Substance misuse: benzodiazepines

Benzodiazepines (BZDs), first introduced in the 1960s, were seen as safer than their predecessors and received little scrutiny until the 1980s,¹ when tolerance, withdrawal symptoms and dependence became increasingly recognised.

Medical and pharmaceutical education and awareness-raising campaigns have resulted in a reduction in benzodiazepine prescribing, but even in 2014, 9.18 million prescriptions were issued in the UK.² At best, BZDs offer only short-term relief of symptoms: they do not address underlying issues, and rebound symptoms on cessation may mean that benefits are outweighed by risks and adverse effects.

The abuse of prescription medicine is a significant and increasing problem. The House of Commons Home Affairs Select Committee said in 2013 that there may be as many as 1.5 million addicted to and/or abusing prescription medication in the UK. The committee called for measures to stop patients from ‘shopping around’ GPs to obtain prescriptions. However, the easy availability of drugs on the internet also needs addressing. It is easy to purchase a thousand 10mg diazepam tablets online for 50p a tablet with no prescription and no checks.

Pharmacology

Hangover and cumulative toxicity may be seen with longer acting BZDs, but rapid-onset BZDs are favoured by drug users.

When a benzodiazepine prescription is appropriate, it is recommended that a short-acting drug such as a ‘Z’ drug or temazepam is used. Where the indication is anxiety, a longer acting drug such as diazepam or lorazepam may be employed. Short-acting drugs may be more addictive than long-acting.

BZDs are fat-soluble, so following prolonged use, it may take several days or even weeks for elimination to be complete. This is particularly so in the elderly, and the Royal College of Psychiatrists suggest that BZDs should not be used in the over-60s.⁴ Elimination of BZDs is renal following hepatic metabolism.

Problems associated with BZDs

GABA-mediated activity means that all BZDs are potentially addictive (at least 40% of recipients will become addicted) and highly prone to abuse. The prescriber must be alert to this possibility. All BZDs are sedating and interact synergistically with other sedatives including alcohol. This means that in association with alcohol and opioids, the risk of oversedation is significant and BZDs were mentioned in 342 of the 2,995 drug-related deaths in the UK in 2013.⁵

Long-term BZD use is associated with cognitive impairment, depression and blunted emotions. Their protracted use in anxiety serves to reduce the patient’s ability to cope and increases anxiety as normal coping mechanisms are bypassed.

The DVLA advises that persistent abuse of or dependence on BDZs should lead to revocation of Group 1 (car and motorcycle) and Group 2 (lorry and bus) licences until independent medical assessment and urine screening deem the patient to be fit to drive. Non-dependent, prescribed use of BDZs does not prevent a patient from driving, but they may be committing a crime if unfit to drive even on prescribed medication.⁶

Current guidance

BZDs are currently used in short courses (meaning a maximum of two to four weeks) for the relief of severe, disabling anxiety or insomnia. Their use for mild anxiety or long-term symptomatic management is no longer considered acceptable. With regard to BZDs as hypnotics, the British National Formulary advises that ‘routine prescribing is undesirable’ and should be limited to ‘short courses in the acutely distressed’.

This is reflected in NICE technology appraisal guidance, covering advice on the use of hypnotics,⁷ and NICE clinical guideline CG11 on generalised anxiety disorder and panic disorder.⁸ Used in line with current guidelines, BZDs remain a useful tool in the management of psychological distress.

Few advocate maintenance of long-term benzodiazepine prescriptions, although there may be very occasional situations, such as in severe mental illness (under the direction of a consultant psychiatrist) or in palliative care, where the harms of enforced withdrawal may outweigh the benefits.

Dealing with non-dependent patients

In patients who have had a prescription for more than four weeks, but do not exhibit evidence of dependence (no drug-seeking behaviour, craving or complaints of withdrawal symptoms), all benzodiazepines should be converted to the equivalent dose of diazepam (to a maximum daily dose of 30mg)⁹ and a slow reduction of 1-2mg per week with regular supportive review should be implemented. This approach will be sufficient in approximately 75% of primary care patients.¹⁰

Dealing with dependent patients

Red flags to problematic use include regular demands for prescriptions and drug-seeking behaviour (suggested by regular, early requests for repeat issue accompanied by excuses such as loss or theft of prescription, and abusive or threatening behaviour when such requests are denied) and any history of substance misuse.

Where there is evidence of dependence, especially at high dosage equivalents, reduction should not be undertaken suddenly, because BZD withdrawal, similar to alcohol withdrawal, may cause serious medical problems leading to seizures and even death (see table 2).

At its maximum licensed dose of 8mg, clonazepam is equivalent to a daily dosage of 160mg diazepam. It is surprising how many drug users manage to obtain this drug from unsuspecting prescribers with no confirmation from any neurologist and at maximum dosage, because they are ‘epileptic’ and ‘nothing else works’.

Such patients and those admitting to using large amount of diazepam bought online are best referred to a local community drug treatment service, especially where other illicit drug use is involved. It is essential that patients receiving opiate substitution therapy (usually methadone or buprenorphine) are not able to obtain additional drugs with abuse potential from their GP.

Consultation techniques

There are a few ground rules for managing drug-dependent patients. The first and most important is to be consistent. Drug users are known to discuss which prescribers are seen to be ‘easy’ and there is anecdotal evidence that the names of such clinicians are sold between users. It is therefore vital that practices have clear policies about prescribing drugs with abuse potential: especially around replacement of ‘lost’ prescriptions and early issue because of holidays or work away from home.

All patients appreciate honest discussion and GMC guidance in Good Medical Practice indicates that: ‘You must work in partnership with patients, sharing with them the information they will need to make decisions about their care’.¹¹

However, this does not mean that patients can demand specific treatment from a clinician, if that treatment is not in the patient’s best interests. As a prescriber, you are able to decline a prescription request you believe may be inappropriate or dangerous. It is essential that the decision and its rationale are recorded in the medical record to inform other health professionals, but also for medicolegal security.

Useful resources

• SMMGP updates and courses http://www.smmgp.org.uk/
• Royal College of GPs curriculum statement on Care of people who misuse drugs and alcohol

Click here to take a test on this article and claim a certificate on MIMS Learning

References

1. Lader, M. History of benzodiazepine dependence. Journal of Substance Abuse Treatment. 1991. 8(1-2). p 53–59
2. 29 June 2015. Prescription Drugs: Written question – 4563 House of Commons
3. RCGP Guide to The Management of Substance Misuse in Primary Care. (2013). London. P160.
4. Royal College of Psychiatrists factsheet on benzodiazepines.
5. Deaths Related to Drug Poisoning in England and Wales, 2013. Office for National Statistics (2014).
6. DVLA’s current medical guidelines for professionals – conditions a to c
7. www.nice.org.uk/guidance/ta77
8. https://www.nice.org.uk/guidance/cg113
9. Drug misuse and dependence: UK guidelines on clinical management. 2007. DH, London.
10. Psychiatric Drugs Explained. Healy, D. 2002. Churchill Livingstone. P148.
11. Good Medical Practice. GMC. 2013. London. Paragraph 49.