PharmacoEconomics

, Volume 24, Issue 7, pp 683–694 | Cite as

Tapering Off Benzodiazepines in Long-Term Users

An Economic Evaluation
  • Richard C. Oude Voshaar
  • Paul F. M. Krabbe
  • Wim J. M. J. Gorgels
  • Eddy M. M. Adang
  • Anton J. L. M. van Balkom
  • Eloy H. van de Lisdonk
  • Frans G. Zitman
Original Research Article

Abstract

Background: Discontinuation of benzodiazepine usage has never been evaluated in economic terms. This study aimed to compare the relative costs and outcomes of tapering off long-term benzodiazepine use combined with group cognitive behavioural therapy (TO+CBT), tapering off alone (TOA) and usual care.

Method: A randomised controlled trial was conducted, incorporating a costeffectiveness analysis from a societal as well as a pharmaceutical perspective.

The cost of intervention treatment, prescribed drugs, healthcare services, productivity loss, and patients’ costs were measured using drug prescription data and cost diaries. Costs were indexed at 2001 prices. The principal outcome was the proportion of patients able to discontinue benzodiazepine use during the 18-month follow-up. A secondary outcome measure was quality of life (Health Utility Index Mark III [HUI-3] and the Medical Outcomes Study 36-item Short-Form Health Survey [SF-36]).

Results: A total of 180 patients were randomised to one of TO+CBT (n = 73), TOA (n = 73) or usual care (n = 34). Intervention treatment costs were an average of €172.99 per patient for TO+CBT and €69.50 per patient for TOA. Both treatment conditions significantly reduced benzodiazepine costs during follow-up compared with usual care. The incremental cost-effectiveness ratios (ICERs) showed that, for each incremental 1% successful benzodiazepine discontinuation, TO+CBT cost €10.30–62.53 versus usual care, depending on the study perspective. However, TO+CBT was extendedly dominated or was dominated by TOA. This resulted in ICERs of €0.57, €10.21 and €48.92 for TOA versus usual care from the limited pharmaceutical, comprehensive pharmaceutical and societal perspective, respectively.

Conclusions: TO+CBT and TOA both led to a reduction in benzodiazepine costs. However, it remains uncertain which healthcare utilisation has a causal relationship with long-term benzodiazepine consumption or its treatment. Although the ICERs indicated better cost effectiveness for TOA than for TO+CBT, the differences were relatively small. The addition of group CBT to tapering off had no clinical or economic advantages. Extrapolation of our data showed that the investment in TOA was paid back after 19 months when corrected for treatment gain with usual care.

Keywords

Usual Care Group Cognitive Behavioural Therapy Cost Diary Usual Care Control Group Successful Discontinuation 

Notes

Acknowledgements

The study was supported by the Dutch Health Care Insurance Council, The Hague, The Netherlands.

The roles each author played in the conduct of the study are as follows.

R.C. Oude Voshaar: critique and revision of design; elaboration of intervention content; recruitment and monitoring of GPs and psychologists; acquisition and analysis of data; drafting the article.

P.F.M. Krabbe: critique and revision of design with respect to QOL; monitoring data acquisition; QOL data analyses; critical revision of article.

W.J.M.J. Gorgels: critique and revision of design; elaboration of intervention content; acquisition and monitoring of GPs; acquisition of data; critical revision of article.

E.M.M. Adang: critique and revision of design with respect to cost effectiveness; monitoring data acquisition; cost-effectiveness data analyses; interpretation of analyses, critical revision of article.

A.J.L.M. van Balkom: acquisition of funding; initial concept and design; elaboration of intervention content; interpretation of analyses, critique and revision of article.

E.H. van de Lisdonk: acquisition of funding; initial concept and design; elaboration of intervention content; interpretation of analyses, critique and revision of article.

F.G. Zitman: acquisition of funding; intial concept and design; elaboration of intervention content; interpretation of analyses; critique and revision of article.

None of the authors have potential conflicts of interest relevant to the contents of the study.

