CNS Drugs

, Volume 23, Issue 1, pp 19–34 | Cite as

Withdrawing Benzodiazepines in Primary Care

Review Article

Abstract

The use of benzodiazepine anxiolytics and hypnotics continues to excite controversy. Views differ from expert to expert and from country to country as to the extent of the problem, or even whether long-term benzodiazepine use actually constitutes a problem. The adverse effects of these drugs have been extensively documented and their effectiveness is being increasingly questioned. Discontinuation is usually beneficial as it is followed by improved psychomotor and cognitive functioning, particularly in the elderly. The potential for dependence and addiction have also become more apparent. The licensing of SSRIs for anxiety disorders has widened the prescribers’ therapeutic choices (although this group of medications also have their own adverse effects). Melatonin agonists show promise in some forms of insomnia. Accordingly, it is now even more imperative that long-term benzodiazepine users be reviewed with respect to possible discontinuation. Strategies for discontinuation start with primary-care practitioners, who are still the main prescribers.

This review sets out the stratagems that have been evaluated, concentrating on those of a pharmacological nature. Simple interventions include basic monitoring of repeat prescriptions and assessment by the doctor. Even a letter from the primary-care practitioner pointing out the continuing usage of benzodiazepines and questioning their need can result in reduction or cessation of use. Pharmacists also have a role to play in monitoring the use of benzodiazepines, although mobilizing their assistance is not yet routine. Such stratagems can avoid the use of specialist back-up services such as psychiatrists, home care, and addiction and alcohol misuse treatment facilities.

Pharmacological interventions for benzodiazepine dependence have been reviewed in detail in a recent Cochrane review, but only eight studies proved adequate for analysis. Carbamazepine was the only drug that appeared to have any useful adjunctive properties for assisting in the discontinuation of benzodiazepines but the available data are insufficient for recommendations to be made regarding its use. Antidepressants can help if the patient is depressed before withdrawal or develops a depressive syndrome during withdrawal. The clearest strategy was to taper the medication; abrupt cessation can only be justified if a very serious adverse effect supervenes during treatment. No clear evidence suggests the optimum rate of tapering, and schedules vary from 4 weeks to several years. Our recommendation is to aim for withdrawal in <6 months, otherwise the withdrawal process can become the morbid focus of the patient’s existence. Substitution of diazepam for another benzodiazepine can be helpful, at least logistically, as diazepam is available in a liquid formulation.

Psychological interventions range from simple support through counselling to expert cognitive-behavioural therapy (CBT). Group therapy may be helpful as it at least provides support from other patients. The value of counselling is not established and it can be quite time consuming. CBT needs to be administered by fully trained and experienced personnel but seems effective, particularly in obviating relapse.

The outcome of successful withdrawal is gratifying, both in terms of improved functioning and abstinence from the benzodiazepine usage. Economic benefits also ensue.

Some of the principles of withdrawing benzodiazepines are listed. Antidepressants may be helpful, as may some symptomatic remedies. Care must be taken not to substitute one drug dependence problem for the original one.

Notes

Acknowledgements

The literature search from which this review is derived was funded by an educational grant from Servier UK Ltd. Prof. Lader has no conflicts of interest that are directly relevant to the content of this review. Prof. Tylee has received consultancy fees and honoraria from Servier, Lilly, Lundbeck, Wyeth, GlaxoSmithKline and Organon for speaking at postgraduate meetings. He is currently receiving a grant from Servier for a qualitative study of patients’ perspectives of depression. Dr Donoghue is a consultant to Servier Laboratories Ltd, and has received honoraria from and had research funded by Servier.

