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Management of chronic insomnia using hypnotics: a friend or a foe?

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Abstract

Epidemiological studies suggest that 10–15% adults meet the present criteria for the diagnosis of insomnia disorder; however, there may be geographical variations. Untreated insomnia disorders have a number of adverse health consequences in addition to economic burden caused by it. Available guidelines mention that CBT-I should be preferred over hypnotics. However, several patients of chronic insomnia are not candidate for CBT-I and for them, hypnotics are the only answer. This paper reviews the literature to answer following questions: What is the current understanding regarding place of hypnotics for in management of insomnia disorder? How many patients misuse or abuse hypnotics, especially benzodiazepines, as commonly believed? Do we have data from human studies regarding low-dose benzodiazepine dependence? What does hypnotics produce—withdrawal insomnia, rebound insomnia or end of dose phenomenon? Are adverse effects of benzodiazepines worse than other psychotropic medications? Is prescription of hypnotics more troublesome than untreated insomnia disorder? Available literature suggests that there is an unreasonable negative bias attached to the use of hypnotics. Only a sub-set of patients who are prescribed hypnotics, meet the criteria for “dependence” in long term. Other patients either discontinue it (as insomnia remits) or change to occasional use (since insomnia may be relapsing remitting disorder), or continue using it in low dose (since insomnia reappears as hypnotics are discontinued, similar to increase in blood sugar after hypoglycemics are discontinued). Meta-analysis shows that adverse effects of hypnotics are comparable to that of other psychotropic medications. Considering the consequences and risks associated with untreated insomnia disorder, even long-term use of hypnotics is justified, however with the careful watch that patients are not increasing the dose. This approach is especially important in geographical areas where trained CBT-I therapists are not available.

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References

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

    Book  Google Scholar 

  2. Anothaisintawee T, Reutrakul S, Van Cauter E, et al. Sleep disturbances compared to traditional risk factors for diabetes development: systematic review and meta-analysis. Sleep Med Rev. 2016;30:11–24. https://doi.org/10.1016/j.smrv.2015.10.002.

    Article  PubMed  Google Scholar 

  3. Ashton H. The diagnosis and management of benzodiazepine dependence. Curr Opin Psychiatry. 2005;18:249–55. https://doi.org/10.1097/01.yco.0000165594.60434.84.

    Article  PubMed  Google Scholar 

  4. Asnis GM, Thomas M, Henderson MA. Pharmacotherapy treatment options for insomnia: a primer for clinicians. Int J Mol Sci. 2016. https://doi.org/10.3390/ijms17010050.

    Article  Google Scholar 

  5. Ballenger JC. Medication discontinuation in panic disorder. J Clin Psychiatry. 1992;53:26–31.

    PubMed  Google Scholar 

  6. Bloom HG, Ahmed I, Alessi CA, et al. Evidence-based recommendations for the assessment and management of sleep disorders in older persons. J Am Geriatr Soc. 2009;57:761–89. https://doi.org/10.1111/j.1532-5415.2009.02220.x.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Brandt J, Leong C. Benzodiazepines and Z-drugs: an updated review of major adverse outcomes reported on in epidemiologic research. Drugs R D. 2017;17:493–507. https://doi.org/10.1007/s40268-017-0207-7.

    Article  PubMed  PubMed Central  Google Scholar 

  8. 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. https://doi.org/10.1056/NEJM198610023151403.

    Article  CAS  PubMed  Google Scholar 

  9. Covi L, Lipman RS, Pattison JH, et al. Length of treatment with anxiolytic sedatives and response to their sudden withdrawal. Acta Psychiatr Scand. 1973;49:51–64. https://doi.org/10.1111/j.1600-0447.1973.tb04398.x.

    Article  CAS  PubMed  Google Scholar 

  10. El-Guebaly N, Sareen J, Stein MB. Are there guidelines for the responsible prescription of benzodiazepines? Can J Psychiatry. 2010;55(11):709–14. https://doi.org/10.1177/070674371005501104.

    Article  PubMed  Google Scholar 

  11. Enomoto M, Kitamura S, Tachimori H, et al. Long-term use of hypnotics: analysis of trends and risk factors. Gen Hosp Psychiatry. 2020;62:49–55. https://doi.org/10.1016/j.genhosppsych.2019.11.008.

