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Adverse Reactions to Zolpidem: Case Reports and a Review of the Literature

Prim Care Companion J Clin Psychiatry 2010;12(6):e1-e8
10.4088/PCC.09r00849bro

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. 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. 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.

Data 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.

Study Selection and Data Extraction: Publications relevant to the objective of this article were obtained (1992–2010), and some adverse neuropsychiatric reactions were summarized.

Data Synthesis: Zolpidem has been associated with the development of adverse neuropsychiatric reactions, such as hallucinations/sensory distortion, amnesia, sleepwalking/somnambulism, and nocturnal eating. 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.

Conclusions: Zolpidem is clinically very effective in treating insomnia. However, while rare, zolpidem-induced unusual complex behavior may develop. Primary care physicians should be alert to the possible unusual complex adverse effects of zolpidem.

Prim Care Companion J Clin Psychiatry 2010;12(6):e1–e8

Submitted: June 9, 2009; accepted April 22, 2010.

Published online: December 9, 2010 (doi:10.4088/PCC.09r00849bro).

Corresponding author: Takuji Inagaki, MD, Faculty of Education, Department of Psychology and Special Support Education, Shimane University, 1060 Nishikawatsu, Matsue, Shimane 690-8504, Japan (inagaki@edu.shimane-u.ac.jp).