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A Systematic Review and Critical Appraisal of Economic Evaluations of Pharmacological Interventions for People with Bipolar Disorder

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Abstract

Background

Bipolar disorder (BD) is a chronic mood disorder that causes substantial psychological and financial burden. Various pharmacological treatments are effective in the management and prevention of acute episodes of BD. In an era of tighter healthcare budgets and a need for more efficient use of resources, several economic evaluations have evaluated the cost effectiveness of treatments for BD.

Objective

The aim of this study was to systematically review and appraise published economic evaluations of pharmacological interventions for BD.

Methods

A systematic search combining search terms specific to BD with a health economics search filter was conducted on six bibliographic databases (EMBASE, MEDLINE, PsycINFO, HTA, NHS EED, CENTRAL) in order to identify trial- or model-based full economic evaluations of pharmacological treatments of any phase of the disorder that were published between 1 January 1990 and 18 December 2015. Studies that met the inclusion criteria were critically appraised using the Quality of Health Economic Studies (QHES) checklist, and synthesised in a narrative way.

Results

The review included 19 economic studies, which varied with regard to the type and number of interventions assessed, the study design, the phase of treatment (acute or maintenance), the source of efficacy data and the method for evidence synthesis, the outcome measures, the time horizon and the countries/settings in which the studies were conducted. The study quality was variable but the majority of studies were of high or fair quality.

Conclusion

Pharmacological interventions are cost effective, compared with no treatment, in the management of BD, both in the acute and maintenance phases. However, it is difficult to draw safe conclusions on the relative cost effectiveness between drugs due to differences across studies and limitations characterising many of them. Future economic evaluations need to consider the whole range of treatment options available for the management of BD and adopt appropriate methods for evidence synthesis and economic modelling, to explore more robustly the relative cost effectiveness of pharmacological interventions for people with BD.

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References

  1. World Health Organization. The ICD-10 classification of mental and behavioural disorders. Clinical descriptions and diagnostic guidelines. WHO; 1992. http://www.who.int/classifications/icd/en/bluebook.pdf?ua=1. Accessed 17 Apr 2016.

  2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Publishing; 2013.

    Book  Google Scholar 

  3. Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2197–223.

    Article  PubMed  Google Scholar 

  4. McCrone P, Dhanasiri S, Patel A, Knapp M, Lawton-Smith S. Paying the price: the cost of mental health care in England to 2026. London: The King’s Fund; 2008.

    Google Scholar 

  5. Runge C, Grunze H. Annual costs of bipolar disorders in Germany. Nervenarzt. 2004;75(9):896–903.

    Article  CAS  PubMed  Google Scholar 

  6. Hakkaart-van Roijen L, Hoeijenbos MB, Regeer EJ, ten Have M, Nolen WA, Veraart CP, et al. The societal costs and quality of life of patients suffering from bipolar disorder in the Netherlands. Acta Psychiatr Scand. 2004;110(5):383–92.

    Article  CAS  PubMed  Google Scholar 

  7. Dilsaver SC. An estimate of the minimum economic burden of bipolar I and II disorders in the United States: 2009. J Affect Disord. 2011;129:79–83.

    Article  PubMed  Google Scholar 

  8. National Institute for Health and Care Excellence. Bipolar disorder: assessment and management. NICE clinical guideline 185. London: NICE; 2014.

    Google Scholar 

  9. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.

    Article  PubMed  PubMed Central  Google Scholar 

  10. National Collaborating Centre for Mental Health. Bipolar disorder: the assessment and management of bipolar disorder in adults, children and young people, in primary and secondary care. Commissioned by the National Institute for Health and Care Excellence. Leicester and London: The British Psychological Society and the Royal College of Psychiatrists; 2014.

  11. Ofman JJ, Sullivan SD, Neumann PJ, Chiou CF, Henning JM, Wade SW, et al. Examining the value and quality of health economic analyses: implications of utilizing the QHES. J Manag Care Pharm. 2003;9(1):53–61.

    PubMed  Google Scholar 

  12. Walker DG, Wilson RF, Sharma R, Bridges J, Niessen L, Bass EB, et al. Best practices for conducting economic evaluations in health care: a systematic review of quality assessment tools. Methods Research Report (prepared by John Hopkins University Evidence-Based Practice Center under contract no. 290-2007-10061-I), AHRQ Publication No. 12(13)-EHC132-EF. Rockville: Agency for Healthcare Research and Quality; 2012. http://www.effectivehealthcare.ahrq.gov/reports/final.cfm. Accessed 17 Apr 2016.

