Hypnosedative-induced complex behaviours : incidence, mechanisms and management.

A number of news items and case reports describing complex behaviours (e.g. sleep driving, sleep cooking, sleep eating, sleep conversations, sleep sex) associated with the use of hypnosedative medications have recently received considerable attention. Regulatory agencies examining these reports have subsequently issued warnings regarding the potential of hypnosedative agents to produce complex behaviours. Despite these warnings, little is known about the likelihood, presentation, treatment or prevention of hypnosedative-induced complex behaviours. The purpose of this review is to evaluate the published evidence regarding the clinical presentation, incidence, mechanism and management of sleep-related behaviours induced by nonbenzodiazepine receptor agonists (NBRAs).Review of the literature identified ten published case reports of NBRA-induced complex behaviours involving 17 unique patients. Fifteen of the 17 patients described in the case reports had taken zolpidem, one had taken zaleplon and one had taken zopiclone. The complex behaviours most commonly reported were sleep eating, sleepwalking with object manipulation, sleep conversations, sleep driving, sleep sex and sleep shopping. Elevated serum concentrations resulting from increased medication dose or drug-drug interactions appeared to play a role in some but not all cases. Sex, age, previous medication exposure and concomitant disease states were not consistently found to be related to the risk of experiencing a medication-induced complex behaviour.From a pharmacological standpoint, enhancement of GABA activity at GABAA receptors (particularly alpha1-GABAA receptors) is a possible mechanism for hypnosedative complex behaviours and amnesia. Evidence suggests that complex behaviour risk may increase with both dose and binding affinity at alpha1-GABAA receptors. The amnesia that accompanies complex behaviours is possibly due to inhibition of consolidation of short- to long-term memory, suggesting that the risk may extend to non-GABAergic hypnosedatives. While amnesia and GABA-related receptor actions are the most frequently discussed mechanisms for complex behaviours in the literature, they do not fully explain such behaviours, suggesting that other mechanisms and factors probably play a role.A number of potential strategies are available to manage or prevent hypnosedative-induced complex behaviours. These include lowering the dose of, or stopping, the offending hypnosedative, switching to a different hypnosedative, treating patients with other classes of medications, using nonpharmacological treatment strategies for patients with sleep disorders, examining drug regimens for potential drug interactions that may predispose patients to experiencing complex behaviours, administering hypnosedative medications appropriately and selecting patients more carefully for treatment in terms of their likelihood of experiencing medication adverse effects.