References

  1. 1.
    Committee on the Review of Medicines. Systematic review of benzodiazepines. BMJ 1980; 280: 910–2CrossRefGoogle Scholar
  2. 2.
    Priest RG, Montgomery SA. Bull R Coll Psychiatry 1988; 12: 107–9CrossRefGoogle Scholar
  3. 3.
    Sussman N. Treating anxiety while minimizing abuse and dependence. J Clin Psychiatry 1993 May; 54 Suppl.: 44–51PubMedGoogle Scholar
  4. 4.
    Logan KE, Lawrie SM. Long term use of hypnotics and anxiolytics may not result in increased tolerance. BMJ 1994; 309: 742–3PubMedCrossRefGoogle Scholar
  5. 5.
    Woods JH, Winger G. Current benzodiazepine issues. Psychopharmacology 1995; 118: 107–15PubMedCrossRefGoogle Scholar
  6. 6.
    Lader M. Benzodiazepines: a risk-benefit profile. CNS Drugs 1994; 1: 377–87CrossRefGoogle Scholar
  7. 7.
    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: 433–8PubMedCrossRefGoogle Scholar
  8. 8.
    Gorenstein C, Bernik MA, Pompeia S. Differential acute psychomotor and cognitive effects of diazepam on long-term benzodiazepine users. Int Clin Psychopharmacol 1994; 9: 145–53PubMedCrossRefGoogle Scholar
  9. 9.
    Larson EB, Kukull WA, Buchner D, et al. Adverse drug reactions associated with global cognitive impairments in elderly persons. Ann Intern Med 1987; 107: 169–73PubMedGoogle Scholar
  10. 10.
    Trewin VF, Lawrence CJ, Veitch GB. An investigation of the association of benzodiazepines and other hypnotics with the incidence of falls in the elderly. J Clin Pharmacol Ther 1992; 17: 129–33CrossRefGoogle Scholar
  11. 11.
    Sorock GS, Shimkin EE. Benzodiazepine sedatives and the risk of falling in a community-dwelling elderly cohort. Arch Intern Med 1988; 148: 2441–4PubMedCrossRefGoogle Scholar
  12. 12.
    Ray WA, Griffin MR, Schaffner W, et al. Psychotropic drug use and the risk of hip fracture. N Engl J Med 198; 316: 363–9Google Scholar
  13. 13.
    Kripke DF, Klauber MR, Wingard DL, et al. Mortality hazard associated with prescription of hypnotics. Biol Psychiatry 1998; 43: 687–93PubMedCrossRefGoogle Scholar
  14. 14.
    Rickeis K, Case WG, Schweizer E, et al. Long-term benzodiazepine users 3 years after participation in a discontinuation program. Am J Psychiatry 1991; 148: 757–61Google Scholar
  15. 15.
    Salzman C, Fisher J, Nobel K, et al. Cognitive improvement following benzodiazepine discontinuation in elderly nursing home residents. Int J Geriatric Psychiatry 1992; 7: 89–93CrossRefGoogle Scholar
  16. 16.
    Tiller JW. Reducing the use of benzodiazepines in general practice. BMJ 1994; 309: 3–4PubMedCrossRefGoogle Scholar
  17. 17.
    Russell VJ, Lader MH, editors. Guidelines for the prevention and treatment of benzodiazepine dependence. London: Mental Health Foundation, 1993Google Scholar
  18. 18.
    Oude Voshaar RC, Couvee JE, van Balkom AJLM, et al. Strategies for discontinuing long-term benzodiazepine use: meta-analysis. Br J Psychiatry 2006; 189: 213–20CrossRefGoogle Scholar
  19. 19.
    Lader M. History of benzodiazepine dependence. J Subst Abuse Treat 1991; 8: 1–2CrossRefGoogle Scholar
  20. 20.
    Ashton H. The diagnosis and management of benzodiazepine dependence. Curr Opin Pychiatry 2005; 18: 249–55CrossRefGoogle Scholar
  21. 21.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd ed., revised. Washington, DC: American Psychiatric Association, 1987Google Scholar
