Managing narcolepsy can be incredibly challenging, but at Philadelphia Integrative Psychiatry, Dr. Danish and his team are committed to providing comprehensive and personalized care. One of the promising treatments we offer is once-nightly sodium oxybate (ON-SXB), which has shown significant potential in helping individuals improve their sleep quality and daytime alertness. This treatment is particularly important to our practice as it offers a simplified medication regimen, reducing the need for a middle-of-the-night dose and thereby minimizing sleep disruptions.

While ON-SXB presents numerous benefits, it is crucial to discuss its pros, cons, and potential for abuse. At Philadelphia Integrative Psychiatry, we do not take these considerations lightly. Sodium oxybate, while effective, has a known potential for misuse, and it is essential to weigh these factors carefully when considering treatment options. Our team is dedicated to ensuring that patients are fully informed and supported in making the best decisions for their health and well-being.

What is Sodium Oxybate Branded as Xywav

Lower Sodium Content: Xywav is a low-sodium formulation compared to its predecessor, Xyrem, containing 92% less sodium. This reduction is significant for patients who need to manage their sodium intake due to cardiovascular concerns. Lower sodium intake is crucial for reducing the risk of hypertension and other cardiovascular diseases, making Xywav a safer option for long-term use in patients with such health considerations.
Mechanism of Action: The exact mechanism of Xywav is not fully understood, but it is believed to work by binding to GABA receptors in the brain, altering the brain's response to sleep. This binding helps stabilize sleep architecture, reducing disruptions and promoting more restful sleep.

Benefits Specific to Xywav

Clinical trials have demonstrated that lower-sodium oxybate significantly improves symptoms of cataplexy and excessive daytime sleepiness (EDS) in narcolepsy patients. The trials showed that discontinuing the medication led to a significant worsening of symptoms compared to those who continued treatment. The medication was generally well tolerated, with side effects similar to those of sodium oxybate, including headache, nausea, and dizziness. Lower-sodium oxybate is administered as an oral solution, with dosing adjusted based on individual needs and conditions. This flexibility in dosing allows for personalization in treatment, ensuring that patients receive the most effective dose with minimal side effects.

How Once-Nightly Sodium Oxybate Improves Narcolepsy Symptoms

The REST-ON clinical study has provided compelling evidence supporting the efficacy of ON-SXB in treating disrupted nighttime sleep associated with narcolepsy. This once-nightly formulation eliminates the need for a second dose in the middle of the night, which is a significant advancement for patients who previously had to wake up for another dose. Key findings include:

Improved Sleep Quality: Participants taking ON-SXB experienced fewer transitions from deeper to lighter sleep stages and reported feeling more refreshed upon waking. This improvement was consistent even among those taking alerting agents during the day, indicating that ON-SXB can be effectively integrated into a broader narcolepsy management plan.
Reduction in Nocturnal Arousals: ON-SXB significantly decreased the frequency of waking up during the night compared to a placebo, enhancing the overall sleep experience. This reduction in nocturnal arousals contributes to better sleep continuity and overall sleep satisfaction.
Enhanced Daytime Alertness: The study also showed improvements in daytime alertness and a reduction in cataplexy episodes, which are sudden losses of muscle tone triggered by strong emotions. This improvement in daytime functioning can lead to better performance in daily activities and improved quality of life.

Quality of Life Improvements are Well Documented

A study on clinician preferences for oxybate treatments highlighted a strong preference for a once-nightly dosing regimen, which was seen as a way to improve patient quality of life and reduce anxiety associated with treatment. Clinicians expressed moderate to high satisfaction with the efficacy and safety of current oxybate medications, but identified the twice-nightly dosing requirement as a significant stressor for patients. If approved, the investigational extended-release sodium oxybate, which requires only a single bedtime dose, could address these concerns and fulfill an unmet need in narcolepsy treatment by alleviating the burden of middle-of-the-night dosing. This shift could lead to greater adherence to treatment plans and improved outcomes for patients.

Dosing

Xywav is available as an oral solution and is typically taken at night. The dosing regimen can be individualized to minimize side effects such as morning grogginess. Patients are advised to take the medication on an empty stomach to optimize absorption and effectiveness. The ability to tailor the dosing schedule to individual needs allows for a more personalized approach to treatment, potentially improving patient satisfaction and adherence.

Side Effects and Precautions

Xywav is available only through a restricted distribution program due to risks of central nervous system depression and potential for abuse.

Most side effects often occur early in treatment and may diminish over time. Common side effects include headache, nausea, dizziness, decreased appetite, and parasomnia. It is crucial for patients to be monitored closely during the initial phases of treatment to manage any adverse effects effectively.

Contraindications:

Xywav should not be used in conjunction with alcohol or other sedative-hypnotic drugs due to the risk of severe sedation and respiratory depression.
It is contraindicated in individuals with succinic semialdehyde dehydrogenase deficiency.

Other Cautions to Consider

Accidental Dosing Errors with Sodium Oxybate

Accidental dosing errors with sodium oxybate can lead to serious adverse events. A study analyzed reports from the FDA Adverse Event Reporting System, focusing on cases where patients accidentally took the second dose too soon after the first. These adverse events included central nervous system depression, bradycardia, respiratory depression, dizziness, seizures, confusion, and nausea. Patients and caregivers should ensure that the second dose is taken at least 2.5 hours after the first to avoid potential complications. This emphasizes the importance of patient education and adherence to prescribed dosing schedules.

Unforeseen Consequences of Prescribed Gamma-Hydroxybutyrate (GHB) for Narcolepsy

A case report discussed a college-aged female with narcolepsy who experienced severe side effects from mistimed administration of GHB, leading to mental depression and respiratory failure. This incident highlights the potential dangers of GHB if not taken as prescribed, emphasizing the need for awareness among both patients and healthcare providers about the risks of mistimed doses. It serves as a reminder for emergency physicians to consider GHB toxicity in patients with narcolepsy who present with altered mental status.

Getting in Touch with Dr. Danish and His Team

Whether you’re struggling with narcolepsy or simply want a comprehensive evaluation, our team is here to help. At Philadelphia Integrative Psychiatry, we offer unique treatment options like ON-SXB and other advanced therapies that are not widely available. Our holistic approach ensures that we treat the whole person, not just the symptoms, providing a tailored treatment plan that fits your individual needs.