Prescribing drugs of dependence in general practice

Part B - Benzodiazepines - Chapter 3

Contraindications and precautions in special groups

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Last revised: 06 Nov 2019

Overview

Benzodiazepines should not be prescribed, or prescribed with extreme caution, to:

  • women who are, or may be, pregnant
  • patients with active SUDs, including alcohol (unless it is a part of an alcohol withdrawal program)
  • patients with medical or mental health conditions that may be worsened by benzodiazepines (eg fibromyalgia, chronic fatigue syndrome, depression, bipolar disorder or impulse control disorders)
  • patients being treated with opioids for chronic pain or addiction
  • patients experiencing grief reactions, as benzodiazepines may suppress and prolong the grieving process.

Benzodiazepines are generally not recommended for use in children.

Benzodiazepines may cause aggression, anxiety, nervousness and disinhibition in children and adolescents. Routine use for anxiety disorders cannot be recommended.157

The use of benzodiazepines in the paediatric population is clinically limited.158 Control of acute febrile or epileptic seizures is the primary indication. Seizures commonly occur in the paediatric populations and while most self-terminate within 5 minutes, those lasting longer may warrant medication to control the seizure and avoid status epilepticus (and neurological compromise).159 Buccal or intranasal midazolam and buccal or rectal diazepam are effective for the treatment of acute seizures in children.160

Note that children may have access to benzodiazepines through their parents, their peers or potentially via the internet.

Benzodiazepines should be avoided during pregnancy and breastfeeding. Non-drug approaches for anxiety and insomnia are preferred.

Women who become pregnant and are already taking benzodiazepines should be tapered down to the lowest effective dose, or have it completely withdrawn. With good withdrawal management, there is no evidence that withdrawal is likely to cause problems with the pregnancy.38

As benzodiazepines are highly fat soluble, they rapidly cross the placenta. Benzodiazepines taken early in pregnancy have been linked to congenital abnormalities (eg oral clefts, pyloric stenosis and alimentary tract atresia).161 This association is considered controversial, and data published in the last 10 years do not indicate an absolute contradiction to benzodiazepines in the first trimester.162 However, avoiding benzodiazepines or tapering off (completely or to the lowest possible dose) is recommended.163

Benzodiazepines taken later in pregnancy (late third trimester), during labour or while breastfeeding are associated with risks to the fetus/neonate. They can cause neonatal drowsiness, respiratory depression, poor temperature regulation, poor feeding, hypotonicity (‘floppy baby syndrome’) and neonatal withdrawal syndrome.35,164

Neonates exposed in utero may benefit from breastfeeding to reduce neonatal withdrawal.165,166

Where a hypnotic is necessary, zolpidem has been suggested.163 However, two studies have reported an association between zolpidem and an increased risk of adverse pregnancy outcomes, including small-for-gestational age, low birth weight and preterm deliveries.35

Note that women misusing benzodiazepines during pregnancy may also be using other drugs including alcohol.

Patients over 60 years of age have the most significant risk of harm with benzodiazepine use (particularly if the patient has additional risk factors for cognitive or psychomotor adverse events) relating to falls, fractures and cognitive decline.50,167

Benzodiazepines are used by approximately 15% of people over 65 years of age in Australia.168 Use of benzodiazepines in this age group is often chronic, despite the combination of harms associated with long-term, physiological changes with ageing (eg hepatic metabolism impairment) and the potential for multiple coexisting pathologies and drug interactions.

Older patients are more sensitive to the CNS depressant effects of psychotropic medications including benzodiazepines. This may result in confusion, night wandering, amnesia, pseudo-dementia38 (refer to 1.5.1.1 Cognitive impairment ), ataxia, falls and fractures.

In older patients, all psychotropic medications have been associated with an increased risk of fractures. The risk increase is moderate and similar across all psychotropic medications. One meta-analysis demonstrated that the relative risk of fractures was 1.34 (95% CI=1.24–1.45) for benzodiazepines, 1.60 (95% CI=1.38–1.86) for antidepressants, 1.59 (95% CI=1.27–1.98) for antipsychotics and 1.38 (95% CI=1.15–1.66) for opioids.169

Older people presenting with anxiety symptoms should be treated initially with antidepressants and psychological therapies, rather than benzodiazepines.170

Sedative use for insomnia has shown statistically significant improvements in sleep, but the magnitude of effect is small and the benefits of these drugs may not justify the increased risk.167 Clinical judgement is required.

Zolpidem and other Z drugs have become preferred drugs to manage insomnia. They are widely used among older adults because of perceived improved safety profiles compared with traditional benzodiazepines. However, accumulating data in recent years in patients over 65 years of age suggest possible safety concerns of these medications (zolpidem specifically) including effects on balance and memory and increased fracture risk. Until better studies or pharmacovigilance data become available to guide patient selection for prescribing zolpidem and other Z drugs, judicious use of these hypnotic agents in older adults is warranted.171

Reduction in the use of benzodiazepines in the elderly is a worthwhile goal if this can be achieved without psychotropic substitution. Older patients require planned interventions including CBT and stepped-dose reduction to reduce long-term benzodiazepine prescription.

Patients living in residential aged care facilities

Prescribing for patients living in residential aged care facilities (RACFs) (and other residential facilities) carries all of the risks associated with benzodiazepine use in older patients and presents further special difficulties.

Accreditation of RACFs has resulted in a heightened awareness of the facility’s responsibilities for quality use of medicines.