  22. 22.
    World Health Organization. International classification of disases. 10th ed. Geneva: World Health Organization, 1992Google Scholar
  23. 23.
    Kan CC, Breteler MHM, Zitman FG. High prevalence of benzodiazepine dependence in out-patient users, based on the DSM-III-R and ICD-10 criteria. Acta Psychiatr Scan 1997; 96: 85–93CrossRefGoogle Scholar
  24. 24.
    Mant A, Duncan-Jones P, Saltman D, et al. Development of long term use of psychotropic drugs by general practice patients. BMJ 1988; 296: 251–4PubMedCrossRefGoogle Scholar
  25. 25.
    Deans HG, Skinner P. Doctors’ views on anxiety management in general practice. J R Soc Med 1992; 85: 83–6PubMedGoogle Scholar
  26. 26.
    Siriwardena AN, Qureshi Z, Gibson S, et al. GP’s attitudes to benzodiazepine and “z-drug” prescribing: a barrier to implementation of evidence and guidance on hypnotics. Br J Gen Pract 2006; 56: 964–7PubMedGoogle Scholar
  27. 27.
    National Institute for Clinical Excellence. Guidance on the use of zaleplon, zolpidem and zopiclone for the short-term management of insomnia. London: National Institute for Clinical Excellent, 2004 Apr. Technology appraisal 77Google Scholar
  28. 28.
    Rogers A, Pilgrim D, Brennan S, et al. Prescribing benzodiazepines in general practice: a new view of an old problem. Health 2007; 11: 181–98PubMedCrossRefGoogle Scholar
  29. 29.
    Zandstra SM, Furer JW, van der Lisdonk EH, et al. Differences in health status between long-term and short-term benzodiazepine users? Br J Gen Pract 2002; 52: 805–8PubMedGoogle Scholar
  30. 30.
    Zandstra SM, van Rijswijk E, Rijnders CA, et al. Long-term benzodiazepine users in family practice: differences from short-term users in mental health, coping behaviour and psychological characteristics. Fam Pract 2004; 21: 266–9PubMedCrossRefGoogle Scholar
  31. 31.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994Google Scholar
  32. 32.
    Wilson RPH, Hatcher J, Barton S, et al. The influence of practice characteristics on the prescribing of benzodiazepines and appetite suppressant drugs. Pharmacoepidemiol Drug Safety 1998; 7: 243–51CrossRefGoogle Scholar
  33. 33.
    Millar HL, Clunie FS, McGilchrist MM, et al. The impact of community benzodiazepine prescribing of hospitalization. J Psychosom Res 1997; 42: 61–9PubMedCrossRefGoogle Scholar
  34. 34.
    Hughes LM, Holden JD, Tree AM. Audit as a method of reducing benzodiazepine prescribing in general practice. J Clin Eff 1997; 2: 79–82Google Scholar
  35. 35.
    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: 408–12PubMedGoogle Scholar
  36. 36.
    Cormack MA, Sweeney KG, Hughes J, et al. Evaluation of an easy cost-effective strategy for cutting benzodiazepine use in general practice. Br J Gen Pract 1994; 44: 5–8PubMedGoogle Scholar
  37. 37.
    Gorgels WJM, Oude Voshar RC, Mol AJ, et al. Predictors of discontinuation of benzodiazepine prescription after sending a letter to long-term benzodiazepine users in family practice. Fam Pract 2006; 23: 65–72PubMedCrossRefGoogle Scholar
  38. 38.
    Baker R, Farooqi A, Tait C, et al. Randomised controlled trial of reminders to enhance the impact of audit in general practice on management of patients who use benzodiazepines. Qual Health Care 1997; 6: 14–8PubMedCrossRefGoogle Scholar
