Benzodiazepines are minor tranquilisers prescribed for a range of reasons including relief of anxiety and to induce sedation.
1.4% of the Australian population reported use of tranquilisers or sleeping pills for non-medical purposes in the year prior to 2007 .
Non-medical use was most prevalent in the 20-29 years age group (2.4% females, 3.4% males) with the 40 years or over age group having the highest proportion of daily or weekly use (34.3%) .
Benzodiazepine use and dependence is commonly considered in two categories for treatment: long term prescribed benzodiazepine users taking therapeutic doses but with possible subsequent iatrogenic dependence, and patients using high doses, abusing their prescription or buying and misusing benzodiazepines [2, 3].
Benzodiazepines affect gamma-amino butyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Benzodiazepines bind to receptors on the GABA–A receptor complex.
Benzodiazepines enhance the activity of GABA, effectively slowing nerve impulses throughout the body. They have sedative-hypnotic, anxiolytic, skeletal muscle relaxant, and anti-convulsant properties.
Benzodiazepines are quickly absorbed orally with peak plasma concentrations from ½ to 2 hours after ingestion and metabolised by the liver.
Differences in the time course of drug action are determined by the lipid solubility of the agent and the clearance of the drug and its active metabolites. Benzodiazepines are classified as long-acting and short-acting. A highly lipid-soluble benzodiazepine such as diazepam is absorbed faster than the relatively more hydrophilic agents e.g oxazepam [4, 5].
Dependence and withdrawal
Dependence can occur in users of benzodiazepines within weeks or months, even at therapeutic doses . Withdrawal typically occurs within two days after ceasing short-acting benzodiazepines (e.g. oxazepam), and between two and ten days after ceasing long-acting benzodiazepines (e.g. diazepam). However, the onset of benzodiazepine withdrawal may be as late as three weeks after cessation of drugs with a long half-life .
Withdrawal symptoms are thought to be influenced by the GABA system  and include:
- poor concentration and memory
- muscle aches
- perceptual disturbances and panic attacks less commonly occur
- seizures and symptoms of psychosis occasionally occur .
Severity of withdrawal symptoms is associated with:
- longer periods of use
- use of high doses
- the use of multiple benzodiazepines and use of short-acting potent benzodiazepines .
Management of withdrawal for mono-dependent benzodiazepine users is most effective when using a gradual reduction of dose [6, 8-9]. In this case it is recommended to apply treatment through the steps of assessment,
- facilitation of patient decision making
- stabilising the current daily dose
- and a change to long acting benzodiazepine where required (such as diazepam).
The changed dose is stabilised, followed by gradual dose reduction of 10%-15% per week, generally over 6-10 weeks, with consistent monitoring and withdrawal support [2, 3, 6, 9].
Access to psychological support may be needed and may range from a single brief consultation, short courses of relaxation, to more formal therapies focused on anxiety and stress management .
The following can be considered for patients with complex issues:
- use of high doses of benzodiazepines and/or patterns of polydrug use
- referral for management within alcohol and other drug services.
Stabilisation and detoxification in an inpatient setting for alcohol or other primary drugs may need to commence prior to benzodiazepine dose reduction [2, 8].
Benzodiazepine use often occurs concurrently with other drug use. Across the population of recent tranquiliser users, 42.5% had used alcohol and 25.2% used cannabis at the same time .
High dose misuse of benzodiazepines is frequently part of a polydrug use pattern  is common among heroin and injecting drug users and associated with higher rates of risk behaviour .
Use of benzodiazepines potentiates other central nervous system depressants such as alcohol and opioids, increasing the possibility of respiratory depression and risk of overdose .
Benzodiazepine dependent polydrug users, particularly alcohol, generally require specialist support for management. Treatment is further complicated as benzodiazepines are commonly used in AOD services to manage withdrawal of a range of substances, particularly alcohol withdrawal .
- Management of benzodiazepine withdrawal - clinical guidelines
- Reconnexion provides resources and services for both clinicians and service users to assist with managing benzodiazepine dependence, anxiety, panic and depression.
- The RACGP provide guidelines to assist general practitioners in relation to appropriate prescribing benzodiazepines. These include a protocol for prescribing of benzodiazepines in high doses on a regular basis and refer to drug dependent, high dose and polydrug dependent patients.
- Factsheet - benzodiazepine withdrawal.
1. Australian Institute of Health and Welfare, National Drug Strategy Household Survey: Detailed Findings. 2007, Australian Institute of Health and Welfare: Canberra.
2. Mental Health and Drug and Alcohol Office, NSW Drug and Alcohol Withdrawal Clinical Practice Guidelines. 2 ed. 2008: NSW Department of Health.
3. Lingford-Hughes, L., Welch, S., and Nutt, D.J., Evidence-based guidelines for the pharmacological management of substance misuse, addiction and comorbidity: recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology, 2004. 18(3):293-335.
4. National Centre for Education and Training on Addiction (NCETA) Consortium, Alcohol and Other Drugs: A Handbook for Health Professionals, 2004: Australian Government Department of Health and Ageing. Canberra.
5. Evans, M., and Waghorn, T. Benzodiazepine Dependence & Withdrawal. GP Drug & Alcohol Supplement, 1998. 9.
6. Denis, C., Fatseas, M., Lavie, E., and Auriacombe, M. Pharmacological interventions for benzodiazepine mono-dependence management in outpatient settings. 2006, Cochrane Database of Systematic Reviews.
7. Saunders, J. and Yang, J., Clinical Protocols for Detoxification in Hospitals and Detoxification Facilities. 2002, Queensland Health.
8. Ashton, H., The diagnosis and management of benzodiazepine dependence. Current Opinion in Psychiatry, 2005. 18(249-255).
9. Taylor, D., Paton, C., and Kerwin, R., The Maudsley 2005-2006 Prescribing Guidelines. 2005, London: Taylor & Francis.