Unwanted effects

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The most common unwanted effects of the anxiolytic benzodiazepines are tiredness, drowsiness, and torpor—so-called 'over-sedation'. The effects are dose and time related, being maximal within the first 2 h after large doses. Drowsiness is most common during the first week of treatment, after which it largely disappears probably due to a true tolerance effect. Smokers seem less affected than non-smokers because they metabolize the drugs more rapidly due to increased liver enzyme activity induced by constituents in the tobacco smoke. Patients should be warned of the potential side-effects of any prescribed benzodiazepine and the initial dosage should be cautious. Both psychomotor skills and intellectual and cognitive skills are affected. In particular, patients should be advised not to drive during the initial adjustment of dosage. Important decisions should be deferred during this period because judgement may be affected.

Benzodiazepines have major effects on memory in patients/9) They differ in their ability to produce memory deficits, with lorazepam being especially powerful. However, most benzodiazepines can cause problems, especially in higher dose and in the elderly.

Psychomotor performance is also affected. Elderly drivers seem particularly at risk. In one survey of drivers over the age of 65 in the Tennessee Medicaid scheme, an increased risk (1.5 of having an injurious crash) was found for those taking a benzodiazepine. (21.) However, the risk was even higher for tricyclic antidepressants and the hazard was strongly dose related.

As with other depressant drugs, potentiation of the effects of alcohol can occur. Patients must be warned not to drink alcohol when taking benzodiazepines, either chronically or intermittently.

Patients taking benzodiazepines may develop paradoxical behavioural responses such as uncontrollable weeping, increased aggression and hostility, and acute rage reactions or uncharacteristic criminal behaviour such as shoplifting. This phenomenon is by no means confined to the benzodiazepines; alcohol is a cardinal example of a drug whose use may lead to excessive violence or criminal behaviour. Paradoxical reactions, including the release of anxiety or hostility, are most common during the initial week of treatment, and usually resolve spontaneously or respond to dose adjustment. One cannot predict who will respond adversely. (22 Benzodiazepines may reduce anxiety levels in depressed patients and thereby uncover suicidal ideation. (23) However, reports of the induction of depression by the benzodiazepines in patients with apparent generalized anxiety disorder is probably the result of an initial misdiagnosis and a failure to detect the underlying depression.

Other unwanted effects include respiratory depression, excessive weight gain, skin rash, impairment of sexual function, menstrual irregularities, and, rarely, blood dyscrasias. The use of benzodiazepines in pregnancy is unestablished, but reports of birth defects among babies born of mothers given these drugs have not been confirmed. Benzodiazepines pass readily into the fetus and can produce respiratory depression in the neonate. Withdrawal effects are also documented. Finally, benzodiazepines pass into the mother's milk and can oversedate the baby, so breast feeding should be discouraged if benzodiazepines are prescribed, especially in high dose.

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