In a subgroup analysis, Wuling capsule was significantly better than control when used as monotherapy or as adjunctive therapy, though investigators suggest adjunctive use may be superior and more study is needed.
After inconsistencies in previously published data, results from a new meta-analysis showed that Wuling capsule, an approved medication by China Food and Drug Administration, might be able to safely and effectively improve sleep quality in patients with insomnia disorder, though future randomized trials will be needed.1
Nineteen randomized controlled trials (RCTs) with a total of 1850 participants were included. In addition to significant effects on sleep quality, investigators found that Wuling capsule reduced the severity of the disorder. In a subgroup analysis, Wuling capsule was significantly better than controls regardless of being used as monotherapy or as adjunctive therapy. Data also showed an add-on effect when used in combination with conventional drugs, suggesting it may be superior as an adjunctive therapy.
Wuling capsule is a single herbal formula derived from Xylaria nigripes mycelia and has been applied in clinical treatment of insomnia disorder for decades in China, but the results of its therapeutic efficacy in studies was inconsistent. To clarify its clinical benefit, senior author Wang Xian Zhong, MD, professor of neurology, Beijing University of Chinese Medicine, and colleagues conducted the study according to the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0.
"The findings of this study are not strong enough to support the use of Wuling capsule as a treatment for insomnia disorder,” Wang et al wrote. "For the future studies, first, we recommend that the design of RCTs and the reporting of clinical study results should be carried out in strict accordance with the requirements of the CONSORT 2010 statement to ensure the scientific quality and rigor of studies."
The dosing of Wuling capsule in all 19 trials was 0.99 g, given 3 times daily. Treatment duration lasted from 4 to 12 weeks, with Pittsburgh Sleep Quality Index (PSQI) as the primary outcome to assess sleep quality. Five of those studies provided data on subscales of PSQI which included sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance and daytime dysfunction. All trials except 9 described adverse events (AEs).
Sleep quality, assessed by PSQI scores, was significantly improved among Wuling capsule-treated patients (mean difference, –1.92; 95% CI, –2.34 to –1.50; P <.00001; I2 = 95%). Notably, 1 trial revealed that Wuling capsule was not superior to placebo on PSQI scores (mean difference, –0.07; 95% CI, –0.98 to 0.84; P = .88).
Additional subgroup analysis revealed that Wuling capsule treatment also significantly lowered PSQI score compared with use of benzodiazepines (mean difference, –1.90; 95% CI, –2.55 to –1.26; P <.00001; I2 = 97%). Pooled results of 4 studies that used Sleep Dysfunction Rating Scale to assess severity of insomnia disorder also showed significantly reduced scores for Wuling capsule-treated patients compared with benzodiazepines. As well, those who used Wuling capsule in combination with benzodiazepines had lowered PSQI scores compared with those solely on benzodiazepines (mean difference, –1.81; 95% CI, –2.84 to –0.78; P = .0006; I2 = 89%). Investigators continued to observe this add-on effect, with lowered scores recorded in those who used Wuling capsule in combination with sedating antidepressants (mean difference, –2.25; 95% CI, –3.02 to –1.48; P <.00001; I2 = 93%) vs those solely on antidepressants, and in those who used Wuling capsule in combination with cognitive behavior therapy (mean difference, –2.76; 95% CI, –4.25 to –1.27; P = .00003) vs cognitive behavior therapy alone.
Compared with controls, Wuling capsule as a monotherapy showed a significantly greater effect on PSQI (mean difference; –1.71; 95% CI, –2.33 to –1.09; P <.00001; I2 = 97%). Additionally, Wuling capsule in combination with conventional drug was more effective than conventional drug alone (mean difference, –2.10; 95% CI, –2.66 to –1.55; P <.000001; I2 = 90%), leading investigators to suggest that it may be a more effective treatment as an adjunctive therapy.
Wuling capsule shows significant lowering of PSQI score no matter if treatment duration was 4 weeks (mean difference, –1.68; 95% CI, –2.13 to –1.22; P <.000001; I2 = 95%) or 8 weeks (mean difference, –2.57; 95% CI, –3.52 to –1.62; P <.000001; I2 = 93%). Although, the results favored an 8-week treatment period.
In the 10 trials that reported AEs, 141 total AEs were listed, with results that showed significantly reduced AEs on Wuling capsule compared with controls (risk ratio [RR], 0.47; 95% CI, 0.34-0.65; P <.000001; I2 = 43%). Subgroup analyses showed no statistical difference whether using Wuling capsule in combination with benzodiazepines compared with benzodiazepines (RR, 0.57; 95% CI, 0.26-1.22; P = .015; I2 = 67%) or compared with placebo (RR, 1.40; 95% CI, 0.56-3.52; P = 0.48).