Benzodiazepines are widely used and one of the most commonly misused classes of prescription drugs in Australia. Dependence on benzodiazepines is more likely to occur with prolonged use and is becoming of increasing concern.

Long-term prescribing and its effects on the CNS are contributing factors to benzodiazepine misuse and dependence. GPs and pharmacists play a key role in educating patients and carers about the safe and appropriate use of benzodiazepines.

Key points

  • Benzodiazepines are not recommended as first-line therapy for insomnia, panic disorders, and anxiety (including anxiety with depression).
  • Consider other treatment options, including non-pharmacological measures, for the respective indication.
  • Treatment duration should be limited to the shortest period of time.
  • Use patient-focused treatment plans to help educate patients about the risks and benefits of benzodiazepines.
  • Consider a multidisciplinary care model to achieve the best health outcome for your patient.

Benzodiazepine misuse

In Australia benzodiazepines are indicated for a range of conditions, including anxiety, sleep and panic disorders, epilepsy, muscle spasms and alcohol dependence.

Common adverse events include over-sedation, drowsiness, slurred speech and dependence.1

International and national guidelines recommend short-term use of benzodiazepines of 2–4 weeks, and as part of a broader management plan that includes other pharmacological or non-pharmacological measures for the treatment of these conditions.2, 3

Continued use of benzodiazepines contributes to a significant risk of dependence and abuse.4, 5 These drugs are commonly implicated in overdose incidents and in drug-related suicide attempts leading to hospital and emergency department admissions.4

They are also present in about one-half to two-thirds of drug deaths, either in motor vehicle accidents, in which they are the most prevalent prescription drug, or in combination with other depressants such as opiates and/or alcohol.6, 7

While the total number of prescriptions of benzodiazepines dispensed through the PBS/RPBS declined from 1992 to 2011,8 the increase in dispensed quantity per script8 and the large number of scripts written annually Australia-wide indicates that most prescriptions relate to long-term use.4

Although benzodiazepines in some cases are prescribed long-term, particularly in the elderly and in complex clinical situations, these drugs should be prescribed with caution as they can be associated with physical and psychological dependence and tolerance often leading to misuse.1

What is dependence syndrome?

The WHO defines dependence as including a strong desire or sense of compulsion to take a substance, difficulty in controlling its use, tolerance and the presence of a withdrawal state.9, 10

The development of dependence with benzodiazepines appears to be similar to that of other classes of addictive drugs. The mechanism of dependence is associated with the disinhibition of dopaminergic neurons located in the midbrain, known as the ventral tegmental area, leading to dopamine surges causing pleasurable sensations.11

These surges also change the expression of glutamatergic receptors, which makes the cells in the midbrain more susceptible to stimulation by glutamate. As a result, the cells respond to future drug exposures with larger dopamine surges that produce more intense pleasure.2, 11

Benzodiazepine use for longer than 4 weeks, particularly at high doses, risks development of dependence that increases with duration of treatment.3 It can also lead to cognitive impairment, delirium, falls and fall-related injuries such as hip fractures, motor vehicle crashes and death.12

Stopping benzodiazepine use can be relatively easy for some patients but may be difficult for others. Estimates suggest that 30% to 40% of patients on benzodiazepine treatment for longer than 1 month will experience significant withdrawal symptoms on abrupt cessation.2, 3, 13

Practical steps for reducing benzodiazepine dependence

When judiciously used, benzodiazepines are therapeutically effective; however, health professionals and patients should be aware of the risk of addiction and dependence associated with long-term use.14

To reduce the risk of benzodiazepine dependence and misuse:

  • use only for appropriate indications1
  • seek specialist advice before considering prescribing a benzodiazepine for panic disorder15
  • consider managing underlying causes and use of behavioural and/or psychological interventions for insomnia and anxiety disorders1, 15
  • reserve for short-term use only for a duration of up to 2–4 weeks
  • assess efficacy at one week1, 5, 13
  • only prescribe to well-known patients
  • assess the risk–benefit ratio of long-term use of benzodiazepines and openly discuss withdrawing from benzodiazepines if appropriate13
  • identify patients who take large doses of benzodiazepines to achieve an intoxicated effect and refer them to a specialist drug and alcohol service.13,16

Encourage collaborative decision making

Maintaining a patient focus ensures that care, including the prescribing or non-prescribing of drugs of dependence, is provided in collaboration with patients and their families and/or carers.16

When discussing dependence with patients, adopt a non-judgemental approach and be empathetic to the individual circumstances.16

Explore issues surrounding the starting or continuing of a benzodiazepine and provide open and honest information with continuing support to help patients make an informed decision.13, 16

A useful tool for managing expectations and providing education is a written management plan to document:16

  • patient and doctor responsibilities, goals and expectations
  • desired outcomes in behavioural terms (ie, obtaining scripts from only one doctor and one pharmacy, attending appointments regularly, consequences of inappropriate patient behaviour such as verbal threats or manipulative behaviour, etc).

