The European Journal of Health Economics

, Volume 13, Issue 3, pp 355–363 | Cite as

Association of antipsychotic polypharmacy with health service cost: a register-based cost analysis

  • Lone Baandrup
  • Jan Sørensen
  • Henrik Lublin
  • Merete Nordentoft
  • Birte Glenthoj
Original Paper



To investigate the association of antipsychotic polypharmacy in schizophrenia with cost of primary and secondary health service use.


Comparative analysis of health service cost for patients prescribed antipsychotic polypharmacy versus antipsychotic monotherapy. Resource utilisation and costs were described using central Danish registers for a 2 year period (2007–2008). We included patients attached to one of two Danish psychiatric referral centres in 1 January 2008 and/or 1 January 2009. Their prescribed treatment with either antipsychotic polypharmacy or monotherapy at the two cross-sectional dates was recorded and used as proxy of polypharmacy exposure during the preceding year. A multivariate generalised linear model was fitted with total costs of primary and secondary health service use as dependent variable, and antipsychotic polypharmacy, diagnosis, age, gender, disease duration, psychiatric inpatient admissions, and treatment site as covariates.


The sample consisted of 736 outpatients with a diagnosis in the schizophrenia spectrum. Antipsychotic polypharmacy was associated with significantly higher total health service costs compared with monotherapy (2007: 25% higher costs; 2008: 17% higher costs) when adjusting for potential confounders and risk factors. A subgroup analysis suggested that the excessive costs associated with antipsychotic polypharmacy were partly accounted for by the functional level of the patients.


The results demonstrate that antipsychotic co-prescribing is associated with increased use of health care services, even though no causal relations can be inferred from an observational study.


Schizophrenia Antipsychotic polypharmacy Health service cost 

JEL Classification




The study was supported by the National Board of Health in Denmark (0-204-02-9/9) as part of the funding for a health technology assessment, and the Wørzner Foundation.

Conflict of interest

The authors have no conflicts of interest to declare.


