Deprescribing benzodiazepine receptor agonists: Evidence-based clinical practice guideline

Kevin Pottie, Wade Thompson, Simon Davies, Jean Grenier, Cheryl A Sadowski, Vivian Welch, Anne Holbrook, Cynthia Boyd, Robert Swenson, Andy Ma, Barbara Farrell, Kevin Pottie, Wade Thompson, Simon Davies, Jean Grenier, Cheryl A Sadowski, Vivian Welch, Anne Holbrook, Cynthia Boyd, Robert Swenson, Andy Ma, Barbara Farrell

Abstract

Objective: To develop an evidence-based guideline to help clinicians make decisions about when and how to safely taper and stop benzodiazepine receptor agonists (BZRAs); to focus on the highest level of evidence available and seek input from primary care professionals in the guideline development, review, and endorsement processes.

Methods: The overall team comprised 8 clinicians (1 family physician, 2 psychiatrists, 1 clinical psychologist, 1 clinical pharmacologist, 2 clinical pharmacists, and 1 geriatrician) and a methodologist; members disclosed conflicts of interest. For guideline development, a systematic process was used, including the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Evidence was generated by conducting a systematic review of BZRA deprescribing trials for insomnia, as well as performing a review of reviews of the harms of continued BZRA use and narrative syntheses of patient preferences and resource implications. This evidence and GRADE quality of evidence ratings were used to generate recommendations. The team refined guideline content and recommendations through consensus and synthesized clinical considerations to address front-line clinician questions. The draft guideline was reviewed by clinicians and stakeholders.

Recommendations: We recommend that deprescribing (tapering slowly) of BZRAs be offered to elderly adults (≥ 65 years) who take BZRAs, regardless of duration of use, and suggest that deprescribing (tapering slowly) be offered to adults aged 18 to 64 who have used BZRAs for more than 4 weeks. These recommendations apply to patients who use BZRAs to treat insomnia on its own (primary insomnia) or comorbid insomnia where potential underlying comorbidities are effectively managed. This guideline does not apply to those with other sleep disorders or untreated anxiety, depression, or other physical or mental health conditions that might be causing or aggravating insomnia.

Conclusion: Benzodiazepine receptor agonists are associated with harms, and therapeutic effects might be short term. Tapering BZRAs improves cessation rates compared with usual care without serious harms. Patients might be more amenable to deprescribing conversations if they understand the rationale (potential for harm), are involved in developing the tapering plan, and are offered behavioural advice. This guideline provides recommendations for making decisions about when and how to reduce and stop BZRAs. Recommendations are meant to assist with, not dictate, decision making in conjunction with patients.

Copyright© the College of Family Physicians of Canada.

Figures

Figure 1.
Figure 1.
Benzodiazepine & Z-Drug (BZRA) Deprescribing Algorithm
Figure 1.
Figure 1.
Benzodiazepine & Z-Drug (BZRA) Deprescribing Algorithm