  39. 39.
    Towle I, Adams J. A novel, pharmacist-led strategy to reduce the prescribing of benzodiazepines in Paisley. Pharm J 2006; 276: 136–8Google Scholar
  40. 40.
    Dollman WB, LeBlanc VT, Stevens LO, et al. Achieving a sustained reduction in benzodiazepine use through implementation of an area-wide multi-strategic approach. J Clin Pharm Ther 2005; 30: 425–32PubMedCrossRefGoogle Scholar
  41. 41.
    Jørgensen VRK. An approach to reduce benzodiazepine and cyclopyrrolone use in general practice: a study based on a Danish population. CNS Drugs 2007; 21: 947–55PubMedCrossRefGoogle Scholar
  42. 42.
    Denis C, Fatseas M, Lavie E, et al. Pharmacological interventions for benzodiazepine mono-dependence in outpatient settings. Cochrane Database Syst Rev 2006; (3): CD005194Google Scholar
  43. 43.
    Cantopher T, Olivieri S, Cleave N, et al. Chronic benzodiazepine dependence: a comparative study of abrupt withdrawal under propranolol cover versus gradual withdrawal. Br J Psychiatry 1990; 156: 406–11PubMedCrossRefGoogle Scholar
  44. 44.
    Hallstrom C, Crouch G, Robson M, et al. The treatment of tranquillizer dependence by propranolol. Postgrad Med J 1988; 64Suppl. 2: 40–4PubMedGoogle Scholar
  45. 45.
    Lader M, Olajide D. A comparison of buspirone and placebo in relieving benzodiazepine withdrawal symptoms. J Clin Psychopharmacol 1987; 7: 11–5PubMedCrossRefGoogle Scholar
  46. 46.
    Lemoine P, Touchon J, Billardon M. Withdrawal of long-term administered lorazepam using six different plans [in French]. Encephale 1997; 23: 290–9PubMedGoogle Scholar
  47. 47.
    Murphy SM, Tyrer P. A double-blind comparison of the effects of gradual withdrawal of lorazepam, diazepam and bromazepam in benzodiazepine dependence. Br J Psychiatry 1991; 158: 511–6PubMedCrossRefGoogle Scholar
  48. 48.
    Schweitzer E, Rickels K, Case WG, et al. Carbamazapine treatment in patients discontinuing long-term benzodiazepine therapy: effects on withdrawal severity and outcome. Arch Gen Psychiatry 1991; 48: 448–52CrossRefGoogle Scholar
  49. 49.
    Schweitzer E, Case WG, Garcia Espana F, et al. Progesterone co-administration in patients discontinuing long-term benzodiazepine therapy: effects on withdrawal severity and taper outcome. Psychopharmacol 1995; 117: 424–9CrossRefGoogle Scholar
  50. 50.
    Tyrer P, Ferguson B, Hallstrom C, et al. A controlled trial of dothiepin and placebo in treating benzodiazepine withdrawal symptoms. Br J Psychiatry 1996; 168: 457–61PubMedCrossRefGoogle Scholar
  51. 51.
    Rickels K, Case G, Schweizer E, et al. Low dose dependence in chronic benzodiazepine users: a preliminary report on 119 patients. Psychopharmacol Bull 1986; 22: 407–15PubMedGoogle Scholar
  52. 52.
    Nathan RG, Robinson D, Cherek DR, et al. Alternative treatments for withdrawing the long-term benzodiazepine user: a pilot study. Int J Addict 1986; 21: 195–211PubMedGoogle Scholar
  53. 53.
    Busto UE, Sykora K, Sellers EM. A clinical scale to assess benzodiazepine withdrawal. J Clin Psychopharmacol 1989; 9: 412–6PubMedCrossRefGoogle Scholar
  54. 54.
    Ashton CH, Rawlins MD, Tyrer SP. A double-blind placebocontrolled study of buspirone in diazepam withdrawal in chronic benzodiazepine users. Br J Psychiatry 1990; 157: 232–8PubMedCrossRefGoogle Scholar
