rogers P, Taylor D (2007) Antipsychotic prescribing quality and ethnicity: a study of hospitalized patients in south east London. J Psychopharmacol 21(2):191–197

    PubMed  CrossRef  Google Scholar 

  79. Connolly A et al (2011) Antipsychotic prescribing in black and white hospitalised patients. J Psychopharmacol 25(5):704–709

    PubMed  CrossRef  Google Scholar 

  80. Mason AS, Nerviano V, DeBurger RA (1977) Patterns of antipsychotic drug use in four Southeastern state hospitals. Dis Nerv Syst 38(7):541–545

    PubMed  CAS  Google Scholar 

  81. Hong IS, Bishop JR (2010) Anticholinergic use in children and adolescents after initiation of antipsychotic therapy. Ann Pharmacother 44(7–8):1171–1180

    PubMed  CrossRef  Google Scholar 

  82. Correll CU et al (2011) Antipsychotic polypharmacy: a survey study of prescriber attitudes, knowledge and behavior. Schizophr Res 131(1–3):58–62

    PubMed  CrossRef  Google Scholar 

  83. Baandrup L et al (2010) Exploring regional variation in antipsychotic coprescribing practice: a Danish questionnaire survey. J Clin Psychiatry 71(11):1457–1464

    PubMed  CrossRef  Google Scholar 

  84. Kreyenbuhl J et al (2007) Adding or switching antipsychotic medications in treatment-refractory schizophrenia. Psychiatr Serv 58(7):983–990

    PubMed  CrossRef  Google Scholar 

  85. Dolder CR, McKinsey J (2011) Antipsychotic polypharmacy among patients admitted to a geriatric psychiatry unit. J Psychiatr Pract 17(5):368–374

    PubMed  CrossRef  Google Scholar 

  86. Auquier P et al (2006) Mortality in schizophrenia. Pharmacoepidemiol Drug Saf 15(12):873–879

    PubMed  CrossRef  Google Scholar 

  87. Joukamaa M et al (2006) Schizophrenia, neuroleptic medication and mortality. Br J Psychiatry 188:122–127

    PubMed  CrossRef  Google Scholar 

  88. Hollis J et al (2006) Antipsychotic medication dispensing and associated odds ratios of death in elderly veterans and war widows, 2001. Aust N Z J Psychiatry 40(11–12):981–986

    PubMed  CrossRef  Google Scholar 

  89. Waddington JL, Youssef HA, Kinsella A (1998) Mortality in schizophrenia. Antipsychotic polypharmacy and absence of adjunctive anticholinergics over the course of a 10-year prospective study. Br J Psychiatry 173:325–329

    PubMed  CAS  CrossRef  Google Scholar 

  90. Baandrup L et al (2010) Antipsychotic polypharmacy and risk of death from natural causes in patients with schizophrenia: a population-based nested case-control study. J Clin Psychiatry 71(2):103–108

    PubMed  CrossRef  Google Scholar 

  91. Hung GB, Cheung HK (2008) Predictors of high-dose antipsychotic prescription in psychiatric patients in Hong Kong. Hong Kong Med J 14(1):35–39

    PubMed  Google Scholar 

  92. Barbui C et al (2007) Factors associated with antipsychotic dosing in psychiatric inpatients: a prospective study. Int Clin Psychopharmacol 22(4):221–225

    PubMed  CrossRef  Google Scholar 

  93. Barnes TR, Paton C (2011) Antipsychotic polypharmacy in schizophrenia: benefits and risks. CNS Drugs 25(5):383–399

    PubMed  CrossRef  Google Scholar 

  94. Baandrup L et al (2012) Association of antipsychotic polypharmacy with health service cost: a register-based cost analysis. Eur J Health Econ 13(3):355–363

    PubMed  CrossRef  Google Scholar 

  95. Hori H et al (2006) Antipsychotic medication and cognitive function in schizophrenia. Schizophr Res 86(1–3):138–146

    PubMed  CrossRef  Google Scholar 

  96. Hori H et al (2012) Several prescription patterns of antipsychotic drugs influence cognitive functions in Japanese chronic schizophrenia patients. Int J Psychiatry Clin Pract 16(2):138–142

