Anxiolytics and Sedatives

Chapter

Abstract

Benzodiazepines are classified as anxiolytics or hypnotics, but the term “sedative” describes a group of drugs, including barbiturates and tricyclic antidepressants as well as benzodiazepines, which are abused. These drugs have different pharmacokinetic characteristics. Patients prescribed benzodiazepines seldom escalate their doses, and primary benzodiazepine abuse is rare. However, secondary abuse of all sedative drugs is common, and high doses are frequently consumed by patients dependent on opiates or alcohol to enhance the effects and by stimulant users to alleviate offset effects after a binge. Benzodiazepines cause dependence on prescribed doses with a clear withdrawal syndrome lasting a few weeks evident in 20–30% patients. The consumption of high doses can result in more severe withdrawal symptoms. Benzodiazepines should never be withdrawn abruptly because of the risk of fits or paranoid psychosis. A stepped care approach to reduction is recommended. All sedative drugs have characteristic pharmacodynamic effects, causing sedation, psychomotor slowing and memory impairment. They increase the risk of accidents and injuries and contribute to specific drug-related harms in abusers. Tolerance develops to some effects but long-term users are impaired compared with non-users. However, gradually stopping the drugs, even after several years of use, results in improvement in functioning, and there is no evidence of lasting impairment or cognitive decline. Newer anxiolytics and SSRIs appear to cause less impairment and have lower abuse potential.

Keywords

Depression Dementia Cocaine Melatonin Diazepam 

References

  1. 1.
    Kerr DI, Ong J. GABA-B receptors. Pharmacol Ther. 1995;67:187–246.PubMedCrossRefGoogle Scholar
  2. 2.
    Nutt DJ. New insights into the role of the GABA(A)-benzodiazepine receptor in psychiatric disorder. Br J Psychiatry. 2001;179:390–6.PubMedCrossRefGoogle Scholar
  3. 3.
    National Institute for Clinical Excellence. Depression: management of depression in primary and secondary care—Clinical guidance. http://www.nice.org.uk. 2004.
  4. 4.
    National Institute for Clinical Excellence. Anxiety: management of anxiety (panic disorder, with or without agoraphobia, and generalised anxiety disorder) in adults in primary, secondary and community care. Clinical Guidance 22. http://www.nice.org.uk. 2004.
  5. 5.
    Mahomed R, et al. Prescribing hypnotics in a mental health trust: what consultants say and what they do. Pharm J. 2002;268:657–9.Google Scholar
  6. 6.
    Goodwin RD, Hasin DS. Sedative use and misuse in the United States. Addiction. 2001;97:555–62.CrossRefGoogle Scholar
  7. 7.
    Hallstrom C, Lader MH. Benzodiazepine withdrawal phenomena. Int Pharmacopsychiatry. 1981;16:235–44.PubMedGoogle Scholar
  8. 8.
    Martinez-Cano H, Vela-Bueno A, De Iceta M, Pomalima R, Martinez-Gras I, Sobrino MP. Benzodiazepine types in high versus therapeutic dose dependence. Addiction. 1996;91:1179–86.PubMedCrossRefGoogle Scholar
  9. 9.
    De Wit H, Griffiths RR. Testing the abuse liability of anxiolytic and hypnotic drugs in humans. Drug Alcohol Depend. 1991;28:83–111.PubMedCrossRefGoogle Scholar
  10. 10.
    Seivewright NA, Dougal W. Benzodiazepine misuse. Curr Opin Psychiatry. 1992;5:408–11.CrossRefGoogle Scholar
  11. 11.
    Wolf B, Grohmann R, Biber D, Brenner PM, Ruther E. Benzodiazepine abuse and dependence in psychiatric inpatients. Pharmacopsychiatry. 1989;22:54–60.PubMedCrossRefGoogle Scholar
  12. 12.