Medication may occasionally be required to control anxiety, agitation or other disturbed behaviours. Staff should be knowledgeable in the appropriate management of challenging behaviours. Where staff have received education in geriatric care, and where the organisational culture is supportive, there is less use of benzodiazepines.170

In a study of sleep quality in patients using benzodiazepines in RACFs, patients who were long-term users slept more poorly than those who were non-users. The effects were worse in patients taking long-acting benzodiazepines.172 Although patients, doctors, nursing staff and families often fear the consequences of benzodiazepine withdrawal in older patients, there is no evidence that patients experience an ‘unmasking’ of depression or anxiety.173

Successful reduction in the rates of benzodiazepine use in RACF patients results in benefits (eg increased mobility and alertness, reduced incontinence and improved wellbeing).174 Discontinuation of benzodiazepines can often be achieved gradually in RACFs, providing patient, family and nursing staff are cooperative.175

Benzodiazepines have been associated with increased fracture risk in patients living in RACFs. However, a reduction in benzodiazepine use may not lead to a decrease in fracture risk if substitution medications are used.176 Reduction in benzodiazepine use for RACF patients is worthwhile if it can be achieved without psychotropic drug substitution.

Use of multiple psychoactive medications (including benzodiazepines) is common in people who have chronic non-malignant pain (CNMP). Where available, it is advisable that a specialist pain or addiction service becomes involved in the care of these patients.177

The relationship bewteen pain, mental illness, SUD and dependence, and the social environment are complex. A range of addictive drugs has been misused in the context of CNMP including alcohol, benzodiazepines, cannabis, opioids and stimulants. Estimates of dependence (on any drug including alcohol) among people with chronic pain varies. In patients on long-term opioids, prevalence of DSM-5 opioid-use disorder may be as high as 26%.178

Benzodiazepines have little place in the management of chronic musculoskeletal pain. There is sparse evidence that these are clinically effective as muscle relaxants. The decision to use benzodiazepines in the context of multiple sclerosis or muscle disorders should be taken on a case-by-case basis with specialist consultation.

There is a strong association between sleep disturbance and CNMP. Evidence suggests that pain and sleep exist in a complex relationship in which pain causes sleep disturbance and sleep disturbance intensifies pain. This association can impair a patient’s daily function and decrease quality of life.179 Assessment of a patient’s sleep disturbance involves review of the contributing impacts of lifestyle, comorbid anxiety or depression, and uncontrolled pain to focus management on an individualised basis.

Benzodiazepines present additional risk for someone being prescribed opioids in terms of overdose (fatal and non-fatal) and psychomotor impairment. Driving presents a particular risk.

CBT can be useful in addressing emergent anxiety symptoms. Simple reassurance and attention to sleep hygiene can be effective with managing the emergent sleep disturbance. 

For the purposes of this guide, comorbidity will refer to situations where people have problems related both to their use of substances (from hazardous through to harmful use and/or dependence) and to their mental health (from problematic symptoms through to highly prevalent conditions such as depression and anxiety, and to the low-prevalence disorders such as psychosis).177

While it is common to refer to a patient’s psychiatric disorder or SUD as primary or secondary, this may have limited clinical use. It is important to establish whether substance use may be contributing to the patient’s psychiatric problems.177

Symptoms of psychiatric disorders (eg depression, anxiety and psychosis) in patients misusing drugs and/or alcohol are the rule rather than the exception. In addition, these psychiatric disorders increase the risk of harmful substance use and patients may be physically unwell. These patients are often the most challenging to engage and treat, and their prognosis is frequently poor.177

The number of placebo-controlled trials is small, and there remains little evidence to guide treatment.177 Available evidence suggests that a substantial proportion of patients with a comorbid SUD mental illness who are treated with benzodiazepines will develop some form of dependence. Therefore, benzodiazepines should largely be avoided, except in the context of withdrawal.180

Patients with personality disorders have a higher risk of dependence and dose escalation, hence benzodiazepines should be avoided in this group.

Patients who have problematic drug use belong to a complex group at high risk of adverse events. A common drug combination that should be noted is alcohol and benzodiazepines.180 When benzodiazepines are combined with other CNS depressants (eg alcohol, opioids), patients are at risk of respiratory depression, heavy sedation, coma and death. It has been reported that the use of antidepressant drugs in combination with benzodiazepines may also increase the risk of overdose, especially in the case of older TCAs.181 Alcohol and benzodiazepines can produce cross tolerance, and regular use of both can make withdrawal more severe and/or protracted.180

Apart from the risk of overdose, harms associated with polydrug use (particularly among people who inject drugs) include a higher rate of infectious and metabolic complications, as well as psychiatric, social and forensic consequences, with an increasing cost to society.182,183 People who are participating in medication-assisted opioid dependence treatment, and who take benzodiazepines regularly or intermittently, tend to do very poorly, with a higher risk of adverse outcomes.21

There is little evidence to guide practitioners in the management of this often difficult-to-treat population. However, when treating polydrug users, it is recommended not to initiate prescription of benzodiazepines. For polydrug users already taking them, it is recommended to reduce and cease prescription of benzodiazepines in a supervised manner.153

Therapeutic monitoring and prescribing should only occur if GPs have extensive experience in addiction medicine, or in conjunction with specialist supervision. When working with known polydrug users, it is essential to collaborate with local drug and alcohol services, and to provide clear guidelines on the accepted harm-minimisation strategies. Clear boundaries are crucial.

Maintenance benzodiazepine prescribing in illicit drug users cannot be recommended on the basis of existing evidence. Although it may reduce illicit benzodiazepine use in some patients,153 it may not be in the best interests of the patient or the wider community. The very rare exception would be under explicit agreement concerning specified short-term indications (such as outpatient alcohol withdrawal) as advised by a drug and addiction medicine specialist with daily, or at most weekly, dosing at a nominated pharmacy and monitoring with urinary drug test. Drug screens may be useful to monitor other benzodiazepines and drug use, especially in this population. 

Summarising the extensive literature on benzodiazepines and driving, the risk of accident increases proportionally to dose. However, there is no dose without increased risk – including stable, longer term dosing. Risk is highest at initiation, with long-acting benzodiazepines and when benzodiazepines are taken with other sedatives, especially alcohol.

Benzodiazepines have especially been shown to impair vision, attention, information processing, memory, motor coordination and combined-skill tasks. All drivers should be advised of increased crash risk when taking benzodiazepines. Patients who experience any degree of sedation should be cautioned not to drive.

