Insomnia hypnotics

Insomnia is a related psychiatric illness having potentially serious consequences. In any given year up to one-third of the general population may experience insomnia and consequently considerable impact on quaUty of life. Potentially serious psychosocial, health, and socioeconomic consequences may foUow. Many sedative—hypnotics additionally have a firmly estabUshed position within the field of anesthesiology as premedication, inducing agents, and/or for maintenance in intensive care medicine. 

Pharmacological Profiles of Anxiolytics and Sedative—Hypnotics. Historically, chemotherapy of anxiety and sleep disorders rehed on a wide variety of natural products such as opiates, alcohol, cannabis, and kawa pyrones. Use of various bromides and chloral derivatives ia these medical iadications enjoyed considerable popularity early ia the twentieth century. Upon the discovery of barbiturates, numerous synthetic compounds rapidly became available for the treatment of anxiety and insomnia. As of this writing barbiturates are ia use primarily as iajectable general anesthetics (qv) and as antiepileptics. These agents have been largely replaced as treatment for anxiety and sleep disorders. 

A class of sedative/hypnotic type drug that exert their effects through the benzodiazepine binding site on GABAa receptors. The class consists both of molecules that contain the benzodiazepine moiety, for example diazepam, lorazepam and flunitrazepam, and the newer, non-benzodiazepine compounds such as zolpidem, zopiclone, indiplon and zaleplon. BzRAs are primarily used for the treatment of anxiety, insomnia and to elicit varying levels of sedation. The wide selection of compounds currently available affords the prescribing clinician extensive options in terms of relative efficacies and durations of action. 

The definition of desired therapeutic and side effects in the case of the benzodiazepines very much depends on the clinical problem in question. The sedative and hypnotic actions are desired effects in the treatment of insomnia, but undesired effects in the treatment of anxiety disorders. Effects that are usually undesired include daytime drowsiness, potentiation of the sedative effects of ethanol, and anterograde amnesia. They are mediated via the benzodiazepine site of GABAa receptors, since they can be antagonized with flumazenil. 

Time taken to fall asleep from full wakefulness. Used clinically as a measure of insomnia, and to determine the effectiveness of hypnotic medications. 

On discontinuation of hypnotic BZDRAs, patients can experience rebound effects, specifically rebound insomnia that may last for one to two nights. Rebound insomnia occurs more frequently after discontinuation of shorter-duration BZDRAs compared with long-duration BZDRAs. Intermittent hypnotic therapy with the lowest dose possible reduces the likelihood of tolerance, dependence, and withdrawal when therapy is stopped. Patients should be counseled that rebound insomnia is not necessarily a return of their original symptoms, and it may take a few nights for rebound symptoms to subside. 

Transient and short-term insomnia should be treated with good sleep hygiene and careful use of sedative-hypnotics if necessary. 

Chronic insomnia calls for careful assessment for a medical cause, non-pharmacologic treatment, and careful use of sedative-hypnotics (intermittently to prevent tolerance and dependence). 

Flurazepam belongs to the class of hypnotic agent used for the treatment of insomnia. 

Ultimately, it is a drug s half-life combined with its potency that dictates its utility as a sedative-hypnotic. Like other benzodiazepines, clonazepam (Klonopin) can be used to treat insomnia, but its long duration of action renders it prone to hangover effects at doses needed to treat insomnia. Nevertheless, low doses of clonazepam (0.25-2 mg) are a treatment for PLMD and are also used to treat RLS. When hangover effects of even low doses of clonazepam are a problem, other benzodiazepines can be used. 

The development of tolerance is a major drawback to the use of benzodiazepines in the long-term treatment of insomnia. Whereas tolerance to the hypnotic effects of benzodiazepines permits them to be used without excessive sedation when treating anxiety disorders, this is counterproductive when attempting to treat insomnia. Patients often find themselves requiring higher doses to obtain the same sedative-hypnotic effect initially accomplished by lower doses. For this reason, careful consideration must be given before benzodiazepines are used to treat chronic insomnia. 

Antihistamines. After alcohol, antihistamines are the most commonly self-administered sleep medications. Foremost among these is diphenhydramine (Benadryl), which is also available as a component in a variety of over-the-counter nighttime medications including Tylenol PM and Excedrin PM. Prescription antihistamines like hydroxyzine (Vistaril, Atarax) are also occasionally used to treat insomnia. Finally, it is the antihistamine effect of some antidepressants and anti-psychotics that contribute to their utility as sedative-hypnotics. 