    Bond AJ, Silveira JC, Lader MH. Effects of single doses of alprazolam alone and alcohol alone and in combination on psychological performance. Hum Psychopharmacol. 1991;6:219–28.CrossRefGoogle Scholar
  13. 13.
    Peles E, Schreiber S, Adelson M. Tricyclic antidepressants abuse, with or without benzodiazepines abuse, in former heroin addicts currently in methadone maintenance treatment (MMT). Eur Neuropsychopharmacol. 2007;18:188–93.PubMedCrossRefGoogle Scholar
  14. 14.
    Darke S. Benzodiazepine use among injecting drug users: problems and implications. Addiction. 1994;89:379–82.PubMedCrossRefGoogle Scholar
  15. 15.
    Stitzer M, Griffiths R, McLellan A, Grabowski J, Hawthorne J. Diazepam use among methadone maintenance patients: patterns and dosages. Drug Alcohol Depend. 1981;8:189–99.PubMedCrossRefGoogle Scholar
  16. 16.
    Sheehan MF, Sheehan DV, Torres A, Coppola A, Francis E. Snorting benzodiazepines. Am J Drug Alcohol Abuse. 1991;17:457–68.PubMedCrossRefGoogle Scholar
  17. 17.
    Strang J, Griffiths P, Abbey J, Gossop M. Survey of injected benzodiazepines among drug users in Britain. BMJ. 1994;308:1082.PubMedCrossRefGoogle Scholar
  18. 18.
    Bond AJ, Seijas D, Dawling S, Lader MH. Systematic absorption and abuse liability of snorted flunitrazepam. Addiction. 1994;89:821–30.PubMedCrossRefGoogle Scholar
  19. 19.
    Launchbury AP, Drake J, Seager H. Misuse of temazepem. BMJ. 1992;305:252–3.PubMedCrossRefGoogle Scholar
  20. 20.
    Oliver P, Keen J. Concomitant drugs of misuse and drug using behaviours associated with fatal opiate-related poisonings in Sheffield, UK, 1997-2000. Addiction. 2003;98(2):191–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Pirnay S, Borron S, Giudicelli C, Tourneau J, Baud F, Ricordel I. A critical review of the causes of death among post-mortem toxicological investigations: analysis of 34 buprenorphine-associated and 35 methadone-associated deaths. Addiction. 2004;99:978–88.PubMedCrossRefGoogle Scholar
  22. 22.
    Lader M. Withdrawal reactions after stopping hypnotics in patients with insomnia. CNS Drugs. 1998;10:425–40.CrossRefGoogle Scholar
  23. 23.
    Schweitzer E, et al. Benzodiazepine dependence and withdrawal: a review of the syndrome and its clinical management. Acta Psychiatrica Scand. 1998;393:95–101.CrossRefGoogle Scholar
  24. 24.
    Royal College of Psychiatrists. Benzodiazepines: risks, benefits and dependence: a re-evaluation. Council Report 59. 1997. http://www.rcpsych.ac.uk/(London).
  25. 25.
    Lader M, Tylee A, Donoghue J. Withdrawing benzodiazepines in primary care. CNS Drugs. 2009;23(1):19–34.PubMedCrossRefGoogle Scholar
  26. 26.
    Voshaar RCO, Couvee JE, Van Balkom AJLM, et al. Strategies for discontinuing long-term benzodiazepine use: meta-analysis. Br J Psychiatry. 2006;189:213–20.PubMedCrossRefGoogle Scholar
  27. 27.
    Denis C, et al. Pharmacological interventions for mono-dependence benzodiazepine management in outpatient settings. Cochrane Database Syst Rev. 2006;CD005194.Google Scholar
  28. 28.
    Schweitzer E, et al. Carbamazepine treatment in patients discontinuing long-term benzodiazepine therapy. Effects on withdrawal severity and outcome. Arch Gen Psychiatry. 1991;48:448–52.CrossRefGoogle Scholar
  29. 29.
