To address continuing concerns about the potential harms associated with benzodiazepine use and misuse, the Royal Australian College of General Practitioners (RACGP) recently released new recommendations that focus on patient-centred care and accountable prescribing. The new guidelines offer a framework to help GPs reduce the risk of benzodiazepine-related substance use disorder (SUD), and identify and manage patients with benzodiazepine-related SUD.

Key points

  • New 2015 RACGP guidelines on prescribing benzodiazepines in general practice focus on patient-centred care, accountable prescribing, and harm reduction.
  • GPs are in a good position to recognise indicators of problematic drug use, such as drug-seeking behaviour and patterns of overuse or escalating use.
  • Various subtle behaviours have been identified as indicators of potential low-dose or therapeutic-dose dependence, such as a patient’s need to carry their tablets with them.
  • Guidelines recommend cessation of benzodiazepine where SUD has been established, using gradual tapering – determined on an individual basis – to minimise withdrawal symptoms.

Benzodiazepines can be associated with significant harm

Benzodiazepines are not recommended as first-line therapy for insomnia or anxiety and, when prescribed, are generally only recommended for short-term use (2–4 weeks).1-3 Long-term use of benzodiazepines can lead to harms (eg, falls, road accidents and overdose), tolerance, dependence and dose escalation.1,2,4

According to the 2013 National Drug Strategy Household Survey, tranquillisers/sleeping pills (including benzodiazepines) were the second most commonly misused medicine behind painkillers/analgesics.5 Benzodiazepines are often used in combination with other drugs, increasing the risk of harm due to overdose or traffic accidents.1

Victorian data for 2009–2014 showed that 51.2% of all deaths due to drug overdose involved benzodiazepines (used alone or in combination with other drugs).6 Another study found that 55% of heroin-related deaths and 88% of methadone-related deaths also involved benzodiazepines.7

In a 2013 study, 78% of benzodiazepine users reported that they obtained their benzodiazepine from a medical practitioner.8 The study found that benzodiazepine users took 3–6 years from first use to progress to regular or problematic use.8 This highlights a window of opportunity for health practitioners to intervene and prevent benzodiazepine misuse and dependence.

New RACGP guidelines to reduce harm from benzodiazepine use

In July 2015, in response to growing concern about the harms associated with benzodiazepine use and misuse, the RACGP released new guidelines on prescribing benzodiazepines in general practice.1,2 Designed to discourage inappropriate use and reduce patient harms, the guidelines provide GPs with:1,2

  • a framework for appropriate and safer prescribing practices
  • information on the risks associated with benzodiazepine use
  • information on non-drug therapies as alternatives to benzodiazepines
  • tools to help manage patients taking benzodiazepines
  • tools to help recognise and manage patients with problematic benzodiazepine use.

For more information on how to reduce the risk of benzodiazepine dependence, see Benzodiazepine dependence: reduce the risk.

Indicators of problematic benzodiazepine use

In the therapeutic setting, the incidence of problematic benzodiazepine use is generally low,4 although it is higher in people who also abuse alcohol and other drugs.4  Acccording to the National Drug Strategy Household Survey, 1.6% of people aged 14 years and over used tranquillisers/sleeping pills (including benzodiazepines) for non-medical purposes in 2013.5

GPs are well placed to identify patients with problematic drug use, encourage patients to seek treatment and work with patients to develop a plan for recovery.

Patterns of overuse or escalating use, and drug-seeking behaviour in a patient may indicate problematic drug use (Table 1).9 Such behaviours include doctor- or prescription-shopping, and scamming to increase supply or obtain more potent formulations.

Table 1: Drug-seeking behaviour indicating problematic benzodiazepine use.1

Behaviour indicating risk but less predictive of problematic use Behaviour highly predictive of problematic use

Seeking early prescription renewal

Complaining aggressively about needing higher doses

Drug hoarding during periods when symptoms are reduced

Requesting specific drugs

Obtaining similar drugs from other sources

Escalating unsanctioned doses 1–2 times

Treating other symptoms with the drug

Selling prescription drugs

Forging prescriptions

Stealing or borrowing another patient's medicines

Injecting oral formulations

Obtaining prescription drugs from non-medical sources

Concurrently abusing illicit drugs

Escalating unsanctioned doses multiple times

Repeatedly losing prescriptions

Identifying patients with substance use disorder (SUD)