According to Austroads, a person is not fit to hold an unconditional licence if they have an alcohol disorder or other SUD (eg substance dependence, heavy frequent alcohol or other substance use) that is likely to impair safe driving.184

The state or territory driver licensing authority may consider a conditional licence. This is subject to periodic review, taking into account the nature of the driving task and information provided by the treating doctor as to whether the following criteria are met:184

  • the person is involved in a treatment program and has been in remission* for at least 1 month
  • there is an absence of cognitive impairments relevant to driving
  • there is absence of ‘end-organ effects’ that impact on driving.

* Remission is attained when there is abstinence from the use of impairing substance(s) or where substance use has reduced in frequency to the point where it is unlikely to cause impairment. Remission may be confirmed by biological monitoring for the presence of drugs.

Some patients with SUD will continue to drive after being warned not to do so. If GPs are aware that a patient continues to drive in a dangerous way, they should:

  • more strongly recommend the patient stops
  • advise the patient that the GP has an obligation to report behaviours that are dangerous to the patient and others
  • consider reporting dangerous behaviour to state or territory licensing authorities.

This is a difficult situation as it will damage the doctor–patient relationship. However, in some cases the risk of damaging the relationship is outweighed by the risk of the patient (and others) being hurt or killed. If in doubt, contact your medical indemnity provider.