References

    1. Anthierens S, Tansens A, Petrovic M, Christiaens T. Qualitative insights into general practitioners views on polypharmacy. BMC Fam Pract. 2010;11:65.
    1. Alexander GC, Sayla MA, Holmes HM, Sachs GA. Prioritizing and stopping prescription medicines. CMAJ. 2006;174(8):1083–4.
    1. Holbrook AM, Crowther R, Lotter A, Cheng C, King D. Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ. 2000;162(2):225–33.
    1. Canadian Institute for Health Information. Drug use among seniors on public drug programs in Canada, 2012. Ottawa, ON: Canadian Institute for Health Information; 2014. Available from: . Accessed 2018 Mar 20.
    1. Vinkers CH, Olivier B. Mechanisms underlying tolerance after long-term benzodiazepine use: a future for subtype-selective GABA receptor modulators? Adv Pharmacol Sci. 2012;2012:416864.
    1. Farrell B, Tsang C, Raman-Wilms L, Irving H, Conklin J, Pottie K. What are priorities for deprescribing for elderly patients? Capturing the voice of practitioners: a modified Delphi process. PLoS One. 2015;10(4):e0122246.
    1. American Psychiatric Association . Diagnostic and statistical manual of mental disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.
    1. American Academy of Sleep Medicine . International classification of sleep disorders. Diagnostic and coding manual. Darien, IL: American Academy of Sleep Medicine; 2001.
    1. Chung KF, Yeung WF, Ho FY, Yung KP, Yu YM, Kwok CW. Cross-cultural and comparative epidemiology of insomnia: the diagnostic and statistical manual (DSM), international classification of diseases (ICD) and international classification of sleep disorders (ICSD) Sleep Med. 2015;16(4):477–82. Epub 2015 Jan 21.
    1. Morin CM, LeBlanc M, Bélanger L, Ivers H, Mérette C, Savard J. Prevalence of insomnia and its treatment in Canada. Can J Psychiatry. 2011;56(9):540–8.
    1. National Institutes of Health. National Institutes of Health State-of-the-Science Conference statement on manifestations and management of chronic insomnia in adults, June 13–15, 2005. Sleep. 2005;28(9):1049–57.
    1. Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2008;4(5):487–504.
    1. Wilson SJ, Nutt DJ, Alford C, Argyropoulos SV, Baldwin DS, Bateson AN, et al. British Association for Psychopharmacology consensus statement on evidence-based treatment of insomnia, parasomnias and circadian rhythm disorders. J Psychopharmacol. 2010;24(11):1577–601. Epub 2010 Sep 2.
    1. Canadian Academy of Child and Adolescent Psychiatry, Canadian Academy of Geriatric Psychiatry, Canadian Psychiatric Association. Thirteen things physicians and patients should question. Toronto, ON: Choosing Wisely Canada; 2017. Available from: . Accessed 2018 Mar 21.
    1. Canadian Geriatrics Society. Geriatrics: five things physicians and patients should question. Toronto, ON: Choosing Wisely Canada; 2017. Available from: . Accessed 2018 Mar 21.
    1. American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated Beers criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63(11):2227–46. Epub 2015 Oct 8.
    1. Rosenberg HC, Chiu TH. Time course for development of benzodiazepine tolerance and physical dependence. Neurosci Biobehav Rev. 1985;9(1):123–31.
    1. Sithamparanathan K, Sadera A, Leung L. Adverse effects of benzodiazepine use in elderly people: a meta-analysis. Asian J Gerontol Geriatr. 2012;7(2):107–11.
    1. Glass J, Lanctôt KL, Herrmann N, Sproule BA, Busto UE. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ. 2005;331(7526):1169. Epub 2005 Nov 11.
    1. Parr JM, Kavanagh DJ, Cahill L, Mitchell G, Young RM. Effectiveness of current treatment approaches for benzodiazepine discontinuation: a meta-analysis. Addiction. 2009;104(1):13–24. Epub 2008 Oct 31.
    1. Gould RL, Coulson MC, Patel N, Highton-Williamson E, Howard RJ. Interventions for reducing benzodiazepine use in older people: meta-analysis of randomised controlled trials. Br J Psychiatry. 2014;204(2):98–107.
    1. Voshaar RC, Couvée JE, van Balkom AJ, Mulder PG, Zitman FG. Strategies for discontinuing long-term benzodiazepine use: meta-analysis. Br J Psychiatry. 2006;189:213–20.
    1. Pollmann AS, Murphy AL, Bergman JC, Gardner DM. Deprescribing benzodiazepines and Z-drugs in community-dwelling adults: a scoping review. BMC Pharmacol Toxicol. 2015;16(1):19.
