study Objectives: To describe zolpidem-associated complex behaviors, including both daytime automatisms and sleeprelated parasomnias. Methods: A case series of eight clinical patients and six legal defendants is presented. Patients presented to the author after an episode of confusion, amnesia, or somnambulism. Legal defendants were being prosecuted for driving under the infl uence, and the author reviewed the cases as expert witness for the defense. Potential predisposing factors including comorbidities, social situation, physician instruction, concomitant medications, and patterns of medication management were considered. Results: Patients and defendants exhibited abnormal behavior characterized by poor motor control and confusion. Although remaining apparently interactive with the environment, all reported amnesia for 3 to 5 hours. In some cases, the episodes began during daytime wakefulness because of accidental or purposeful ingestion of the zolpidem and are considered automatisms. Other cases began after ingestion of zolpidem at the time of going to bed and are considered parasomnias. Risk factors for both wake and sleep-related automatic complex behaviors include the concomitant ingestion of other sedating drugs, a higher dose of zolpidem, a history of parasomnia, ingestion at times other than bedtime or when sleep is unlikely, poor management of pill bottles, and living alone. In addition, similar size and shape of two medications contributed to accidental ingestion in at least one case.
Conclusions
s C i e n T i F i C i n V e s T i g a T i O n sT he ingestion of zolpidem and other hypnotic sedative medications for the treatment of insomnia has been associated with sleepwalking and other complex behaviors including sleep eating and sleep driving.1-5 When ingested during the daytime, hypnotic sedatives impair cognition, memory, and motor performance. 6 There are also reports of a high frequency of blood levels of hypnotic sedatives in drivers apprehended for driving under the infl uence (DUI).7-9 An advisory letter was sent and change in package insert information occurred on March 14, 2007, alerting physicians and the public to the possibility of complex behaviors with all hypnotic sedatives.According to the prescribing information for Ambien and Ambien CR, zolpidem is an imidazopyridine chemical class agent available in the US since 1992. It is chemically unrelated to benzodiazepine and barbiturate hypnotic sedatives. Zolpidem in vitro binds the BZ1 receptor of the GABA(A) complex with high affi nity ratio for the alpha1/alpha5 subunits. Mean peak concentrations were 59 (range 29 to 113) after ingestion of the 5 mg tablet and 121 (range 58 to 272) after ingestion of the 10 mg tablet (ng/mL). Time to maximum concentration was 1.6 h for both doses (but 2.2 h if taken with food) with a half-life of approximately 2.6 h (range 1.4 to 4.5) The zolpidem extended release formulation 12.5 mg tablets produced a maximum concentration of 134 (69 to 197) at 1.5 hours. Co-administration with fl uoxetine increased ha...