  13. Chiou CF, Hay JW, Wallace JF, Bloom BS, Neumann PJ, Sullivan SD, et al. Development and validation of a grading system for the quality of cost-effectiveness studies. Med Care. 2003;41(1):32–44.

    Article  PubMed  Google Scholar 

  14. Spiegel BM, Targownik LE, Kanwal F, Derosa V, Dulai GS, Gralnek IM, et al. The quality of published health economic analyses in digestive diseases: a systematic review and quantitative appraisal. Gastroenterology. 2004;127(2):403–11.

    Article  PubMed  Google Scholar 

  15. Foster WJ, Tufail W, Issa AM. The quality of pharmacoeconomic evaluations of age-related macular degeneration therapeutics: a systematic review and quantitative appraisal of the evidence. Br J Ophthalmol. 2010;94(9):1118–26.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Jones M, Lewis S, Parrott S, Coleman T. Systematic critical review of previous economic evaluations of smoking cessation during pregnancy. BMJ Open. 2015;5(11):e008998.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Pignone M, Saha S, Hoerger T, Lohr KN, Teutsch S, Mandelblatt J. Challenges in systematic reviews of economic analyses. Ann Intern Med. 2005;142(12 Pt 2):1073–9.

    Article  PubMed  Google Scholar 

  18. Ekman M, Lindgren P, Miltenburger C, Meier G, Locklear J. Cost effectiveness of quetiapine in patients with acute bipolar depression and in maintenance treatment after an acute depressive episode. Pharmacoeconomics. 2012;30(6):513–30.

    Article  PubMed  Google Scholar 

  19. Bridle C, Palmer S, Bagnall AM, Darba J, Duffy S, Sculpher M, et al. A rapid and systematic review and economic evaluation of the clinical and cost-effectiveness of newer drugs for treatment of mania associated with bipolar affective disorder. Health Technol Assess. 2004;8(19):iii–iv, 1–187.

  20. Caresano C, Di SG, Fagiolini A, Maina G, Perugi G, Ripellino C, et al. Cost-effectiveness of asenapine in the treatment of patients with bipolar I disorder with mixed episodes in an Italian context. Adv Ther. 2014;31(8):873–90.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Klok RM, Al Hadithy AF, van Schayk NP, Antonisse AJ, Caro JJ, Brouwers JR, et al. Pharmacoeconomics of quetiapine for the management of acute mania in bipolar I disorder. Expert Rev Pharmacoecon Outcomes Res. 2007;7(5):459–67.

    Article  PubMed  Google Scholar 

  22. Namjoshi MA, Rajamannar G, Jacobs T, Sanger TM, Risser R, Tohen MF, et al. Economic, clinical, and quality-of-life outcomes associated with olanzapine treatment in mania. Results from a randomized controlled trial. J Affect Disord. 2002;69(1–3):109–18.

    Article  PubMed  Google Scholar 

  23. Revicki DA, Paramore LC, Sommerville KW, Swann AC, Zajecja JM, Depakote Comparator Study Group. Divalproex sodium versus olanzapine in the treatment of acute mania in bipolar disorder: health-related quality of life and medical cost outcomes. J Clin Psychiatry. 2003;64(3):288–94.

    Article  CAS  PubMed  Google Scholar 

  24. Sawyer L, Azorin JM, Chang S, Rinciog C, Guiraud-Diawara A, Marre C, et al. Cost-effectiveness of asenapine in the treatment of bipolar I disorder patients with mixed episodes. J Med Econ. 2014;17(7):508–19.

    Article  PubMed  Google Scholar 

  25. Uttley L, Kearns B, Ren S, Stevenson M. Aripiprazole for the treatment and prevention of acute manic and mixed episodes in bipolar I disorder in children and adolescents: a NICE single technology appraisal. Pharmacoeconomics. 2013;31(11):981–90.

    Article  PubMed  Google Scholar 

  26. Rajagopalan K, Meyer K, O’Day K, Denno M, Loebel A. Cost-effectiveness of lurasidone vs. quetiapine extended-release (XR) in patients with bipolar depression. J Med Econ. 2015;18(10):821–7.