For a patient who has been using benzodiazepines long term and has signs of dependence, consider determining a score of withdrawal symptoms using the CIWA-B Benzodiazepine Withdrawal Scale.17

The score can be used to start an open discussion on gradual withdrawal of the benzodiazepine, leading to a more patient-focused management plan.

Refer to Therapeutic Guidelines3 or the Victorian Government Alcohol and Other Drug Withdrawal Practice Guidelines18 for further information on withdrawal regimens.

Consider a shared care approach

Pharmacists and nurses can also contribute to reducing the risk of benzodiazepine dependence and misuse by considering the following practice points:

  • reinforce the importance of short-term use and tapering of benzodiazepine dose
  • inform patients about side effects and withdrawal symptoms when supplying the medicine
  • counsel on the use of the medicine and the context of its use
  • advise of the possibility of tolerance and dependence associated with long-term use
  • monitor for signs of dependence (ie, drug-seeking behaviour, need for increased dose, unwillingness to withdraw from treatment)
  • refer the patient to the doctor if signs of dependence are identified
  • provide details of patient support groups, for example, Reconnexion.

Additionally, in developing a withdrawal management plan, prescribers can enlist the help of the patient's pharmacist to dispense the medication at regular intervals as staged supply.13

Information for patients

Offering fact sheets will help educate patients, particularly when a benzodiazepine is not appropriate, or in those seeking repeat prescriptions. Fact sheet examples include:

References

  1. Australian Medicines Handbook. Adelaide: Australian Medicines Handbook, 2015. [AMH Online].
  2. Hood SD, Norman A, Hince DA, et al. Benzodiazepine dependence and its treatment with low dose flumazenil. Br J Clin Pharmacol 2014;77:285–94. [PubMed].
  3. Expert Group for Psychotropic. Therapeutic Guidelines: Psychotropic: Benzodiazepines, zolpidem and zoplicone: problem use. [eTG online] (accessed 3 June 2015).
  4. The Royal Australasian College of Physicians. Submission to the Therapeutics Goods Administration (TGA) Advisory Committee on Medicines Scheduling 2013. [Online RACP members only] (accessed 27 May 2015).
  5. Jones KA, Neilsen S, Bruno R, et al. Benzodiazepines: Their role in aggression and why GPs should prescribe with caution. Aust Fam Physician 2011;40:862–5. [PubMed].
  6. Australian Institute of Criminology. Benzodiazepine use and harms among police detainees in Australia. 2007. [Online] (accessed 26 May 2015).
  7. Victoria Parliament Drugs and Crime Prevention Committee. Inquiry into the misuse/ abuse of benzodiazepines and other forms of pharmaceutical drugs in Victoria. 2008. [Online] (accessed 21 March 2017).
  8. Islam MM, Conigrave KM, Day CA, et al. Twenty-year trends in benzodiazepine dispensing in the Australian population. Intern Med J 2014;44:57–64. [PubMed].
  9. Lader M. Benzodiazepine harm: how can it be reduced? Br J Clin Pharmacol 2014;77:295–301. [PubMed].
  10. World Health Organization. Management of substance abuse. [Online] (accessed 26 May 2015).
  11. National Institute on Drug Abuse. Well-Known Mechanism Underlies Benzodiazepines' Addictive Properties. 2012. [Online] (accessed 23 June 2015).
  12. Johnson B, Streltzer J. Risks associated with long-term benzodiazepine use. Am Fam Physician, 2013;88:224–5. [PubMed].
  13. Drug and Alcohol Services South Australia. Benzodiazepines. 2014. [Online] (accessed 27 May 2015).
  14. Ananth J. Benzodiazepines: selective use to avoid addiction. Postgrad Med 1982;72:271–6. [PubMed].
  15. Expert Group for Psychotropic. Therapeutic Guidelines: Psychotropic: Panic disorder. 2015. [eTG online] (accessed 5 June 2015).
  16. Royal Australian College of General Practitioners. Clinical guidelines: Prescribing drugs of dependence in general practice, Part A. 2015. [Online] (accessed 1 June 2015).
  17. Government of South Australia. Benzodiazepine Withdrawal Scale ( CIWA-B). 2013. [Online] (accessed 20 Mar 2017)..
  18. Frei M, Kenny P, Swan A, et al. Alcohol and Other Drug Withdrawal: Practice Guidelines 2012. [Online] (accessed 1 June 2015).