    Article  PubMed  Google Scholar 

  12. Findley JD, Robinson WW, Peregrino L. Addiction to secobarbital and chlordiazepoxide in the rhesus monkey by means of a self-infusion preference procedure. Psychopharmacologia. 1972;26:93–114. https://doi.org/10.1007/BF00422097.

    Article  CAS  PubMed  Google Scholar 

  13. Ge L, Guyatt G, Tian J, Pan B, Chang Y, Chen Y, Li H, Zhang J, Li Y, Ling J, Yang K. Insomnia and risk of mortality from all-cause, cardiovascular disease, and cancer: systematic review and meta-analysis of prospective cohort studies. Sleep Med Rev. 2019;48: 101215.

    Article  PubMed  Google Scholar 

  14. Gillin JC, Spinweber CL, Johnson LC. Rebound insomnia: a critical review. J Clin Psychopharmacol. 1989;9(3):161–72.

    Article  CAS  PubMed  Google Scholar 

  15. Green A, Bensky M, Kemer L, Stein O, Dagan Y. Do chronic hypnotics users truly develop tolerance. J Insomn Sleep Disord. 2019;1(1):102.

    Google Scholar 

  16. Griffiths RR, Weerts EM. Benzodiazepine self-administration in humans and laboratory animals–implications for problems of long-term use and abuse. Psychopharmacology. 1997;134(1):1–37.

    Article  CAS  PubMed  Google Scholar 

  17. Guarino J, Boisse N, Gay M. Differentiation of high versus low dose chronic benzodiazepine dependence in the rat. In: Problems of drug dependence: proceedings of the annual scientific meeting, the College on Problems of Drug Dependence, Inc. US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute on Drug Abuse, 1988; p 330.

  18. Hajak G, Clarenbach P, Fischer W, Rodenbeck A, Bandelow B, Broocks A, Rüther E. Rebound insomnia after hypnotic withdrawal in insomniac outpatients. Eur Arch Psychiatry Clin Neurosci. 1998;248(3):148–56.

    Article  CAS  PubMed  Google Scholar 

  19. Hartelius H, Larsson A-K, Lepp M, et al. A controlled long-term study of flunitrazepam, nitrazepam and placebo, with special regard to withdrawal effects. Acta Psychiatr Scand. 1978;58:1–15. https://doi.org/10.1111/j.1600-0447.1978.tb06915.x.

    Article  CAS  PubMed  Google Scholar 

  20. Hedström AK, Hössjer O, Trolle Lagerros Y, et al. Short- and long-term mortality following hypnotic use. J Sleep Res. 2020. https://doi.org/10.1111/jsr.13061.

    Article  PubMed  Google Scholar 

  21. Hirschtritt ME, Olfson M, Kroenke K. Balancing the risks and benefits of benzodiazepines. JAMA. 2021;325(4):347–8. https://doi.org/10.1001/jama.2020.22106.

    Article  CAS  PubMed  Google Scholar 

  22. Hockenhull J, Black JC, Haynes CM, et al. Non-medical use of benzodiazepines and Z-drugs in the United Kingdom. Br J Clin Pharmacol. 2020. https://doi.org/10.1111/bcp.14397 (Epub ahead of print).

    Article  PubMed  Google Scholar 

  23. Kales A, Scharf MB, Kales JD. Rebound insomnia: a new clinical syndrome. Science. 1978;201:1039–41. https://doi.org/10.1126/science.684426.

    Article  CAS  PubMed  Google Scholar 

  24. Kales A, Soldatos CR, Bixler EO, et al. Rebound insomnia and rebound anxiety: a review. Pharmacology. 1983;26:121–37. https://doi.org/10.1159/000137794.

    Article  CAS  PubMed  Google Scholar 

  25. Kim YH, Kim HB, Kim DH, Kim JY, Shin HY. Use of hypnotics and the risk of or mortality from heart disease: a meta-analysis of observational studies. Korean J Intern Med. 2018;33(4):727–36. https://doi.org/10.3904/kjim.2016.282.

    Article  PubMed  Google Scholar 

  26. Kuhn BN, Kalivas PW, Bobadilla AC. Understanding addiction using animal models. Front Behav Neurosci. 2019;13:262. https://doi.org/10.3389/fnbeh.2019.00262.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kurko TAT, Saastamoinen LK, Tähkäpää S, et al. Long-term use of benzodiazepines: definitions, prevalence and usage patterns—a systematic review of register-based studies. Eur Psychiatry. 2015;30:1037–47. https://doi.org/10.1016/j.eurpsy.2015.09.003.

