, Volume 28, Issue 9, pp 751–764 | Cite as

Cost Effectiveness of Adjunctive Quetiapine Fumarate Extended-Release Tablets with Mood Stabilizers in the Maintenance Treatment of Bipolar I Disorder

  • Tatia Chay Woodward
  • Eskinder Tafesse
  • Peter Quon
  • Arthur Lazarus
Original Research Article


Background: Bipolar I disorder (BPD I) is a recurrent illness that affects 1%of the US population and constitutes a large economic burden. However, few studies have investigated the cost effectiveness of maintenance treatment options for BPD I.

Objective: To determine the cost effectiveness of maintenance treatment with quetiapine fumarate extended-release (XR) tablets in combination with mood stabilizers (lithium or divalproex) in comparison with the following treatments: placebo in combination with lithium or divalproex; no maintenance treatment; lithium monotherapy; lamotrigine monotherapy; olanzapine monotherapy; and aripiprazole monotherapy.

Methods: The analysis was conducted from the societal and payer perspectives in the US, using a Markov model. The model simulated a cohort of 1000 stabilized BPD I patients and estimated the quarterly risk in three health states: euthymia, mania and depression. Efficacy data were derived from two randomized, double-blind trials comparing quetiapine + lithium/divalproex with placebo + lithium/divalproex for up to 2 years, as well as other published literature. Resource data were extracted from published literature. Drug costs, hospitalizations and physician visits were among the direct costs. Indirect costs included absenteeism, and mortality rates included suicide. Benefits and costs were discounted at 3% and the price reference year was 2009. Endpoints included number of acute mood episodes, hospitalizations due to an acute mood event and costs per QALY. Probabilistic sensitivity analysis (PSA) was conducted to evaluate uncertainty in the model inputs.

Results: Treatment with quetiapine XR+ lithium/divalproex was associated with reductions in acute mania (46%), acute depression (41%) and related hospitalizations (44%) compared with placebo + lithium/divalproex, and similar reductions in events were observed relative to lithium monotherapy. In the base-case analysis from the payer perspective, the discounted incremental cost per QALY for quetiapine XR+ lithium/divalproex compared with placebo + lithium/divalproex was $US22 959, and compared with lithium monotherapy was $US100 235, while all other comparators were dominated. PSA showed these results to be robust to select assumptions. Conclusions: Quetiapine XR+ lithium/divalproex may be a cost-effective maintenance treatment option for patients with BPD I.

Supplementary material

40273_2012_28090751_MOESM1_ESM.pdf (159 kb)
Supplementary material, approximately 163 KB.


