Sleep-Wake Neurobiology and Pharmacology

Kai Spiegelhalder, Christoph Nissen, Dieter Riemann, Spiegelhalder, Kai, Nissen, Christoph, Riemann, Dieter

Insomnia and circadian rhythm sleep disorders affect large proportions of the population and have pronounced effects on quality of life and daytime performance. While the neurobiology of insomnia is not yet fully understood, circadian rhythm sleep disorders are assumed to be caused by a mismatch between the individual circadian phase position and the desired sleep-wake schedule. Benzodiazepines and non-benzodiazepine positive allosteric GABAA receptor modulators improve sleep onset and maintenance in the short-term treatment of insomnia. However, tolerance and dependence are important side effects. Sedating antidepressants are frequently prescribed for insomnia, however, only few randomised controlled trials have been published so far. Melatonin and melatonin receptor agonists are considered to be an option for the treatment of insomnia especially because of their minimal abuse potential and safety. First data on orexin (aka hypocretin) receptor antagonists are promising, however, the risk-benefit ratio needs to be further evaluated. With respect to circadian rhythm sleep disorders, there is solid evidence from meta-analyses supporting the use of melatonin in jet lag disorder to accelerate entrainment to the new time zone, and in delayed sleep phase disorder to advance sleep-wake rhythms. In addition to that, there is evidence supporting the use of melatonin in patients with shift work disorder in order to promote daytime sleep after night shifts.