    1. Ramakrishnan K, Scheid DC. Treatment options for insomnia. Am Fam Physician. 2007;76(4):517–26.
    1. Schünemann HJ, Wierioch W, Etxeandia I, Falavigna M, Santesso N, Mustafa R, et al. Guidelines 2.0: systematic development of a comprehensive checklist for a successful guideline enterprise. CMAJ. 2014;186(3):E123–42. Epub 2013 Dec 16.
    1. Farrell B, Pottie K, Rojas-Fernandez CH, Bjerre LM, Thompson W, Welch V. Methodology for developing deprescribing guidelines: using evidence and GRADE to guide recommendations for deprescribing. PLoS One. 2016;11(8):e0161248.
    1. Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924–6.
    1. Curran HV, Collins R, Fletcher S, Kee SE, Woods B, Iliffe S. Older adults and withdrawal from benzodiazepine hypnotics in general practice: effects on cognitive function, sleep, mood and quality of life. Psychol Med. 2003;33(7):1223–37.
    1. Morgan S, Smolina K, Mooney D, Raymond C, Bowen M, Gorczynski C, et al. The Canadian Rx atlas. 3rd ed. Vancouver, BC: University of British Columbia, Centre for Health Services and Policy Research; 2013.
    1. Baillargeon L, Landreville P, Verreault R, Beauchemin J, Grégoire JP, Morin CM. Discontinuation of benzodiazepines among older insomniac adults treated with cognitive-behavioural therapy combined with gradual tapering: a randomized trial. CMAJ. 2003;169(10):1015–20.
    1. Belleville G, Guay C, Guay B, Morin CM. Hypnotic taper with or without self-help treatment of insomnia: a randomized clinical trial. J Consult Clin Psychol. 2007;75(2):325–35.
    1. Garfinkel D, Zisapel N, Wainstein J, Laudon M. Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach. Arch Intern Med. 1999;159(20):2456–60.
    1. Habraken H, Soenen K, Blondeel L, Van Elsen J, Bourda J, Coppens E, et al. Gradual withdrawal from benzodiazepines in residents of homes for the elderly: experience and suggestions for future research. Eur J Clin Pharmacol. 1997;51(5):355–8.
    1. Morin CM, Bastien C, Guay B, Radouco-Thomas M, Leblanc J, Vallières A. Randomized clinical trial of supervised tapering and cognitive behavior therapy to facilitate benzodiazepine discontinuation in older adults with chronic insomnia. Am J Psychiatry. 2004;161(2):332–42.
    1. Pat-Horenczyk R, Hacohen D, Herer P, Lavie P. The effects of substituting zopiclone in withdrawal from chronic use of benzodiazepine hypnotics. Psychopharmacology (Berl) 1998;140(4):450–7.
    1. Shapiro CM, Sherman D, Peck DF. Withdrawal from benzodiazepines by initially switching to zopiclone. Eur Psychiatry. 1995;10(Suppl 3):145s–51s.
    1. Vissers FHJA, Knipschild PG, Crebolder HFJM. Is melatonin helpful in stopping the long-term use of hypnotics? A discontinuation trial. Pharm World Sci. 2007;29(6):641–6.
    1. Voshaar RCO, Gorgels WJ, Mol AJ, van Balkom AJ, van de Lisdonk EH, Breteler MH, et al. Tapering off long-term benzodiazepine use with or without group cognitive−behavioural therapy: three-condition, randomised controlled trial. Br J Psychiatry. 2003;182:498–504.
    1. Paquin AM, Zimmerman K, Rudolph JL. Risk versus risk: a review of benzodiazepine reduction in older adults. Expert Opin Drug Saf. 2014;13(7):919–34. Epub 2014 Jun 6.
    1. Okuji Y, Matsuura M, Kawasaki N, Kometani S, Shimoyama T, Sato M, et al. Prevalence of insomnia in various psychiatric diagnostic categories. Psychiatry Clin Neurosci. 2002;56(3):239–40.
    1. Neylan T, Reynolds C, Kupfer D. Sleep disorders. In: Hales RE, Yudofsky SC, editors. Textbook of clinical psychiatry. Washington, DC: American Psychiatric Publishing; 2003. pp. 975–1000.
    1. Wooten V, Buysse D. Sleep in psychiatric disorders. In: Chokroverty S, editor. Sleep disorders medicine: basic sciences, technical considerations, and clinical aspects. 3rd ed. New York, NY: Saunders; 2009.
    1. Chang PP, Ford DE, Mead LA, Cooper-Patrick L, Klag MJ. Insomnia in young men and subsequent depression. The Johns Hopkins Precursors Study. Am J Epidemiol. 1997;146(2):105–14.
    1. Ohayon MM, Shapiro CM. Sleep disturbances and psychiatric disorders associated with posttraumatic stress disorder in the general population. Compr Psychiatry. 2000;41(6):469–78.
    1. Pigeon W. Insomnia as a risk factor for disease. In: Sateia MJ, Buysse DJ, editors. Insomnia: diagnosis and treatment. London, UK: Informa Healthcare; 2010. pp. 31–41.