    Gerra G, Zaimovic A, Giusti F, Moi G, Brewer C. Intravenous flumazenil versus oxazepam tapering in the treatment of benzodiazepine withdrawal: a randomised, placebo-controlled study. Addict Biol. 2002;7:385–95.PubMedCrossRefGoogle Scholar
  30. 30.
    Bond AJ, Lader MH, Shotriya R. Comparative effects of a repeated dose regime of diazepam and buspirone on subjective ratings, psychological tests and the EEG. Eur J Clin Pharm. 1983;24:463–7.CrossRefGoogle Scholar
  31. 31.
    Curran HV, Collins R, Fletcher S, Kee SCY, 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;33:1223–37.PubMedCrossRefGoogle Scholar
  32. 32.
    Darke S, Ross J. The use of antidepressants among injecting drug users in Sydney, Australia. Addiction. 2000;95:407–17.PubMedCrossRefGoogle Scholar
  33. 33.
    Woods JH, Katz JL, Winger G. Benzodiazepine use, abuse and consequences. Pharmacol Rev. 1992;44:151–347.PubMedGoogle Scholar
  34. 34.
    Wittenborn JR, Flaherty CF, McGough WE, Nash RJ. Psychomotor changes during initial day of benzodiazepine medication. Br J Clin Pharmacol. 1979;7:69S–76S.PubMedCrossRefGoogle Scholar
  35. 35.
    Buffet-Jerrott SE, Stewart SH. Cognitive and sedative effects of benzodiazepine use. Curr Pharm Des. 2002;8:45–58.CrossRefGoogle Scholar
  36. 36.
    Lucki I, Rickels K, Geller AM. Chronic use of benzodiazepines and psychomotor and cognitive test performance. Psychopharmacology. 1986;88:426–33.PubMedCrossRefGoogle Scholar
  37. 37.
    Golombok S, Moodley P, Lader M. Cognitive impairment in long-term benzodiazepines users. Psychol Med. 1988;18:365–74.PubMedCrossRefGoogle Scholar
  38. 38.
    Petursson H, Gudjonsson G, Lader M. Psychiatric performance during withdrawal form long-term benzodiazepine treatment. Psychopharmacology. 1983;81:345–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Curran HV. Benzodiazepines, memory and mood: a review. Psychopharmacology. 1991;105:1–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Curran H. Tranquillising memories: a review of the effects of benzodiazepines on human memory. Biol Psychol. 1986;23:179–213.PubMedCrossRefGoogle Scholar
  41. 41.
    Curran HV, Gorenstein C. Differential effects of lorazepam and oxazepam on priming. Int Clin Psychopharmacol. 1993;8:37–42.PubMedCrossRefGoogle Scholar
  42. 42.
    Curran HV, Bond A, O’Sullivan G, Bruce M, Marks I, Lelliot P, Shine P, Lader M. Memory functions, alprazolam and exposure therapy: a controlled longitudinal trial of agoraphobia with panic disorder. Psychol Med. 1994;24:969–76.PubMedCrossRefGoogle Scholar
  43. 43.
    Gorenstein C, Bernik MA, Pompeia S. Differential acute psychomotor and cognitive effects of diazepam on long-term benzodiazepine users. Int Clin Psychopharmacol. 1994;9:145–53.PubMedCrossRefGoogle Scholar
  44. 44.
    Barker MJ, Greenwood KM, Jackson M, Crowe SF. Cognitive effects of long-term benzodiazepine use: a meta-analysis. CNS Drugs. 2004;18:37–48.PubMedCrossRefGoogle Scholar
  45. 45.
    Gray S, Lai KV, Larson EB. Drug-induced cognition disorders in the elderly: incidence, prevention and management. Drug Saf. 1999;21:101–22.PubMedCrossRefGoogle Scholar
  46. 46.
    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;22:285–93.PubMedCrossRefGoogle Scholar
  47. 47.
