Insomnia zolpidem

FOR INSOMNIA ZOLPIDEM (AMBIEN ), ZALEPLON (SONATA ), ESZOPICLONE (ESTORRA , LUNESTA ), AND INDIPLON... 

Zolpidem (1) is an effective hypnotic agent indicated for the short-term treatment of insomnia. Zolpidem interacts with the GABAa receptor, and its pharmacological effect is blocked by the benzodiazepine-receptor antagonist fiumazenil (Sanger and Depoortere, 1998). Zolpidem displaces benzodiazepines more selectively from the cerebellum than the hippocampus or spinal cord, consistent with preferential interaction with the ajGABAA receptor subtype (sometimes referred to as the benzodiazepine coi receptor). Studies... 

Zolpidem [ban, inn] (zolpidem tartrate [usanJ Ambien Stilnoct and many other names) is one of the imidazopyridines, and a non-benzodiazepine BENZODIAZEPINE BINDING-SITE AGONIST. Most of its properties are similar to diazepam, but with less ANTICONVULSANT, SEDATIVE and SKELETAL MUSCLE RELAXANT properties. It has HYPNOTIC activity and has been used to treat insomnia, zolpidem tartrate zolpidem. 

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 two selective GABA j receptor agonists currently marketed in the United States, zaleplon and Zolpidem, are a pyrazolopyrimidine and a imidaz-opyridine, respectively. Both of these drugs are approved only for the shortterm treatment of insomnia. 

A rebound sleep disturbance has been found after only 7—10 days of treatment with therapeutic doses of triazolam (Greenblatt et al. 1987). Others have described a withdrawal syndrome after substitution of a short-acting benzodiazepine for a long-acting benzodiazepine (Conell and Berhn 1983). Rebound insomnia may occur with zolpidem. 

Haldol for agitation, lorazepam for anxiety, temazepam or zolpidem for insomnia. 

Declerck A. C., Ruwe F., O Hanlon J. F., Wauquier A. (1992). Effects of Zolpidem and fhmitrazepam on nocturnal sleep of women subjectively complaining of insomnia. Psychopharmacology 106, 497-501. 

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. 

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. 

Insomnia Trazodone Quetiapine Zolpidem Temazepam Chloral hydrate ... 

Buspar containing buspirone is indicated in short-term anxiety. Diazepam, Stilnoct containing zolpidem, Heminevrin containing clomethiazole, and Phenergan containing promethazine are all indicated in insomnia. 

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. 

There is less therapeutic experience with the newer zaleplon than with zolpidem. Zaleplon has a rapid onset and a half-life of approximately 1 hour. It is extensively metabolized by aldehyde dehydrogenase, so that less than 1% of a dose is excreted unchanged. Because of its rapid onset of action and short biological half-life, zaleplon is well suited for treatment of sleep onset insomnia. Its short half-life often does not ensure a full 8 hours of sleep. 

C. Zolpidem is effective at relieving sleep-onset insomnia. The other agents listed could also induce sleep, although each would be expected to produce more disruption of sleep rhythm than would zolpi-dem. 

In the treatment of children and adolescents with anxiety disorders clinicians have a wide variety of pharmacologic options beyond the antidepressants (Shader and Greenblatt, 1995 Lydiard et ah, 1996 Riddle et ah, 1999). The benzodiazepines (BZs), with their favorable safety profile and quick onset of action, are attractive alternatives for the treatment of acute anxiety. While the clinical effectiveness of buspirone has not been proven in children, buspirone is used alone or in combination with other drugs in the treatment of anxiety disorders. The antihistamines are often used to treat insomnia and may reduce acute mild agitation. Zolpidem (Ambien) is occasionally used for its sedative properties. This chapter reviews the structure, proposed mechanisms of action, pharmacodynamic principles, and pharmacokinetic principles of these drugs. 

Trials of different modified-release formulations of zaleplon, zolpidem, and a similar selective GABA hypnotic, indiplon, are ongoing. These versions may help improve the sleep of those patients who have sleep maintenance insomnia or early-morning awakening. 