  55. 55.
    Gerra G, Marcato A, Caccavari R, et al. Effectiveness of flumazenil (Ro 15-1788) in the treatment of benzodiazepine withdrawal. Curr Ther Res 1993; 54: 580–7CrossRefGoogle Scholar
  56. 56.
    Lader M, Farr I, Morton S. A comparison of alpidem and placebo in relieving benzodiazepine withdrawal symptoms. Int Clin Psychopharmacol 1993; 8: 31–6PubMedCrossRefGoogle Scholar
  57. 57.
    Ashton H. The treatment of benzodiazepine dependence. Addiction 1994; 89: 1535–41PubMedCrossRefGoogle Scholar
  58. 58.
    Busto UE, Kaplan HL, Zawertailo L, et al. Pharmacologic effects and abuse liability of bretazenil, diazepam, and alprazolam in humans. Clin Pharmacol Ther 1994; 55: 451–63PubMedCrossRefGoogle Scholar
  59. 59.
    Hayward P, Wardle J, Higgitt A, et al. Changes in “withdrawal symptoms” following discontinuation of low-dose diazepam. Psychopharmacol 1996; 125: 392–7CrossRefGoogle Scholar
  60. 60.
    Busto UE, Naranjo CA, Bremner KE, et al. Safety of ipsapirone treatment compared with lorazepam: discontinuation effects. J Psychiatry Neurosci 1998; 23: 35–44PubMedGoogle Scholar
  61. 61.
    Romach MK, Kaplan HL, Busto UE, et al. A controlled trial of ondansetron, a 5-HT3 antagonist, in benzodiazepine discontinuation. J Clin Psychopharmacol 1998; 18: 121–31PubMedCrossRefGoogle Scholar
  62. 62.
    Lilja J, Larsson S, Skinhoj KT, et al. Evaluation of programs for the treatment of benzodiazepine dependency. Subst Use Misuse 2001; 36: 1213–31PubMedCrossRefGoogle Scholar
  63. 63.
    McGregor C, Machin A, White JM. In-patient benzodiazepine withdrawal: comparison of fixed and symptom-triggered taper methods. Drug Alcohol Rev 2003; 22: 175–80PubMedCrossRefGoogle Scholar
  64. 64.
    Mercier-Guyon C, Chabannes JP, Saviuc P. The role of captodiamine in the withdrawal from long-term benzodiazepine treatment. Curr Med Res Opin 2004; 20: 1347–55PubMedCrossRefGoogle Scholar
  65. 65.
    Sanchez-Craig M, Capell 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: 1313–27CrossRefGoogle Scholar
  66. 66.
    Saxon L, Hiltunen AJ, Hjemdahl P, et al. Gender-related differences in response to placebo in benzodiazepine withdrawal: a single-blind pilot study. Psychopharmacol 2001; 153: 231–7CrossRefGoogle Scholar
  67. 67.
    Schweizer E, Rickeis K. Failure of buspirone to manage benzodiazepine withdrawal. Am J Psychiatry 1986; 143: 1590–2PubMedGoogle Scholar
  68. 68.
    Schweizer E, Rickels K, Case WG, et al. Long-term use of benzodiazepines: effects of gradual taper. Arch Gen Psychiatry 1990; 47: 908–15PubMedCrossRefGoogle Scholar
  69. 69.
    Tyrer P, Murphy S, Oates G, et al. Psychological treatment for benzodiazepine dependence. Lancet 1985; 1(8436): 1042–3PubMedCrossRefGoogle Scholar
  70. 70.
    Voderholzer U, Riemann D, Hornyak M, et al. A double-blind, randomized and placebo-controlled study on the polysomnographic withdrawal effects of zopiclone, zolpidem and triazolam in healthy subjects. Eur Arch Psychiatry Clin Neurosci 2001; 251: 117–23PubMedCrossRefGoogle Scholar
  71. 71.
    Vorma H, Naukkarinen H, Sarna S, et al. Treatment of outpatients with complicated benzodiazepine dependence: comparison of two approaches. Addict 2002; 97: 851–9CrossRefGoogle Scholar