    PubMed  CrossRef  CAS  Google Scholar 

  97. Elie D et al (2010) Cognitive effects of antipsychotic dosage and polypharmacy: a study with the BACS in patients with schizophrenia and schizoaffective disorder. J Psychopharmacol 24(7):1037–1044

    PubMed  CAS  CrossRef  Google Scholar 

  98. Kontis D et al (2010) Doubtful association of antipsychotic polypharmacy and high dosage with cognition in chronic schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 34(7):1333–1341

    PubMed  CAS  CrossRef  Google Scholar 

  99. Taylor D (2010) Antipsychotic polypharmacy—confusion reigns. The Psychiatrist 34:41–43

    CrossRef  Google Scholar 

  100. Taylor DM et al (2012) Augmentation of clozapine with a second antipsychotic—a meta-analysis. Acta Psychiatr Scand 125(1):15–24

    PubMed  CAS  CrossRef  Google Scholar 

  101. Taylor DM, Smith L (2009) Augmentation of clozapine with a second antipsychotic—a meta-analysis of randomized, placebo-controlled studies. Acta Psychiatr Scand 119(6):419–425

    PubMed  CAS  CrossRef  Google Scholar 

  102. Sommer IE et al (2012) Pharmacological augmentation strategies for schizophrenia patients with insufficient response to clozapine: a quantitative literature review. Schizophr Bull 38(5):1003–1011

    PubMed  CrossRef  Google Scholar 

  103. Wang J et al (2010) Sulpiride augmentation for schizophrenia. Schizophr Bull 36(2):229–230

    PubMed  CrossRef  Google Scholar 

  104. Paton C, Whittington C, Barnes TR (2007) Augmentation with a second antipsychotic in patients with schizophrenia who partially respond to clozapine: a meta-analysis. J Clin Psychopharmacol 27(2):198–204

    PubMed  CAS  CrossRef  Google Scholar 

  105. Barbui C et al (2009) Does the addition of a second antipsychotic drug improve clozapine treatment? Schizophr Bull 35(2):458–468

    PubMed  CrossRef  Google Scholar 

  106. Correll CU et al (2009) Antipsychotic combinations vs monotherapy in schizophrenia: a meta-analysis of randomized controlled trials. Schizophr Bull 35(2):443–457

    PubMed  CrossRef  Google Scholar 

  107. Goren JL et al (2008) When is antipsychotic polypharmacy supported by research evidence? Implications for QI. Jt Comm J Qual Patient Saf 34(10):571–582

    PubMed  Google Scholar 

  108. Patrick V, Levin E, Schleifer S (2005) Antipsychotic polypharmacy: is there evidence for its use? J Psychiatr Pract 11(4):248–257

    PubMed  CrossRef  Google Scholar 

  109. Gardos G (2005) Antipsychotic polypharmacy or monotherapy? Neuropsychopharmacol Hung 7(2):72–77

    PubMed  Google Scholar 

  110. Cipriani A, Boso M, Barbui C (2009) Clozapine combined with different antipsychotic drugs for treatment resistant schizophrenia. Cochrane Database Syst Rev (3):CD006324

    Google Scholar 

  111. Reeves RR, Mack JE (2004) Worsening schizoaffective disorder with aripiprazole. Am J Psychiatry 161:1308

    PubMed  CrossRef  Google Scholar 

  112. Ramaswamy S, Vijay D, William M et al (2004) Aripiprazole possibly worsens psychosis. Int Clin Psychopharmacol 19:45–48

    PubMed  CrossRef  Google Scholar 

  113. Kane JM, Correll CU (2010) Pharmacologic treatment of schizophrenia. Dialogues Clin Neurosci 12(3):345–357

    PubMed  Google Scholar 

  114. Essock SM et al (2011) Effectiveness of switching from antipsychotic polypharmacy to monotherapy. Am J Psychiatry 168(7):702–708

    PubMed  CrossRef  Google Scholar 

  115. Suzuki T et al (2004) Revising polypharmacy to a single antipsychotic regimen for patients with chronic schizophrenia. Int J Neuropsychopharmacol 7(2):133–142