  1. 1.
    American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002 Apr; 159 (4 Suppl.): 1–50Google Scholar
  2. 2.
    Merikangas KR, Akiskal HS, Angst J, et al. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry 2007 May; 64 (5): 543–52PubMedCrossRefGoogle Scholar
  3. 3.
    Revicki DA, Matza LS, Flood E, et al. Bipolar disorder and health-related quality of life: review of burden of disease and clinical trials. Pharmacoeconomics 2005; 23 (6): 583–94PubMedCrossRefGoogle Scholar
  4. 4.
    Sharma R, Markar HR. Mortality in affective disorder. J Affect Disord 1994 Jun; 31 (2): 91–6PubMedCrossRefGoogle Scholar
  5. 5.
    Kleinman L, Lowin A, Flood E, et al. Costs of bipolar disorder. Pharmacoeconomics 2003; 21 (9): 601–22PubMedCrossRefGoogle Scholar
  6. 6.
    Begley CE, Annegers JF, Swann AC, et al. The lifetime cost of bipolar disorder in the US: an estimate for new cases in 1998. Pharmacoeconomics 2001; 19 (5 Pt 1): 483–95PubMedCrossRefGoogle Scholar
  7. 7.
    Wyatt RJ, Henter I. An economic evaluation of manicdepressive illness: 1991. Soc Psychiatry Psychiatr Epidemiol 1995 Aug; 30 (5): 213–9PubMedGoogle Scholar
  8. 8.
    McIntyre RS, Woldeyohannes HO, Yasgur BS, et al. Maintenance treatment in bipolar disorder: a focus on aripiprazole. Expert Rev Neurother 2007 Aug; 7 (8): 919–25PubMedCrossRefGoogle Scholar
  9. 9.
    Suppes T, Vieta E, Liu S, et al., Trial 127 investigators. Maintenance treatment for patients with bipolar I disorder: results from a North American study of quetiapine in combination with lithium or divalproex (trial 127). Am J Psychiatry 2009 Apr; 166 (4): 476–88Google Scholar
  10. 10.
    Vieta E, Suppes T, Eggens I, et al. Efficacy and safety of quetiapine in combination with lithium or divalproex for maintenance of patients with bipolar I disorder (International Trial 126). J Affect Disord 2008 Aug; 109 (3): 251–63PubMedCrossRefGoogle Scholar
  11. 11.
    Figueroa C, Brecher M, Hamer-Maansson JE, et al. Pharmacokinetic profiles of extended release quetiapine fumarate compared with quetiapine immediate release. Prog Neuropsychopharmacol Biol Psychiatry 2009 Mar 17; 33 (2): 199–204PubMedCrossRefGoogle Scholar
  12. 12.
    Calvert NW, Burch SP, Fu AZ, et al. The cost-effectiveness of lamotrigine in the maintenance treatment of adults with bipolar I disorder. J Manag Care Pharm 2006 May; 12 (4): 322–30PubMedGoogle Scholar
  13. 13.
    Bowden CL, Calabrese JR, Sachs G, et al.Aplacebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder. Arch Gen Psychiatry 2003 Apr; 60 (4): 392–400PubMedCrossRefGoogle Scholar
  14. 14.
    Prescribing information: Seroquel XR. Wilmington (DE): AstraZeneca Pharmaceuticals LP [online]. Available from URL: [Accessed 2009 Oct 1]
  15. 15.
    Tohen M, Calabrese JR, Sachs GS, et al. Randomized, placebo-controlled trial of olanzapine as maintenance therapy in patients with bipolar I disorder responding to acute treatment with olanzapine. Am J Psychiatry 2006 Feb; 163 (2): 247–56PubMedCrossRefGoogle Scholar
  16. 16.
    Keck Jr PE, Calabrese JR, McQuade RD, et al. A randomized, double-blind, placebo-controlled 26-week trial of aripiprazole in recently manic patients with bipolar I disorder. J Clin Psychiatry 2006 Apr; 67 (4): 626–37PubMedCrossRefGoogle Scholar
  17. ]17.
    US Department of Health and Human Services; Centers for Disease Control and Prevention. Deaths: final data for 2004. Natl Vital Stat Rep 2007 Aug 21; 55 (19) [online]. Available from URL: [Accessed 2010 Jun 3]
  18. 18.
    Simon GE, Hunkeler E, Fireman B, et al. Risk of suicide attempt and suicide death in patients treated for bipolar disorder. Bipolar Disord 2007 Aug; 9 (5): 526–30PubMedCrossRefGoogle Scholar
  19. 19.
    Fleurence RL, Hollenbeak CS. Rates and probabilities in economic modelling: transformation, translation and appropriate application. Pharmacoeconomics 2007; 25 (1):3–6PubMedCrossRefGoogle Scholar
  20. 20.
    Calabrese JR, Bowden CL, Sachs G, et al. A placebocontrolled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder. J Clin Psychiatry 2003 Sep; 64 (9): 1013–24PubMedCrossRefGoogle Scholar
  21. 21.
    Brazier J, Roberts J, Deverill M. The estimation of a preference-based measure of health from the SF-36. J Health Econ 2002 Mar; 21 (2): 271–92PubMedCrossRefGoogle Scholar
  22. 22.
    Red Book™ for Windows®. Version 61127. Montvale (NJ): Thomson Reuters, 2009Google Scholar
  23. 23.
    Kessler RC, Akiskal HS, Ames M, et al. Prevalence and effects of mood disorders on work performance in a nationally representative sample of US workers. Am J Psychiatry 2006 Sep; 163 (9): 1561–8PubMedCrossRefGoogle Scholar
  24. 24.
    US Department of Labor, Bureau of Labor Statistics. Consumer price indexes [online]. Available from URL: [Accessed 2007 Oct 10]Google Scholar
  25. 25.
    Hirth RA, Chernew ME, Miller E, et al. Willingness to pay for a quality-adjusted life year: in search of a standard. Med Decis Making 2000 Jul; 20 (3): 332–42PubMedCrossRefGoogle Scholar
  26. 26.
    Fleurence RL, Chatterton ML, Dixon JM, et al. Economic outcomes associated with atypical antipsychotics in bipolar disorder: a systematic review. Prim Care Companion J Clin Psychiatry 2007; 9 (6): 419–28PubMedCrossRefGoogle Scholar
  27. 27.
    Soares-Weiser K, Bravo Vergel Y, Beynon S, et al. A systematic review and economic model of the clinical effectivenes and cost-effectiveness of interventions for preventing relapse in people with bipolar disorder. Health Technol Assess 2007; 11 (39): iii-iv, ix–206Google Scholar
  28. 28.
    McKendrick J, Cerri KH, Lloyd A, et al. Cost effectiveness of olanzapine in prevention of affective episodes in bipolar disorder in the United Kingdom. J Psychopharmacol 2007 Aug; 21 (6): 588–96PubMedCrossRefGoogle Scholar
  29. 29.
    Kupfer DJ, Frank E, Grochocinski VJ, et al. Stabilization in the treatment of mania, depression and mixed states. Acta Neuropsychiatr 2000; 12: 110–4Google Scholar
  30. 30.
    Kessing LV, Munk-Jorgensen P. Does type of first contact in depressive and bipolar disorders predict subsequent hospitalisation and risk of suicide? J Affect Disord 2004 Nov 15; 83 (1): 65–71PubMedCrossRefGoogle Scholar
  31. 31.
    Gonzalez-Pinto AM, Dardennes R, de Zélicourt M, et al. Inpatient care costs of patients with bipolar I disorder: a comparison between two European centers. J Affect Disord 2010 Nov; 121 (1-2): 152–5PubMedCrossRefGoogle Scholar
  32. 32.
    Revicki DA, Wood M. Patient-assigned health state utilities for depression-related outcomes: differences by depression severity and antidepressant medications. J Affect Disord 1998 Feb; 48 (1): 25–36PubMedCrossRefGoogle Scholar
  33. 33.
    McIntyre RS, Konarski JZ. Tolerability profiles of atypical antipsychotics in the treatment of bipolar disorder. J Clin Psychiatry 2005; 66 Suppl. 3: 28–36PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2010

Authors and Affiliations

  • Tatia Chay Woodward
    • 1
  • Eskinder Tafesse
    • 2
  • Peter Quon
    • 1
  • Arthur Lazarus
    • 2
  1. 1.United Biosource CorporationBethesdaUSA
  2. 2.AstraZeneca Pharmaceuticals LPWilmingtonUSA

Personalised recommendations