اثر ضد افسردگی nigripes Xylaria در بیماران مبتلا به صرع: در یک مطالعه دوسوکور چند تصادفی

Purpose The comorbidity of depression in patients with epilepsy is common and treatment is still controversial. This pilot study was aimed at evaluating the efficacy and safety of Xylaria nigripes for treating depressive symptoms in patients with epilepsy during 12 weeks of treatment. Methods A multicenter, double-blind, placebo-controlled, randomized superiority study was performed. A total of 104 patients with epilepsy who fulfilled the study criteria were randomized 1:1 to receive Xylaria nigripes (the Wu Ling group) or placebo (the placebo group) treatment in the 12-week period of study. The participants were visited on weeks 0, 2, 4, 8, and 12 of the treatment course. Results Eighty-one patients finished all of the visits. The primary efficacy endpoint in this study was the total effective rate for depression, which was significantly greater in the Wu Ling group (51.3%, n = 39) than in the placebo group (35.7%, n = 42, 0.51–0.36 = 0.15, 95% CI −0.06 to 0.37, U = 2.83, P = 0.002) after 12 weeks of treatment. No differences in seizure frequency or changes in severity were found between the Wu Ling and the placebo groups. In addition, the quality of life and seizure worry subscale scores in patients with epilepsy were also improved more notably in the Wu Ling group than in the placebo group (P < 0.05). Most of the adverse effects (AEs) in this study were mild and had no differences between the Wu Ling and the placebo groups. Conclusion Xylaria nigripes could alleviate depressive symptoms within 12 weeks treatment and was well tolerated in patients with epilepsy.

Depression is the most frequently occurring psychiatric comorbidity in patients with epilepsy, with an average prevalence of 20–30% [1] and [2]. Depression has significant negative impacts on quality of life in patients with epilepsy [3], and is associated with a poor response to pharmacological and surgical treatments of epileptic disorders [4] and [5]. However, depressive symptoms in epilepsy have not been fully recognized by neurologists. The treatment for comorbid depression in patients with epilepsy is also challenging. Some reports of pharmaceutical and psychotherapeutic approaches for depressive symptoms in patients with epilepsy are open-labeled [6], [7], [8] and [9]. The safety of selective serotonin reuptake inhibitor (SSRI) antidepressants in patients with epilepsy is still controversial. Although some investigations showed that SSRIs had little effects on seizure frequency [10] and [11], others indicated that SSRIs could exacerbate seizures by lowering the seizure threshold or by interacting with antiepileptic drugs (AEDs) [12] and [13], especially when taken in overdose [14] and [15]. There have been no guidelines, expert consensus or recommendations for the treatment of comorbidity of depression in patients with epilepsy until now. Randomized clinical trials and new therapies are urgently needed. Xylaria nigripes (also referred to as Wu Ling Shen) is a traditional Chinese medicine which belongs to the Xylariaceae family of fungi. It grows several feet underground in the fungus combs of the Odontotermes termite species during the spring and summer seasons, and contains many bioactive molecules such as glycosides, steroids and amino acids [16] and [17]. Studies demonstrated Xylaria nigripes had antidepressant and sleep-regulating effects, and was used to treat depression and insomnia in clinical practice [18] and [19]. In a multicenter randomized double-blind parallel study, Xylaria nigripes (under the brand name ‘Wu Ling Capsule’) had a similar effect to Deanxit to alleviate depressive, anxiety and insomia symptoms in patients with depression [20]. In animal studies, Xylaria nigripes was found to prolong the latency of convulsive seizure and delay the kindling process in penty1enetetrazol induced rat epilepsy models [21]. The pharmacological mechanisms of Xylaria nigripes appeared to be complicated. As indicated by Ma et al. [22], Xylaria nigripes promoted the activity of glutamate decarboxylase and the combination of γ-aminobutyric acid (GABA) with GABA receptors. It also had anti-oxidative and anti-inflammatory effects [23], [24] and [25]. In this study, therefore, we used Xylaria nigripes as an anti-depressive therapy in patients with comorbidity of epilepsy and depression to evaluate its effects on depression and safety for seizures. The primary objective of this study was to evaluate the efficacy of Xylaria nigripes on depressive symptoms in patients with epilepsy during 12 weeks of treatment. The secondary objectives included two aspects: (1) assessing the influences of Xylaria nigripes on seizure frequency, seizure severity, sleep quality and quality of life for patients with epilepsy; (2) evaluating the safety of Xylaria nigripes in patients with epilepsy.

In conclusion, Xylaria nigripes could be an acceptable treatment to alleviate depressive symptoms in patients with epilepsy after at least 12 weeks of treatment. It could also improve some aspects of quality of life for patients with epilepsy without increasing the risk of exacerbating epileptic seizures, and be well tolerated. Overall, the WL-2010 study was still a preliminary small scale pilot study, but its results could help to evaluate feasibility, time, adverse events and effective size of a full-scale research project. A study with better screening tools, a larger sample size and a longer follow-up period would be expected in the future.