Withdrawal from benzodiazepine hypnotic

• regular use of benzodiazepine hypnotics (e.g. temazepam, nitrazepam) rapidly leads to tolerance - patients may report continued efficacy with use of benzodiazepine hypnotics but probably this is because of the rebound insomnia that occurs if the hynotic is stopped (1)
  
  
• adverse effects associated with the use of benzodiazepine hypnotics (to which the elderly are most vulnerable) include confusion, oversedation, increased risks of falls and consequent fractures (1)
  
  
• withdrawal from a benzodiazepine hypnotic must be agreed between the clinician and the patient - patients should never be forced or threatened (1)
  
  
• switching benzodiazepines may be advantageous for a variety of reasons, e.g. to a drug with a longer half-life prior to discontinuation or in the event of non-availability of a specific benzodiazepine (2)
  • with relatively short-acting benzodiazepines such as alprazolam and lorazepam, it is not possible to achieve a smooth decline in blood and tissue concentrations during benzodiazepine withdrawal
    • these drugs are eliminated fairly rapidly with the result that concentrations fluctuate with peaks and troughs between each dose
    • it is necessary to take the tablets several times a day and many people experience a "mini-withdrawal", sometimes a craving, between each dose
    • 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
      • 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 nitrazepam 10mg nocte (1)
  • week 1 - nitrazepam 5mg, diazepam 5mg
  • week 2 - stop nitrazepam, diazepam 10mg
  • week 4 - diazepam 9mg
  • week 6- diazepam 8mg
  • continue reducing dose of diazepam by 1mg every fortnight - tapering of dose may be slower if necessary
    
    
• example withdrawal schedule for patient on temazepam 20mg nocte (1)
  • week 1 - temazepam 10mg, diazepam 5mg
  • week 2 - stop temazepam, diazepam 10mg
  • week 4 - diazepam 9mg
  • week 6 - diazepam 8mg
  • continue reducing dose of diazepam by 1mg every fortnight - tapering of dose may be slower if necessary

Hepatic and renal impairment

• concomitant renal or hepatic impairment should be taken into consideration when prescribing benzodiazepines. Extra precautions apply in patients with hepatic dysfunction as diazepam and other longer-acting benzodiazepines may accumulate to toxic levels. For example, switching to diazepam may not be appropriate in this group of patients
• in patients with renal impairment, cerebral sensitivity to benzodiazepines is increased, so lower doses may be needed.
• refer to the individual benzodiazepine’s Summary of Product Characterstics (SPC) for dosing guidance when administering to patients with renal or hepatic impairment

Notes (4) :

• approximate Z-drugs equivalent to 5mg diazepam
  • zaleplon 10mg
  • zopiclone 7.5mg
  • zolpidem 10mg

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
4. RCGP (2007). Drug misuse and dependence: UK guidelines on clinical management