    Barker MJ, Greenwood KM, Jackson M, et al. Persistence of ­cognitive effects after withdrawal from long-term benzodiazepine use: a meta-analysis. Arch Clin Neuropsychol. 2004;19:437–54.PubMedCrossRefGoogle Scholar
  48. 48.
    Verdoux H, Lagnaoui R, Begaud B. Is benzodiazepine use a risk factor for cognitive decline and dementia? A literature review of epidemiological studies. Psychol Med. 2005;35:307–15.PubMedCrossRefGoogle Scholar
  49. 49.
    Salzman C, Fisher J, Nobel K, Glassman R, Wolfson A, Kelley M. Cognitive improvement following benzodiazepine discontinuation in elderly nursing home residents. Int J Geriatr Psychiatry. 1992;7:89–93.CrossRefGoogle Scholar
  50. 50.
    Tata PR, Rollings J, Collins M, Pickering A, Jacobson RR. Lack of cognitive recovery following withdrawal from long-term benzodiazepine use. Psychol Med. 1994;24:203–13.PubMedCrossRefGoogle Scholar
  51. 51.
    Kilic C, Curran HV, Noshirvani H, Marks IM, Basoglu M. Long-term effects of alprazolam on memory: a 3.5 year follow-up of agoraphobial panic patients. Psychol Med. 1999;29:225–31.PubMedCrossRefGoogle Scholar
  52. 52.
    Wadsworth EJK, Moss SC, Simpson SA, Smith AP. Psychotropic medication use and accidents, injuries and cognitive failures. Hum Psychopharmacol. 2005;20:391–400.PubMedCrossRefGoogle Scholar
  53. 53.
    Kallin K, Lundin-Olsson L, Jensen J, Nyberg L, Gustafson Y. Predisposing and precipiataing factors for falls among older people in residential care. Public Health. 2002;116:263–71.PubMedGoogle Scholar
  54. 54.
    Taylor S, McCracken CF, Wilson KC, et al. Extent and appropriateness of benzodiazepine use. Results from an elderly urban community. Br J Psychiatry. 1998;173:433–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Ray WA, Griffin MR, Schaffner W, Baugh DK, Melton 3rd LJ. Psychotropic drug use and the risk of hip fracture. New Engl J Med. 1987;316:363–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Sternbacka M, Jansson B, Leufman A, Romelsjo A. Association between use of sedatives or hypnotics, alcohol consumption, or other risk factors and single injurious fall or multiple injurious falls: a longitudinal general population study. Alcohol. 2002;28:9–16.CrossRefGoogle Scholar
  57. 57.
    Cumming RG, Le Couteur DG. Benzodiazepines and risk of hip fractures in older people: a review of the evidence. CNS Drugs. 2003;17:825–37.PubMedCrossRefGoogle Scholar
  58. 58.
    O’Hanlon JF, de Gier JJ. Drugs and driving (Taylor and Francis, London, 1986). Addiction. 2003; 98:191–7.Google Scholar
  59. 59.
    Currie D, Hashemi K, Fothergill J, Findlay A, Harris A, Hindmarch I. The use of antidepressants and benzodiazepines in the perpetrators and victims of accidents. Occup Med. 1995;45:323–5.CrossRefGoogle Scholar
  60. 60.
    Skegg DCC, Richards SM, Doll R. Minor tranquillisers and road accidents. BMJ. 1979;1:917–9.PubMedCrossRefGoogle Scholar
  61. 61.
    Thomas RE. Benzodiazepine use and motor vehicle accidents. Systematic review of reported association. Can Fam Physician. 1998;44:799–808.PubMedGoogle Scholar
  62. 62.
    Barbone F, McMahon AD, Davey PG, et al. Association of road-traffic accidents with benzodiazepine use. Lancet. 1998;352:1331–6.PubMedCrossRefGoogle Scholar
  63. 63.