  1. Mehdi T. Benzodiazepines revisited. BJMP 2012;5(1):a501.
  2. Ashton H. The diagnosis and management of benzodiazepine dependence. Curr Opin Psychiatry 2005;18(3):249–55.
  3. Dell’osso B, Lader M. Do benzodiazepines still deserve a major role in the treatment of psychiatric disorders? A critical reappraisal. Eur Psychiatry 2013;28(1):7–20
  4. Committee on Safety of Medicines. Current problems – Benzodiazepines, dependence and withdrawal symptoms. London: Committee on Safety of Medicines, 1988. [Accessed 12 June 2015]
  5. Islam MM, Conigrave KM, Day CA, Nguyen Y, Haber PS. Twenty-year trends in benzodiazepine dispensing in the Australian population. Intern Med J 2014;44(1):57–64.
  6. Nicholas R, Lee N, Roche A. Pharmaceutical drug misuse in Australia: Complex issues, balanced responses. Adelaide: National Centre for Education and Training on Addiction (NCETA); 2011.
  7. Drugs and Crime Prevention Committee (DCPC). Inquiry into the misuse/abuse of benzodiazepines and other forms of pharmaceutical drugs in Victoria – Final report. Melbourne: DCPC; 2007.
  8. Sirdifield C, Anthierens S, Creupelandt H, et al. General practitioners’ experiences and perceptions of benzodiazepine prescribing: Systematic review and meta-synthesis. BMC Fam Pract 2013;14:191.
  9. Balon R. Benzodiazepines revisited. Psychother Psychosom. 2013;82(6):353–54.
  10. Haw C, Stubbs J. Benzodiazepines – A necessary evil? A survey of prescribing at a specialist UK psychiatric hospital. J Psychopharmacol 2007;21(6):645–9.
  11. Medicare Australia Statistics. Pharmaceutical Benefits Schedule Item Reports [internet]. [Accessed 4 April 2014].
  12. Coroners Court of Victoria. Coroners Prevention Unit – Pharmaceutical drugs in fatal overdose: A coroner’s perspective. Melbourne: Coroners Court of Victoria; 2015.
  13. Hollingworth SA, Siskind DJ, Nissen LM, Robinson M, Hall WD. Patterns of antipsychotic medication use in Australia 2002–2007. Aust N Z J Psychiatry 2010;44(4):372–7
  14. Britt HC, Miller GC, Henderson J, et al. A decade of Australian general practice activity 2003–04 to 2012–13. Sydney: Sydney University Press; 2013
  15. Rintoul AC, Dobbin MD, Nielsen S, Degenhardt L, Drummer OH. Recent increase in detection of alprazolam in Victorian heroin-related deaths. Med J Aust 2013;198(4):206–09.
  16. Australian Institute of Health and Welfare. 2010 National Drug Strategy Household Survey report. Cat. no. PHE 145. Canberra: AIHW; 2011.
  17. McGregor C, Gately N, Flemming J. Prescription drug use among detainees: Prevalence, sources and links to crime. Trends and issues in crime and criminal justice no.423. Canberra: Australian Institute of Criminology; 2011.
  18. Mitchell MD, Gehrman P, Perlis M, Umscheid CA. Comparative effectiveness of cognitive behavioral therapy for insomnia: A systematic review. BMC Fam Pract 2012;13:40.
  19. Nielsen S, Bruno R, Degenhardt L, et al. The sources of pharmaceuticals for problematic users of benzodiazepines and prescription opioids. Med J Aust 2013;199(10):696–99
  20. Alcohol and other Drugs Council of Australia (ADCA). Misuse of prescription drugs. Canberra: ADCA; 2003.
  21. Mental Health and Drug and Alcohol Office (MHDAO). NSW Opioid Treatment Program: Clinical guidelines for methadone and buprenorphine treatment. Sydney: MHDAO; 2006
  22. Pilgrim JL, McDonough M, Drummer OH. A review of methadone deaths between 2001 and 2005 in Victoria, Australia. Forensic Sci Int 2013;226(1–3):216–22.
  23. Ross J, Darke S. The nature of benzodiazepine dependence among heroin users in Sydney, Australia. Addiction 2000;95(12):1785–93
  24. Kirwan A, Dietze P, Lloyd B. Victorian drug trends 2011: findings from the Illicit Drug Reporting System (IDRS). Sydney: National Drug and Alcohol Reseach Centre, University of New South Wales; 2012.
  25. Baldwin DS, Aitchison K, Bateson A, et al. Benzodiazepines: risks and benefits. A reconsideration. J Psychopharmacol 2013;27(11):967–71.
  26. Quaglio G, Lugoboni F, Fornasiero A, et al. Dependence on zolpidem: two case reports of detoxification with flumazenil infusion. Int Clin Psychopharmacol 2005;20(5):285–87
  27. Sethi PK, Khandelwal DC. Zolpidem at supratherapeutic doses can cause drug abuse, dependence and withdrawal seizure. J Assoc Physicians India 2005;53:139–40.
  28. Harter C, Piffl-Boniolo E, Rave-Schwank M. Development of drug withdrawal delirium after dependence on zolpidem and zoplicone. Psychiatr Prax 1999;26(6):309.
  29. Huedo-Medina TB, Kirsch I, Middlemass J, Klonizakis M, Siriwardena AN. Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: meta-analysis of data submitted to the Food and Drug Administration. BMJ 2012;345:e8343
  30. Mental Health and Drug and Alcohol Office (MHDAO). NSW Drug and Alcohol Withdrawal Clinical Practice Guidelines. Sydney: MHDAO; 2008.
  31. World Health Organization. Lexicon of alcohol and drug terms published by the World Health Organization. Geneva: WHO; 2014 [Accessed 14 January 2014].
  32. Vinkers CH, Olivier B. Mechanisms Underlying Tolerance after Long-Term Benzodiazepine Use: A Future for Subtype-Selective GABA(A) Receptor Modulators? Adv Pharmacol Sci 2012;2012:416864.
  33. Longo LP, Johnson B. Addiction: Part I. Benzodiazepines – Side effects, abuse risk and alternatives. Am Fam Physician 2000;61(7):2121–28
  34. Argyropoulos SV, Nutt DJ. The use of benzodiazepines in anxiety and other disorders. Eur Neuropsychopharmacol 1999;9 Suppl 6:S407–12
  35. Therapeutic Guidelines. eTG complete [internet.] Melbourne: Therapeutic Guidelines Limited; 2013 [Accessed 26 Decemeber 2013]
  36. 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.
  37. Ashton H. Benzodiazepine withdrawal: outcome in 50 patients. Br J Addict 1987;82(6):665–71.
  38. Ford C, Law F. Guidance for the use and reduction of misuse of benzodiazepines and other hypnotics and anxiolytics in general practice. London: SMMGP; 2014.
  39. Smith DE, Wesson DR. Benzodiazepine dependency syndromes. J Psychoactive Drugs 1983;15(1–2):85–95
  40. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th edn. Arlington VA: American Psychiatric Publishing; 2013.
