Withdrawal from Z drugs

• 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
      
      
• 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 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 (5) :

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

Reference:

• (1) Pulse 2004; 64 (10): 50-3.
• (2) http://www.rcgp.org.uk/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)
• (4) NHS Specialist Pharmacy Service (January 2022). Choosing an equivalent dose of oral benzodiazepine
• (5) RCGP (2007). Drug misuse and dependence: UK guidelines on clinical management