Benzodiazepine Dependence

The first benzodiazepine was marketed in 1959. It was described as a 'minor tranquilliser' and an alternative to barbiturates. Benzodiazepines act by enhancing the effect of gamma-aminobutyric acid on the GABA-A receptor, thereby resulting in CNS depression. They are anxiolytic, hypnotic, anticonvulsant and muscle relaxants. They also cause psychomotor retardation.

They are useful in the short-term. However, long-term use (more than 3 months, possibly even after a few weeks) is associated with dependence and withdrawal syndrome ¹.

Following CSM advice in 1988² the number of prescriptions for benzodiazepines has markedly reduced - but benzodiazepines are still being prescribed inappropriately. Benzodiazepines are in class C of the Misuse of Drugs Act, 1971. Recreational use of benzodiazepines is also an increasing problem.

1. Safe withdrawal.
2. Cessation of use.

1. Do not prescribe benzodiazepines in someone with a history of drug misuse and dependence.³
2. National Service Framework for mental health and CSM² advise prescribing lowest possible doses of benzodiazepines and only prescribe for 2-4 weeks. It is important to remember that patients can get withdrawal symptoms between doses if they are given short-acting benzodiazepines.
3. Use only for severe or disabling anxiety or insomnia.
4. Try alternatives to benzodiazepines, such as relaxation techniques. Low dose tricyclic antidepressants are used for the short-term treatment of insomnia. However, the data to support this use is lacking and there is the risk of developing dependence.
5. Advise patients of risk of dependence and impaired reaction times.⁴
6. Elderly patients are particularly prone to adverse effects of benzodiazepines and, therefore, need to be careful.
7. Benzodiazepines also cross the placenta leading to neonatal side-effects.

• Recurrence of original disorder.
• Rebound symptoms - last a few days.
• Withdrawal syndrome:
  • Common symptoms: increased anxiety, tremor, irritability, restlessness, depression, dizziness, sweating, insomnia, nightmares, abdominal pain, tachycardia and hypertension (usually mild)
  • Serious symptoms: seizures, delirium, confusion
  • Other symptoms: anorexia, nausea, tinnitus, excessive sensitivity to light and sound, depersonalisation and derealisation.

Two groups of patients to manage:

• Those using benzodiazepines for a chronic disorder for a long time, e.g. insomnia, and who do not abuse their prescription.
• Those who abuse their prescription or buy benzodiazepines illicitly - usually associated with other substance misuse, e.g. opiates.

Management of benzodiazepine dependence in non-abusing patients

1. Only make a diagnosis of dependence if patient fits above criteria.
2. Begin with advisory letters and patient information.
3. Try consultation with GP and practice nurse: provide education on why benzodiazepines are harmful when used chronically. Explain difficulties that may arise with continued prescribing.
4. Relaxation therapies.
5. Graded discontinuation may be useful:^1,5
   • Consider switching to longer-acting benzodiazepine, e.g. diazepam (see dose conversion table below). Longer-acting forms are less likely to produce rapid onset of withdrawal symptoms. Use benzodiazepine conversion equivalence table.
   • Gradually reduce dose, e.g. by 10% every seven to ten days. For example, if a patient has been on 40 mg of diazepam once daily for a year, then begin by reducing the dose to 35 mg for a week, then 30 mg for a week, then 25 mg for a week, etc. If this patient developed withdrawal symptoms at a reduction to 35 mg then consider going back to 39 mg and then reduce to 38 mg a week later, and so on.
   • Another example is withdrawal of temazepam. If a patient is on 20 mg of temazepam at night then reduce dose to 17.5 mg for a week, then 15 mg and then 12.5 mg, and so on. Alternatively, the patient can be converted to diazepam (see table below) and then the diazepam dose can be tapered as above.
   • Have regular contact and consider only prescribing for a week at a time.
   • May need a longer period over which to reduce - one approach is a symptom guided taper.
6. Other psychological therapies - consider in all patients, e.g. cognitive-behavioural therapy, and supportive therapies.⁵

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Dose conversion table for equivalent doses of benzodiazepines to diazepam 5 mg

More novel approaches - (use not clearly established):

• Antidepressants, if depression emerges (associated with long-term use).⁷
• Anticonvulsants.
• Buspirone.
• Beta-blockers - relief of specific symptoms, e.g. palpitations.⁸
• Short-term flumazenil infusions.⁹

These have a variety of effects on withdrawal symptoms and discontinuation rates.

Management of dependence in illicit benzodiazepine users

• Avoid prescribing benzodiazepines if at all possible - determine exactly what they are needed for and consider alternatives.
• This is a good opportunity for assessing dependence of other substances, e.g. alcohol. Consider a urinary drug screen to detect if other drugs of abuse are being used.
• Benzodiazepines are prescribed in the management of opioid maintenance - this is not always necessary.
• Benzodiazepines are used during alcohol detoxification schedules to prevent occurrence of withdrawal seizures - high doses are not needed. Carbamazepine has been used in patients on high doses.

• Confirm that the patient has a problem - use DSM list.
• Does the patient abuse other drugs, e.g. alcohol, cannabis - urine screen may be helpful, but ensure you have the patient's consent.
• Educate the patient - cover the problems with abusing benzodiazepines, offer support and assistance, advise them on methods available to stop abusing benzodiazepines - e.g. graded reduction.
• May need to offer alternative therapy for their insomnia, such as, relaxation therapy or stress reduction.
• If the patient agrees to reduce benzodiazepines then a signed contract may help them to commit.
• Educate the patient about the withdrawal syndrome and how to counteract it, e.g. relaxation therapy.
• Reduce dose of benzodiazepine, e.g. 10% reduction in dose every 7-10 days.
• Regular follow-up: this will be based on how each individual patient does. For example, if the patient is developing withdrawal symptoms frequently then they will need to be seen more frequently. Otherwise review weekly as dose of benzodiazepine is tapered.