  41. Willems IA, Gorgels WJ, Oude Voshaar RC, Mulder J, Lucassen PL. Tolerance to benzodiazepines among long-term users in primary care. Fam Pract 2013;30(4):404–10.
  42. Griffin CE 3rd, Kaye AM, Bueno FR, Kaye AD. Benzodiazepine pharmacology and central nervous system-mediated effects. Ochsner J 2013;13(2):214–23.
  43. Roche. Valium (diazepam) Product Information. Date of first TGA inclusion 1994. Date of most recent amendment 2012. Sydney: Roche Products Pty Ltd; 2012.
  44. Alphapharm. Kalma (alprazolam) Product Information. Date of first TGA inclusion 1998. Most recent amendment 2014. Sydney: Alphapharm Pty Ltd; 2014.
  45. Alphapharm. Temaze (temazepam) Product Information. Date of first TGA inclusion 1998. Date of most recent amendment 2014. Sydney: Alphapharm Pty Ltd; 2014.
  46. Aspen. Ativan (lorazepam) Product Information. Date of first TGA inclusion 1993. Date of most recent amendment 2013. Sydney: Aspen Pharma Pty Ltd; 2013.
  47. Tiplady B, Bowness E, Stien L, Drummond G. Selective effects of clonidine and temazepam on attention and memory. J Psychopharmaco 2005;19(3):259–65.
  48. Buffett-Jerrott SE, Stewart SH. Cognitive and sedative effects of benzodiazepine use. Curr Pharm Des 2002;8(1):45–58.
  49. Barker MJ, Greenwood KM, Jackson M, Crowe SF. Cognitive effects of long-term benzodiazepine use: A meta-analysis. CNS Drugs 2004;18(1):37–48.
  50. Billioti de Gage S, Begaud B, Bazin F, et al. Benzodiazepine use and risk of dementia: Prospective population based study. BMJ 2012;345:e6231.
  51. Wu CS, Wang SC, Chang IS, Lin KM. The association between dementia and long-term use of benzodiazepine in the elderly: Nested casecontrol study using claims data. Am J Geriatr Psychiatry 2009;17(7):614–20.
  52. Gallacher J, Elwood P, Pickering J, et al. Benzodiazepine use and risk of dementia: Evidence from the Caerphilly Prospective Study (CaPS). J Epidemiol Community Health 2012;66(10):869–73.
  53. Amieva H, Le Goff M, Millet X, et al. Prodromal Alzheimer’s disease: Successive emergence of the clinical symptoms. Ann Neurol 2008;64(5):492–98.
  54. Mura T, Proust-Lima C, Akbaraly T, et al. Chronic use of benzodiazepines and latent cognitive decline in the elderly: Results from the Threecity study. Eur Neuropsychopharmacol 2013;23(3):212–23.
  55. Dassanayake T, Michie P, Carter G, Jones A. Effects of benzodiazepines, antidepressants and opioids on driving: A systematic review and meta-analysis of epidemiological and experimental evidence. Drug Saf 2011;34(2):125–56.
  56. Chouinard G. Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound. J Clin Psychiatry 2004;65 Suppl 5:7–12.
  57. Ashton H. Benzodiazepines: How they work and how to withdraw. Newcastle: The Ashton Manual; 2002.
  58. Nielsen M, Hansen EH, Gotzsche PC. What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors. Addiction 2012;107(5):900–08.
  59. Ashton H. Protracted withdrawal syndromes from benzodiazepines. J Subst Abuse Treat 1991;8(1–2):19–28.
  60. Schweizer E, Rickels K. Benzodiazepine dependence and withdrawal: a review of the syndrome and its clinical management. Acta Psychiatr Scand Suppl 1998;393:95–101.
  61. McCleery J, Cohen DA, Sharpley AL. Pharmacotherapies for sleep disturbances in Alzheimer’s disease. Cochrane Database Syst Rev 2014;3:Cd009178.
  62. Olsen Y. Clinical Guidelines for the use of benzodiazepines among patients receiving medication assissted treatment for opioid dependence. Baltimore: Baltimore Sustance Abuse Systems; 2013.
  63. van Marwijk H, Allick G, Wegman F, Bax A, Riphagen, II. Alprazolam for depression. Cochrane Database Syst Rev. 2012;7:CD007139.
  64. Guideline Working Group for the Treatment of Patients with Anxiety Disorders in Primary Care. Clinical Practice Guideline for Treatment of Patients with Anxiety Disorders in Primary Care. UETS no 2006/10 ed. Madrid: National Plan for the NHS of the MSC. Health Technology Assessment Unit; 2008.
  65. Busto U, Sellers EM, Naranjo CA, et al. Withdrawal reaction after long-term therapeutic use of benzodiazepines. N Engl J Med 1986;315(14):854–59.
  66. 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.
  67. Kenny P, Swan A, Berends L, et al. Alcohol and other drug withdrawal: Practice guidelines 2009. Melbourne: Turning Point Alcohol and Drug Centre; 2009.
  68. Psychotropic Drugs Committee. Practice Guideline 5: Guidelines for use of benzodiazepines in psychiatric practice: Royal Australian and New Zealand College of Psychiatrists. Melbourne 2008 (update, first issued 1991).
  69. Reconnexion. Beyond benzodiazepines: Helping people recover from benzodiazepine dependence and withdrawal – For health practitioners. Redman T, Cannard G, editors. Melbourne: Reconnexion Inc; 2010.
  70. Lader M. Withdrawal reactions after stopping hypnotics in patients with insomnia. CNS Drugs1998;10(6):425–40.
  71. Ashton H. Benzodiazepine dependency. In: Baum A, Newman S, Weinman J, West R, McManus C, editors. Cambridge Handbook of Psychology and Medicine. Cambridge: Cambridge University Press; 1997.
  72. Balter MB, Ban TA, Uhlenhuth EH. International study of expert judgment on therapeutic use of benzodiazepines and other pyschotherapeutic medications: I. Current concerns. Hum Psychopharmacol Clin Exp 1993;8:253–61.
  73. Starcevic V. The reappraisal of benzodiazepines in the treatment of anxiety and related disorders. Expert Rev Neurother 2014:1–12.
  74. American Psychiatric Association Task Force on Benzodiazepine Dependency. Benzodiazepine dependence, toxicity, and abuse. Washington, DC: AMA; 1990.
  75. Sheehan D, Raj A. Benzodiazepines. In: Shatzberg A, Nemeroff C, editors. The American Psychiatric Publishing Textbook of Psychopharmacology. 4th edn. Arlington, VA: American Psychiatric Publishing; 2009.
  76. Tvete IF, Bjorner T, Aursnes IA, Skomedal T. A 3-year survey quantifying the risk of dose escalation of benzodiazepines and congeners to identify risk factors to aid doctors to more rationale prescribing. BMJ Open 2013;3(10):e003296.
  77. Longo LP, Parran T, Jr., Johnson B, Kinsey W. Addiction: Part II. Identification and management of the drug-seeking patient. Am Fam Physician 2000;61(8):2401–08.
  78. Oster G, Huse DM, Adams SF, Imbimbo J, Russell MW. Benzodiazepine tranquilizers and the risk of accidental injury. Am J Public Health 1990;80(12):1467–70.