One principal difference between the medications is half-life, that is, the time required to metabolize 50% of the compound present in the body. Zolpidem has a half-life of 1.4-4.5 honrs, zaleplon has a half-life of 0.9-1.1 hours, and eszopiclone has a half-life of abont 6 honrs. The key is the markedly shorter half-lives that are displayed by many other sedative-hypnotics, as shown in Eigure 9.1. Only eszopiclone has been shown effective for the long-term (np to 6 months) treatment of chronic insomnia. 

Acute Phase Treatment. Hypnotic medications are useful for short-term treatment of insomnia, but they should always be accompanied by behavioral and psychoeducational treatments, including a review of good sleep hygiene practices. It may also include more aggressive measures such as relaxation training, sleep restriction therapy, and stimulus control therapy. 

Nevertheless, sedative-hypnotic agents often play a useful role in treatment. In particular, by providing a successful night s sleep, these medications can break the cycle of anxious anticipation and dread that afflicts the insomnia sufferer during the night. We generally prefer using zolpidem or zaleplon as a first-line treatment for early-to-middle insomnia. Late insomnia often responds well to trazodone or eszopiclone, and trazodone often is a first choice in the presence of substance abuse for all insomnias. 

Whichever sedative-hypnotic agent is selected, the following guidelines can help ensure a safe and effective treatment. Use the minimal therapeutic dose at first to decrease possible hangover effects. Consider using the medication on an as-needed basis if the insomnia is intermittent, and after 2-4 weeks attempt a trial off medication to see if it is still required. Many individuals with chronic insomnia will relapse after a 14-28 day trial of treatment, but this time frame also affords an opportunity to implement sleep hygiene improvements. 

Long-Term Treatment. When sleep medications are used on a long-term basis, they are potentially not helping the problem but contributing to it. Unfortunately, this all too commonly results when a hypnotic medication is started without giving any thought to changing the behaviors that sustain the insomnia. 

What to do with the patient who is a long-time user of sedative-hypnotics is often a difficult clinical decision. The most successful treatment approaches seem to be those that are gradual and address the insomnia from a multimodal perspective. Many of the sedative-hypnotics with moderate or longer half-lives will display rebound insomnia on discontinuation and this only complicates the treatment picture. At some point, one has to ask if discontinuing the chronic use of a sedative-hypnotic, in the absence of any harmful effects, is treating the patient or the prescriber. 

Diazepam is used for the control of anxiety and tension, the relief of muscle spasms, and the management of acute agitation during alcohol withdrawal, but it itself may be habit-forming. Chlordiazepoxide has similar uses and its synthesis is somewhat analogous to diazepam. Flurazepam is a hypnotic, useful for insomnia treatment. It is reported to provide 7-8 hr of restful sleep. 

Temazepam is a moderately effective hypnotic. Insomnia may again reappear upon completion of drug treatment. The most frequently used synonym for this drug is galcion. 

The sedative-hypnotic action of chloral hydrate should be explained by the formation of trichloroethanol, which is synthesized as a result of its reduction in tissues. Despite the fact that the precise mechanism of action of chloral hydrate is not known, it evidently acts analogous to ethanol on the CNS by inCTeasing membrane permeability, which leads to sedation or sleep. Chloral hydrate can be used for insomnia as an alternative to benzodiazepines. Synonyms for this drug are aquachloral, chloradorm, chloratol, noctec, and others. 

The sedative hypnotic ethchlorvynol has approximately the same activity and toxicity as phenobarbital however, its hypnotic effect develops and dissipates qnicker. It is nsed mnch less than benzodiazepines in treating insomnia for a nnmber of reasons. 

Ethinamate is a hypnotic, which does not have, however, a considerable advantage over barbiturates and benzodiazepines, and is used much less in treating insomnia. Synonyms for this drug are valamide, ivalmad, valamin, and others. 

Glutethimide is a hypnotic and sedative agent intended to treat insomnia. The hypnotic effect is roughly analogous to that of pentobarbital. It is given to patients who cannot... 

Drug abuse and dependence Sedative/hypnotics have produced withdrawal signs and symptoms following abrupt discontinuation. These reported symptoms range from mild dysphoria and insomnia to a withdrawal syndrome that may include abdominal and muscle cramps, vomiting, sweating, tremors, and convulsions. Zolpidem does not reveal any clear evidence for withdrawal syndrome. 

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