Paradox of choice: Insomnia drug improves nocturnal enuresis, a BMJ case report.

In recent years, several therapies based on International Children's Continence Society recommendations have been used to treat nocturnal enuresis (NE). However, some children are resistant to current treatments.

Several reports have examined sleep depth and sleep architecture in individuals with NE because these may be important factors associated with this condition. Children with NE are generally believed to be deep sleepers with impaired arousability. However, recent studies using all-night electroencephalography or biomotion sensors have shown that children with NE are relatively light sleepers. To date, the utility of a sleep-based approach to treating NE has not been explored. In the current issue of BMJ case reports, Matsumoto has shown the beneficial effects of an insomnia drug, Suvorexant in NE.

Suvorexant is an orexin receptor antagonist that was newly developed for the treatment of insomnia. Sleep polysomnography has indicated that it can increase both N2 and rapid eye movement (REM) sleep. Specifically, it promotes the natural transition from wakefulness to sleep by inhibiting orexin neurons that promote wakefulness in the arousal system. Furthermore, it induces physiological sleep that is not excessively deep compared with conventional sleep-inducing drugs.

In other words, suvorexant inactivates wakefulness rather than promoting sleep. This suggests that suvorexant may be useful in treating patients with NE caused by excessively deep sleep.

The patient was a 12-year-old boy with normal growth and development, no learning difficulties, no attention-deficit/ hyperactivity disorder, no family problems, normal renal function, normal bladder capacity, and no family history of NE. Daytime toilet training was completed at 3 years of age, and since then, no daytime incontinence occurred. The patient was able to control his urination while awake. He was diagnosed with primary monosymptomatic NE.

Prior to the administration of suvorexant, the patient had already been treated with behaviour modification, desmopressin, an enuresis alarm, anticholinergics, tricyclic antidepressants and traditional Kampo medicine. However, bed-wetting remained continuous until he was 12 years old. All treatment strategies were ineffective and not a single day went by without bed-wetting.

Prior to the start of suvorexant treatment, sleep polysomnography was performed to derive the sleep architecture at baseline. Suvorexant (15mg) was then started with 0.25 tablets once a day before sleep. The drug dosage was increased gradually while monitoring the presence of side effects.

With suvorexant, the frequency of NE gradually decreased from 14 of 14 days (100%) to 5 of 14 days (35.7%). Sleep polysomnography indicated that rapid eye movement (REM) sleep increased from 101.5min (19.9%) before suvorexant to 122.1min (24.9%) with suvorexant. Furthermore, N2 increased from 233min (45.6%) to 287.5min (58.7%) during non-REM sleep. In contrast, N3 decreased from 160min (31.3%) to 65min (13.3%) during non-REM sleep. (Table)

The case report is unique because no previous reports have described a successful reduction in the frequency of NE via sleep manipulations. This case revealed two main points. The first was that suvorexant had a therapeutic effect on a patient with intractable NE by reducing the frequency of NE. Second, the reduction in the frequency of NE may have been due to suvorexant-induced alterations in sleep architecture in the patient, specifically the conversion of deep sleep to lighter sleep.

In future, this novel treatment could be applied to patients with intractable NE (especially NE caused by excessive sleep depth), those with NE who are currently receiving other treatments and patients with NE caused by fatigue. This case provides an important clue regarding the cause of NE and will hopefully support the design of future randomised trials.

Source: BMJ case reports: Matsumoto T. BMJ Case Rep 2021;14:e239621. doi:10.1136/bcr-2020- 239621