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Benzodiazepines

1. Introduction

prescription pad Benzodiazepines are among the most important drugs that specifically produce sedation1 and sleep. They are used for psychiatric and neurological indications including anxiety, insomnia, alcohol withdrawal, convulsions, and muscle spasm; amnesic properties are helpful for surgery and painful or distressing procedures. In 2011 over 11 million prescriptions for benzodiazepines were dispensed in England in the primary-care setting; benzodiazepines accounted for about 60% of prescriptions for hypnotics2 and anxiolytics (for more information, see under Benzodiazepine prescribing trends).

Almost all therapeutic and adverse effects of benzodiazepines arise from their action on the CNS. Introduced in the 1960s, benzodiazepines superseded barbiturates3 for most indications because, unlike barbiturates, benzodiazepines on their own were almost incapable of causing profound CNS depression, fatal respiratory depression, or cardiovascular collapse.

A crucial disadvantage of the benzodiazepines is their potential for inducing dependence4 and the distressing symptoms of benzodiazepine withdrawal. Tolerance5 can develop to therapeutic effects of benzodiazepines and the efficacy of these drugs wanes on persistent use. A benzodiazepine should not be used for longer than 2–4 weeks for the management of insomnia or anxiety. It should be prescribed only for severe symptoms and if interventions such as psychological treatment and sleep hygiene6 have proved inadequate.

During treatment, drowsiness (which could persist for many hours) can affect tasks requiring alertness such as driving.

In all cases the therapeutic benefits of benzodiazepine need to be balanced against potential adverse effects and the possibility of dependence. In addition to inducing dependence, long-term use of benzodiazepine can affect cognitive7 and emotional functioning (see under Sedation and other adverse CNS effects).

Benzodiazepines are deliberately abused for recreational purposes and might be taken in association with other legal and illicit substances; risks arising from such abuse8 are not covered in this module.

The non-benzodiazepine hypnotics zaleplon, zolpidem and zopiclone, share many pharmacological properties of the benzodiazepines; however, they are structurally distinct and are not specifically considered in this module.

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Persistence of benzodiazepines in the body

The persistence of benzodiazepines in the body can be categorised by their half lives as follows:

Short-acting (half-life of drug and metabolites shorter than 6 hours)

Intermediate-acting (half-life of drug and metabolites 6–24 hours)

Long-acting (half-life of drug and metabolites longer than 24 hours)

Midazolam

Oxazepam

Alprazolam

Loprazolam

Lorazepam

Lormetazepam

Temazepam

Chlordiazepoxide

Clobazam

Clonazepam

Diazepam

Flurazepam

Nitrazepam


  1. Reduction of anxiety, irritability or excitement; inducing calmness
  2. A substance that induces sleep
  3. Substances derived from barbituric acid which depress the central nervous system and were formerly used mainly as sedatives or hypnotics; barbiturates in current use include phenobarbital and thiopental
  4. Psychological craving or physiological reliance on a chemical substance; also termed habituation
  5. Tolerance follows repetitive exposure to a drug, leading to a reduction of the pharmacological effect of that drug
  6. Conditions that promote sleep: eg fixed times for retiring and waking, avoiding caffeine and alcohol late at night, avoiding heavy meals at night, taking regular exercise (gentle exercise in the evening), and comfortable sleeping environment
  7. Mental functioning involving processes that include perception, recognition, conceptualisation, judgement, and reasoning
  8. Excessive use of a substance that can modify psychological or other body function and can lead to effects that are harmful to the individual or to others
  9. Substances derived from barbituric acid which depress the central nervous system and were formerly used mainly as sedatives or hypnotics; barbiturates in current use include phenobarbital and thiopental
  10. Tolerance follows repetitive exposure to a drug, leading to a reduction of the pharmacological effect of that drug
  11. Psychological craving or physiological reliance on a chemical substance; also termed habituation