Zolpidem side effects

Zolpidem, chemically unrelated to benzodiazepines or barbiturates, acts selectively at the y-aminobutyric acidA (GABAA)-receptor and has minimal anxiolytic and no muscle relaxant or anticonvulsant effects. It is comparable in effectiveness to benzodiazepine hypnotics, and it has little effect on sleep stages. Its duration is approximately 6 to 8 hours, and it is metabolized to inactive metabolites. Common side effects are drowsiness, amnesia, dizziness, headache, and GI complaints. Rebound effects when discontinued and tolerance with prolonged use are minimal, but theoretical concerns about abuse exist. It appears to have minimal effects on next-day psychomotor performance. The usual dose is 10 mg (5 mg in the elderly or those with liver impairment), which can be increased up to 20 mg nightly. Cases of psychotic reactions and sleep-eating have been reported. 

Principal side effects are gastrointestinal and central nervous system symptoms, including drowsiness, dizziness, and diarrhea. Zolpidem may increase the depressant effects of other sedative drugs, such as the an-tipsychotics, tricyclic antidepressants, and antihistamines. 

In general, side effects of zolpidem and zaleplon are similar to those of short-acting benzodiazepines. These agents should not be considered free of abuse potential. 

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). 

Buspirone may be an effective anxiolytic in the elderly patient and less likely than BZDs to produce excessive sedation ( 352, 353, 354 and 355). Dizziness, however, may be a problem. Zolpidem or zaleplon, particularly in lower doses (i.e., 2.5 to 5.0 mg at bedtime) may be viable alternatives ( 356). The elimination half-life of these two agents is approximately 3 hours in the elderly. Although it has sleep-enhancing properties similar to BZD hypnotics, it is less likely to alter sleep architecture. Whereas antidepressants and b -blockers may be useful alternatives in younger patients, no data document their effectiveness for anxiety in elderly patients ( 307). Although antipsychotics may be helpful in reducing severe agitation, their side effect profile makes them unsuitable for use in subjective anxiety states ( 300, 307). 

BZDs such as chlordiazepoxide (Librium) or diazepam (Valium) may be prescribed to treat anxiety, seizures, acute stress reactions, and panic attacks, or to alleviate the side effects of drug or alcohol withdrawal. Those BZDs with a more sedating effect, such as estazo-lam (ProSom) or triazolam (Halcion), may be prescribed for short-term treatment of sleep disorders. However, the newer generation of non-BZD agents—zolpidem (Ambi-en) and (Sonata)—are less potentially addictive hypnotic drugs than the BZDs. 

A range of medications is available to treat insomnia, ranging from herbal preparations such as valerian to the recently introduced z compounds, zopiclone, zolpidem and zaleplon. Many drugs used for other primary purposes have sedative and sleep-inducing properties as side effects these include many tricyclic antidepressants and antihistamines. 

Two types of receptor have been identified, termed Bzl and Bz2. These receptors occupy different sub-units of the GABA-A receptor and therefore have different affinities for the benzodiazepine ligands. For example, the potent hypnotic zolpidem binds to the Bzl receptor that is linked to the alpha-1 site on the GABA-A receptor while the hypnotic zopiclone binds to the Bz2 receptor which occupies both the alpha-2 and 3 sites on the GABA receptor. This selectivity for the Bzl receptor may account for the fewer side effects of zolpiden in comparison to other hypnotic benzodiazepines. 

Toner LC, Tsambiras BM, Catalano G, Catalano MC, Cooper DS. Central nervous system side effects associated with zolpidem treatment. Clin Neuropharmacol 2000 23 54-8. 

The CNS contains a wide variety of neurotransmitters and high concentrations of receptors. Mechanisms of action of many drugs are often complex combinations of receptor-based actions. Some of the most widely used (and abused) drugs are hypnotics/sedatives, for treatment of insonmia. Barbiturates such as amylo-barbitone have been used for many years, but suffer from side-effects and are addictive. Thiopentone sodium salt (sodium pentothal), however, is very useful as a short-acting intravenous anaesthetic. The benzodiazepines, such as diazepam (Valium) and alprazolam (Xanax), are safer drags for insomnia and also can be used for treatment of anxiety and muscle spasms. Zolpidem (Ambien) is a newer and more selective hypnotic. 

Current treatment for insomnia centers on GABAa ( aminobutyric acid) receptor signalling and includes GABAa receptor positive allosteric modulators (PAMs), for example, agents such as zolpidem (Ambien, 2). While zolpidem has been off patent since 2007, another similar compound, eszopiclone (Lunesta, 3), is still prescribed for insomnia, with sales in 2010 reaching almost 1 biUion. These compounds are classified as sedative-hypnotics and their side effecTs include cognitive impairment, musculoskeletal impairment, and mild dysphoria. ... 

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