There are various causes of nocturia, and many patients experience nocturia accompanied by insomnia caused by waking up in the middle of the night. In such cases, clinicians may prescribe pharmaceuticals such as sleep aids. However, the adverse effects of these drugs, such as drug dependence and muscle relaxation, make them difficult to use, especially in older adults. On the other hand, Yokukansan, a traditional Japanese medicine, is highly effective and safe for the treatment of sleep disorders. In the present study, we administered Yokukansan to treat nocturia with insomnia and investigated changes in subjective symptoms related to sleep and lower urinary tract symptoms before and after administration.

We included patients from our institution who had been diagnosed with nocturia and were assessed to have sleep disorders based on a cut-off value of 5.5 of Pittsburgh Sleep Quality Index (PSQI) Global scores. Patients received 2.5 g of Yokukansan (Tsumura and Co., Tokyo, Japan) three times a day for 12 weeks. Medications for lower urinary tract symptoms and sleep disturbance, such as α1 adrenergic receptor blockers, β3 adrenergic receptor agonists, anticholinergic agents, and sleeping pills, were not altered during Yokukansan administration. We evaluated and compared Overactive bladder symptom scores (OABSS), hours of undisturbed sleep (HUS), and PSQI scores before treatment and after 12 weeks of Yokukansan administration. Additionally, we divided patients into two groups based on the severity of disordered sleep according to the PSQI-Global score (6-10, intermediate sleep; >10, poor sleep) and analyzed the improvement rates of sleep after treatment.
 Statistical significance was considered at P<0.05. The ethics review board of our institution approved this study.

There were 35 patients (17 men, 18 women) included in the analysis. The mean age was 73.2±10.5 years. Seven patients (20.0%) complained of mild difficulty to take the medication orally, and three patients (8.6%) showed mild gastrointestinal symptoms. However, all patients were able to complete this 12-week clinical study. The OABSS total score significantly improved from 4.9±1.8 before treatment to 2.9±1.9 after Yokukansan administration (P<0.001). In particular, nocturia (OABSS Q2) improved from 2.7±0.5 to 1.7±0.9 (P<0.001), and the number of nocturnal urinations decreased from 3.8±2.1 to 2.1±1.9 (P<0.001). Interestingly, urinary urgency (OABSS Q3) significantly improved from 1.3±1.0 to 0.7±0.9 after the treatment. HUS increased from 2.2±0.6 h to 3.5±1.1 h (P<0.001), and PSQI-Global scores also improved from 11.9±3.1 to 10.0±1.4 (P<0.001). Furthermore, the degree of disordered sleep improved in nine patients (40.9%) from severe to mild after administration of Yokukansan.

The present study confirmed that Yokukansan was effective in patients with nocturia associated with waking in the middle of the night. The subjects of this study were relatively elderly and included many patients with severe sleep disorders. However, treatment with Yokukansan for the patients with nocturia due to sleep disturbance was relatively safe and improved sleep quality without severe adverse events.  The 12-week Yokukansan treatment improved OAB symptoms not only nocturia but also urinary urgency using the OABSS. Overall, the results of this study suggests that Yokukansan has the potential as an effective treatment option for nocturia with sleep problems and OAB.

Based on this clinical study, we concluded that Yokukansan oral administration may be one of the effective treatment strategies for the patients with nocturia due to sleep disturbance.