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BRITISH NATIONAL FORMULARY
4.1 HYPNOTICS AND ANXIOLYTICS
Revised November 2013
Most anxiolytics ('sedatives') will induce sleep when given at night and most hypnotics will sedate when given during the day. Prescribing of these drugs is widespread but dependence (both physical and psychological) and tolerance occurs. This may lead to difficulty in withdrawing the drug after the patient has been taking it regularly for more than a few weeks (see Dependence and Withdrawal, below). Hypnotics and anxiolytics should therefore be reserved for short courses to alleviate acute conditions after causal factors have been established.
Benzodiazepines are the most commonly used anxiolytics and hypnotics; they act at benzodiazepine receptors which are associated with gamma-aminobutyric acid (GABA) receptors. Older drugs such as meprobamate and barbiturates (section 4.1.3) are not recommended - they have more side-effects and interactions than benzodiazepines and are much more dangerous in overdosage.
A paradoxical increase in hostility and aggression may be reported by patients taking benzodiazepines. The effects range from talkativeness and excitement, to aggressive and antisocial acts. Adjustment of the dose (up or down) usually attenuates the impulses. Increased anxiety and perceptual disorders are other paradoxical effects. Increased hostility and aggression after barbiturates and alcohol usually indicates intoxication.
Hypnotics and anxiolytics may impair judgement and increase reaction time, and so affect ability to drive or operate machinery; they increase the effects of alcohol. Moreover the hangover effects of a night dose may impair driving on the following day. See also Drugs and Driving under General Guidance.
DEPENDENCE AND WITHDRAWAL
Withdrawal of a benzodiazepine should be gradual because abrupt withdrawal may produce confusion, toxic psychosis, convulsions, or a condition resembling delirium tremens. Abrupt withdrawal of a barbiturate is even more likely to have serious effects.
The benzodiazepine withdrawal syndrome may develop at any time up to 3 weeks after stopping a long-acting benzodiazepine, but may occur within a day in the case of a short-acting one. It is characterised by insomnia, anxiety, loss of appetite and of body-weight, tremor, perspiration, tinnitus, and perceptual disturbances. Some symptoms may be similar to the original complaint and encourage further prescribing; some symptoms may continue for weeks or months after stopping benzodiazepines.
Benzodiazepine withdrawal should be flexible and carried out at a reduction rate that is tolerable for the patient. The rate should depend on the initial dose of benzodiazepine, duration of use, and the patient's clinical response. Short-term users of benzodiazepines (2–4 weeks only) can usually taper off within 2–4 weeks. However, long-term users should be withdrawn over a much longer period of several months or more.
A suggested protocol for withdrawal for prescribed long-term benzodiazepine patients is as follows:
Transfer patient stepwise, one dose at a time over about a week, to an equivalent daily dose of diazepam(1) preferably taken at night
Reduce diazepam dose, usually by 1–2 mg every 2–4 weeks (in patients taking high doses of benzodiazepines, initially it may be appropriate to reduce the dose by up to one-tenth every 1–2 weeks). If uncomfortable withdrawal symptoms occur, maintain this dose until symptoms lessen
Reduce diazepam dose further, if necessary in smaller steps; steps of 500 micrograms may be appropriate towards the end of withdrawal. Then stop completely.
For long-term patients, the period needed for complete withdrawal may vary from several months to a year or more
Withdrawal symptoms for long-term users usually resolve within 6–18 months of the last dose. Some patients will recover more quickly, others may take longer. The addition of beta-blockers, antidepressants and antipsychotics should be avoided where possible. Counselling can be of considerable help both during and after the taper.
IMPORTANT: BENZODIAZEPINE INDICATIONS
Benzodiazepines are indicated for the short-term relief (two to four weeks only) of anxiety that is severe, disabling, or causing the patient unacceptable distress, occurring alone or in association with insomnia or short-term psychosomatic, organic, or psychotic illness.
The use of benzodiazepines to treat short-term 'mild' anxiety is inappropriate.
Benzodiazepines should be used to treat insomnia only when it is severe, disabling, or causing the patient extreme distress.
Approximate equivalent doses, diazepam 5 mg
alprazolam 250 micrograms
clobazam 10 mg
clonazepam 250 micrograms
flurazepam 7.5–15 mg
chlordiazepoxide 12.5 mg
loprazolam 0.5–1 mg
lorazepam 500 micrograms
lormetazepam 0.5–1 mg
nitrazepam 5 mg
oxazepam 10 mg
temazepam 10 mg
FOOTNOTE by Professor C Heather Ashton DM, FRCP, November 26, 2013
The above BNF guidance seems to suggest that all long-term prescribed benzodiazepine users should switch to diazepam in order to withdraw. However, many such users can successfully withdraw directly from their current benzodiazepine, providing it is available in small enough doses to allow for gradual reduction. Nevertheless, some long-term users find it difficult to withdraw from their prescribed benzodiazepine (usually patients on short-acting benzodiazepines such as lorazepam or alprazolam). In this case, transferring to diazepam, which is long-acting, may be preferable. A suggested protocol, using diazepam substitution, is given in the BNF above.
The reasons for considering diazepam substitution are fully explained in the Ashton Manual, Chapter 2, which also contains several sample withdrawal schedules, both with and without diazepam substitution.
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