Nonetheless, many complaints of insomnia are unfounded because the patient has unreal expectations concerning sleep. Elderly people fail to appreciate that it is normal to sleep less and less deeply as they age. Napping during the day also decreases the need for sleep at night. Some people can manage on 5 to 6 hours of sleep a night indefinitely, and yet worry that this is insufficient. Explanation and reassurance relieve their worries.
A substantial number of patients, in general, persistently complain of insomnia (primary insomnia). However, careful evaluation may reveal a link to stress, both transient and persistent. Giving drugs may initiate a long-term process that ends in drug-related insomnia without the basic problems being solved.
Short-term symptomatic relief is acceptable when the stress is undoubtedly severe but transient. Even so, the hypnotic agent must be chosen carefully. The elimination half-life is the most important consideration. Drugs with half-lives of more than 12 hours, such as flurazepam(Drug information on flurazepam), are only appropriate when an anxiolytic effect is required during the day and sleep induction is needed at night. Drugs with shorter half-lives encourage sleep onset but do not cause too many residual sedative effects the next day.
The management of chronic insomnia is much more problematic, especially in the elderly.17,18 Eszopiclone and zolpidem(Drug information on zolpidem) are short-acting and can—at a modest dosage—help ensure a good night’s sleep without much risk of residual sedative effects.19 Eszopiclone is licensed in the United States for long-term use in chronic insomnia and is already used extensively, but further evaluation in real-life settings is necessary.
Zolpidem and zaleplon(Drug information on zaleplon) can be used in a way that is strategically different from the way other longer-acting drugs are used. Hypnotics are traditionally taken every night before bed to induce or maintain sleep. However, the severity of insomnia usually varies from night to night. Consequently, regular use may often be unnecessary, and it increases the risk of habituation and dependence. Very short-acting compounds are unlikely to leave residual effects, even if taken up to 5 hours or so before the expected time of wakening. Consequently, the patient with insomnia can refrain from regular use of a hypnotic for sleep and instead wait an hour or so after going to bed to see whether natural sleep supervenes before resorting to medication.
Other hypnotics
A series of compounds is being developed based on melatonin(Drug information on melatonin). This hormone is important in the regulation of sleep and is secreted at night. Some elderly persons with insomnia seem to be deficient in melatonin. Preparations include long-acting formulations of melatonin, such as Circadin.20,21 Ramelteon is a melatonin (MT)1 and MT2 agonist. It is approved in the United States for insomnia and is effective in maintaining sleep. It has a favorable safety profile (dizziness and nausea are the most common adverse effects).22
A long history exists of using histamine antagonists such as promethazine and diphenhydramine(Drug information on diphenhydramine) hydrochloride as hypnotics. These tend to be rather unselective and can produce excessive sedation and sometimes weight gain. They are not associated with dependence or abuse, however. Selective histamine H1 antagonists are under development.23 Sedative antidepressants such as trazodone, low-dose doxepin(Drug information on doxepin), and mirtazapine(Drug information on mirtazapine) are also widely used as hypnotics, particularly in patients with insomnia and comorbid depression.24 This use is unsupported by convincing controlled data.25 Any antiarousal sleep-promoting effects are largely mediated through antihistaminic effects.
Conclusions
In many countries, insomnia is still largely treated with benzodiazepines. Nevertheless, controversy and disagreement continue to rage about the risk-to-benefit ratio of these compounds.26 Short-term use is well established, and a database showing favorable results serves as a rationale for this approach. However, studies on long-term use are still limited. While both the efficacy and safety of long-term use remain unclear, acceptance of current guidelines that limit the use of benzodiazepines seems wise. Of all the hypnotics, the z-drugs are still the drugs of choice and their use is supported by comprehensive databases. Many newer compounds with novel modes of action are in development.27
The management of insomnia is complex and is hampered by a dearth of information concerning the relative merits of various treatment modalities. Educating the patient about sleep hygiene may be the simplest way to reduce insomnia (Table 2). Much research is also needed on the optimum strategies for combining both drug and nondrug therapies, and on identifying predictors of response