    Article  PubMed  Google Scholar 

  27. Calvert NW, Burch SP, Fu AZ, Reeves P, Thomson TR. The cost-effectiveness of lamotrigine in the maintenance treatment of adults with bipolar I disorder. J Manag Care Pharm. 2006;12(4):322–30.

    PubMed  Google Scholar 

  28. Fajutrao L, Paulsson B, Liu S, Locklear J. Cost-effectiveness of quetiapine plus mood stabilizers compared with mood stabilizers alone in the maintenance therapy of bipolar I disorder: results of a Markov model analysis. Clin Ther. 2009;31(Pt 1):1456–68.

    Article  PubMed  Google Scholar 

  29. McKendrick J, Cerri KH, Lloyd A, D’Ausilio A, Dando S, Chinn C. Cost effectiveness of olanzapine in prevention of affective episodes in bipolar disorder in the United Kingdom. J Psychopharmacol. 2007;21(6):588–96.

    Article  CAS  PubMed  Google Scholar 

  30. Revicki DA, Hirschfeld RM, Aheam EP, Weisler RH, Palmer C, Keck PE Jr. Effectiveness and medical costs of divalproex versus lithium in the treatment of bipolar disorder: results of a naturalistic clinical trial. J Affect Disord. 2005;86(2–3):183–93.

    Article  CAS  PubMed  Google Scholar 

  31. Soares-Weiser K, Bravo Vergel Y, Beynon S, Dunn G, Barbieri M, Duffy S, et al. A systematic review and economic model of the clinical effectiveness and cost-effectiveness of interventions for preventing relapse in people with bipolar disorder. Health Technol Assess. 2007;11(39):iii–iv, ix–206.

  32. Woodward TC, Tafesse E, Quon P, Kim J, Lazarus A. Cost-effectiveness of quetiapine with lithium or divalproex for maintenance treatment of bipolar I disorder. J Med Econ. 2009;12(4):259–68.

    Article  PubMed  Google Scholar 

  33. Woodward TC, Tafesse E, Quon P, Lazarus A. Cost effectiveness of adjunctive quetiapine fumarate extended-release tablets with mood stabilizers in the maintenance treatment of bipolar I disorder. Pharmacoeconomics. 2010;28(9):751–64.

    Article  PubMed  Google Scholar 

  34. Chisholm D, van Ommeren M, Ayuso-Mateos JL, Saxena S. Cost-effectiveness of clinical interventions for reducing the global burden of bipolar disorder. Br J Psychiatry. 2005;187:559–67.

    Article  PubMed  Google Scholar 

  35. Chisholm D, Saxena S. Cost effectiveness of strategies to combat neuropsychiatric conditions in sub-Saharan Africa and South East Asia: mathematical modelling study. BMJ. 2012;344:e609.

    Article  PubMed  PubMed Central  Google Scholar 

  36. National Institute for Health and Care Excellence. Process and methods guides. Guide to the methods of technology appraisal. London: NICE; 2013.

    Google Scholar 

  37. Lamers LM, Bouwmans CA, van Straten A, Donker MC, Hakkaart L. Comparison of EQ-5D and SF-6D utilities in mental health patients. Health Econ. 2006;15(11):1229–36.

    Article  CAS  PubMed  Google Scholar 

  38. Brazier J, Roberts J, Tsuchiya A, Busschbach J. A comparison of the EQ-5D and SF-6D across seven patient groups. Health Econ. 2004;13(9):873–84.

    Article  PubMed  Google Scholar 

  39. Revicki DA, Hanlon J, Martin S, Gyulai L, Nassir Ghaemi S, Lynch F, et al. Patient-based utilities for bipolar disorder-related health states. J Affect Disord. 2005;87(2–3):203–10.

    Article  PubMed  Google Scholar 

  40. Hayhurst H, Palmer S, Abbott R, Johnson T, Scott J. Measuring health-related quality of life in bipolar disorder: relationship of the EuroQol (EQ-5D) to condition-specific measures. Qual Life Res. 2006;15(7):1271–80.

    Article  PubMed  Google Scholar 

  41. Dolan P. Modeling valuations for EuroQol health states. Med Care. 1997;35(11):1095–108.

    Article  CAS  PubMed  Google Scholar 

  42. Heeg B, Buskens E, Botteman M, Caleo S, Ingham M, Damen J, et al. The cost-effectiveness of atypicals in the UK. Value Health. 2008;11(7):1007–21.