    Hemmelgarn B, Suissa S, Huang A, Boivin JF, Pinard G. Benzodiazepine use and the risk of motor vehicle crash in the elderly. JAMA. 1997;278:27–31.PubMedCrossRefGoogle Scholar
  64. 64.
    Ray WA, Fought RL, Decker MD. Psychoactive drugs and the risk of injurious motor vehicle crashes in elderly drivers. Am J Epidemiol. 1992;136:873–83.PubMedCrossRefGoogle Scholar
  65. 65.
    Paton C. Benzodiazepines and disinhibition: a review. Psychiatr Bull. 2002;26:460–2.CrossRefGoogle Scholar
  66. 66.
    Bond AJ. Drug-induced behavioural disinhibition. Incidence, mechanisms and therapeutic implications. CNS Drugs. 1998;9:41–57.CrossRefGoogle Scholar
  67. 67.
    Preston K, Griffiths R, Cone E, Darwin W, Gorodetzky C. Diazepam and methadone blood levels following concurrent administration of diazepam and methadone. Drug Alcohol Depend. 1986;18:195–202.PubMedCrossRefGoogle Scholar
  68. 68.
    Farre M, Teran M, Roset P, Mas M. Abuse liability of flunitrazepam among methadone-maintained patients. Psychopharmacology. 1998;140:486–95.PubMedCrossRefGoogle Scholar
  69. 69.
    Lintzeris N, Mitchell TB, Bond AJ, Nestor L, Strang J. Interactions on mixing diazepam with methadone or buprenorphine in maintenance patients. J Clin Psychopharmacol. 2006;26:274–83.PubMedCrossRefGoogle Scholar
  70. 70.
    Lintzeris N, Mitchell TB, Bond AJ, Nestor L, Strang J. Pharmacodynamics of diazepam co-administered with methadone or buprenorphine under high dose conditions in opioid dependent patients. Drug Alcohol Depend. 2007;91:187–94.PubMedCrossRefGoogle Scholar
  71. 71.
    Sramek JJ, Tansman M, Suri A, et al. Efficacy of buspirone in generalized anxiety disorder with coexisting mild depressive symptoms. J Clin Psychiatry. 1996;57:287–91.PubMedGoogle Scholar
  72. 72.
    Lader M. Anxiolytic effect of hydroxyzine: a double-blind trial versus placebo and buspirone. Hum Psychopharmacol. 1999;14 Suppl 1:S94–S102.CrossRefGoogle Scholar
  73. 73.
    Montgomery SA. Pregabalin for the treatment of generalised anxiety disorder. Expert Opin Pharmacother. 2006;7:2139–54.PubMedCrossRefGoogle Scholar
  74. 74.
    National Institute for Clinical Excellence. Insomnia—newer ­hypnotic drugs. Zaleplon,zolpidem and zopiclone for the ­management of insomnia. Technology Appraisal 77. http://www.nice.org.uk. 2004.
  75. 75.
    Benca RM. Diagnosis and treatment of chronic insomnia: a review. Psychiatr Serv. 2005;56:332–43.PubMedCrossRefGoogle Scholar
  76. 76.
    Glass J, Lanctot KL, Herrmann N, et al. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ. 2005;331:1169.PubMedCrossRefGoogle Scholar
  77. 77.
    Zisapel N. Development of a melatonin-based formulation for the treatment of insomnia in the elderly. Drug Dev Res. 2000;50:226–34.CrossRefGoogle Scholar
  78. 78.
    James SP, Mendelson WB. The use of trazodone as a hypnotic: a critical review. J Clin Psychiatry. 2004;65:752–5.PubMedCrossRefGoogle Scholar
  79. 79.
    Morin CM, Koetter U, Bastien C, et al. Valerian-hops combination and diphenhydramine for treating insomnia: a randomized placebo-controlled clinical trial. Sleep. 2005;28:1465–71.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Addiction, Institute of PsychiatryKing’s College LondonLondonUK
  2. 2.Institute of PsychiatryKings CollegeLondonUK

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