A sleep specialist rules out other etiologies of mirth in a person with narcolepsy who is taking calcium, magnesium, potassium, and sodium oxybates (brand name: Xywav) and solriamfetol.

By Jeffrey McGovern, MD, FAASM, FCCP

“Frame your mind to mirth and merriment, which bars a thousand harms and lengthen life”—William Shakespeare (The Taming of the Shrew, Scene 2 introduction)

Narcolepsy is a disorder primarily characterized by excessive daytime sleepiness and signs of rapid eye movement (REM)-sleep dissociation manifested in type 1 pattern as cataplexy and abnormal manifestations of REM sleep on polysomnography (PSG) and multiple sleep latency testing (MSLT). An essential feature of the diagnosis is the presence of a mean sleep latency less than or equal to eight minutes and two or more sleep-onset REM periods (SOREMPs) on an MSLT.1

Treatment options include attention to sleep hygiene as well as an assortment of older and newer alerting and wake-promoting agents. As narcolepsy has been associated with cataplexy and fragmented sleep, the introduction of sodium oxybate and recently low-sodium oxybate—or calcium, magnesium, potassium, and sodium oxybates (brand name: Xywav)—has helped to reduce both associated features.

Case Report of Mirth in Patient on Xywav

The patient is a 43-year-old female with a family history of narcolepsy. She originally presented one year before with excessive daytime sleepiness (Epworth Sleepiness Score of 12/24) without signs of sleep apnea or restless legs syndrome. After a careful history and physical, she underwent in-lab PSG followed directly by MSLT with five naps. The PSG revealed a sleep efficiency of 97% with REM latency at 54 minutes and REM density of 29%. There was no evidence of sleep apnea or limb movements. The MSLT revealed a mean sleep latency of 24 seconds with SOREMPs in naps two, three, and five. She denied any history of cataplexy and was diagnosed with narcolepsy type 2. 

Her sleep pattern was deemed to be adequate. She wanted to discuss the role of wake-promoting agents. A regimen including solriamfetol 150 mg (brand name: Sunosi) was initiated, but because of fragmented sleep and residual sleepiness, sodium oxybate at divided doses was started concomitantly. For several months she remained wakeful without residual sleepiness during the day. During the COVID pandemic when she was confined to work from home, she decided to stop the sodium oxybate and compensate with daytime napping. She denied at that time any adverse effects from the nocturnal regimen. Not using her sodium oxybate led unfortunately to her insurance not approving refills of this medication as they assumed she was noncompliant. 

After a long period of appeal from the office perspective, insurance finally approved the resumption of nocturnal medication in the form of calcium, magnesium, potassium, and sodium oxybate. The patient started Xywav at night at equivalent doses to sodium oxybate. In scheduled follow-up, she continued to remain compliant and keep on track with both drugs (based on clinical review and monitoring of her Pennsylvania Drug Management Program). 

In a recent follow-up, she acknowledged compliance with her regimen but admitted to a sensation of mirth since starting Xywav. She tried not to take the nocturnal regimen with resultant excessive daytime sleepiness but resolution of the mirth—which she described as a pleasant sensation and not associated with anger. She also reported that this sensation lessened with eating. She denied it was a problem and insisted on continuing the regimen, given its overall benefit. Other causes were investigated and ruled out as an etiology of her mirth.

Sleep Medicine Context

Calcium, magnesium, potassium, and sodium oxybate is indicated for the treatment of cataplexy and excessive daytime sleepiness in patients 7 years of age and older with narcolepsy.2 The safety of calcium, magnesium, potassium, and sodium oxybate in patients with narcolepsy was evaluated in a 16-week double-blind, placebo-controlled, randomized withdrawal study in patients with cataplexy who previously were taking sodium oxybate or another anticataplectic medication. The patients achieved a stable, tolerable, and effective dosage over eight weeks. There were no reports of feelings of mirth or giddiness in this clinical trial of Xywav in patients with narcolepsy.3 

The safety of calcium, magnesium, potassium, and sodium oxybate was also evaluated through a double-blind, placebo-controlled, randomized withdrawal study in patients with idiopathic hypersomnia. The difference in this study versus the narcolepsy trial is that the stimulants or alerting agents were allowed if the patients were taking the same dosing regimen for over two months. The agents listed included solriamfetol. Most of the patients (53%) were taking a stimulant agent. Again, there were no reports of feelings of mirth or giddiness in patients.4

The patient’s report of mirth while taking Xywav is clearly the opposite of the reported side effects of depression and, in less severe cases, aggressive behavior.2 The patient still notes favorable waking effects of the nocturnal medicine, and it is possible that the sensation of mirth may be enhancing her compliance. Possible etiologies for this effect may be the addition of the stimulant (solriamfetol). The safety study provided by Jazz Pharmaceuticals did not include patients with stimulant therapy in their narcolepsy arm.     

In addition, although the patient denied any feelings of anxiety while taking her regimen for narcolepsy, the sensation of mirth may represent a forme fruste of anxiety. The lessening of the mirth by consuming food is likely because of the effect on bioavailability.

Role of the Sleep Specialist

This case highlights the manifestation of mirth in a patient with narcolepsy taking calcium, magnesium, potassium, and sodium oxybates, also known by the brand name Xywav. Given the importance of this medicine in the armamentarium of the sleep specialist, it is important to query patients about all side effects, even those that may be pleasantly experienced.

References

  1. American Academy of Sleep Medicine. International Classification of Sleep Disorders, 3rd ed. 2014;146-61.
  2. XYWAV® (calcium, magnesium, potassium, and sodium oxybates) oral solution, CII. Prescribing information. Jazz Pharmaceuticals Inc.
  3. XYWAV® (calcium, magnesium, potassium, and sodium oxybates) oral solution, CII. Prescribing information. Jazz Pharmaceuticals Inc. Study 1; NCT03030599.
  4. XYWAV® (calcium, magnesium, potassium, and sodium oxybates) oral solution, CII. Prescribing information. Jazz Pharmaceuticals Inc. Study 2; NCT03533114.

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