  72. 72.
    Vorma H, Naukkarinen H, Sarna S, et al. Long-term outcome after benzodiazepine withdrawal treatment in subjects with complicated dependence. Drug Alcohol Dep 2003; 70: 309–14CrossRefGoogle Scholar
  73. 73.
    Oude Voshaar RC, Gorgels WJ, Mol AJ, 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: 498–504CrossRefGoogle Scholar
  74. 74.
    Ries RK, Roy-Byrne R, Ward NG, et al. Carbamazepine treatment for benzodiazepine withdrawal. Am J Psychiatry 1989; 146: 536–7PubMedGoogle Scholar
  75. 75.
    Brogden RN, Goa KL. Flumazenil: a reappraisal of its pharmacological properties and therapeutic efficacy as a benzodiazepine antagonist. Drugs 1991; 42: 1061–89PubMedCrossRefGoogle Scholar
  76. 76.
    Higgitt A, Lader M, Fonaghy P. The effect of the benzodiazepine antagonist Ro-1578 on psychophysiological performance and subjective measures in normal subjects. Psychopharmacology 1986; 89: 395–403PubMedCrossRefGoogle Scholar
  77. 77.
    File SE, Baldwin HA. Flumazenil: a possible treatment for benzodiazepine withdrawal anxiety. Lancet 1987; II: 106–7CrossRefGoogle Scholar
  78. 78.
    Lader MH, Morton SV. A pilot study of the effects of flumazenil on symptoms persisting after benzodiazepine withdrawal. J Psychopharmacol 1992; 6: 357–63PubMedCrossRefGoogle Scholar
  79. 79.
    Gerra G, Marcato A, Caccavari R, et al. Effectiveness of flumazenil (Ro 15-1788) in the treatment of benzodiazepine withdrawal. Curr Ther Res 1993; 54: 580–7CrossRefGoogle Scholar
  80. 80.
    Saxon L, Hjemdahl P, Hiltunen AJ, et al. Effects of flumazenil in the treatment of benzodiazepine withdrawal: a double-blind pilot study. Psychopharmacol 1997; 131: 153–60CrossRefGoogle Scholar
  81. 81.
    Gerra G, Zaimovic A, Giusti F, et al. Intravenous flumazenil versus oxazepam tapering in the treatment of benzodiazepine withdrawal: a randomized placebo-controlled study. Addict Biol 2002; 7: 385–95PubMedCrossRefGoogle Scholar
  82. 82.
    Nutt DJ, Glue P, Lawson C, et al. Flumazenil provocation of panic attacks. Arch Gen Psychiatry 1990; 47: 9176–25CrossRefGoogle Scholar
  83. 83.
    Mintzer MZ, Stoller KB, Griffiths RR. A controlled study of flumazenil-precipitated withdrawal in low-dose benzodiazepoine users. Psychopharmacology 1999; 147: 200–9PubMedCrossRefGoogle Scholar
  84. 84.
    Bernik MA, Gorenstein C, Veira Filho AHG. Stressful reactions and panic attacks induced by flumazenil in chronic benzodiazepine users. J Psychopharmacol 1998; 12: 146–50PubMedCrossRefGoogle Scholar
  85. 85.
    Rickels K, DeMartinis N, Rynn N, et al. Pharmacologic strategies for discontinuing benzodiazepine treatment. J Clin Psychopharmacol 1999; 19: 12–6SCrossRefGoogle Scholar
  86. 86.
    Olajide D, Lader M. Depression following withdrawal from long-term benzodiazepine use: a report of four cases. Psychol Med 1984; 14: 937–40PubMedCrossRefGoogle Scholar
  87. 87.
    Zitman FG, Couvee JE. Chronic benzodiazepine use in general practice patients with depression: an evaluation of controlled treatment and taper-off. Br J Psychiatry 2001; 178: 317–24PubMedCrossRefGoogle Scholar
  88. 88.
    Gilhooly TC, Webster MGO, Poole NW, et al. What happens when doctors stop prescribing temazepam? Use of alternative therapies. Br J Gen Pract 1998; 48: 1601–2PubMedGoogle Scholar
