Insomnia is present in up to one third of the adult population worldwide. It can present independently or coexist with other medical conditions such as mental illnesses, metabolic, or cardiovascular diseases highlighting the importance of treating this multifaceted disorder. Insomnia is associated with an abnormal state of hyperarousal (increased somatic, cognitive, and cortical activation) and orexin has been identified as a key promoter of arousal and vigilance.
The current standards of care for the treatment of insomnia recommend non-pharmacological interventions (e.g. CBT I) as first-line treatment and if behavioural interventions are not effective or available, pharmacotherapy. In contrast to most hypnotics used for decades (benzodiazepines and ‘Z-drugs’), the latest Orexin Receptor Antagonists do not modulate the activity of γ-aminobutyric acid receptors, the main inhibitory mechanism of the central nervous system. Instead, they temporarily block the orexin pathway, causing a different pattern of effects, e.g. fewer morning or next-day effects such as motor dyscoordination, and cognitive impairment. The pharmacological properties of these drugs are the basis of these different characteristics. Orexin receptor antagonists seem to be devoid of any dependence and tolerance-inducing effects, rendering them a viable option for longer-term treatment. Safety studies have not shown any exacerbation of existing respiratory problems, but more real-world safety and pharmacovigilance experience is needed. This plenary lecture provides an overview of the role of orexin in the sleep wake cycle, its mechanism of action, its relation to insomnia, and key features of available drugs mediating orexin signalling.
Speakers
Chair: Dr Trudi Seneviratne, Registrar, Royal College of Psychiatrists
Professor Ramalingam N Chithiramohan MBBS FRCpsych