    1. Chokroverty S. Clinical companion to sleep disorders medicine. 2nd ed. Boston MA: Butterworth-Heinemann; 2000.
    1. Stamatakis KA, Punjabi NM. Effects of sleep fragmentation on glucose metabolism in normal subjects. Chest. 2010;137(1):95–101. Epub 2009 Jun 19.
    1. Merlino G, Gigli GL, Valente M. Sleep disturbances in dialysis patients. J Nephrol. 2008;21(Suppl 13):S66–70.
    1. De Santo RM, Bartiromo M, Cesare CM, Cirillo M. Sleep disorders occur very early in chronic kidney disease. J Nephrol. 2008;21(Suppl 13):S59–65.
    1. Grenier J. A decision tree approach to the differential diagnosis of insomnia. In: Billard M, editor. Sleep: physiology, investigations and medicine. New York, NY: Springer; 2003. pp. 191–9.
    1. Jansen J, Naganathan V, Carter SM, McLachlan AJ, Nickel B, Irwig L, et al. Too much medicine in older people? Deprescribing through shared decision making. BMJ. 2016;353:i2893.
    1. Reeve E, To J, Hendrix I, Shakib S, Roberts MS, Wiese MD. Patient barriers to and enablers of deprescribing: a systematic review. Drugs Aging. 2013;30(10):793–807.
    1. Tannenbaum C, Martin P, Tamblyn R, Benedetti A, Ahmed S. Reduction of inappropriate benzodiazepine prescriptions among older adults through direct patient education: the EMPOWER cluster randomized trial. JAMA Intern Med. 2014;174(6):890–8.
    1. Vicens C, Bejarano F, Sempere E, Mateu C, Fiol F, Socias I, et al. Comparative efficacy of two interventions to discontinue long-term benzodiazepine use: cluster randomised controlled trial in primary care. Br J Psychiatry. 2014;204(6):471–9. Epub 2014 Feb 13.
    1. Schweizer E, Rickels K, Case WG, Greenblatt DJ. Long-term therapeutic use of benzodiazepines. II. Effects of gradual taper. Arch Gen Psychiatry. 1990;47(10):908–15.
    1. Denis C, Fatseas M, Lavie E, Auriacombe M. Pharmacological interventions for benzodiazepine mono-dependence management in outpatient settings. Cochrane Database Syst Rev. 2013;(6):CD005194.
    1. Gorgels WJ, Oude Voshaar RC, Mol AJ, van de Lisdonk EH, van Balkom AJ, Breteler MH, et al. Predictors of discontinuation of benzodiazepine prescription after sending a letter to long-term benzodiazepine users in family practice. Fam Pract. 2006;23(1):65–72. Epub 2005 Aug 17.
    1. Cormack MA, Owens RG, Dewey ME. The effect of minimal interventions by general practitioners on long-term benzodiazepine use. J R Coll Gen Pract. 1989;39(327):408–11.
    1. Morin CM, Bélanger L, Bastien C, Vallières A. Long-term outcome after discontinuation of benzodiazepines for insomnia: a survival analysis of relapse. Behav Res Ther. 2005;43(1):1–14.
    1. O’Connor K, Marchand A, Brousseau L, Aardema F, Mainguy N, Landry P, et al. Cognitive-behavioural, pharmacological and psychosocial predictors of outcome during tapered discontinuation of benzodiazepine. Clin Psychol Psychother. 2008;15(1):1–14.
    1. Voshaar RC, Gorgels WJ, Mol AJ, van Balkom AJ, Mulder J, van de Lisdonk EH, et al. Predictors of long-term benzodiazepine abstinence in participants of a randomized controlled benzodiazepine withdrawal program. Can J Psychiatry. 2006;51(7):445–52.
    1. Soldatos CR, Dikeos DG, Whitehead A. Tolerance and rebound insomnia with rapidly eliminated hypnotics: a meta-analysis of sleep laboratory studies. Int Clin Psychopharmacol. 1999;14(5):287–303.
    1. Van Rijnsoever C, Täuber M, Choulli MK, Keist R, Rudolph U, Mohler H, et al. Requirement of α5-GABA receptors for the development of tolerance to the sedative action of diazepam in mice. J Neurosci. 2004;24(30):6785–90.
    1. Busto U, Sellers EM, Naranjo CA, Cappell H, Sanchez-Craig M, Sykora K. Withdrawal reaction after long-term therapeutic use of benzodiazepines. N Engl J Med. 1986;315(14):854–9.
    1. Rickels K, Schweizer E, Case WG, Greenblatt DJ. Long-term therapeutic use of benzodiazepines. I. Effects of abrupt discontinuation. Arch Gen Psychiatry. 1990;47(10):899–907.
    1. Qaseem A, Kansagara D, Forciea M, Cooke M, Denberg TD, Clinical Guidelines Committee of the American College of Physicians Management of chronic insomnia disorder in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016;165(2):125–33. Epub 2016 May 3.
