Laura B. Herpel, MD

Looking at the Future of Insomnia Management

Looking ahead, dual orexin receptor antagonists (DORAs) are expected to become a first-line option for treating chronic insomnia, especially as the population ages. A 40-week clinical trial demonstrated the safety and tolerability of daridorexant in patients aged 65 and older, who made up nearly 42% of the study group. This data is compelling as the medical community seeks safer alternatives for elderly patients. DORAs appear to address insomnia without the risk of memory issues, falls, or addiction, which are associated with other sleep aids like GABA agents.

Moreover, reassuring evidence shows that daridorexant does not appear to cause withdrawal symptoms, as demonstrated in trials assessing benzodiazepine withdrawal. The hope is that, in the future, insurance companies will recognize the long-term safety and effectiveness of DORAs, leading to increased access as a first-line treatment. These medications may replace higher-risk alternatives, offering a safer and more tolerable choice for patients with chronic insomnia.

For physicians treating chronic insomnia, it is essential to educate patients about how daridorexant works and potential adverse effects. It is important to set realistic expectations, as the benefits of the medication improve over time. Along with medication, addressing other sleep-related factors and maintaining regular follow-up with patients are key to successful treatment. Positive outcomes in practice suggest that DORAs may be a valuable option for many patients with chronic insomnia.

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A panelist discusses how dual orexin receptor antagonists (DORAs), particularly daridorexant, are poised to become a first-line treatment for chronic insomnia, especially for elderly patients, due to their safety, tolerability, and lack of withdrawal symptoms, while highlighting the importance of patient education and regular follow-up for optimal results.

Daridorexant and Next-Day Function: What Patients Are Reporting

The best candidates for daridorexant, a dual orexin receptor antagonist, are individuals who suffer from chronic insomnia and require nightly sleep aids due to their persistent sleep issues. When considering this treatment, the age of the patient and any underlying comorbidities play a significant role in the decision-making process. Chronic insomnia patients who need long-term sleep support, with a focus on safety and tolerability, are ideal candidates for this medication.

However, daridorexant is not suitable for all patients. Specifically, those with narcolepsy should not be prescribed this medication, as it blocks orexin receptors, and orexin is already deficient in individuals with narcolepsy. This could exacerbate symptoms, including excessive sleepiness or even cataplexy, a condition involving loss of muscle tone triggered by strong emotions. Additionally, caution is needed when prescribing daridorexant to patients with chronic kidney or liver disease due to potential complications.

For patients with chronic insomnia, especially those complaining of daytime sleepiness, daridorexant is considered a preferable option. The medication provides an effective solution to help manage sleep and minimize adverse effects such as daytime sleepiness. If patients have concerns related to parasomnia or memory issues, daridorexant remains a strong candidate compared to other sleep aids. Working with patients to address their sleep challenges while providing a safer and well-tolerated treatment is crucial for effective management of chronic insomnia.

A panelist discusses how dual orexin receptor antagonists (DORAs) are ideal for patients with chronic insomnia who require long-term sleep support, emphasizing their safety, tolerability, and effectiveness, while cautioning against use in patients with narcolepsy, parasomnia history, or severe kidney or liver disease.

Clinical Perspectives on DORAs for Insomnia Management

The dual orexin receptor antagonist (DORA) class of medications is often considered a first-line treatment for chronic insomnia, particularly when patients experience sleep maintenance issues, insufficient total sleep time, or challenges with sleep latency and wakefulness after sleep onset. While DORAs are FDA-approved for treating chronic insomnia, other medications like selective serotonin reuptake inhibitors, trazodone, and off-label options such as doxepin or mirtazapine are sometimes used in clinical practice. However, DORAs are preferred for their superior tolerability, lack of withdrawal symptoms, and favorable adverse effect profiles. This makes them a more suitable option for long-term management of chronic insomnia, especially for patients who need consistent and safe sleep support.

Patients seeking treatment for insomnia commonly report difficulties with daytime functioning, including excessive sleepiness and fatigue. Addressing these concerns is crucial in treatment planning, and evidence from clinical trials shows that DORAs, particularly daridorexant, can significantly improve next-day sleepiness. It’s essential for health care providers to communicate these benefits to patients, as the impact on daytime functioning is a major concern for many individuals with insomnia. With DORAs, patients can experience relief from daytime fatigue, ultimately enhancing their ability to function normally during the day.

To assess the effectiveness of treatments like DORAs, questionnaires such as the Insomnia Daytime Symptoms and Impacts Questionnaire are valuable tools for evaluating next-day functioning. These tools provide a clear measure of improvements in sleepiness, cognition, and mood. Educating patients about the clinical trial results and the potential for better daytime functioning can help set realistic expectations and build trust in the treatment approach. By addressing these concerns upfront, clinicians can help patients feel more confident in their treatment plan.

A panelist discusses how dual orexin receptor antagonists (DORAs) are considered a first-line treatment for chronic insomnia, particularly for sleep maintenance issues, due to their superior tolerability, lack of withdrawal symptoms, and positive impact on daytime functioning.

Why Choose a DORA? Clinical Considerations for Patients With Insomnia

When choosing among sleep aids like dual orexin receptor antagonists (DORAs), benzodiazepines, Z-drugs, or melatonin receptor agonists, clinicians base their decisions on factors such as the patient's comorbidities, the chronicity of insomnia, and the adverse effect profile of the medications. DORAs, in particular, are preferred for patients with chronic insomnia, especially when sleep maintenance issues are involved. Benzodiazepines and Z-drugs are typically reserved for short-term use, such as during emotional or traumatic events, due to their withdrawal potential and risk of tolerance. DORAs offer a safer long-term solution, with better tolerability, minimal withdrawal effects, and no significant impact on memory or mobility, making them suitable for older patients who may have multiple comorbidities.

Another advantage of DORAs is their safety profile, particularly for patients with sleep apnea or those on other medications, including pain relievers or anxiolytics. DORAs do not exacerbate respiratory suppression or interact negatively with other medications, making them a strong choice for patients with these overlapping health issues. For patients with chronic insomnia and accompanying sleep-disordered breathing, DORAs have proven effective in promoting quality sleep without worsening other medical conditions.

To evaluate the efficacy and next-day functioning of patients on DORAs, clinicians often use the Insomnia Daytime Symptoms and Impacts Questionnaire. This tool measures the impact of insomnia on cognition, alertness, sleepiness, and mood, providing a visual scale for patients to rate their symptoms. Significant improvements in daytime sleepiness have been observed with the 50-mg dose of DORAs, highlighting their effectiveness. Other assessments, such as the Insomnia Severity Index and the Epworth Sleepiness Scale, are also used to monitor patient progress and ensure optimal treatment outcomes.

A panelist discusses how clinicians choose between sleep aids like dual orexin receptor antagonists (DORAs) and other medications based on patient comorbidities, chronicity of insomnia, and adverse effect profiles, with DORAs offering a safer, long-term solution for patients with chronic insomnia and sleep maintenance issues.

Laura B. Herpel, MD

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