Use of hypnotics
Despite the fact that man spends approximately one-third of his life asleep, the purpose of sleep still remains a mystery. The clinical importance of sleep is reflected in the frequency and severity of complaints about insomnia, a condition that signifies unsatisfactory or insufficient sleep. Problems may involve difficulty in getting to sleep, disturbing dreams, early wakening, and day-time drowsiness due to poor sleep at night. In most cases, these symptoms are fairly transient and may be associated with a specific or identifiable event such as a family or work situation, a temporary financial problem, etc. Should the sleep disturbance persist for longer than 3 weeks, specific treatment may be indicated. The Association of Sleep Disorders Centres has classified sleep disorders into two broad classes – disorders of initiating and maintaining sleep (DIMS) and disorders of excessive somnolence (DOES); these definitions have now been appended to the DSM–IV. The hypnogram of a patient with an underlying psychiatric illness may be characterized by a delay in sleep onset, the presence of residual muscular activity causing frequent awakenings, fragmented sleep, reduced REM and slow-wave sleep, and day-time drowsiness. Such disorders are generally not associated with a recent or transient event and the cause cannot usually be identified. Often such changes in the sleep architecture are associated with major psychiatric disorders such as depression, mania, psychosis or severe anxiety states.
For the purpose of considering the prescribing of hypnotics, insomnia may be classified into three major types:
1. Transient insomnia. This occurs in normal sleepers who experience an acute stress or stressful situation lasting for a few days, for example, air travel to a different time zone or hospitalization.
2. Short-term insomnia. This is usually associated with situational stress caused, for example, by bereavement or which may be related to conflict at work or in the family.
3. Long-term insomnia. Studies suggest that insomnia in up to 50% of patients in this category is related to an underlying psychiatric illness.
Of the remainder of the patients in this category, chronic alcohol or drug abuse may be the cause of the sleep disruption. Whenever the use of hypnotics is considered appropriate, it is universally agreed that patients should be given the smallest effective dose for the shortest period of time necessary. This recommendation applies particularly to elderly patients. For transient and short-term insomnia there is no clear consensus, although in practice the use of a medium or short half-life hypnotic for a few days is sometimes recommended when sleep disturbance is associated with shift work or ‘‘jet-lag’’. For chronic insomnia, careful investigation of the underlying cause of the condition is essential before hypnotics are routinely prescribed. Should the insomnia be associated with a psychiatric condition or drug abuse, specific treatment of the core illness will often obviate the need for hypnotics.
For all practical purposes, the benzodiazepines are the group of drugs most widely used to treat insomnia. These may be divided into three classes based on their pharmacokinetic characteristics:
1. Short half-life drugs, such as triazolam, midazolam and brotizolam, with elimination half-lives of about 6 hours.
2. Intermediate half-life drugs, such as temazepam, lormetazepam and loprazolam, with half-lives of 6–12 hours.
3. Long half-life drugs, such as nitrazepam, flurazepam and flunitrazepam, with half-lives over 12 hours.
The elimination half-lives of a number of commonly used hypnotics. It should be noted that many of the drugs in current use have active metabolites which considerably prolong the duration of their pharmacological effect. This is particularly true for the elderly patient in whom the half-life of the hypnotic is prolonged due to decreased metabolism and renal clearance; such individuals are also more sensitive to the sedative effects of any psychotropic medication. In general, the efficacy of hypnotics for short-term use is well established and there is a close relationship between their pharmacokinetic and pharmacodynamic profiles. The most widely used hypnotic in the UK, for example, is temazepam, which is relatively slowly absorbed and therefore has only a marginal effect on the sleep latency but facilitates sleep duration.The short elimination half-lives of drugs such as brotizolam ensure that residual sedative effects do not occur during the day. In contrast, fast elimination hypnotics such as midazolam and triazolam, which are effective in treating sleep onset insomnia, often give rise to rebound insomnia on withdrawal. It should be emphasized that the abrupt withdrawal of hypnotics, particularly when they have been given for several weeks or longer, is generally accompanied by REM rebound which results in an increased frequency of dreams and nightmares and can precipitate disturbed sleep and anxiety. Slow reduction in the night-time dose of the hypnotic over several days may reduce the risk of such a rebound. Regarding the efficacy of hypnotics when used long-term, there is evidence that sleep latency shows more tolerance than sleep time. Furthermore, it is generally accepted that each hypnotic has a minimal effective dose and that increasing this does little to improve the duration of sleep but is more likely to increase the side effects.
