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reduction in dose of the substituted benzodiazepine - the BNF suggests that the substituted benzodiazepine can then be withdrawn in steps of about one-eighth (range one-tenth to one-quarter) every fortnight - however the rate of tapering needs to be individually adjusted according to the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

Approximate equivalence to oral diazepam (3)

• approximate equivalence is useful when switching a benzodiazepine to diazepam, or when switching one benzodiazepine to another, using diazepam as an intermediate step. Doses should be tapered according to individual response
• alprazolam
  • aprazolam 250 micrograms is approximately equivalent to diazepam 5mg
  • alprazolam is used short-term for severe anxiety
    • daily dose is usually given in 2 or 3 divided doses
      
• chlordiazepoxide
  • chlordiazepoxide 12.5mg is approximately equivalent to diazepam 5mg
  • chlordiazepoxide is used short-term for anxiety, muscle spasm and alcohol withdrawal
    • daily dose is usually given in 3 or 4 divided doses
      
• clobazam
  • clobazam 10mg is approximately equivalent to diazepam 5mg
  • clobazam is used short-term for severe anxiety and as adjunctive therapy in psychosis, schizophrenia and epilepsy
    • daily dose can be given in divided doses or as a single dose at night
    • doses higher than 30mg should be given in divided doses
      
• clonazepam
  • clonazepam 250 micrograms is approximately equivalent to diazepam 5mg
  • clonazepam is used for the treatment of epilepsy
    • dose may be given as a single daily dose at night or in 3 or 4 divided doses
      
• flurazepam
  • flurazepam 7.5mg to 15mg, is approximately equivalent to diazepam 5mg
  • flurazepam is used short-term for the treatment of insomnia
    • dose is taken at bedtime
      
• loprazolam
  • loprazolam 500 micrograms to 1mg, is approximately equivalent to diazepam 5mg
  • loprazolam is used short-term for the treatment of insomnia
    • dose is taken at bedtime
      
• lorazepam
  • lorazepam 500 micrograms is approximately equivalent to diazepam 5mg
  • lorazepam is used short-term for severe anxiety, associated insomnia, and as a pre-medication
    • dose is taken in divided doses (for anxiety) or at night (for insomnia)
    • when used as a pre-medication before dental or general surgery the dose is taken the night before the operation and a second dose one to two hours before the procedure
      
• lormetazepam
  • lormetazepam 500 micrograms to 1mg, is approximately equivalent to diazepam 5mg
  • lormetazepam is used short-term for the treatment of insomnia
    • dose is taken at bedtime
      
• nitrazepam
  • nitrazepam 5mg is approximately equivalent to diazepam 5mg
  • nitrazepam is used short-term for the treatment of insomnia
    • dose is taken at bedtime
      
• oxazepam
  • oxazepam 10mg is approximately equivalent to diazepam 5mg
  • oxazepam is used short-term for severe anxiety and associated insomnia
    • dose is taken in three or four divided doses (for anxiety) or at bedtime (for insomnia)
      
• temazepam
  • temazepam 10mg is approximately equivalent to diazepam 5mg
  • temazepam is used short-term for the treatment of insomnia, and as pre-medication before minor surgical and investigative procedures
    • dose is taken at bedtime (for insomnia), or half to one hour before the procedure (as pre-medication)

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

• 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 (2021).Equivalent doses of oral benzodiazepines
3. NHS Specialist Pharmacy Service (July 2025). Oral benzodiazepines and choosing equivalent doses