Although benzodiazepines, zolpidem, zaleplon, and eszopiclone are the mainstay of pharmacotherapy for insomnia, other sedating drugs, such as trazodone, diphenhydramine, or chloral hydrate, also may be used. Insomnia should first be addressed diagnostically, and in most cases, nonpharmacological interventions should be attempted before treatment with a hypnotic is instituted. Hypnotic agents should be administered in the lowest effective dose. Medications commonly prescribed for insomnia, along with their recom-... 

Individuals on very small amounts of heroin are prescribed diazepam for anxiety, agitation or craving, zopiclone or zolpidem for insomnia, hyoscine butylbromide (Buscopan) for stomach cramps, and diphenoxylate/atropine (Lomotil) for diarrhoea, over a seven-day period. The medication schedule provided to the user explains which drug is for which symptoms, and the maximum doses of each that can be taken in a day, which for diazepam varies during the course. The basic medication regime is included in the Appendix. 

There is a need for more comparisons with short to medium half-life BZDs for the treatment of insomnia to show that zolpidem has any advantages over the BZDs. One placebo-controlled, randomized polysomnographic study of 24 patients with chronic insomnia found that zolpidem (10 mg) was comparable with triazolam (0.5 mg) and superior to placebo in enhancing sleep efficacy. Further, rebound insomnia occurred during the posttreatment, 3-day withdrawal phase in the triazolam group, but not in the zolpidem or the placebo groups (149). 

Depressed individuals effectively treated with SSRIs often report persistent insomnia and require adjunctive sleep-promoting therapy. A study of the efficacy of zolpidem in this patient population showed that a dose of 10 mg was effectively and safely coadministered with an SSRI, resulting in improved self-rated sleep, daytime functioning, and well-being (150). 

Several psychotic reactions to zolpidem have been reported-two cases of amnestic psychotic reaction and a psychotic reaction with hallucinations in an anorectic patient (151). Zolpidem 5 mg was prescribed for a 34-year-old woman with chronic insomnia. Twenty minutes after taking the recommended adult dose (10 mg), she experienced feelings of objects in her environment. She then slept uneventfully and recalled the unusual experience in the morning. Zolpidem may also cause transient cognitive and behavioral problems similar to those of BZDs (152). 

Case Example Zolpidem was abused by a 33-year-old man who had been prescribed 10 mg/day for insomnia associated with depression. The patient took 30 mg and noticed improvement of depressive symptoms. With continued escalated doses (up to 150 to 280 mg/day), tolerance developed. He occasionally noticed signs of intoxication with severe ataxia after doses of 80 to 100 mg but never experienced the more common side effects of high-dose zolpidem. Dose reduction caused depressive mood recurrence with apathy and drug-craving. A grand mal seizure after ingesting 60 to 80 mg resolved without supportive measures (155). 

To manage withdrawal insomnia, we recommend the supplemental use of hypnotics such as zolpidem or a sedating antidepressant such as trazodone. Rickels et al. recommend the supplemental use of hypnotics such as diphenhydramine, doxylamine, or chloral hydrate or a sedating TCA such as doxepin ( 259). These investigators also recommend that chronic BZD users with evidence of depression or panic be treated with adequate doses of an appropriate antidepressant, a management technique that may help patients succeed in discontinuation. 

Even after relatively short periods of administration, discontinuation of short and intermediate half-life BZDs, such as triazolam and temazepam, may result in marked worsening of sleep, even worse than baseline levels (i.e., rebound insomnia), although this does not seem to occur with zolpidem (95, 102, 103, 109, 110, 113, 285, 297, 316, 325, 326, 327, 328, 329, 330, 331,332, 333, 334, 335, 336 and 337). Gradual dose reduction may attenuate the incidence of rebound, and with flurazepam and quazepam, little sleep disturbance occurs, even after abrupt drug withdrawal ( 99, 100, 101, 102, 103,104, 105 and 106, 280, 338, 339, 340 and 341). 

Differences in the development of tolerance and the occurrence of rebound insomnia have been well established with rapidly versus slowly eliminated BZD hypnotics. A meta-analysis of sleep laboratory studies has recently shown that tolerance with intermediate and long-term use clearly developed with triazolam but only marginally with midazolam and zolpidem. Rebound insomnia on the first withdrawal night was intense with triazolam and mild with zolpidem. The data led to the... 

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