Withdrawing Benzodiazepines in Patients With Anxiety Disorders
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The large class of CNS-depressant medications—the benzodiazepines—have been extensively used for over 50 years, anxiety disorders being one of the main indications. A substantial proportion (perhaps up to 20–30 %) of long-term users becomes physically dependent on them. Problems with their use became manifest, and dependence, withdrawal difficulties and abuse were documented by the 1980s. Many such users experience physical and psychological withdrawal symptoms on attempted cessation and may develop clinically troublesome syndromes even during slow tapering. Few studies have been conducted to establish the optimal withdrawal schedules. The usual management comprises slow withdrawal over weeks or months together with psychotherapy of various modalities. Pharmacological aids include antidepressants such as the SSRIs especially if depressive symptoms supervene. Other pharmacological agents such as the benzodiazepine antagonist, flumazenil, and the hormonal agent, melatonin, remain largely experimental. The purpose of this review is to analyse the evidence for the efficacy of the usual withdrawal regimes and the newer agents. It is concluded that little evidence exists outside the usual principles of drug withdrawal but there are some promising leads.
KeywordsBenzodiazepines Dependence Withdrawal Clinical risks Abuse Flumazenil Circadin
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Conflict of Interest
Malcolm Lader and Andri Kyriacou declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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- 8.Rcpsych.ac.uk. Benzodiazepines [Internet]. 2015 [cited 19 June 2015]. Available from: http://www.rcpsych.ac.uk/healthadvice/treatmentswellbeing/benzodiazepines.aspx.
- 9.Mehdi T. Benzodiazepines revisited. Br J Med Pract Manage. 2012;5(1):a501.Google Scholar
- 11.Petursson H, Lader M. Dependence on tranquillizers. Oxford: Oxford University Press; 1984.Google Scholar
- 19.Lader M. Long-term anxiolytic therapy: the issue of drug withdrawal. J Clin Psychiatry. 1987;1(48 Suppl):12–6.Google Scholar
- 21.Russell J, Lader M. Guidelines for the prevention and treatment of benzodiazepine dependence. London: The Mental Health Foundation; 1994.Google Scholar
- 25.••Lingford-Hughes A, Welch S, Peters L, Nutt D. BAP updated guidelines: evidence-based guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity: recommendations from BAP. J Psychopharmacol. 2012;26(7):899–952. An authoritative review on the features and management of various types of addiction.CrossRefPubMedGoogle Scholar
- 26.Ashton C. Benzodiazepines: how they work & how to withdraw. Newcastle: University of Newcastle; 2001.Google Scholar
- 29.Denis D, Fatseas M, Lavie E, Auriscombe M. Pharmacological interventions for benzodiazepine mono-dependence management in outpatient settings. Cochrane Database Syst Rev. 2007. CD005194.Google Scholar
- 30.Murphy S, 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(4):511–6.Google Scholar
- 36.Efficacy of drug treatments for Generalised Anxiety Disorder: systematic review and meta-analysis. BMJ. 2011;342(mar16 2):d1718-d1718.Google Scholar
- 37.••Baldwin D, Anderson I, Nutt D, Allgulander C, Bandelow B, den Boer J, 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. An authoritative survey of the treatments available to treat various anxiety disorders.CrossRefPubMedGoogle Scholar
- 40.Crockford D, White W, Campbell B. Gabapentin use in benzodiazepine dependence and detoxification. Can J Psychiatr. 2001;46:287.Google Scholar
- 41.Chessick C, Allen M, Thase M. Azapirones for generalized anxiety disorder. Cochrane Database Syst Rev. 2015;3, CD006115.Google Scholar
- 43.Guaiana G, Barbui C, Cipriani A. Hydroxyzine for generalised anxiety disorder. Cochrane Database Syst Rev. 2010;12. CD006815.Google Scholar
- 48.Peles E, Hetzroni T, Bar-Hamburger R, Adelson M, Schreiber S. Melatonin for perceived sleep disturbances associated with benzodiazepine withdrawal among patients in methadone maintenance treatment: a double-blind randomized clinical trial. Addiction. 2007;102(12):1947–53.CrossRefPubMedGoogle Scholar
- 57.Baillargeon L, Landreville P, Verreault R, Beauchemin J, Gregoire J, Morin C. Discontinuation of benzodiazepines among older insomniac adults treated with cognitive-behavioural therapy combined with gradual tapering; a randomized trial. Can Med Assoc J. 2003;169:1015–20.Google Scholar
- 68.Gerra G, Zaimovic A, Giusti F, Moi G, Brewer C. Intravenous flumazenil versus oxazepam tapering in the treatment of benzodiazepine withdrawal: a randomized, placebo-controlled study. Addict Biol. 2002;7(4):385–95.Google Scholar