References

  1. 1.
    Taylor S, McCracken CFM, Wilson KCM. Extent and appropriateness of benzodiazepine use. Br J Psychiatry 1998; 173: 433–438PubMedCrossRefGoogle Scholar
  2. 2.
    Tu K, Marrrlani MM, Hux JE, et al. Progressive trends in the prevalence of benzodiazepine prescribing in older people in Ontario, Canada. J Am Geriatr Soc 2001; 49: 1341–1345PubMedCrossRefGoogle Scholar
  3. 3.
    Zandstra SM, Führer JW, Van de Lisdonk EH, et al. Different study criteria affect the prevalence of benzodiazepine use. Soc Psychiatry Psychiatr Epidemiol 2002; 37 (3): 139–144PubMedCrossRefGoogle Scholar
  4. 4.
    USA Food and Drug Administration. Prescribing of minor tranquillizers. FDA Drug Bull 1980; 10: 2–3Google Scholar
  5. 5.
    Committee on the Review of Medicines. Systematic review of the benzodiazepines. BMJ 1980; 1: 910–912Google Scholar
  6. 6.
    Knuistingh-Neven A, de Graaff WJ, Lucassen PLBJ, et al. NHG-standaard Slapeloosheid en slaapmiddelen. Huisarts Wet 1992; 35: 212–219Google Scholar
  7. 7.
    Neomagus Gill, Terluin B, Aulbers LPJ, et al. NHG-standaard Angststoornissen. Huisarts Wet 1997; 40: 167–175Google Scholar
  8. 8.
    Ashton H. Guidelines for the rational use of benzodiazepines: when and what to use. Drugs 1994; 48: 25–40PubMedCrossRefGoogle Scholar
  9. 9.
    Kan CC, Breteler MH, Zitman FG. High prevalence of benzodiazepine dependence in out-patient users, based on the DSM-III-R and ICD-10 criteria. Acta Psychiatr Scand 1997; 96: 85–93PubMedCrossRefGoogle Scholar
  10. 10.
    Rummans TA, Davis Jr LJ, Morse RM, et al. Learning and memory impairment in older, detoxified, benzodiazepine-dependent patients. Mayo Clin Proc 1993; 68: 731–737PubMedCrossRefGoogle Scholar
  11. 11.
    Tata PR, Rollings J, Collins M, et al. Lack of cognitive recovery following withdrawal from long-term benzodiazepine use. Psychol Med 1994; 24: 203–213PubMedCrossRefGoogle Scholar
  12. 12.
    Paterniti S, Dufouil C, Alperovitch A. Long-term benzodiazepine use and cognitive decline in the elderly: the epidemiology of vascular aging study. J Clin Psychopharmacol 2002; 22: 285–293PubMedCrossRefGoogle Scholar
  13. 13.
    Rickels K, Lucki I, Schweizer E, et al. Psychomotor performance of long-term benzodiazepine users before, during, and after benzodiazepine discontinuation. J Clin Psychopharmacol 1999; 19: 107–113PubMedCrossRefGoogle Scholar
  14. 14.
    Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people: a systematic review and meta-analysis. I: psychotropic drugs. J Am Geriatr Soc 1999; 47: 30–39PubMedGoogle Scholar
  15. 15.
    Hemmelgarn B, Suissa S, Huang A, et al. Benzodiazepine use and the risk of motor vehicle crash in the elderly. JAMA 1997; 278: 27–31PubMedCrossRefGoogle Scholar
  16. 16.
    Piepenbrink JF, editor. College voor zorgverzekeringen. Use of benzodiazepines 1993–1998 [in German]. Amstelveen: Geneesmiddelen Informatie Project (GIP-signaal), 2000Google Scholar
  17. 17.
    Herings RMC. Drugs as determinants of accidents [in German]. Utrecht: Faculteit Pharmacie, 1994Google Scholar
  18. 18.
    Panneman MJ, Goettsch WG, Kramarz P, et al. The costs of benzodiazepine-associated hospital-treated fall injuries in the EU: a Phanno study. Drugs Aging 2003; 20 (11): 833–839PubMedCrossRefGoogle Scholar
  19. 19.
    Cormack MA, Howells E. Factors linked to the prescribing of benzodiazepines by general practice principals and trainees. Fam Pract 1992; 9 (4): 466–471PubMedCrossRefGoogle Scholar
  20. 20.
    Holton A, Riley P, Tyrer P. Factors predicting long-term outcome after chronic benzodiazepine therapy. J Affect Disord 1992; 24 (4): 245–252PubMedCrossRefGoogle Scholar
  21. 21.
    Burke KC, Meek WJ, Krych R, et al. Medical services use by patients before and after detoxification from benzodiazepine dependence. Psychiatr Serv 1995; 46 (2): 157–160PubMedGoogle Scholar
