More than 90% of zolpidem exists in its protein-bound form, and it is rapidly absorbed with a bioavailability of approximately 70%. Zolpidem shows greater selectivity for α-containing receptors compared to zopiclone, triazolam, or midazolam. Zolpidem appears to potentiate GABA-ergic transmission, thus resulting in the inhibition of neural excitation. 4 Zolpidem interacts with the distinct binding sites of the γ-aminobutyric acid (GABA) receptor complex in a fashion similar to the benzodiazepines. Unlike benzodiazepines, the pharmacologic activity of zolpidem results from selective binding to central benzodiazepine receptors of the ω1 subtype, 3 but zolpidem possesses low affinities for the ω2 and ω3 receptor subtypes. In Table 1, reported cases of zolpidem-induced adverse reactions are presented.Ī dose of zolpidem 10 mg in the nonelderly and a reduced dose of 5 mg in elderly individuals are clinically effective. Some adverse neuropsychiatric reactions are summarized. We reviewed publications relevant to zolpidem-induced adverse neuropsychiatric reactions selected on the basis of our experience and by a PubMed search (1992-2010) using the terms zolpidem or side effects or adverse effects or adverse reactions. In light of the accumulating reports of adverse psychiatric reactions to zolpidem, we review the literature pertaining to this subject and present 2 case reports from our own clinical practice. There have been several reports describing neuropsychiatric reactions such as visual hallucinations/sensory distortion, delirium, amnesia, sleepwalking/somnambulism, and nocturnal eating associated with zolpidem use. On the other hand, while rare, the number of reported adverse reactions has begun to increase.
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The following 4 variables should be considered when prescribing zolpidem: (1) gender: women have been found to have a significantly higher serum zolpidem concentration than men (2) zolpidem dose: the adverse reactions that develop are dose dependent (3) protein binding affinity: a high proportion of zolpidem is protein bound therefore, low serum albumin results in a higher level of free zolpidem leading to adverse psychiatric reactions and (4) cytochrome P450 (CYP) isoenzyme inhibition: concomitant administration of zolpidem and other drugs may cause interactions that lead to increased concentrations of zolpidem.Ĭonclusions: Zolpidem is clinically very effective in treating insomnia. Study Selection and Data Extraction: Publications relevant to the objective of this article were obtained (1992-2010), and some adverse neuropsychiatric reactions were summarized.ĭata Synthesis: Zolpidem has been associated with the development of adverse neuropsychiatric reactions, such as hallucinations/sensory distortion, amnesia, sleepwalking/somnambulism, and nocturnal eating. In light of the accumulating reports of adverse reactions to zolpidem, we present 2 case reports of zolpidem-induced adverse effects and review the literature on this subject.ĭata Sources: Articles were selected by the authors on the basis of our experience and by a PubMed search using the terms zolpidem or side effects or adverse effects or adverse reactions. However, zolpidem-induced adverse effects have begun to be reported in the literature, but few systemic descriptions of the adverse effects (especially for psychotic reactions) of zolpidem have been undertaken.
Objective: Zolpidem, a nonbenzodiazepine hypnotic, is very effective and widely prescribed in clinical practice for the treatment of insomnia and is thought to have few adverse effects. Takuji Inagaki, MD Tsuyoshi Miyaoka, MD Seiichi Tsuji, MD Yasushi Inami, MD Akira Nishida, MD and Jun Horiguchi, MD Adverse Reactions to Zolpidem: Case Reports and a Review of the Literature
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