    Article  CAS  PubMed  Google Scholar 

  28. Laughren TP, Battey Y, Greenblatt DJ, et al. A controlled trial of diazepam withdrawal in chronically anxious outpatients. Acta Psychiatr Scand. 1982;65:171–9. https://doi.org/10.1111/j.1600-0447.1982.tb00838.x.

    Article  CAS  PubMed  Google Scholar 

  29. Linden M, Bär T, Geiselmann B. Patient treatment insistence and medication craving in long-term low-dosage benzodiazepine prescriptions. Psychol Med. 1998;28:721–9. https://doi.org/10.1017/S0033291798006734.

    Article  CAS  PubMed  Google Scholar 

  30. Malow BA, Byars K, Johnson K, et al. A practice pathway for the identification, evaluation, and management of insomnia in children and adolescents with autism spectrum disorders. Pediatrics. 2012;130(Suppl):S106–24. https://doi.org/10.1542/peds.2012-0900I.

    Article  PubMed  Google Scholar 

  31. Mason M, Cates CJ, Smith I. Effects of opioid, hypnotic and sedating medications on sleep-disordered breathing in adults with obstructive sleep apnoea. Cochrane Database Syst Rev. 2015. https://doi.org/10.1002/14651858.CD011090.pub2.

    Article  PubMed  Google Scholar 

  32. Meng L, Zheng Y, Hui R. The relationship of sleep duration and insomnia to risk of hypertension incidence: a meta-analysis of prospective cohort studies. Hypertens Res. 2013;36:985–95. https://doi.org/10.1038/hr.2013.70.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Moloney ME, Konrad R, Zimmer CR. The medicalization of sleeplessness: a public health concern. Am J Public Health. 2011;101:1429–33. https://doi.org/10.2105/AJPH.2010.300014.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Parsaik AK, Mascarenhas SS, Khosh-Chashm D, Hashmi A, John V, Okusaga O, Singh B. Mortality associated with anxiolytic and hypnotic drugs—a systematic review and meta-analysis. Aust N Z J Psychiatry. 2016;50(6):520–33.

    Article  PubMed  Google Scholar 

  35. Perlis M, Gehrman P, Riemann D. Intermittent and long-term use of sedative hypnotics. Curr Pharm Des. 2008;14:3456–65. https://doi.org/10.2174/138161208786549290.

    Article  CAS  PubMed  Google Scholar 

  36. Petursson H, Lader MH. Withdrawal from long-term benzodiazepine treatment. Br Med J. 1981. https://doi.org/10.1136/bmj.283.6292.643.

    Article  Google Scholar 

  37. Petursson H, Lader MH. Benzodiazepine dependence. Br J Addict. 1981;76(2):133–45. https://doi.org/10.1111/j.1360-0443.1981.tb00218.x.

    Article  CAS  PubMed  Google Scholar 

  38. Pillai V, Cheng P, Kalmbach DA, et al. Prevalence and predictors of prescription sleep aid use among individuals with DSM-5 insomnia: the role of hyperarousal. Sleep. 2016;39:825–32. https://doi.org/10.5665/sleep.5636.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Pillai V, Roth T, Roehrs T, Moss K, Peterson EL, Drake CL. Effectiveness of benzodiazepine receptor agonists in the treatment of insomnia: an examination of response and remission rates. Sleep. 2017;40(2):zsw044. https://doi.org/10.1093/sleep/zsw044.

    Article  Google Scholar 

  40. Pinto LR Jr, Alves RC, Caixeta E, et al. New guidelines for diagnosis and treatment of insomnia. Arq Neuropsiquiatr. 2010;68:666–75. https://doi.org/10.1590/S0004-282X2010000400038.

    Article  PubMed  Google Scholar 

  41. Rickels K, Case WG, Downing RW, Winokur A. Long-term diazepam therapy and clinical outcome. JAMA. 1983;250(6):767–71. https://doi.org/10.1001/jama.1983.03340060045024.

    Article  CAS  PubMed  Google Scholar 

  42. Riemann D, Baglioni C, Bassetti C, et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017;26:675–700. https://doi.org/10.1111/jsr.12594.

    Article  PubMed  Google Scholar 

  43. Riemann D, Spiegelhalder K, Feige B, et al. The hyperarousal model of insomnia: a review of the concept and its evidence. Sleep Med Rev. 2010;14:19–31. https://doi.org/10.1016/j.smrv.2009.04.002.