    Article  PubMed  Google Scholar 

  43. Briggs A, Wild D, Lees M, Reaney M, Dursun S, Parry D, et al. Impact of schizophrenia and schizophrenia treatment-related adverse events on quality of life: direct utility elicitation. Health Qual Life Outcomes. 2008;6:105.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Mangalore R. The utility approach to valuing health states in schizophrenia. Mental Health Res Rev. 2000;7:11–5.

    Google Scholar 

  45. Boyle SE, Jones GL, Walters SJ. Physical activity, quality of life, weight status and diet in adolescents. Qual Life Res. 2010;19(7):943–54.

    Article  PubMed  Google Scholar 

  46. Sobocki P, Ekman M, Agren H, Krakau I, Runeson B, Martensson B, et al. Health-related quality of life measured with EQ-5D in patients treated for depression in primary care. Value Health. 2007;10(2):153–60.

    Article  PubMed  Google Scholar 

  47. Brazier J, Roberts J, Deverill M. The estimation of a preference-based measure of health from the SF-36. J Health Econ. 2002;21(2):271–92.

    Article  PubMed  Google Scholar 

  48. Brazier J, Connell J, Papaioannou D, Mukuria C, Mulhern B, Peasgood T, et al. A systematic review, psychometric analysis and qualitative assessment of generic preference-based measures of health in mental health populations and the estimation of mapping functions from widely used specific measures. Health Technol Assess. 2014;18(34):vii–viii, xiii–xxv, 1–188.

  49. Jonsson B. Ten arguments for a societal perspective in the economic evaluation of medical innovations. Eur J Health Econ. 2009;10(4):357–9.

    Article  PubMed  Google Scholar 

  50. Sculpher M. The role and estimation of productivity costs in economic evaluation. In: Drummond M, McGuire A, editors. Economic evaluation in health care. Merging theory with practice. New York: Oxford University Press; 2001. p. 94–112.

    Google Scholar 

  51. Knies S, Severens JL, Ament AJ, Evers SM. The transferability of valuing lost productivity across jurisdictions. Differences between national pharmacoeconomic guidelines. Value Health. 2010;13(5):519–27.

    Article  PubMed  Google Scholar 

  52. Higgins JP, Green S, editors. Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration; 2011. http://www.cochrane-handbook.org. Accessed 17 Sep 2016.

  53. Briggs A. Economic evaluation and clinical trials: size matters. BMJ. 2000;321(7273):1362–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Faria R, Gomes M, Epstein D, White IR. A guide to handling missing data in cost-effectiveness analysis conducted within randomised controlled trials. Pharmacoeconomics. 2014;32(12):1157–70.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Barton P, Bryan S, Robinson S. Modelling in the economic evaluation of health care: selecting the appropriate approach. J Health Serv Res Policy. 2004;9:110–8.

    Article  PubMed  Google Scholar 

  56. Petrou S, Gray A. Economic evaluation using decision analytical modelling: design, conduct, analysis, and reporting. BMJ. 2011;342:d1766.

    Article  PubMed  Google Scholar 

  57. Sonnenberg FA, Beck JB. Markov models in medical decision making: a practical guide. Med Decis Making. 1993;13:322–38.

    Article  CAS  PubMed  Google Scholar 

  58. Kessing LV, Hansen MG, Andersen PK, Angst J. The predictive effect of episodes on the risk of recurrence in depressive and bipolar disorders: a life-long perspective. Acta Psychiatr Scand. 2004;109(5):339–44.

    Article  CAS  PubMed  Google Scholar 

  59. Caro JJ. Pharmacoeconomic analyses using discrete event simulation. Pharmacoeconomics. 2005;23:323–32.

    Article  PubMed  Google Scholar 

  60. Mohiuddin S. A systematic and critical review of model-based economic evaluations of pharmacotherapeutics in patients with bipolar disorder. Appl Health Econ Health Policy. 2014;12(4):359–72.

    Article  PubMed  Google Scholar 

  61. Newcomer JW. Antipsychotic medications: metabolic and cardiovascular risk. J Clin Psychiatry. 2007;68(Suppl 4):8–13.

    PubMed  Google Scholar 

  62. Yumru M, Savas HA, Kurt E, Kaya MC, Selek S, Savas E, et al. Atypical antipsychotics related metabolic syndrome in bipolar patients. J Affect Disord. 2007;98(3):247–52.