The use of the word 'dependence' has changed. Once used interchangeably with addiction and misuse, it has returned to its pharmacological definition: a state that develops during chronic drug treatment in which cessation elicits an abstinence reaction (withdrawal).1

The new DSM-5 criteria have established a new condition, 'substance use disorder' (SUD), to reduce confusion associated with the terms of dependence, abuse and addiction; and to reduce the stigma to patients given these labels.1 The DSM-5 criteria combine a cluster of cognitive, behavioural and physiological symptoms into a complex condition called SUD, involving combinations of interacting patient and drug factors.1

Diagnosing SUD based on the DSM-5 criteria

SUD is diagnosed when a patient meets at least two of 11 criteria across four categories (impaired control, social impairment, risky use, and pharmacology) within a 12-month period (Table 2).1 SUD severity can be classified as:

  • mild (2–3 symptoms/criteria)
  • moderate (4–5 symptoms/criteria) or
  • severe (≥ 6 symptoms/criteria).1

Table 2. DSM-5 criteria for diagnosing a sedative, hypnotic or anxiolytic use disorder

a Not considered to be met for individuals taking sedatives, hypnotics or anxiolytics under medical supervision.

Category Symptoms / criteria
Impaired control criteria
  • Often taken in larger amounts or over longer period than was intended
  • Persistent desire or unsuccessful efforts to reduce or control use
  • Large amount of time dedicated to obtaining or using the medicine, or recovering from the effects
  • Craving or strong desire for, or urge to use, the medicine
Social impairment criteria
  • Recurrent use affecting ability to fulfil obligations at work, school or home
  • Continued use despite persistent or recurrent social problems caused or exacerbated by the medicine
  • Cessation or reduction of important social, occupational or recreational activities due to use
Risky use criteria
  • Recurrent use in physically hazardous situations
  • Continued use despite persistent or recurrent physical or psychological problems caused or exacerbated by the medicine
Pharmacological criteria
  • Tolerance, defined as either:a

- need for markedly increasing amounts of the medicine

- a markedly diminished effect with continued use of the same amount of the medicine

  • Withdrawal manifested as either one of the following:

- characteristic withdrawal syndrome (refer to p 557–558 of DSM-5)

- the drug (or a closely related substance such as alcohol) is taken to relieve or avoid withdrawal symptoms.

Types of benzodiazepine dependence

In addition to the three severity levels of SUD, there are different types of benzodiazepine dependence.1,10 These are:

  • low-dose or therapeutic-dose dependence – where benzodiazepines are prescribed for insomnia or anxiety and taken at doses that are within therapeutically recommended limits despite dose escalation over time1,10
  • prescribed high-dose dependence – where people on prescribed benzodiazepines start to need higher doses. Patients with this type of dependence may ask their doctor to escalate the dose and, once the limit is reached, may contact other doctors to obtain more10
  • recreational high-dose dependence – where benzodiazepine is used, often at doses higher than therapeutic doses, for recreational purposes (eg, to increase the effects of illicit drugs or reduce withdrawal symptoms of other drugs of abuse).1,10

Be aware of subtle behaviours in patients with low-dose dependence

Patients with low-dose dependence may exhibit subtle behaviours that can include:1,10

  • a need to carry their tablets around with them
  • a tendency to take an extra dose in anticipation of a stressful event or sleeping in a strange bed
  • returning regularly to obtain repeat prescriptions, often before running out of the previous supply
  • needing benzodiazepines in order to carry out their day-to-day activities
  • continuing benzodiazepine use despite the resolution of the initial indication for the prescription
  • having difficulty stopping or reducing their dose due to withdrawal symptoms.

Patients with low-dose dependence do not typically abuse other drugs or alcohol.1 Assess each patient's behaviour against the DSM-5 SUD criteria (Table 2) to gauge severity of the dependence.

Managing benzodiazepine withdrawal in primary care

For a small number of patients, stable long-term use of benzodiazepines may be justified, on a case-by-case basis, if:1

  • a patient’s quality of life improves with stable use. This may require specialist consultation. Document the decision to continue long-term benzodiazepine therapy and regularly review and reassess the risks and benefits of benzodiazepine use.
  • a patient struggles to reduce and stop benzodiazepine use. In this group you may consider continuing patients on low-dose benzodiazepines, with ongoing regular reviews as part of a long-term plan for cessation of benzodiazepine use.