Despite the fact that man spends approximately one-third of his life asleep, the purpose of sleep still remains a mystery. The clinical importance of sleep is reflected in the frequency and severity of complaints about insomnia, a condition that signifies unsatisfactory or insufficient sleep. Problems may involve difficulty in getting to sleep, disturbing dreams, early wakening, and day-time drowsiness due to poor sleep at night. In most cases, these symptoms are fairly transient and may be associated with a specific or identifiable event such as a family or work situation, a temporary financial problem, etc. Should the sleep disturbance persist for longer than 3 weeks, specific treatment may be indicated. The Association of Sleep Disorders Centres has classified sleep disorders into two broad classes – disorders of initiating and maintaining sleep (DIMS) and disorders of excessive somnolence (DOES); these definitions have now been appended to the DSM–IV. The hypnogram of a patient with an underlying psychiatric illness may be characterized by a delay in sleep onset, the presence of residual muscular activity causing frequent awakenings, fragmented sleep, reduced REM and slow-wave sleep, and day-time drowsiness. Such disorders are generally not associated with a recent or transient event and the cause cannot usually be identified. Often such changes in the sleep architecture are associated with major psychiatric disorders such as depression, mania, psychosis or severe anxiety states.
For the purpose of considering the prescribing of hypnotics, insomnia may be classified into three major types:
1. Transient insomnia. This occurs in normal sleepers who experience an acute stress or stressful situation lasting for a few days, for example, air travel to a different time zone or hospitalization.
2. Short-term insomnia. This is usually associated with situational stress caused, for example, by bereavement or which may be related to conflict at work or in the family.
3. Long-term insomnia. Studies suggest that insomnia in up to 50% of patients in this category is related to an underlying psychiatric illness.
Of the remainder of the patients in this category, chronic alcohol or drug abuse may be the cause of the sleep disruption. Whenever the use of hypnotics is considered appropriate, it is universally agreed that patients should be given the smallest effective dose for the shortest period of time necessary. This recommendation applies particularly to elderly patients. For transient and short-term insomnia there is no clear consensus, although in practice the use of a medium or short half-life hypnotic for a few days is sometimes recommended when sleep disturbance is associated with shift work or ‘‘jet-lag’’. For chronic insomnia, careful investigation of the underlying cause of the condition is essential before hypnotics are routinely prescribed. Should the insomnia be associated with a psychiatric condition or drug abuse, specific treatment of the core illness will often obviate the need for hypnotics.
For all practical purposes, the benzodiazepines are the group of drugs most widely used to treat insomnia. These may be divided into three classes based on their pharmacokinetic characteristics:
1. Short half-life drugs, such as triazolam, midazolam and brotizolam, with elimination half-lives of about 6 hours.
2. Intermediate half-life drugs, such as temazepam, lormetazepam and loprazolam, with half-lives of 6–12 hours.
3. Long half-life drugs, such as nitrazepam, flurazepam and flunitrazepam, with half-lives over 12 hours.
The elimination half-lives of a number of commonly used hypnotics. It should be noted that many of the drugs in current use have active metabolites which considerably prolong the duration of their pharmacological effect. This is particularly true for the elderly patient in whom the half-life of the hypnotic is prolonged due to decreased metabolism and renal clearance; such individuals are also more sensitive to the sedative effects of any psychotropic medication. In general, the efficacy of hypnotics for short-term use is well established and there is a close relationship between their pharmacokinetic and pharmacodynamic profiles. The most widely used hypnotic in the UK, for example, is temazepam, which is relatively slowly absorbed and therefore has only a marginal effect on the sleep latency but facilitates sleep duration.The short elimination half-lives of drugs such as brotizolam ensure that residual sedative effects do not occur during the day. In contrast, fast elimination hypnotics such as midazolam and triazolam, which are effective in treating sleep onset insomnia, often give rise to rebound insomnia on withdrawal. It should be emphasized that the abrupt withdrawal of hypnotics, particularly when they have been given for several weeks or longer, is generally accompanied by REM rebound which results in an increased frequency of dreams and nightmares and can precipitate disturbed sleep and anxiety. Slow reduction in the night-time dose of the hypnotic over several days may reduce the risk of such a rebound. Regarding the efficacy of hypnotics when used long-term, there is evidence that sleep latency shows more tolerance than sleep time. Furthermore, it is generally accepted that each hypnotic has a minimal effective dose and that increasing this does little to improve the duration of sleep but is more likely to increase the side effects.
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