DORAs as First-Line Therapy

In the treatment of chronic insomnia, dual orexin receptor antagonists (DORAs) are typically positioned as a first-line option due to their efficacy in both initiating and maintaining sleep. These medications are preferred because they tend to have a more favorable adverse effect profile compared to other available treatments, such as benzodiazepines or Z-drugs. DORAs help manage insomnia without the risk of dependence, tolerance, or cognitive issues that are often associated with older agents. However, if DORAs do not produce the desired results, alternative medications may be considered.

Patient-reported benefits with DORAs are generally positive, especially regarding next-day functioning. Most patients report feeling more alert and able to perform daily tasks without experiencing the grogginess or excessive sleepiness that can accompany other sleep medications. Nonetheless, concerns about the potential for habit formation, tolerance, or withdrawal are common. To address these concerns, patients are sometimes advised to start the medication on a day when they have no obligations, allowing them to safely evaluate how the medication affects their daytime functioning.

The ideal candidates for DORA therapy are typically those with psychophysiologic insomnia, where patients experience excessive wakefulness and hypervigilance at night. These individuals often describe their minds racing or being overly activated during sleep attempts. DORAs can be especially effective for these patients, as the medication’s mechanism targets the reduction of wakefulness. In contrast, older patients, who may be at higher risk of falls due to medications like benzodiazepines, may also benefit from DORAs. However, DORAs are contraindicated in individuals with narcolepsy, particularly those who have comorbid insomnia.