    1. Agency for Healthcare Research and Quality . Effective Health Care Program: management of insomnia disorder. Rockville, MD: Agency for Healthcare Research and Quality; 2015. Available from: . Accessed 2018 Mar 22.
    1. Buysse DJ. Insomnia. JAMA. 2013;309(7):706–16.
    1. Seyffert M, Lagisetty P, Landgraf J, Chopra V, Pfeiffer PN, Conte ML, et al. Internet-delivered cognitive behavioral therapy to treat insomnia: a systematic review and meta-analysis. PLoS One. 2016;11(2):e0149139.
    1. Trauer JM, Qian MY, Doyle JS, Rajaratnam SM, Cunnington D. Cognitive behavioral therapy for chronic insomnia: a systematic review and meta-analysis. Ann Intern Med. 2015;163(3):191–204.
    1. Get your sleep back. Sleepwell Nova Scotia [website]; 2018. Available from: . Accessed 2018 Mar 22.
    1. Ritterband LM, Thorndike FP, Gonder-Frederick LA, Magee JC, Bailey ET, Saylor DK, et al. Efficacy of an Internet-based behavioral intervention for adults with insomnia. Arch Gen Psychiatry. 2009;66(7):692–8. Erratum in: Arch Gen Psychiatry 2010;67(3):311.
    1. Tyrer P, Murphy S, Riley P. The benzodiazepine withdrawal symptom questionnaire. J Affect Disord. 1990;19(1):53–61.
    1. Baglioni C, Battagliese G, Feige B, Spiegelhalder K, Nissen C, Voderholzer U, et al. Insomnia as a predictor of depression: a meta-analytic evaluation of longitudinal epidemiological studies. J Affect Disord. 2011;135(1–3):10–9. Epub 2011 Feb 5.
    1. Roth T, Jaeger S, Jin R, Kalsekar A, Stang PE, Kessler RC. Sleep problems, comorbid mental disorders, and role functioning in the National Comorbidity Survey Replication. Biol Psychiatry. 2006;60(12):1364–71. Epub 2006 Sep 6.
    1. Chung KH, Li CY, Kuo SY, Sithole T, Liu WW, Chung MH. Risk of psychiatric disorders in patients with chronic insomnia and sedative-hypnotic prescription: a nationwide population-based follow-up study. J Clin Sleep Med. 2015;11(5):543–51.
    1. Bateson AN. Basic pharmacologic mechanisms involved in benzodiazepine tolerance and withdrawal. Curr Pharm Des. 2002;8(1):5–21.
    1. Lam RW, Kennedy SH, Grigoriadis S, McIntyre RS, Milev R, Ramasubbu R, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy. J Affect Disord. 2009;117(Suppl 1):S26–43. Epub 2009 Aug 11.
    1. Bandelow B, Lichte T, Rudolf S, Wiltink J, Beutel ME. The German guidelines for the treatment of anxiety disorders. Eur Arch Psychiatry Clin Neurosci. 2015;265(5):363–73.
    1. Katzman MA, Bleau P, Blier P, Chokka P, Kjernisted K, Van Ameringen M, et al. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14(Suppl 1):S1. Epub 2014 Jul 2.
    1. Baldwin DS, Anderson IM, Nutt DJ, Allgulander C, Bandelow B, den Boer JA, et al. Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: a revision of the 2005 guidelines from the British Association for Psychopharmacology. J Psychopharmacol. 2014;28(5):403–39. Epub 2014 Apr 8.
    1. Canadian Medical Protective Association [website]. Risk management in elderly patients: medication issues. Ottawa, ON: Canadian Medical Protective Association; 2011. Available from: . Accessed 2018 Mar 22.
    1. Canadian Medical Protective Association [website]. Adverse events—physician-prescribed opioids. Ottawa, ON: Canadian Medical Protective Association; 2009. Available from: . Accessed 2018 Mar 27.
    1. Greenfield D, Brown J. Current medicolegal status of prescribing benzodiazepines: a special case. Natl Crim Justice Ref Serv. 1995:41–52.
    1. Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, et al. The Global Rating Scale complements the AGREE II in advancing the quality of practice guidelines. J Clin Epidemiol. 2012;65(5):526–34. Epub 2011 Dec 19.
    1. Panel on Prevention of Falls in Older Persons, American Geriatrics Society and British Geriatrics Society. Summary of the Updated American Geriatrics Society/British Geriatrics Society clinical practice guideline for prevention of falls in older persons. J Am Geriatr Soc. 2011;59(1):148–57.
    1. Gillespie LD, Robertson M, Gillespie WJ, Sherrington C, Gates S, Clemson LM, et al. Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev. 2012;(9):CD007146.
    1. Coussement J, De Paepe L, Schwendimann R, Denhaerynck K, Dejaeger E, Milisen K. Interventions for preventing falls in acute- and chronic-care hospitals: a systematic review and meta-analysis. J Am Geriatr Soc. 2008;56(1):29–36. Epub 2007 Nov 20.

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