  79. Lloyd B. Trends in alcohol and drug related ambulance attendences in Melbourne 2010–11. Melbourne: Turning Point Alcohol and Drug Centre; 2012.
  80. Lloyd B. Ambo Project: Alcohol and drug related ambulance attendance in Victoria 2011–12. Melbourne: Turning Point Alcohol and Drug Centre and Ambulance Victoria; 2013.
  81. Tinetti ME. Clinical practice. Preventing falls in elderly persons. N Engl J Med 2003;348(1):42–49.
  82. Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med 1988;319(26):1701–07.
  83. Woolcott JC, Richardson KJ, Wiens MO, et al. Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Arch Intern Med 2009;169(21):1952–60.
  84. Kripke DF Langer RD, Kline LE. Hypnotics’ association with mortality or cancer: A matched cohort study. BMJ Open 2012;2(1):e000850.
  85. Jaussent I, Ancelin ML, Berr C, et al. Hypnotics and mortality in an elderly general population: A 12-year prospective study. BMC Med 2013;11:212.
  86. National Institute on Drug Abuse. Prescription Drugs: Abuse and Addiction: NIDA; 2001, revised 2011.
  87. Heit HA, Lipman AG. Pain: Substance Abuse Issue in the Treatment of Pain. In: Moore RJ, editor. Biobehavioral Approaches to Pain. New York: Springer Science+Business Media, LLC; 2009.
  88. Johnson C, Baxter B, Brough R, Buchanan J. Benzodiazepine prescribing: Lessons from interprofessional dialogue. Aust Fam Physician 2007;36(4):245–46.
  89. Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based guidelines for the pharmacological treatment of anxiety disorders: Recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2005;19(6):567–96.
  90. Mugunthan K, McGuire T, Glasziou P. Minimal interventions to decrease long-term use of benzodiazepines in primary care: A systematic review and meta-analysis. Br J Gen Pract 2011;61(590):e573–78.
  91. de Gier NA, Gorgels WJ, Lucassen PL, et al. Discontinuation of long-term benzodiazepine use: 10-year follow-up. Fam Pract 2011;28(3):253–59.
  92. 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):890–98.
  93. Spinks A, Bulbeck K, Del Mar C, Glasziou P, Nikles J, Group AcftPBW. Using benzodiazeines: the best evidence. Brisbane: Centre for General Practice, The University of Queensland; 2000.
  94. Bandelow B, Sher L, Bunevicius R, et al. Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care. Int J Psychiatry Clin Pract 2012;16(2):77–84.
  95. Rogers A, Pilgrim D, Brennan S, et al. Prescribing benzodiazepines in general practice: a new view of an old problem. Health (London) 2007;11(2):181–98.
  96. Fava GA, Gatti A, Belaise C, Guidi J, Offidani E. Withdrawal symptoms after selective serotonin reuptake inhibitor discontinuation: A systematic review. Psychother Psychosom 2015;84(2):72–81.
  97. Nielsen M, Hansen EH, Gotzsche PC. Dependence and withdrawal reactions to benzodiazepines and selective serotonin reuptake inhibitors. How did the health authorities react? Int J Risk Saf Med 2013;25(3):155–68.
  98. Evans EA, Sullivan MA. Abuse and misuse of antidepressants. Subst Abuse Rehabil 2014;5:107–20.
  99. Klein-Schwartz W, Schwartz EK, Anderson BD. Evaluation of quetiapine abuse and misuse reported to poison centers. J Addict Med 2014;8(3):195–98.
  100. Martin P, Tamblyn R, Ahmed S, Tannenbaum C. A drug education tool developed for older adults changes knowledge, beliefs and risk perceptions about inappropriate benzodiazepine prescriptions in the elderly. Patient Educ Couns 2013;92(1):81–7.
  101. Wilson SJ, Nutt DJ, Alford C, 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.
  102. Ministry of Health Singapore. Prescribing of Benzodiazepines: MOH Clinical Practice Guidelines 2/2008. Singapore: MOH; 2008.
  103. Guideline Working Group for the Treatment of Patients with Insomnia in Primary Care. Clinical Practice Guidelines for the Management of Patients with Insomnia in Primary Care. UETS No 2007/5–1. Madrid: Ministry of Health and Social Policy. Health Technology Assessment Unit; 2009.
  104. Britt HC, Miller GC, Henderson J, et al. General practice activity in Australia 2009–10. Canberra: Australian Institute of Health of Welfare; 2010.
  105. Pagel JF, Parnes BL. Medications for the treatment of sleep disorders: An overview. Prim Care Companion J Clin Psychiatry 2001;3(3):118–25.
  106. Wilson S, Nutt DJ. Recommended diagnosis and management of insomnia. Prescriber 2014.
  107. 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.
  108. Bonnet M, Arand D. Treatment of insomnia [internet].Waltham, MA: UpToDate; 2014 [updated 17 April 2015]. [Accessed 4 April 2014].
  109. Katz DA, McHorney CA. Clinical correlates of insomnia in patients with chronic illness. Arch Intern Med 1998;158(10):1099–107.
  110. Krystal AD. Psychiatric comorbidity: the case for treating insomnia. Sleep Med Clin 2006;1:359.
  111. Cunnington D, Junge MF, Fernando AT. Insomnia: prevalence, consequences and effective treatment. Med J Aust 2013;199(8):S36–40.
  112. Cunnington D. Non-benzodiazepine hypnotics: do they work for insomnia? BMJ 2013;346:e8699.
  113. 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.
  114. Arroll B, Fernando A 3rd, Falloon K, Warman G, Goodyear-Smith F. Development, validation (diagnostic accuracy) and audit of the Auckland Sleep Questionnaire: a new tool for diagnosing causes of sleep disorders in primary care. J Prim Health Care 2011;3(2):107–13.
  115. Kierlin L. Sleeping without a pill: non pharmacological treatments for insomnia. J Pscychiatr Pract 2008;14(6):403–07.
  116. Hasora P, Kessmann J. Nonpharmacological management of chronic insomnia. Am Fam Physician 2009;79(2):125–30.
  117. Montgomery P, Dennis J. Cognitive behavioural interventions for sleep problems in adults aged 60+. Cochrane Database Syst Rev 2003(1):CD003161.
  118. Buysse DJ, Germain A, Moul DE, et al. Efficacy of brief behavioral treatment for chronic Insomnia in older adults. Arch Intern Med 2011;171(10):887–95.
  119. Fernando A 3rd, Arroll B, Falloon K. A double-blind randomised controlled study of a brief intervention of bedtime restriction for adult patients with primary insomnia. J Prim Health Care 2013;5(1):5–10.
