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The Effects of
Tranquillization:
Benzodiazepine Use in
Canada
Health Canada Publication: 1982
3. APPROPRIATE USES OF BENZODIAZEPINES
Use as Anti-Anxiety Agents and Hypnotics
Benzodiazepine drugs have a definite place in the armamentarium of the physician. The primary role of these drugs is as anti-anxiety agents in acute or chronic incapacitating disorders characterized by anxiety. Current practice defines these states as Generalized Anxiety Disorders and Panic Disorders.[49] Panic takes the form of unpredictable acute anxiety of sudden onset resulting in feelings of intense apprehension and frequently includes physical symptoms such as palpitations, breathlessness, chest pains, etc. Generalized Anxiety refers to continuing and steady severe anxiety lasting long after a stressful situation has occurred or without any precipitation stress.*
Numerous studies have demonstrated the superiority of benzodiazepines over placebo in reducing anxiety.[50] It is claimed, however, that some uncertainty still exists regarding the anti-anxiety properties of the benzodiazepines as separate from their well-established sedating effects.[51]
Severe insomnia is another condition for which these drugs are prescribed. Some benzodiazepines are promoted solely as hypnotics (e.g. flurazepam, triazolam), but a number of others, which first came on the market as anti-anxiety agents, are currently used in somewhat larger doses as sleeping medications (diazepam, oxazepam).
Use in Non-Psychiatric Conditions
Benzodiazepines have also been found to be useful in acute alcohol withdrawal. However, controlled conditions are recommended for the use of these drugs in withdrawal.[52] Other uses include the treatment of some types of continuous seizures, and of a variety of neuromuscular disorders such as cerebral palsy, tetanus, and stiff-man syndrome.[53] Diazepam, in particular, is used extensively in pre-anaesthetic procedures, as an intravenous anaesthetic during minor surgery, and in a variety of diagnostic tests generally administered in hospitals.[54,55]
One literature review of the efficacy of benzodiazepines in nonpsychiatric medical practice, particularly their effects on the cardiovascular and gastrointestinal systems, concludes with a plea for large clinical trials carried out over a prolonged time period. Because of currently conflicting evidence, such studies are judged necessary to answer the question whether the benzodiazepines "affect only anxiety and muscular tension or whether they also affect organ systems known to be linked in important pathophysiological ways to the nervous system."[56]
Psychiatric contraindications
While benzodiazepines have a clear role in diminishing acute anxiety they do not appear to be effective in treating severe psychiatric disorders such as schizophrenia. Nor have benzodiazepines been found superior to antidepressant drugs for depression,[57] although there is some evidence accumulating that they may be of value for depressive disorders in which anxiety is a major component.[58] As noted earlier, it would appear that these drugs are contraindicated in those disorders in which aggressive behaviour predominates,[59,60] as they frequently release rage reactions and increase hostility. Such reactions have also been observed by clinicians in previously non-aggressive patients.
Duration of Use and Dosage
Given this wide spectrum of uses, the following discussion will focus on the most common uses, those associated with anxiety reduction and sleep disorders.
It is generally agreed that, lacking evidence that the anti-anxiety properties of these drugs exceed two to four weeks, and since anxiety is typically episodic, courses of one to two weeks are recommended.[61] Dependence on diazepam, the most extensively studied benzodiazepine, is estimated to occur anywhere from two weeks to four months after initial use, depending on dosage.[62]
Another reason for the recommended course of only one to two weeks, is the opportunity provided to assess the individual dose response. There is considerable evidence that dose requirements for patients vary greatly, to the extent that "...it is virtually impossible to predict a clinical response at a particular dose in a particular patient."[63]
Sensitivity to these drugs clearly increases with age (thus initial doses should be lower in older age groups than for younger people) as well as with some disorders, such as liver disease. Females appear to be less sensitive to diazepam than males, and smokers may require up to 50 per cent more compound than non-smokers for equivalent action.[64] Thus gender, age, smoking behaviour, liver functioning as well as recent use of other substances such as alcohol and other central nervous system drugs will profoundly affect the individual's response to benzodiazepines.
Appropriateness in Pregnancy, Pediatric Medicine, the Elderly
There are certain life stages during which benzodiazepines should be used only with caution and under very limited conditions. For example, there is now general agreement that these drugs, like many others, should rarely be used in the first trimester of pregnancy because of risks to the developing foetus.[65] Since pregnancy is typically not confirmed until four to six weeks after conception, use of these drugs is unwise for women of child-bearing age who are at risk of becoming pregnant. Because benzodiazepines cross the placental barrier and accumulate in the foetus when given in a continued dosage regimen, there are problems associated with their use in the latter part of pregnancy and during labour. Newborn infants whose mothers have used these drugs for extended periods have shown a variety of symptoms such as respiratory distress and poor sucking. The abrupt withdrawal from the drugs at birth appears also to result in irritability, tremors, diarrhea and other disorders.[66]
Benzodiazepines accumulate in breast milk, causing possible sedation and feeding difficulties in the infant.[67] Thus, many women may prefer not to use these drugs during labour or immediately thereafter.
In childhood, a clear indication exists for use of benzodiazepines in the control of convulsions, in which intravenous as well as oral forms are used.[68] As with adults, these drugs are used in various anaesthetic procedures with children.
As mentioned earlier, sensitivity to these drugs increases with age, thus it is not surprising to find a higher incidence of side effects among the elderly. Excessive drowsiness and sedation are more than twice as common in the elderly after using diazepam than in a younger population.[69] It has been recommended that the drugs with a short half-life be used for this population. However, there is as yet no controlled research indicating their greater safety and efficacy over the older benzodiazepines. In addition, some recent clinical reports indicate there may be more severe problems on withdrawal from the short half-life benzodiazepines.
In view of their frequent use of multiple medications, their diminished capacity to metabolize and excrete drugs, and the current lack of clarity on the safest and most efficacious benzodiazepines to use in the elderly, careful monitoring of this population is particularly important.[70]
* These states must be clearly distinguished from the type of anxiety commonly experienced by most individuals in response to situational stresses and which takes milder forms such as occasional sleeplessness, feelings of irritability and tension, and so forth.
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