    Article  PubMed  Google Scholar 

  44. Roehrs T, Roth T. Hyperarousal in insomnia: pre-sleep and diurnal cortisol levels in response to chronic zolpidem treatment. Sleep Med. 2019;61:52–6. https://doi.org/10.1016/j.sleep.2019.04.010.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Roehrs T. Rebound insomnia: its determinants and significance. Am J Med. 1990;88:39S-42S. https://doi.org/10.1016/S0002-9343(13)80001-0.

    Article  CAS  PubMed  Google Scholar 

  46. Roth T, Roehrs T, Pies R. Insomnia: pathophysiology and implications for treatment. Sleep Med Rev. 2007;11:71–9. https://doi.org/10.1016/j.smrv.2006.06.002.

    Article  PubMed  Google Scholar 

  47. Sateia MJ, Buysse DJ, Krystal AD, et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of sleep medicine clinical practice guideline. J Clin Sleep Med. 2017;13:307–49. https://doi.org/10.5664/jcsm.6470.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Schneider-Helmert D, et al. Why low-dose benzodiazepine-dependent insomniacs can’t escape their slee** pills. Acta Psychiatr Scand. 1988;78:706–11. https://doi.org/10.1111/j.1600-0447.1988.tb06408.x.

    Article  CAS  PubMed  Google Scholar 

  49. Schonmann Y, Goren O, Bareket R, et al. Chronic hypnotic use at 10 years—does the brand matter? Eur J Clin Pharmacol. 2018;74:1623–31. https://doi.org/10.1007/s00228-018-2531-4.

    Article  CAS  PubMed  Google Scholar 

  50. Schutte-Rodin S, Broch L, Buysse D, et al. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2008;4:487–504. https://doi.org/10.5664/jcsm.27286.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Sellers EM, Ciraulo DA, DuPont RL, et al. Alprazolam and benzodiazepine dependence. J Clin Psychiatry. 1993;54:64–75.

    PubMed  Google Scholar 

  52. Seppala LJ, Wermelink AMAT, de Vries M, et al. Fall-risk-increasing drugs: a systematic review and meta-analysis: II. Psychotropics. J Am Med Dir Assoc. 2018;19(371):e11-371.e17. https://doi.org/10.1016/j.jamda.2017.12.098.

    Article  Google Scholar 

  53. Sirdifield C, Chipchase SY, Owen S, et al. A systematic review and meta-synthesis of patients’ experiences and perceptions of seeking and using benzodiazepines and Z-drugs: towards safer prescribing. Patient. 2017;10:1–15. https://doi.org/10.1007/s40271-016-0182-z.

    Article  PubMed  Google Scholar 

  54. Smith SM, Dart RC, Katz NP, et al. Classification and definition of misuse, abuse, and related events in clinical trials: ACTTION systematic review and recommendations. Pain. 2013;154:2287–96. https://doi.org/10.1016/j.pain.2013.05.053.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Soldatos CR, Dikeos DG, Whitehead A. Tolerance and rebound insomnia with rapidly eliminated hypnotics: a meta-analysis of sleep laboratory studies. In: Database of Abstracts of Reviews of Effects (DARE): quality-assessed reviews [Internet]. 1999. York (UK): Centre for Reviews and Dissemination (UK); 1995. Available from: https://www.ncbi.nlm.nih.gov/books/NBK67701/.

  56. Soyka M, Queri S, Küfner H, Rösner S. Where are 1.9 million drug addicts hiding? Neurologist. 2005;76(1):72–7. https://doi.org/10.1007/s00115-004-1828-y.

    Article  CAS  Google Scholar 

  57. Soyka M. Abuse of, and dependence on, medically prescribed drugs. In: Henn F, Sartorius N, Helmchen H, Lauter H, editors. Contemporary psychiatry. Berlin: Springer; 2001. https://doi.org/10.1007/978-3-642-59519-6_133.

    Chapter  Google Scholar 

  58. Soyka M. Treatment of benzodiazepine dependence. N Engl J Med. 2017;376:1147–57. https://doi.org/10.1056/NEJMra1611832.

