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Benzodiazepines

3.1 Sedation and other adverse CNS effects

prescription pad Dose-related unwanted drowsiness and sedation are the most common adverse effects of benzodiazepines. With increasing dose, sedation progresses to stupor1.

Drowsiness from a benzodiazepine can persist the following day and interfere with activities requiring alertness.

The depressant effect of benzodiazepines is selective for certain brain structures and quite different to the CNS depressant effects of volatile anaesthetics (such as isoflurane and sevoflurane) or barbiturates (such as phenobarbital and thiopental); an excessive dose of a benzodiazepine rarely leads to coma or profound respiratory or cardiovascular depression (see also under Respiratory adverse effects and Cardiovascular adverse effects).

Because of their muscle relaxant properties, some benzodiazepines are licensed for the management of painful muscle spasms and certain dystonias and involuntary movements. However, in other circumstances, benzodiazepines can occasionally produce muscle weakness and poor muscle coordination (ataxia).

Other effects resulting from benzodiazepine-induced CNS depression include increased reaction time, slurred speech (dysarthria), visual disorders, diplopia2, blurred vision, apathy, vertigo3, and confusion.

Long-term effects

Long-term use of a benzodiazepine is associated with:

  • depression or aggravation of depression. In these circumstances the disinhibiting4 effect of benzodiazepines may precipitate suicide. For this reason a benzodiazepine must not be used alone for treating depression or anxiety associated with depression
  • poor concentration and attention
  • impaired general intellectual ability. Cognitive5 function may take 6 months or longer to improve after stopping the benzodiazepine. In the elderly, underlying dementia may be exacerbated
  • emotional blunting. The ability to feel pleasure or sorrow may be impaired in long-term users of benzodiazepines
  • impaired visual-spatial ability and motor6 skills
  • amnesic effects—see under Memory impairment
  • increased reaction time

Driving

prescription pad The ability to drive or operate machinery may be impaired by benzodiazepine-induced drowsiness (which may be persist to the following day), as well as by other less frequent effects such as ataxia7. A driver’s use of a benzodiazepine increases the risk of motor traffic accident—inability to maintain road position may account for much of the increased risk. Interplay between the condition for which a benzodiazepine is prescribed and the CNS effects of the benzodiazepine will affect overall driving ability. The ability to drive and undertake skilled tasks may change as the condition responds to treatment and also as tolerance develops.

Factors which increase risk

In those with physiological CNS depression (manifested, for example, by reduced breathing rate, reduced heart rate and reduced level of consciousness), a benzodiazepine can further impair CNS function. Those with hepatic or renal impairment are at risk of benzodiazepine accumulation and, therefore, at higher risk of CNS depression.

The risk of CNS depression increases with the potency of a benzodiazepine and its persistence in the body (see table of equivalent doses under Dependence and withdrawal).

The incidence of benzodiazepine-induced CNS adverse effects is higher in the elderly, especially in the frail. The elderly are at higher risk of confusion, falls and of hospitalisation; long-acting benzodiazepines may be particularly problematic.

Concurrent administration of alcohol or another CNS depressant substance (see Interactions) can be hazardous.

Use of a benzodiazepine in patients with myasthenia gravis8, which involves impaired neuromuscular transmission, may increase the risk of muscle weakness.

Risk-reduction measures

A benzodiazepine should ideally be avoided in those with CNS depression or those taking medicines and other substances that depress the CNS. In myasthenia gravis and other conditions involving muscle weakness, a benzodiazepine should either be avoided or used with close monitoring of muscle function and respiratory function.

The benzodiazepine dose should be reduced in the elderly, the frail and those with marked hepatic or renal impairment. In these individuals benzodiazepines that are less liable to accumulation should be selected.

Activity

Can you think of the costs (to society and to the individual) associated with long-term use of benzodiazepines?

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  1. A state of mental numbness and near-unconsciousness
  2. ‘Double vision’; a single object seen as two objects
  3. Sensation of whirling or rotation of surroundings and loss of balance
  4. Loss of inhibition which can lead to lack of restraint and disregard for social conventions
  5. Mental functioning involving processes that include perception, recognition, conceptualisation, judgement, and reasoning
  6. Involves or relates to movement of muscle or describes muscle, nerve or brain centre that produces or affects motion
  7. Impaired muscle coordination, thereby affecting the ability to maintain posture or control the strength or direction of limb movement
  8. A progressive illness with fatigue and muscle weakness, which results from impaired muscle response to nerve impulse (because of autoimmune disorder affecting the neuromuscular junction)
  9. Loss of inhibition which can lead to lack of restraint and disregard for social conventions
  10. Mental functioning involving processes that include perception, recognition, conceptualisation, judgement, and reasoning