    PubMed  CAS  CrossRef  Google Scholar 

  116. Chong SA et al (2006) Reducing polypharmacy through the introduction of a treatment algorithm: use of a treatment algorithm on the impact on polypharmacy. Ann Acad Med Singapore 35(7):457–460

    PubMed  Google Scholar 

  117. Constantine RJ, Andel R, Tandon R (2010) Trends in adult antipsychotic polypharmacy: progress and challenges in Florida’s Medicaid program. Community Ment Health J 46(6):523–530

    PubMed  CrossRef  Google Scholar 

  118. Goh YL et al (2011) Reducing antipsychotic polypharmacy among psychogeriatric and adult patients with chronic schizophrenia. Perm J 15(2):52–56

    PubMed  Google Scholar 

  119. Hazra M et al (2011) Impact of feedback from pharmacists in reducing antipsychotic polypharmacy in schizophrenia. Psychiatry Clin Neurosci 65(7):676–678

    PubMed  CrossRef  Google Scholar 

  120. Mistler LA, Mellman TA, Drake RE (2009) A pilot study testing a medication algorithm to reduce polypharmacy. Qual Saf Health Care 18(1):55–58

    PubMed  CAS  CrossRef  Google Scholar 

  121. Thompson A et al (2010) Effectiveness of a cognitive behavioural workbook for changing beliefs about antipsychotic polypharmacy: analysis from a cluster randomized controlled trial. J Eval Clin Pract 16(3):520–528

    PubMed  Google Scholar 

  122. Thompson A et al (2008) The DEBIT trial: an intervention to reduce antipsychotic polypharmacy prescribing in adult psychiatry wards—a cluster randomized controlled trial. Psychol Med 38(5):705–715

    PubMed  CAS  CrossRef  Google Scholar 

  123. Patrick V et al (2006) Best practices: an initiative to curtail the use of antipsychotic polypharmacy in a state psychiatric hospital. Psychiatr Serv 57(1):21–23

    PubMed  CrossRef  Google Scholar 

  124. Robst J (2012) Changes in antipsychotic medication use after implementation of a Medicaid mental health carve-out in the US. Pharmacoeconomics 30(5):387–396

    PubMed  CrossRef  Google Scholar 

  125. Baandrup L et al (2010) Evaluation of a multifaceted intervention to limit excessive antipsychotic co-prescribing in schizophrenia out-patients. Acta Psychiatr Scand 122(5):367–374

    PubMed  CrossRef  Google Scholar 

  126. Chuang WC, Crismon ML (2003) Evaluation of a schizophrenia medication algorithm in a state hospital. Am J Health Syst Pharm 60(14):1459–1467

    PubMed  Google Scholar 

  127. Finnerty MT et al (2011) Long-term impact of web-based tools, leadership feedback, and policies on inpatient antipsychotic polypharmacy. Psychiatr Serv 62(10):1124–1126

    PubMed  CrossRef  Google Scholar 

  128. Kennedy NB, Procyshyn RM (2000) Rational antipsychotic polypharmacy. Can J Clin Pharmacol 7(3):155–159

    PubMed  CAS  Google Scholar 

  129. Goff DC, Dixon L (2011) Antipsychotic polypharmacy: are two ever better than one? Am J Psychiatry 168(7):667–669

    PubMed  CrossRef  Google Scholar 

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  1. 1st Psychiatric Department, Psychiatric Hospital of Attica, Athens, Greece

    Dimitrios Kontis M.D., Ph.D. & Eirini Theochari M.D.

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Correspondence to Dimitrios Kontis M.D., Ph.D. .

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  1. Sha'ar Menashe Mental Health Center, Hadera, 38814, Israel

    Michael S. Ritsner

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© 2013 Springer Science+Business Media Dordrecht

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Kontis, D., Theochari, E. (2013). Preclinical and Clinical Investigation of Antipsychotic Polypharmacy: What Is the Evidence?. In: Ritsner, M. (eds) Polypharmacy in Psychiatry Practice, Volume I. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5805-6_4

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