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Adverse Effects of Benzodiazepines

Oversedation is a dose-related extension of the sedative/hypnotic effects of benzodiazepines. Symptoms include drowsiness, poor concentration, incoordination, muscle weakness, dizziness and mental confusion. When benzodiazepines are taken at night as sleeping pills, sedation may persist the next day as "hangover" effects, particularly with slowly eliminated preparations. However, tolerance to the sedative effects usually develops over a week or two and anxious patients taking benzodiazepines during the day rarely complain of sleepiness although fine judgement and some memory functions may still be impaired.

Oversedation persists longer and is more marked in the elderly and may contribute to falls and fractures. Acute confusional states have occurred in the elderly even after small doses of benzodiazepines.

Oversedation from benzodiazepines contributes to accidents at home and at work and studies from many countries have shown a significant association between the use of benzodiazepines and the risk of serious traffic accidents. People taking benzodiazepines should be warned of the risks of driving and of operating machinery .

Drug interactions

Benzodiazepines have additive effects with other drugs with sedative actions including other hypnotics, some antidepressants (e.g. amitriptyline [Elavil], doxepin [Adapin, Sinequan]), major tranquillisers or neuroleptics (e.g. prochlorperazine [Compazine], trifluoperazine [Stelazine]), anticonvulsants (e.g. phenobarbital, phenytoin [Dilantin], carbamazepine [Atretol, Tegretol]), sedative antihistamines (e.g. diphenhydramine [Benadryl], promethazine [Phenergan]), opiates (heroin, morphine, meperidine), and, importantly, alcohol. Patients taking benzodiazepines should be warned of these interactions. If sedative drugs are taken in overdose, benzodiazepines may add to the risk of fatality.

Memory impairment

Benzodiazepines have long been known to cause amnesia, an effect which is utilised when the drugs are used as premedication before major surgery or for minor surgical procedures. Loss of memory for unpleasant events is a welcome effect in these circumstances. For this purpose, fairly large single doses are employed and a short-acting benzodiazepine (e.g. midazolam) may be given intravenously.

Oral doses of benzodiazepines in the dosage range used for insomnia or anxiety can also cause memory impairment. Acquisition of new information is deficient, partly because of lack of concentration and attention. In addition, the drugs cause a specific deficit in "episodic" memory, the remembering of recent events, the circumstances in which they occurred, and their sequence in time. By contrast, other memory functions (memory for words, ability to remember a telephone number for a few seconds, and recall of long-term memories) are not impaired. Impairment of episodic memory may occasionally lead to memory lapses or "blackouts". It is claimed that in some instances such memory lapses may be responsible for uncharacteristic behaviours such as shop-lifting.

Benzodiazepines are often prescribed for acute stress-related reactions. At the time they may afford relief from the distress of catastrophic disasters, but if used for more than a few days they may prevent the normal psychological adjustment to such trauma.

Bereavement, psychotherapy

In the case of loss or bereavement they may inhibit the grieving process which may remain unresolved for many years. In other anxiety states, including panic disorder and agoraphobia, benzodiazepines may inhibit the learning of alternative stress-coping strategies, including cognitive behavioural treatment.

Paradoxical stimulant effects

Benzodiazepines occasionally cause paradoxical excitement with increased anxiety, insomnia, nightmares, hallucinations at the onset of sleep, irritability, hyperactive or aggressive behaviour, and exacerbation of seizures in epileptics. Attacks of rage and violent behaviour, including assault (and even homicide), have been reported, particularly after intravenous administration but also after oral administration. Less dramatic increases in irritability and argumentativeness are much more common and are frequently remarked upon by patients or by their families. Such reactions are similar to those sometimes provoked by alcohol. They are most frequent in anxious and aggressive individuals, children, and the elderly. They may be due to release or inhibition of behavioural tendencies normally suppressed by social restraints. Cases of "baby-battering", wife-beating and "grandma-bashing" have been attributed to benzodiazepines.

Depression, emotional blunting

Long-term benzodiazepine users, like alcoholics and barbiturate-dependent patients, are often depressed, and the depression may first appear during prolonged benzodiazepine use. Benzodiazepines may both cause and aggravate depression, possibly by reducing the brain's output of neurotransmitters such as serotonin and norepinephrine (noradrenaline). However, anxiety and depression often co-exist and benzodiazepines are frequently prescribed for mixed anxiety and depression. Sometimes the drugs seem to precipitate suicidal tendencies in such patients. Of the first 50 of the patients attending my withdrawal clinic (reported in 1987), ten had taken drug overdoses requiring hospital admission while on chronic benzodiazepine medication; only two of these had a history of depressive illness before they were prescribed benzodiazepines. The depression lifted in these patients after benzodiazepine withdrawal and none took further overdoses during the 10 months to 3.5 years follow-up period after withdrawal. In 1988 the Committee on Safety of Medicines in the UK recommended that "benzodiazepines should not be used alone to treat depression or anxiety associated with depression. Suicide may be precipitated in such patients".

"Emotional anaesthesia", the inability to feel pleasure or pain, is a common complaint of long-term benzodiazepine users. Such emotional blunting is probably related to the inhibitory effect of benzodiazepines on activity in emotional centres in the brain. Former long-term benzodiazepine users often bitterly regret their lack of emotional responses to family members - children and spouses or partners - during the period when they were taking the drugs. Chronic benzodiazepine use can be a cause of domestic disharmony and even marriage break-up.

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