  1. 1.
    Mangalore, R., Knapp, M.: Cost of schizophrenia in England. J. Ment. Health Policy Econ. 10(1), 23–41 (2007)PubMedGoogle Scholar
  2. 2.
    Stargardt, T., Weinbrenner, S., Busse, R., et al.: Effectiveness and cost of atypical versus typical antipsychotic treatment for schizophrenia in routine care. J. Ment. Health Policy Econ. 11(2), 89–97 (2008)PubMedGoogle Scholar
  3. 3.
    Canales, P.L., Olsen, J., Miller, A.L., et al.: Role of antipsychotic polypharmacotherapy in the treatment of schizophrenia. CNS Drugs 12(3), 179–188 (1999)CrossRefGoogle Scholar
  4. 4.
    Botts, S., Hines, H., Littrell, R.: Antipsychotic polypharmacy in the ambulatory care setting, 1993–2000. Psychiatr. Serv. 54(8), 1086 (2003)PubMedCrossRefGoogle Scholar
  5. 5.
    Broekema, W.J., de Groot, I.W., Van Harten, P.N.: Simultaneous prescribing of atypical antipsychotics, conventional antipsychotics and anticholinergics-a European study. Pharm. World Sci. 29(3), 126–130 (2007)PubMedCrossRefGoogle Scholar
  6. 6.
    Clark, R.E., Bartels, S.J., Mellman, T.A., et al.: Recent trends in antipsychotic combination therapy of schizophrenia and schizoaffective disorder: implications for state mental health policy. Schizophr. Bull. 28(1), 75–84 (2002)PubMedCrossRefGoogle Scholar
  7. 7.
    Harrington, M., Lelliott, P., Paton, C., et al.: The results of a multi-centre audit of the prescribing of antipsychotic drugs for in-patients in the UK. Psychiatr. Bull. 26, 414–418 (2002)CrossRefGoogle Scholar
  8. 8.
    McCue, R.E., Waheed, R., Urcuyo, L.: Polypharmacy in patients with schizophrenia. J. Clin. Psychiatry 64(9), 984–989 (2003)PubMedCrossRefGoogle Scholar
  9. 9.
    Centorrino, F., Goren, J.L., Hennen, J., et al.: Multiple versus single antipsychotic agents for hospitalized psychiatric patients: case-control study of risks versus benefits. Am. J. Psychiatry 161(4), 700–706 (2004)PubMedCrossRefGoogle Scholar
  10. 10.
    Kingsbury, S.J., Yi, D., Simpson, G.M.: Psychopharmacology: rational and irrational polypharmacy. Psychiatr. Serv. 52(8), 1033–1036 (2001)PubMedCrossRefGoogle Scholar
  11. 11.
    Miller, A.L., Craig, C.S.: Combination antipsychotics: pros, cons, and questions. Schizophr. Bull. 28(1), 105–109 (2002)PubMedCrossRefGoogle Scholar
  12. 12.
    Barbui, C., Signoretti, A., Mule, S., et al.: Does the addition of a second antipsychotic drug improve clozapine treatment? Schizophr. Bull. 35(2), 458–468 (2009)PubMedCrossRefGoogle Scholar
  13. 13.
    Freudenreich, O., Goff, D.C.: Antipsychotic combination therapy in schizophrenia. A review of efficacy and risks of current combinations. Acta Psychiatr. Scand. 106(5), 323–330 (2002)PubMedCrossRefGoogle Scholar
  14. 14.
    Lerner, V., Libov, I., Kotler, M., et al.: Combination of “atypical” antipsychotic medication in the management of treatment-resistant schizophrenia and schizoaffective disorder. Prog. Neuropsychopharmacol. Biol. Psychiatry 28(1), 89–98 (2004)PubMedCrossRefGoogle Scholar
  15. 15.
    Mouaffak, F., Tranulis, C., Gourevitch, R., et al.: Augmentation strategies of clozapine with antipsychotics in the treatment of ultraresistant schizophrenia. Clin. Neuropharmacol. 29(1), 28–33 (2006)PubMedCrossRefGoogle Scholar
  16. 16.
    Pandurangi, A.K., Dalkilic, A.: Polypharmacy with second-generation antipsychotics: a review of evidence. J Psychiatr Pract 14(6), 345–367 (2008)PubMedCrossRefGoogle Scholar
  17. 17.
    Stahl, S.M., Grady, M.M.: A critical review of atypical antipsychotic utilization: comparing monotherapy with polypharmacy and augmentation. Curr. Med. Chem. 11(3), 313–327 (2004)PubMedCrossRefGoogle Scholar
  18. 18.
    Tranulis, C., Skalli, L., Lalonde, P., et al.: Benefits and risks of antipsychotic polypharmacy: an evidence-based review of the literature. Drug Saf 31(1), 7–20 (2008)PubMedCrossRefGoogle Scholar
  19. 19.