    Article  CAS  PubMed  Google Scholar 

  59. Takaesu Y, Komada Y, Asaoka S, et al. Factors associated with long-term use of hypnotics among patients with chronic insomnia. PLoS ONE. 2014. https://doi.org/10.1371/journal.pone.0113753.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Takeshima N, Ogawa Y, Hayasaka Y, et al. Continuation and discontinuation of benzodiazepine prescriptions: a cohort study based on a large claims database in Japan. Psychiatry Res. 2016;237:201–7. https://doi.org/10.1016/j.psychres.2016.01.040.

    Article  PubMed  Google Scholar 

  61. Tan KR, Brown M, Labouébe G, et al. Neural bases for addictive properties of benzodiazepines. Nature. 2010;463:769–74. https://doi.org/10.1038/nature08758.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Treves N, Perlman A, Kolenberg Geron L, et al. Z-drugs and risk for falls and fractures in older adults-a systematic review and meta-analysis. Age Ageing. 2018;47:201–8. https://doi.org/10.1093/ageing/afx167.

    Article  PubMed  Google Scholar 

  63. Tyrer P, Owen R, Dawling S. Gradual withdrawal of diazepam after long-term therapy. Lancet. 1983;321(8339):1402–6. https://doi.org/10.1016/S0140-6736(83)92355-3.

    Article  Google Scholar 

  64. Tyrer P, Rutherford D, Huggett T. Benzodiazepine withdrawal symptoms and propranolol. Lancet. 1981;317(8219):520–2. https://doi.org/10.1016/S0140-6736(81)92861-0.

    Article  Google Scholar 

  65. US Food and Drug Administration. FDA requiring boxed warning updated to improve safe use of benzodiazepine drug class. US FDA; 2020.

    Google Scholar 

  66. Votaw VR, Geyer R, Rieselbach MM, McHugh RK. The epidemiology of benzodiazepine misuse: a systematic review. Drug Alcohol Depend. 2019;1(200):95–114.

    Article  Google Scholar 

  67. Wang S-H, Chen W-S, Tang S-E, et al. Benzodiazepines associated with acute respiratory failure in patients with obstructive sleep apnea. Front Pharmacol. 2019;9:1513. https://doi.org/10.3389/fphar.2018.01513.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wardle-Pinkston S, Slavish DC, Taylor DJ. Insomnia and cognitive performance: a systematic review and meta-analysis. Sleep Med Rev. 2019;48: 101205. https://doi.org/10.1016/j.smrv.2019.07.008.

    Article  PubMed  Google Scholar 

  69. World Health Organization. Lexicon of alcohol and drug terms. World Health Organization; 1994.

    Google Scholar 

  70. Yanagita T, Takahashi S. Dependence liability of several sedative-hypnotic agents evaluated in monkeys. J Pharmacol Exp Ther. 1973;185(2):307–16.

    CAS  PubMed  Google Scholar 

  71. Yanagita T. Dependence-producing effects of anxiolytics. In: Hoffmeister F, Stille G, editors. Psychotropic agents. Handbook of experimental pharmacology (continuation of Handbuch der experimentellen Pharmakologie), vol 55/2. Berlin: Springer; 1981. https://doi.org/10.1007/978-3-642-67767-0_8.

    Chapter  Google Scholar 

  72. Zhang XJ, Li QY, Wang Y, et al. The effect of non-benzodiazepine hypnotics on sleep quality and severity in patients with OSA: a meta-analysis. Sleep Breath. 2014;18:781–9. https://doi.org/10.1007/s11325-014-0943-7.

    Article  PubMed  Google Scholar 

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  1. Department of Psychiatry, All India Institute of Medical Sciences, Kalyani, 741245, India

    Aniruddha Basu

  2. Department of Psychiatry, All India Institute of Medical Sciences, Rishikesh, 249203, India

    Tanmay Joshi

  3. Department of Psychiatry, All India Institute of Medical Sciences, Raibareli, 229405, India

    Arghya Pal

  4. Department of Psychiatry and Division of Sleep Medicine, All India Institute of Medical Sciences, Rishikesh, 249203, India

    Ravi Gupta

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RG conceived the study. TJ and AP searched literature. AB and RG reviewed it. RG and TJ prepared first draft. AB and AP critically reviewed it and provided scientific content to bring it to final shape.

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Basu, A., Joshi, T., Pal, A. et al. Management of chronic insomnia using hypnotics: a friend or a foe?. Sleep Biol. Rhythms 20, 39–46 (2022). https://doi.org/10.1007/s41105-021-00363-4

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