  22. 22.
    Bashir K, King M, Ashworth M. Controlled evaluation of brief intervention by general practitioners to reduce chronic use of benzodiazepines. Br J Gen Pract 1994; 44 (386): 408–412PubMedGoogle Scholar
  23. 23.
    Morgan JD, Wright DJ, Chrystyn H. Pharmacoeconomic evaluation of a patient education letter aimed at reducing long-term prescribing of benzodiazepines. Pharm World Sci 2002; 24 (6), 231–235PubMedCrossRefGoogle Scholar
  24. 24.
    Ashton H. Benzodiazepine withdrawal: outcome in 50 patients. Br J Addict 1987; 82 (6): 665–671PubMedCrossRefGoogle Scholar
  25. 25.
    Rickels K, Case WG, Schweizer E, et al. Long-term benzodiazepine users 3 years after participation in a discontinuation program. Am J Psychiatry 1991; 148 (6): 757–761PubMedGoogle Scholar
  26. 26.
    Gorgels WJ, Oude Voshaar RC, Mol AJ, et al. Discontinuation of long-term benzodiazepine use by sending a letter to users in family practice: a prospective controlled intervention study. Drug Alcohol Depend 2005; 78 (1): 49–56PubMedCrossRefGoogle Scholar
  27. 27.
    Oude Voshaar RC, Gorgels WJ, Mol AJ, et al. Tapering off long-term benzodiazepine use with or without simultaneous group cognitive-behavioural therapy: three-condition randomised controlled trial. Br J Psychiatry 2003; 182: 498–502CrossRefGoogle Scholar
  28. 28.
    Oude Voshaar RC, Gorgels WJMJ, Mol AJJ, et al. Long-term outcome of three-condition, usual care controlled controlled, randomised benzodiazepine discontinuation study. Br J Psychiatry 2006; 188: 188–189CrossRefGoogle Scholar
  29. 29.
    Furlong WJ, Feeny DH, Torrance GW, et al. Multiplicative multi-attribute utility function for the health utility index mark 3 (HUI3) system: a technical report. Working paper 98-11. Toronto (ON): McMaster University Centre for Health Economics and Policy Analysis, 1998Google Scholar
  30. 30.
    Furlong WJ, Feeny DH, Torrance GW, et al. The Health Utilities Index (HUI) system for assessing health-related quality of life in clinical studies. Ann Med 2001; 33: 375–384PubMedCrossRefGoogle Scholar
  31. 31.
    Ware JE, Sherbourne CD. The MOS 36-item Short-Form Health Survey (SF-36): I. Conceptual framework and item selection. Med Care 1992; 30: 473–483PubMedCrossRefGoogle Scholar
  32. 32.
    Van der Zee KI, Snaderman R. Measuring general health status with the RAND-36. Users manual [in German]. Groningen: Nothern Center of Health Care Research, 1993Google Scholar
  33. 33.
    WHO Collaborating Centre for Drugs Statistics Methodology. Guidelines ATC classification and DDD assignment. 1st ed. Oslo: WHO/NCM, 1996Google Scholar
  34. 34.
    Oostenbrink JB, Koopmanschap MA, Rutten FFH. Handleiding voor kostenonderzoek, methoden en richtlijnprijzen voor economische evaluaties in de gezondheidszorg. Amstelveen: College voor zorgverzekeringen, 2000Google Scholar
  35. 35.
    Commissie Farmaceutische Hulp van bet College voor zorgverzekekeringen (CVZ). Farmacotherapeutische kompas. Amstelveen: CVZ, 2002: 53–66, 69-81Google Scholar
  36. 36.
    CBS statistieken, bron statline [online]. Available from URL:http://www.cbs.nl [Accessed 2002 Aug]Google Scholar
  37. 37.
    Rodrigo EK, King ME, Williams P. Health of long-term benzodiazepine users. BMJ 1988; 296: 603–606PubMedCrossRefGoogle Scholar
  38. 38.
    Simpson RJ, Power KG, Wallace LA. Controlled comparison of the characteristics of long-term benzodiazepine users in general practice. Br J Gen Pract 1990; 40: 22–26PubMedGoogle Scholar
  39. 39.
    Van Hulten R, Teeuw KB, Bakker A, et al. Health-related quality of life in current benzodiazepine users and general population controls. In: Blue boy — why not? Studies on benzodiazepine use in a Dutch community [dissertation]. Utrecht: Rolf van Hulten & Stichting Kalamiteit, 1998: 73–88Google Scholar
  40. 40.