    Correll, C.U., Rummel-Kluge, C., Corves, C., et al.: Antipsychotic combinations vs monotherapy in schizophrenia: a meta-analysis of randomized controlled trials. Schizophr. Bull. 35, 443–457 (2009)PubMedCrossRefGoogle Scholar
  20. 20.
    Paton, C., Whittington, C., Barnes, T.R.: Augmentation with a second antipsychotic in patients with schizophrenia who partially respond to clozapine: a meta-analysis. J. Clin. Psychopharmacol. 27(2), 198–204 (2007)PubMedCrossRefGoogle Scholar
  21. 21.
    Taylor, D.M., Smith, L.: Augmentation of clozapine with a second antipsychotic—a meta-analysis of randomized, placebo-controlled studies. Acta Psychiatr. Scand. 119(6), 419–425 (2009)PubMedCrossRefGoogle Scholar
  22. 22.
    Stahl, S.M., Grady, M.M.: High-cost use of second-generation antipsychotics under California’s Medicaid program. Psychiatr. Serv. 57(1), 127–129 (2006)PubMedCrossRefGoogle Scholar
  23. 23.
    Zhu, B., Ascher-Svanum, H., Faries, D.E., et al.: Cost of antipsychotic polypharmacy in the treatment of schizophrenia. BMC Psychiatry 8, 19 (2008)PubMedCrossRefGoogle Scholar
  24. 24.
    Knapp, M., Mangalore, R., Simon, J.: The global costs of schizophrenia. Schizophr. Bull. 30(2), 279–293 (2004)PubMedCrossRefGoogle Scholar
  25. 25.
    Tediosi, F., Parazzini, F., Garattini, L.: Cost of schizophrenia studies: a methodological review. Hepac 1, 14–19 (2000)CrossRefGoogle Scholar
  26. 26.
    Andersen, T.F., Madsen, M., Jørgensen, J., et al.: The Danish National Hospital Register. A valuable source of data for modern health sciences. Dan. Med. Bull. 46(3), 263–268 (1999)PubMedGoogle Scholar
  27. 27.
    Munk-Jorgensen, P., Mortensen, P.B.: The Danish Psychiatric Central Register. Dan. Med. Bull. 44(1), 82–84 (1997)PubMedGoogle Scholar
  28. 28.
    Olivarius, N.F., Hollnagel, H., Krasnik, A., et al.: The Danish National Health Service Register. A tool for primary health care research. Dan. Med. Bull. 44(4), 449–453 (1997)PubMedGoogle Scholar
  29. 29.
    Barber, J., Thompson, S.: Multiple regression of cost data: use of generalised linear models. J. Health Serv. Res. Policy 9(4), 197–204 (2004)PubMedCrossRefGoogle Scholar
  30. 30.
    Loosbrock, D.L., Zhao, Z., Johnstone, B.M., et al.: Antipsychotic medication use patterns and associated costs of care for individuals with schizophrenia. J. Ment. Health Policy Econ. 6(2), 67–75 (2003)PubMedGoogle Scholar
  31. 31.
    Biancosino, B., Barbui, C., Marmai, L., et al.: Determinants of antipsychotic polypharmacy in psychiatric inpatients: a prospective study. Int. Clin. Psychopharmacol. 20(6), 305–309 (2005)PubMedCrossRefGoogle Scholar
  32. 32.
    Ito, H., Koyama, A., Higuchi, T.: Polypharmacy and excessive dosing: psychiatrists’ perceptions of antipsychotic drug prescription. Br. J. Psychiatry 187, 243–247 (2005)PubMedCrossRefGoogle Scholar
  33. 33.
    Koyama, A., Ito, H., Nakanishi, M., et al.: Addition of antipsychotics to medication regimens during schizophrenic inpatient care. Psychiatry Clin. Neurosci. 62(1), 56–64 (2008)PubMedCrossRefGoogle Scholar
  34. 34.
    Muijen, M., Silverstone, T.: A comparative hospital survey of psychotropic drug prescribing. Br. J. Psychiatry 150, 501–504 (1987)PubMedCrossRefGoogle Scholar
  35. 35.
    Sim, K., Su, A., Chan, Y.H., et al.: Clinical correlates of antipsychotic polytherapy in patients with schizophrenia in Singapore. Psychiatry Clin. Neurosci. 58(3), 324–329 (2004)PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Lone Baandrup
    • 1
  • Jan Sørensen
    • 2
  • Henrik Lublin
    • 1
  • Merete Nordentoft
    • 3
  • Birte Glenthoj
    • 1
  1. 1.Centre for Neuropsychiatric Schizophrenia ResearchCopenhagen University Hospital, Mental Health Services - Capital Region of Denmark, GlostrupGlostrupDenmark
  2. 2.Centre for Applied Health Services Research and Technology AssessmentUniversity of Southern DenmarkOdenseDenmark
  3. 3.Copenhagen University Hospital, Mental Health Services - Capital Region of Denmark, BispebjergCopenhagen NVDenmark

Personalised recommendations