    Article  CAS  PubMed  Google Scholar 

  63. DuMouchel W, Fram D, Yang X, Mahmoud RA, Grogg AL, Engelhart L, et al. Antipsychotics, glycemic disorders, and life-threatening diabetic events: a Bayesian data-mining analysis of the FDA adverse event reporting system (1968–2004). Ann Clin Psychiatry. 2008;20(1):21–31.

    Article  PubMed  Google Scholar 

  64. Guo JJ, Keck PE Jr, Corey-Lisle PK, Li H, Jiang D, Jang R, et al. Risk of diabetes mellitus associated with atypical antipsychotic use among patients with bipolar disorder: a retrospective, population-based, case–control study. J Clin Psychiatry. 2006;67(7):1055–61.

    Article  CAS  PubMed  Google Scholar 

  65. McKnight RF, Adida M, Budge K, Stockton S, Goodwin GM, Geddes JR. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379(9817):721–8.

    Article  CAS  PubMed  Google Scholar 

  66. Osby U, Brandt L, Correia N, Ekbom A, Sparen P. Excess mortality in bipolar and unipolar disorder in Sweden. Arch Gen Psychiatry. 2001;58(9):844–50.

    Article  CAS  PubMed  Google Scholar 

  67. Tondo L, Isacsson G, Baldessarini R. Suicidal behaviour in bipolar disorder: risk and prevention. CNS Drugs. 2003;17(7):491–511.

    Article  CAS  PubMed  Google Scholar 

  68. Rihmer Z, Kiss K. Bipolar disorders and suicidal behaviour. Bipolar Disord. 2002;4(Suppl 1):21–5.

    Article  PubMed  Google Scholar 

  69. Cipriani A, Hawton K, Stockton S, Geddes JR. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. BMJ. 2013;346:f3646.

    Article  PubMed  Google Scholar 

  70. Caldwell DM, Ades AE, Higgins JP. Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ. 2005;331(7521):897–900.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Mavridis D, Giannatsi M, Cipriani A, Salanti G. A primer on network meta-analysis with emphasis on mental health. Evid Based Ment Health. 2015;18(2):40–6.

    Article  PubMed  Google Scholar 

  72. Lu G, Ades AE. Assessing evidence consistency in mixed treatment comparisons. J Am Stat Assoc. 2006;101:447–59.

    Article  CAS  Google Scholar 

  73. Briggs A, Sculpher M, Claxton K. Decision modelling for health economic evaluation. New York: Oxford University Press; 2006.

    Google Scholar 

  74. Fenwick E, Claxton K, Sculpher M. Representing uncertainty: the role of cost-effectiveness acceptability curves. Health Econ. 2001;10(8):779–87.

    Article  CAS  PubMed  Google Scholar 

  75. Fenwick E, O’Brien BJ, Briggs A. Cost-effectiveness acceptability curves: facts, fallacies and frequently asked questions. Health Econ. 2004;13(5):405–15.

    Article  PubMed  Google Scholar 

  76. Desgagne A, Castilloux AM, Angers JF, LeLorier J. The use of the bootstrap statistical method for the pharmacoeconomic cost analysis of skewed data. PharmacoEconomics. 1998;13(5 Pt 1):487–97.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors wish to thank Eric Slade, who agreed to act as a third reviewer to resolve any disagreements between the authors regarding the selection of eligible studies for the review and the quality assessment of included studies.

Author Contributions

IM designed the systematic review and carried out the literature searches. Both authors  assessed the eligibility of studies against inclusion criteria; IM did the data extraction, which was subsequently checked by JL. Both authors undertook the quality appraisal of included studies and interpreted the review findings. IM drafted the manuscript to which JL contributed. Both authors approved the final version of the manuscript.

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Correspondence to Ifigeneia Mavranezouli.

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Ifigeneia Mavranezouli and Joran Lokkerbol declare they have no conflicts of interest.

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Mavranezouli, I., Lokkerbol, J. A Systematic Review and Critical Appraisal of Economic Evaluations of Pharmacological Interventions for People with Bipolar Disorder. PharmacoEconomics 35, 271–296 (2017). https://doi.org/10.1007/s40273-016-0473-1

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