For patients with complex, multiple morbidities, consult mental health and addiction specialists and other relevant specialists (eg, neurologists) to develop an appropriate treatment plan for the patient.1

Consider a stepped approach, starting with minimal interventions such as advisory letters before progressing to more intense methods. An advisory letter can be sent following an audit of a patient's benzodiazepine prescription.2 The letter can outline the harms and risks of benzodiazepine use and invite the patient to consult the doctor about alternative therapies.2 For a sample advisory letter, see Appendix E RACGP Prescribing drugs of dependence in general practice, Part A Clinical governance framework.

Maintain a strong therapeutic alliance with the patient, and any other health care providers involved in their treatment, to increase their likelihood of successful benzodiazepine cessation.1,2

Withdrawal symptoms will vary between patients, depending on the type of benzodiazepine dependence (low-dose, prescribed high-dose or recreational high-dose).1 This means a withdrawal management plan should be tailored for each patient.1

Common withdrawal symptoms include anxiety, insomnia, irritability, myoclonic jerks, palpitations, and sensory disturbances, such as photophobia and hyperacusis (oversensitivity to certain frequency and volume ranges).1,3

Encourage all patients with dependence to cease taking the benzodiazepine and offer detoxification programs regularly.1

Management of benzodiazepine withdrawal may include:1

  • reviewing and discussing prescription records with patients
  • sending advisory letters suggesting cessation or dose reduction and offering advice on ways to gradually reduce benzodiazepine use
  • acknowledging that benzodiazepine withdrawal can be stressful
  • advising patients to make lifestyle changes such as exercising regularly and avoiding alcohol
  • encouraging family and friends to support patients by providing further encouragement or practical help
  • advising patients to avoid stimulants (eg, coffee and chocolate) that can cause anxiety, panic and insomnia
  • informing patients of non-pharmacological methods (eg, exercise, relaxation techniques) to cope with anxiety and insomnia due either to the primary condition or the withdrawal process
  • referring patients to appropriate services (eg, psychological or support groups).b

RACGP guidelines recommend that benzodiazepine prescriptions be obtained from a single prescriber and a single pharmacy during gradual dose reduction.1 It is important to maintain regular communication with other health professionals involved in the patient's care, such as the pharmacist, counsellor, psychiatrist or addiction service.1

In some cases, in addition to gradual dose reduction protocols, psychological therapies, such as cognitive behavioural therapy, may aid discontinuation of benzodiazepines.1,11,12

Additional pharmacotherapy (eg, carbamazepine, antidepressants or melatonin) is generally used to treat withdrawal symptoms, such as anxiety, sleep problems or seizures, rather than as a substitute for benzodiazepines.1 However, the evidence to support the use of these medicines in benzodiazepine withdrawal is limited.1,12

b Refer to drug or alcohol dependence services if the patient has a concurrent drug or alcohol problem or if the service specialises in benzodiazepine dependence.

Tapering benzodiazepine use

Gradual dose reduction of the prescribed benzodiazepine is recommended for patients with SUD, so as to minimise or avoid withdrawal symptoms (Table 3).1 Sudden cessation of benzodiazepines in patients on high doses may result in seizures.3

The rate of benzodiazepine withdrawal should be determined for each patient, taking into consideration the drug, dose, duration of treatment, withdrawal symptoms, and patient factors (eg, personality, lifestyle, previous experiences, and specific vulnerabilities).1,3

For patients prescribed long-term benzodiazepines within or slightly above the therapeutic dose range, dose reduction at 15% of starting dose per week may be well tolerated.3

For samples of benzodiazepine withdrawal protocols, see RACGP Prescribing drugs of dependence in general practice, Part B: Benzodiazepines, Resource D.2 Benzodiazepine reduction in the practice population.

Table 3: Guidance on tapering benzodiazepines.1

Duration of use Recommended duration of tapering Comments
< 6 to 8 weeks May not be required Consider tapering benzodiazepine, particularly if patients is taking a high-dose benzodiazepine or a medicine with short or intermediate half-life
8 weeks to 6 months Slowly over 2–3 weeks
6 months to 1 year Slowly over 4–8 weeks Tapering will minimise withdrawal symptoms
Advise patients to avoid alcohol and stimulants
> 1 year Slowly over 2–4 months

Stabilise patients taking high-dose benzodiazepines on diazepam prior to dose reduction.

