Treating Insomnia in the Elderly: Orexin Receptor Antagonist


Karl Doghramji, MD: Lemborexant is an orexin receptor antagonist, and by antagonizing orexin receptors it promotes sleep, both maintenance as well as sleep onset. It basically is a hypnotic or sleep-promoting agent. Lemborexant has been studied in more than 2000 patients in 2 pivotal clinical trials, one lasting approximately 1 month and the other lasting 6 months. The first trial involved actual sleep laboratory data, and the second trial was mainly subjective in nature.

The orexin neurotransmission system in the central nervous system is thought to promote wakefulness along with many other neurotransmitters such as dopamine, norepinephrine, serotonin, and acetylcholine. However, the orexin system seems to also be important in terms of maintaining good balance between sleep and wakefulness.

Whereas many systems promote sleep and others promote wakefulness, the orexin system seems to favor wakefulness but also seems to favor a harmonious relationship between sleep and wakefulness. When we’re asleep we remain asleep, when we’re awake we remain awake. The absence of the orexin’s neurotransmission is thought to typify narcolepsy, which is a condition where people fall asleep a lot during the day when they’re supposed to be awake and wake up a great deal at night when they’re supposed to be asleep. So antagonizing that neurotransmission system, which is what lemborexant does and what suvorexant, which is another medication now available for insomnia, does; by antagonizing the orexin system, also called the hypocretin system, those 2 medications are thought to promote sleep onset and maintenance.

Transcript edited for clarity.

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