withdrawal from benzodiazepine hypnotic

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  • 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

Drug

BNF

Maudsley Guidelines

UK Guidelines (3)

UK NHS Specialist Pharmacy Service guidance (4)

Diazepam

5mg

5mg

5mg

 

Alprazolam

250 micrograms

 

250 micrograms

 

Chlordiazepoxide

 12.5mg

12.5mg

12.5 -15mg

Chlordiazepoxide 12.5mg is approximately equivalent to diazepam 5mg. Chlordiazepoxide is used short-term for severe anxiety, muscle spasm and alcohol withdrawal. The daily dose is usually given in 3 or 4 divided doses

Clobazam

10mg

 

10mg

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. The 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*

250 micrograms

250 micrograms

250 micrograms

Clonazepam 250 micrograms is approximately equivalent to diazepam 5mg. Clonazepam is used for the treatment of epilepsy. The dose may be given as a single daily dose at night or in 3 or 4 divided doses.

Flurazepam

7.5 -15mg

 

7.5 -15mg

Flurazepam 7.5mg to 15mg, is approximately equivalent to diazepam 5mg. Flurazepam is used short-term for the treatment of insomnia. The dose is taken at bedtime.

Loprazolam

0.5 -1mg

 

0.5 -1mg

Loprazolam 500 micrograms to 1mg, is approximately equivalent to diazepam 5mg. Loprazolam is used short-term for the treatment of insomnia. The dose is taken at bedtime.

Lorazepam

 500 micrograms

500 micrograms

500 micrograms

Lorazepam 500 micrograms is approximately equivalent to diazepam 5mg. Lorazepam is used short-term for severe anxiety, associated insomnia, and as a pre-medication. The 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

0.5 -1mg

0.5 -1mg

0.5 -1mg

Lormetazepam 500 micrograms to 1mg, is approximately equivalent to diazepam 5mg. Lormetazepam is used short-term for the treatment of insomnia. The dose is taken at bedtime.

Nitrazepam

5mg

5mg

5mg

Nitrazepam 5mg is approximately equivalent to diazepam 5mg. Nitrazepam is used short-term for the treatment of insomnia. The dose is taken at bedtime.

Oxazepam

10mg

10mg

10 -15mg

Oxazepam 10mg is approximately equivalent to diazepam 5mg. Oxazepam is used short-term for severe anxiety and associated insomnia. The dose is taken in three or four divided doses (for anxiety) or at bedtime (for insomnia).

Temazepam

10mg

10mg

10mg

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. The 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

* 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:

Last edited 01/2022

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