  120. Troxel WM, Germain A, Buysse DJ. Clinical management of insomnia with brief behavioral treatment (BBTI). Behav Sleep Med 2012;10(4):266–79.
  121. The Royal Australian College of General Practitioners. Brief behavioural therapy: insomnia in adults. Melbourne: RACGP; 2014. [Accessed 4 October 2014].
  122. Montgomery P, Dennis J. Physical exercise for sleep problems in adults aged 60+. Cochrane Database Syst Rev 2002(4):CD003404.
  123. Riemann D, Perlis ML. The treatments of chronic insomnia: a review of benzodiazepine receptor agonists and psychological and behavioral therapies. Sleep Med Rev 2009;13(3):205–14.
  124. Therapeutic Goods Administration (TGA). Zolpidem (Stilnox®) and next day impairment. Canberra: Australian Government Department of Health; 2014 [updated 1 August 2014]. [Accessed 2 September 2014].
  125. National Precribing Service. Melatonin prolonged-release tablets (Circadin®) for insmonia. Sydney: NPS; 2011.
  126. Lemoine P, Nir T, Laudon M, Zisapel N. Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J Sleep Res 2007;16(4):372–80.
  127. Clay E, Falissard B, Moore N, Toumi M. Contribution of prolonged-release melatonin and anti-benzodiazepine campaigns to the reduction of benzodiazepine and Z-drugs consumption in nine European countries. Eur J Clin Pharmacol 2013;69(4):1–10.
  128. Baldwin DS, Anderson IM, Nutt DJ, 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.
  129. Mental Health: Australian Bureau of Statistics; 2010 [updated 13 November 2013]. [Accessed 27 December 2013].
  130. Canadian Agency for Drugs and Technologies in Health. Short- and Long-Term Use of Benzodiazepines in Patients with Generalized Anxiety Disorder: A Review of Guidelines. Ottawa: CADTH; 2014.
  131. National Collaborating Centre for Mental Health. Generalised anxiety disorder and panic disorder (with or without agoraphobia) in adults: management in primary, secondary and community care. National Institute for Health and Care Excellence clinical guideline 113. London: NICE; 2011.
  132. Bystritsky A, Khalsa SS, Cameron ME, Schiffman J. Current diagnosis and treatment of anxiety disorders. P T 2013;38(1):30–57.
  133. The Royal Australian College of General Practitioners. Depression and anxiety: Internet based or computerised CBT (iCBT or CCBT). Melbourne: RACGP; 2014. [Accessed 4 October 2014].
  134. The Royal Australian college of General Practitioners. Bibliotherapy: Depression. Melbourne: RACGP; 2014. [Accessed 4 October 2014].
  135. Bandelow B, Seidler-Brandler U, Becker A, Wedekind D, Ruther E. Meta-analysis of randomized controlled comparisons of psychopharmacological and psychological treatments for anxiety disorders. World J Biol Psychiatry 2007;8(3):175–87.
  136. Hofmann SG, Sawyer AT, Korte KJ, Smits JA. Is it Beneficial to Add Pharmacotherapy to Cognitive-Behavioral Therapy when Treating Anxiety Disorders? A Meta-Analytic Review. Int J Cogn Ther 2009;2(2):160–75.
  137. Furukawa TA, Watanabe N, Churchill R. Psychotherapy plus antidepressant for panic disorder with or without agoraphobia: Systematic review. Br J Psychiatry 2006;188:305–12.
  138. Furukawa TA, Watanabe N, Churchill R. Combined psychotherapy plus antidepressants for panic disorder with or without agoraphobia. Cochrane Database Syst Rev 2007(1):CD004364.
  139. Tyrer P, Baldwin D. Generalised anxiety disorder. Lancet 2006;368(9553):2156–66.
  140. Bystritsky A. Pharmacotherapy for generalized anxiety disorder [internet]. Waltham, MA: UpToDate; 2013. [Accessed April 2015].
  141. Berney P, Halperin D, Tango R, Daeniker-Dayer I, Schulz P. A major change of prescribing pattern in absence of adequate evidence: Benzodiazepines versus newer antidepressants in anxiety disorders. Psychopharmacol Bull 2008;41(3):39–47.
  142. Bandelow B, Reitt M, Röver C, Michaelis S, Görlich Y, Wedekind D. Efficacy of treatments for anxiety disorders: a meta-analysis. Int Clin Psychopharmacol. 2015 Apr 29; Epub 2015 Apr 29.
  143. American Psychiatric Association. Practice guideline for the treatment of patients with panic disorder. 2nd edn. Arlington VA: American Psychiatric Publishing, Inc; 2009.
  144. Offidani E, Guidi J, Tomba E, Fava GA. Efficacy and tolerability of benzodiazepines versus antidepressants in anxiety disorders: A systematic review and meta-analysis. Psychother Psychosom 2013;82(6):355–62.
  145. Moylan S, Staples J, Ward SA, et al. The efficacy and safety of alprazolam versus other benzodiazepines in the treatment of panic disorder. J Clin Psychopharmacol 2011;31(5):647–52.
  146. Bostwick JR, Casher MI, Yasugi S. Benzodiazepines: A versatile clinical tool. Curr Psychiatr 2012;11(4).
  147. Nutt DJ. Overview of diagnosis and drug treatments of anxiety disorders. CNS Spectr 2005;10(1):49–56.
  148. Scottish Intercollegiate Guidelines Network. The Management of Harmful Drinking and Alcohol Dependence in Primary Care. Guideline No.74. Edinburgh: SIGN, Healthcare Improvement Scotland; 2004.
  149. National Institute for Health and Care Excellence. Alcohol-use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence. London: NICE; 2011. [Accessed April 2015].
  150. Amato L, Minozzi S, Vecchi S, Davoli M. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev 2010(3):CD005063.
  151. Gitlow S. Substance Use Disorders: A Practical Guide. Philadelphia, PA: Lippincott Williams and Wilkins; 2006.
  152. Liu J, Wang LN. Baclofen for alcohol withdrawal. Cochrane Database Syst Rev 2013;2:CD008502.
  153. Lingford-Hughes AR, Welch S, Peters L, Nutt DJ, British Association for Psychopharmacology ERG. BAP updated guidelines: Evidencebased guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity: Recommendations from BAP. J Psychopharmacol 2012;26(7):899–952.
  154. The Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines Team for Bipolar Disorder. Australian and New Zealand clinical practice guidelines for the treatment of bipolar disorder. Aust N Z J Psychiatry 2004;38(5):280–305.
  155. Scottish Intercollegiate Guidelines Network. Diagnosis and management of epilepsy in adults: A national clinical guideline. Guideline No. 70. Edinburgh: SIGN, Healthcare Improvement Scotland; 2003.
