教育演講5:治療失眠與使用安眠藥之新知
Advances in the management of insomnia and utilization of hypnotics 

程 序 表

E5-5
安眠藥相關的複雜睡眠行為之研究新進展
黃宗正
台大醫院精神醫學部

  In recent years, complex sleep-related behaviors (CSBs) induced by hypnosedatives have been the focus of much attention, especially after the US Food and Drug Administration (FDA) requested that manufacturers of 13 kinds of hypnosedative drugs modify their product labeling to include new safety warnings about these potentially dangerous behaviors in March, 2007. CSBs are officially categorized as “Parasomnias” in The International Classification of Sleep Disorder: Diagnostic and Coding Manual, 2nd Edition (ICSD-2), which defines parasomnias as undesirable physical events or experiences that occur during entry into sleep, within sleep, or during arousal from sleep. CSBs are complex activities (normally associated with wakefulness) that occurred when the patient is in a sleep-like state after taking a hypnosedative drug and that the patient has little or no memory upon awakening the next morning. CSBs include sleepwalking with object manipulation, sleep related eating disorder, sleepdriving, sleep conversation, sleepsex, etc. Clinical awareness of the potential associated danger is necessary because some CSBs can result in serious harm.
  Although benzodiazepines have been used for more than 40 years, only a few published reports have identified them as being involved in CSBs. Triazolam is particularly associated with largest number of amnesia and CSBs. Regarding non-benzodiazepine receptor agonist (NBRA), zolpidem is most frequently reported to be related to the occurrence of CSBs. Our empirical study showed that a higher dose of zolpidem (>10 mg/day) was the only significant predictor of CSBs (OR=13.1). The study provides important information for clinicians since zolpidem is the number one prescribed hypnotic agent in Taiwan, USA and many other countries.
  The exact mechanisms responsible for CSBs are unknown. Activation of GABA activity via α1-GABAA receptors is a possible mechanism causing CSBs since α1 subunit is especially associated with amnestic effect. Agents with higher binding affinity at α1-GABAA receptors, such as zolpidem, may increase the risk of CSBs. Besides, one study found that A15G variant at the GABA(A) α1 receptor subunit gene confers a high risk of zolpidem-induced CSBs.
  However, a recent study showed that a higher dose of zolpidem was correlated with CSBs only in adults younger than 65 years old and not in the elderly subjects. Therefore? new studies are needed for a complete investigation about other potential risk factors of hypnosedative-related CSBs.