Withdrawal from benzodiazepine anxiolytic

• if benzodiazepine anxiolytics are used chronically then there is a consequent tolerance to the anxiolytic effects of the benzodiazepine
  • the UK Committee on Safety of Medicines suggest that anxiolytic efficacy is not retained after regular treatment for 4 months with a benzodiazepine anxiolytic
• long-term use of benzodiazepine anxiolytics is associated with adverse effects such as dependence, increasing anxiety and depression
• withdrawal from a benzodiazepine anxiolytic must be agreed between the clinician and the patient. The risks of continued benzodiazepine use should be explained. An agreed schedule for reduction of and gradual withdrawal from the benzodiazepine should also be agreed:
  • this will involve substitution of the benzodiazepine anxiolytic with a long-acting benzodiazepine (e.g. diazepam) and a subsequent gradual reduction in dose of the substituted benzodiazepine - the BNF suggests that the substituted benzodiazepine can then be withdrawn in steps of about one-eighth (range one-tenth to one-quarter) every fortnight - however the rate of tapering needs to be individually adjusted according to the patient's needs taking into consideration factors such as type and dosage of benzodiazepine, reasons for use, duration of use, lifestyle, environmental stresses, and personality. This reflects that, even with gradual dosage reduction, symptoms of withdrawal such as insomnia, anxiety and perceptual disturbances may occur
    
    
• for people withdrawing from these potent, short-acting drugs it has been advised that they switch to an equivalent dose of a benzodiazepine with a long half-life such as diazepam (2)
  • diazepam is available as 2mg tablets which could be halved to give 1mg doses to allow the dose to be reduced in stages of 1mg every 1 -4 weeks or more
  • the manufacturer has no safety or efficacy data to support the use of halved diazepam 2mg tablets, therefore this would be an off-licence use of the product
  • extra precautions apply in patients with hepatic dysfunction as diazepam and other longer-acting drugs may accumulate to toxic levels
    • switching to diazepam may not be appropriate in this group of patients
    • concomitant renal or hepatic impairment should be taken into consideration when prescribing all benzodiazepines
      
      
• Table below summarises the approximate equivalent doses of oral benzodiazepines licensed in the UK (2)
  • figures included in this table are not exact for reasons such as inter-patient variability, differing half-lives and differing sedative properties
  • information should be interpreted using clinical and pharmaceutical knowledge and applied cautiously with doses titrated against patient response

Inter-patient variability and differing half-lives mean the figures can never be exact and should be interpreted using clinical and pharmaceutical knowledge

* while there is broad agreement in the literature about equivalent doses of benzodiazepines, clonazepam has a wide reported equivalence range and particular care is needed with this medicine

• example withdrawal schedule for patient on a starting dose of lorazepam 1mg tds (1)
• week 1
  • morning dose - lorazepam 1mg
  • midday dose - lorazepam 1 mg
  • evening dose - lorazepam 0.5mg, diazepam 5mg
• week 2
  • morning dose - lorazepam 0.5mg, diazepam 5mg
  • midday dose - lorazepam 1mg
  • evening dose - lorazepam 0.5mg, diazepam 5mg
• week 3
  • morning dose - lorazepam 0.5mg, diazepam 5mg
  • midday dose - lorazepam 0.5mg. diazepam 5mg
  • evening dose - lorazepam 0.5mg, diazepam 5mg
• week 4
  • morning dose - lorazepam 0.5mg, diazepam 4mg
  • midday dose - lorazepam 0.5mg, diazepam 5mg
  • evening dose - stop lorazepam, diazepam 10mg
• week 5
  • morning dose - stop lorazepam, diazepam 8mg
  • midday dose - lorazepam 0.5mg, diazepam 4mg
  • evening dose - diazepam 10mg
• week 6
  • morning dose - diazepam 8mg
  • midday dose - stop lorazepam, diazepam 8mg
  • evening dose - diazepam 10mg
• week 8
  • morning dose - diazepam 6mg
  • midday dose - diazepam 8mg
  • evening dose - diazepam 10mg
• week 10
  • morning dose - diazepam 6mg
  • midday dose - diazepam 6mg
  • evening dose - diazepam 10mg
• subsequently - aim to reduce dosage of diazepam by 2mg every 2 weeks until a total dosage of 10-15mg daily is achieved. Then reduce in steps of 1mg every 2 weeks or according to progress. Once a dose of approximately diazepam 20mg has been achieved then switch to twice-daily dosage - further dose reduction involves reductions in morning dose first, night time dose last (1)

Reference:

1. Pule (2004), 64 (10), 50-3.
2. NHS Specialist Pharmacy Service.Equivalent doses of oral benzodiazepines (Accessed July 8th 2021)
3. Independent Expert Working Group. Drug misuse and dependence: UK guidelines on clinical management. Update 2017 London: Department of Health. Accessed via https://www.gov.uk/government/publications/drug-misuse-and-dependence-uk-guidelines-on-clinical-management (Accessed July 8th 2021)