doras

DORAs, or dual orexin receptor antagonists, are a class of prescription medications used to treat insomnia by targeting the brain’s orexin system. Orexin A and orexin B are wake-promoting neuropeptides that bind to two receptors, OX1R and OX2R. By blocking both receptors, DORAs reduce wake signals and help promote sleep initiation and maintenance.

Three DORAs are approved for adults: suvorexant (Belsomra), lemborexant (Dayvigo), and daridorexant (Quviviq). Suvorexant was approved in 2014, lemborexant in 2019, and daridorexant in 2022. They are taken orally at or near bedtime, with dosing guided by efficacy, tolerability, and potential interactions. Dose adjustments may be needed for liver impairment or concomitant medications.

Clinical use and safety considerations. DORAs are indicated for chronic insomnia characterized by difficulty with sleep onset and/or maintenance. Compared with traditional GABAergic hypnotics (benzodiazepines and Z-drugs), DORAs act on the orexin system rather than enhancing GABA activity, and they are generally perceived to have a lower potential for abuse and dependence, though misuse and daytime impairment can occur. Common adverse effects include somnolence and dizziness; less frequent events include abnormal dreams and sleep-related behaviors. Caution is advised in individuals with narcolepsy, and patients should avoid activities requiring full alertness the day after dosing until they understand their response. DORAs are metabolized mainly by cytochrome P450 enzymes (notably CYP3A), so strong inhibitors or inducers can affect exposure; hepatic impairment may necessitate dose adjustment or avoidance.

Ongoing research seeks to optimize efficacy and tolerability and to explore additional indications and populations for orexin receptor antagonists.