In patients taking high-dose and/or short half-life benzodiazepines, guidelines recommend stabilisation on an equivalent dose of diazepam (a long half-life benzodiazepine) before starting dose reduction (Table 4).3 In patients taking multiple types of benzodiazepine, the stabilisation dose can be calculated by adding the various diazepam equivalents.3

Table 4: Dose equivalents to diazepam 5 mg

Diazepam stabilisation doses should not exceed 80 mg/day3 and should be administered in divided daily doses at fixed times.3,13

Medicine Approximate equivalent dose (mg)
alprazolam 0.5
bromazepam 3
clobazam 10
clonazepam 0.25
diazepam 5
flunitrazepam 0.5
lorazepam 1
nitrazepam 5
oxazepam 15
temazepam 10

After a few days of stabilisation gradually reduce the dose by 10%–20% each week over several weeks.13 If dose reduction is managed in an outpatient setting, review progress regularly.13

Patients with severe benzodiazepine withdrawal should be managed with diazepam in hospital.3

When to seek specialist advice or consider specialist referrals

Consider specialist referral for patients who are at higher risk of dependence, who have more complex needs or for patients at risk of adverse events.2

For patients for whom an optimal treatment regimen and monitoring plan have been determined and implemented, specialist referral may be warranted if:2

  • there is unexpected dose escalation
  • the upper range of drug dose is reached
  • there is suspected abuse or misuse
  • the patient has a high level of distress
  • the patient's risk category has changed
  • the patient's comorbid psychiatric or psychological disorder is poorly controlled
  • there are unusual opioid needs or there are suspicions of drug diversion.

If patients pose a risk to themselves or others, or are at risk from others, consider referral to a hospital.2

Information for patients

Minimise the risk of dependence and help patients stop taking benzodiazepines by providing information for patients on non-pharmacological management of anxiety and insomnia, the risks associated with benzodiazepine use, and ways to stop taking benzodiazepines.

Fact sheets you can give to your patients include:

Reviewers

Dr Evan Ackermann, Chair, RACGP National Standing Committee – Quality

Dr RFW Moulds, Medical advisor, Therapeutic Guidelines

References

  1. Royal Australian College of General Practitioners. Prescribing drugs of dependence in general practice, Part B: Benzodiazepines. East Melbourne: RACGP, 2015. [Online] (accessed 18 September 2015).
  2. Royal Australian College of General Practitioners. Prescribing drugs of dependence in general practice, Part A. Clinical governance framework. East Melbourne: RACGP, 2015. [Online] (accessed 21 September 2015).
  3. Therapeutic Guidelines. Benzodiazepines, zolpidem and zopiclone: problem use. West Melbourne: eTG, 2015. [eTG Online] (accessed 30 September 2015).
  4. Tvete IF, Bjorner T, Aursnes IA, et al. 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:e003296. [PubMed].
  5. Australian Institute of Health and Welfare. National Drug Strategy Household Survey. Canberra: AIHW, 2013. [Online] (accessed 24 September 2015).
  6. Coroner's Court of Victoria. Pharmaceutical drugs in fatal overdose: A coroner's perspective. Melbourne: Coroner's Court of Victoria, 2015. [Online] (accessed 29 September 2015).
  7. Ross J and Darke S. The nature of benzodiazepine dependence among heroin users in Sydney, Australia. Addiction 2000;95:1785-93. [PubMed].
  8. Nielsen S, Bruno R, Degenhardt L, et al. The sources of pharmaceuticals for problematic users of benzodiazepines and prescription opioids. Med J Aust 2013;199:696-9. [PubMed].
  9. Longo LP, Parran T, Jr., Johnson B, et al. Addiction: part II. Identification and management of the drug-seeking patient. Am Fam Physician 2000;61:2401-8. [PubMed].
  10. Ashton H. Benzodiazepines: How they work and how to withdraw. The Ashton Manual. Newcastle, United Kingdom: The Institute of Neuroscience, Newcastle University, 2002. [Online] (accessed 29 September 2015).
  11. Darker CD, Sweeney BP, Barry JM, et al. Psychosocial interventions for benzodiazepine harmful use, abuse or dependence. Cochrane Database Syst Rev 2015;5:CD009652. [PubMed].
  12. Parr JM, Kavanagh DJ, Cahill L, et al. Effectiveness of current treatment approaches for benzodiazepine discontinuation: a meta-analysis. Addiction 2009;104:13-24. [PubMed].
  13. Australian Medicines Handbook. Diazepam. Adelaide: AMH, 2015. [Online] (accessed 30 September 2015).