  156. Walker C, Brown K, Peterson C, et al. A socio-economic longitudinal study of epilepsy: Needs, perceptions and experiences of people with epilepsy. Epilepsy Foundation of Victoria and Epilepsy Australia; 2011.
  157. Ipser JC, Stein DJ, Hawkridge S, Hoppe L. Pharmacotherapy for anxiety disorders in children and adolescents. Cochrane Database Syst Rev 2009(3):CD005170.
  158. Witek MW, Rojas V, Alonso C, Minami H, Silva RR. Review of benzodiazepine use in children and adolescents. Psychiatr Q 2005;76(3):283–96.
  159. Harbord MG, Kyrkou NE, Kyrkou MR, Kay D, Coulthard KP. Use of intranasal midazolam to treat acute seizures in paediatric community settings. J Paediatr Child Health 2004;40(9-10):556–58.
  160. Humphries LK, Eiland LS. Treatment of acute seizures: is intranasal midazolam a viable option? J Pediatr Pharmacol Ther 2013;18(2):79–87.
  161. Wikner BN, Stiller CO, Bergman U, Asker C, Kallen B. Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: neonatal outcome and congenital malformations. Pharmacoepidemiol Drug Saf 2007;16(11):1203–10.
  162. Bellantuono C, Tofani S, Di Sciascio G, Santone G. Benzodiazepine exposure in pregnancy and risk of major malformations: a critical overview. Gen Hosp Psychiatry 2013;35(1):3–8.
  163. Maine Benzodiazepine Study Group. Guidelines for the use of benzodiazepines in office practice in the state of Maine. Maine: Maine Benzodiazepine Study Group; 2008.
  164. Uzun S, Kozumplik O, Jakovljevic M, Sedic B. Side effects of treatment with benzodiazepines. Psychiatr Danub 2010;22(1):90–93.
  165. Yoshida K, Smith B, Kumar R. Psychotropic drugs in mothers’ milk: A comprehensive review of assay methods, pharmacokinetics and of safety of breast-feeding. J Psychopharmacol 1999;13(1):64–80.
  166. Pons G, Rey E, Matheson I. Excretion of psychoactive drugs into breast milk. Pharmacokinetic principles and recommendations. Clin Pharmacokinet 1994;27(4):270–89.
  167. Glass J, Lanctot 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.
  168. Windle A, Elliot E, Duszynski K, Moore V. Benzodiazepine prescribing in elderly Australian general practice patients. Aust N Z J Public Health 2007;31(4):379–81.
  169. Takkouche B, Montes-Martinez A, Gill SS, Etminan M. Psychotropic medications and the risk of fracture: a meta-analysis. Drug Saf 2007;30(2):171–84.
  170. Council of the College of Psychiatry Ireland. A consensus statement on the use of benzodiazepines in specialist mental health services: EAP03/2012 Position Paper; 2012.
  171. Levy HB. Non-benzodiazepine hypnotics and older adults: what are we learning about zolpidem? Expert Rev Clin Pharmacol 2014;7(1):5–8.
  172. Bourgeois J, Elseviers MM, Van Bortel L, Petrovic M, Vander Stichele RH. Sleep quality of benzodiazepine users in nursing homes: A comparative study with nonusers. Sleep Med 2013;14(7):614–21.
  173. 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(3):242–48.
  174. Gilbert A, Owen N, Innes JM, Sansom L. Trial of an intervention to reduce chronic benzodiazepine use among residents of aged-care accommodation. Aust N Z J Med 1993;23(4):343–47.
  175. Jones KA, Nielsen S, Bruno R, Frei M, Lubman DI. Benzodiazepines – their role in aggression and why GPs should prescribe with caution. Aust Fam Physician 2011;40(11):862–65.
  176. Briesacher BA, Soumerai SB, Field TS, Fouayzi H, Gurwitz JH. Medicare part D’s exclusion of benzodiazepines and fracture risk in nursing homes. Arch Intern Med 2010;170(8):693–98.
  177. NSW Department of Health. NSW Clinical Guidelines: For the care of persons with comorbid mental illness and substance use disorders in acute care settings. Sydney: NSW Department of Health; 2009.
  178. Boscarino JA, Rukstalis M, Hoffman SN, et al. Risk factors for drug dependence among out-patients on opioid therapy in a large US healthcare system. Addiction 2010;105(10):1776–82.
  179. Brennan MJ, Lieberman JA 3rd. Sleep disturbances in patients with chronic pain: effectively managing opioid analgesia to improve outcomes. Curr Med Res Opin. 2009 May;25(5):1045-55.
  180. Mills K, Deady M, Proudfoot H, et al. Guidelines on the management of co-occuring alcohol and other drug and mental health conditions in alcohol and other drug treatment settings. Sydney: National Drug and Alcohol Research Centre, University of New South Wales; 2010.
  181. Darke S, Ross J. The use of antidepressants among injecting drug users in Sydney, Australia. Addiction 2000;95(3):407–17.
  182. Darke S, Hall W, Ross M, Wodak A. Benzodiazepine use and HIV risk-taking behaviour among injecting drug users. Drug Alcohol Depend 1992;31(1):31–36.
  183. Darke S, Ross J, Mills K, Teesson M, Williamson A, Havard A. Benzodiazepine use among heroin users: baseline use, current use and clinical outcome. Drug Alcohol Rev 2010;29(3):250–55.
  184. Austroads. Assessing fitness to drive for commercial and private vehicle drivers. 4th edn. Sydney: Austroads; 2013.
  185. Bond A, Lader M. Anxiolytics and sedatives. In: Verster JC, Brady K, Galanter M, Conrod P, editors. Drug abuse and addiction in medical illness: Causes, consequences and treatment. New York: Springer; 2012.
  186. Krystal AD. The treatment of primary insomnia. CNS Spectr 2009;14(12 Suppl 13):6–10.
  187. Howard P, Twycross R, Shuster J, Mihalyo M, Wilcock A. Benzodiazepines. J Pain Symptom Manage 2014;47(5):955–64.
  188. National Prescribing Service (NPS). NPS News: Which treatment for what anxiety disorder? Sydney: NPS; 2009.
  189. Lader M, Tylee A, Donoghue J. Withdrawing benzodiazepines in primary care. CNS Drugs 2009;23(1):19–34.
  190. Joint National Formulary Committee. British National Formulary. London: British Medical Association and Royal Pharmaceutical Society of Great Britain; 2011.
  191. Parr JM, Kavanagh DJ, Cahill L, Mitchell G, Mc DYR. Effectiveness of current treatment approaches for benzodiazepine discontinuation: a meta-analysis. Addiction 2009;104(1):13–24.
  192. Vicens C, Bejarano F, Sempere E, 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):471–79.
  193. Denis C, Fatseas M, Lavie E, Auriacombe M. Pharmacological interventions for benzodiazepine mono-dependence management i
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