    Gray A, Marshall M, Lockwood A, et al. Poblems in conducting economic evaluations alongside clinical trials. Br J Psychiatry 1997; 170: 47–52PubMedCrossRefGoogle Scholar
  41. 41.
    Zitman FG, Couvee JE. Chronic benzodiazepine use in general practice patients with depression: an evaluation of controlled treatment and taper-off. Report on behalf of the Dutch Chronic Benzodiazepine Working Group. Br J Psychiatry 2001; 178: 317–324PubMedCrossRefGoogle Scholar
  42. 42.
    Schweizer E, Rickels K, Case WG, et al. Long-term therapeutic use of benzodiazepines: II. Effects of gradual taper. Arch Gen Psychiatry 1990; 47: 908–915PubMedCrossRefGoogle Scholar
  43. 43.
    Schweizer E, Rickels K, De Martinis N, et al. The effect of personality on withdrawal severity and taper outcome in benzodiazepine dependent patients. Psychol Med 1998; 28: 713–720PubMedCrossRefGoogle Scholar
  44. 44.
    Rickels K, DeMartinis N, Garcia-Espana F, et al. Imipramine and buspirone in treatment of patients with generalized anxiety disorder who are discontinuing long-term benzodiazepine therapy. Am J Psychiatry 2000; 157: 1973–1979PubMedCrossRefGoogle Scholar
  45. 45.
    Higgitt A, Golombok S, Fonagy P, et al. Group treatment of benzodiazepine dependence. Br J Addict 1987; 82: 517–532PubMedCrossRefGoogle Scholar
  46. 46.
    Sanchez-Craig M, Cappell H, Busto U, et al. Cognitive-behavioural treatment for benzodiazepine dependence: a comparison of gradual versus abrupt cessation of drug intake. Br J Addict 1987; 82: 1317–1327PubMedCrossRefGoogle Scholar
  47. 47.
    Otto MW, Pollack MH, Sachs GS, et al. Discontinuation of benzodiazepine treatment: efficacy of cognitive-behavioral therapy for patients with panic disorder. Am J Psychiatry 1993; 150: 1485–1490PubMedGoogle Scholar
  48. 48.
    Elsesser K, Sartory G, Maurer J. The efficacy of complaints management training in facilitating benzodiazepine withdrawal. Behav Res Ther 1996; 34: 149–156PubMedCrossRefGoogle Scholar
  49. 49.
    Charney DA, Paraherakis AM, Gill KJ. The treatment of sedative-hypnotic dependence: evaluating clinical predictors of outcome. J Clin Psychiatry 2000; 61: 190–195PubMedCrossRefGoogle Scholar
  50. 50.
    Baillargeon L, Landreville P, Verreault R, et al. Discontinuation of benzodiazepines among older insomniac adults treated with cognitive-behavioural therapy combined with gradual tapering: a randomized trial. CMAJ 2003; 169 (10): 1015–1020PubMedGoogle Scholar
  51. 51.
    Morin CM, Bastien C, Guay B, et al. Randomized clinical trial of supervised tapering and cognitive behaviour therapy to facilitate benzodiazepine discontinuation in older adults with chronic insomnia. Am J Psychiatry 2004; 161: 332–342PubMedCrossRefGoogle Scholar
  52. 52.
    Couvee JE, Timmermans EAY, Zitman FG. The long-term outcome of a benzodiazepine discontinuation programme in depressed outpatients. J Affect Disord 2002; 70 (2): 133–141PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2006

Authors and Affiliations

  • Richard C. Oude Voshaar
    • 1
  • Paul F. M. Krabbe
    • 2
  • Wim J. M. J. Gorgels
    • 3
  • Eddy M. M. Adang
    • 2
  • Anton J. L. M. van Balkom
    • 4
  • Eloy H. van de Lisdonk
    • 3
  • Frans G. Zitman
    • 5
  1. 1.Department of Psychiatry, (hp 333)Radboud University Nijmegen Medical CentreNijmegenThe Netherlands
  2. 2.Department of Medical Technology AssessmentRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  3. 3.Department of General Practice and Family MedicineRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  4. 4.Department of Psychiatry and Institute for Research in Extramural MedicineVU University Medical Center AmsterdamAmsterdamThe Netherlands
  5. 5.Department of PsychiatryLeiden University Medical CenterLeidenThe Netherlands

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