  89. 89.
    Spiegel DA. Psychological strategies for discontinuing benzodiazepine treatment. J Clin Psychopharmacol 1999; 6: 17–22SCrossRefGoogle Scholar
  90. 90.
    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. Can Med Assoc J 2003; 169: 1015–20Google Scholar
  91. 91.
    Gosselin P, Ladouceur R, Morin CM, et al. Benzodiazepine discontinuation among adults with GAD: a randomized trial of cognitive-behavioral therapy. J Consult Clin Psychol 2006; 74: 908–19PubMedCrossRefGoogle Scholar
  92. 92.
    Edinger JD, Wohlgemuth WK. The significance and management of persistent primary insomnia: the past, present and future of behavioural insomnia therapies. Sleep Med Rev 1999; 3: 101–18PubMedCrossRefGoogle Scholar
  93. 93.
    Morgan K, Dixon S, Mathers N, et al. Psychological treatment for insomnia in the regulation of long-term hypnotic use. Health Technol Assess 2004; 8: 1–68Google Scholar
  94. 94.
    Fletcher J, Fahey T, McWilliam J. Relationship between the provision of counselling and the prescribing of antidepressants, hypnotics and anxiolytics in general practice. Br J Gen Pract 1995; 45: 467–9PubMedGoogle Scholar
  95. 95.
    Van Tulder MW, Assendelft WJJ, Koes BW, et al. Method guidelines for systematic reviews in the Cochrane Collaboration Back Review Group for Spinal Disorders. Spine 1997; 22: 2323–30PubMedCrossRefGoogle Scholar
  96. 96.
    Lader M. Tranquillizers and antidepressants: when to take them, how to stop. London: Sheldon Press, 2008Google Scholar
  97. 97.
    Hawley CJ, Tattersal M, Dellaportas C, et al. Comparison of long-term benzodiazepine users in three settings. B J Psychiatry 1994; 165: 792–6CrossRefGoogle Scholar
  98. 98.
    Holden JD, Hughes IM, Tree A. Benzodiazepine prescribing and withdrawal for 3234 patients in 15 general practices. Fam Pract 1994; 11: 358–62PubMedCrossRefGoogle Scholar
  99. 99.
    Curran HV, Collins R, Fletcher 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: 1223–37PubMedCrossRefGoogle Scholar
  100. 100.
    Iliffe S, Curran HV, Collins R, et al. Attitudes to long-term use of benzodiazepine hypnotics by older people in general practice: findings from interviews with service users and providers. Aging Ment Health 2004; 8: 242–8PubMedCrossRefGoogle Scholar
  101. 101.
    O’Connor KP, Belanger L, Marchand A, et al. Psychological distress and adaptational problems experienced during discontinuation of benzodiazepines. Addict Behav 1999; 24: 537–41PubMedCrossRefGoogle Scholar
  102. 102.
    O’Connor KP, Marchand A, Belanger L, et al. Psychological distress and adaptational problems associated with benzodiazepine withdrawal and outcome. Addict Behav 1004; 29: 583–93CrossRefGoogle Scholar
  103. 103.
    Tyrer P, Rutherford D, Huggett T. Benzodiazepine withdrawal symptoms and propranolol. Lancet 1981; I: 520–2CrossRefGoogle Scholar
  104. 104.
    Stahl S. Don’t ask, don’t tell, but benzodiazepines are still the leading treatments for anxiety disorders. J Clin Psychiatr 2002; 63: 756–7CrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  1. 1.Institute of PsychiatryKing’s College LondonLondonEngland
  2. 2.John Moores UniversityLiverpoolScotland

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