U.O. Neurologia, Azienda Sanitaria di Firenze, Florence, Italy.
Eur J Clin Pharmacol. 2012 Jun;68(6):903-12. doi: 10.1007/s00228-012-1213-x. Epub 2012 Jan 21.
In a recent meta-analysis of 38 double-blind randomized controlled trials (RCTs) comparing pregabalin (PGB) to placebo, we found 20 adverse events (AEs) to be significantly associated with PGB treatment. In the present study, we evaluated whether the incidence of these 20 AEs differs across distinct disorders in which PGB was investigated.
Among the 38 previously identified RCTs of PGB, we selected only those including a PGB 600 mg/day arm and subsequently classified them into four distinct groups according to the disorder in which PGB was investigated: (1) drug-resistant partial epilepsy, (2) psychiatric disorders, (3) fibromyalgia, and (4) neuropathic pain. We used risk differences (RDs) to quantify the placebo-corrected proportion of subjects discontinuing PGB due to intolerable AEs and to determine the placebo-corrected incidence of each of the 20 PGB AEs across the four disorders.
Twenty-two RCTs were included in this study. Neither the proportion of subjects discontinuing PGB due to intolerable AEs nor the incidence of PGB AEs (with the exception of ataxia) differed significantly across the four disorders. Ataxia was more common in drug-resistant partial epilepsy compared to fibromyalgia. When limiting analyses to subjects on placebo, most vestibulo-cerebellar AEs (ataxia, diplopia, and blurred vision) were found to be more common in drug-resistant partial epilepsy compared to all other disorders. Diplopia and blurred vision were more common in epilepsy than in neuropathic pain; and ataxia had a higher incidence in epilepsy than in anxiety disorder and fibromyalgia. Among other CNS AEs, somnolence was more common in epilepsy compared to neuropathic pain and in anxiety disorders alone compared to neuropathic pain and fibromyalgia. Asthenia was also more common in epilepsy than in neuropathic pain and fibromyalgia.
Although drug-resistant partial epilepsy is associated with a higher probability of developing vestibulo-cerebellar AEs, the risk for PGB toxicity does not differ across distinct disorders.
在最近对 38 项比较普瑞巴林（PGB）与安慰剂的双盲随机对照试验（RCT）的荟萃分析中，我们发现 20 种不良事件（AE）与 PGB 治疗显著相关。在本研究中，我们评估了在研究 PGB 的不同疾病中，这些 20 种 AE 的发生率是否存在差异。
在之前确定的 38 项 PGB RCT 中，我们仅选择了包含 PGB 600mg/天治疗组的 RCT，并根据 PGB 研究的疾病将其分为四个不同的组：（1）耐药性部分性癫痫；（2）精神疾病；（3）纤维肌痛；（4）神经性疼痛。我们使用风险差异（RD）来量化因无法耐受的 AE 而停止 PGB 治疗的受试者比例，并确定在四种疾病中每种 20 种 PGB AE 的安慰剂校正发生率。
本研究纳入了 22 项 RCT。因无法耐受的 AE 而停止 PGB 治疗的受试者比例或 PGB AE 的发生率（共济失调除外）在四种疾病中均无显著差异。与纤维肌痛相比，耐药性部分性癫痫患者的共济失调更常见。当将分析限制在安慰剂组的受试者时，发现大多数前庭小脑 AE（共济失调、复视和视力模糊）在耐药性部分性癫痫中比在其他所有疾病中更为常见。与神经性疼痛相比，癫痫患者的复视和视力模糊更为常见；与焦虑障碍和纤维肌痛相比，癫痫患者的共济失调发生率更高。在其他中枢神经系统 AE 中，与神经性疼痛相比，癫痫患者的嗜睡更为常见，与神经性疼痛和纤维肌痛相比，焦虑障碍患者的嗜睡更为常见。与神经性疼痛和纤维肌痛相比，癫痫患者的乏力更为常见。
尽管耐药性部分性癫痫与前庭小脑 AE 发生的可能性更高相关，但 PGB 毒性的风险在不同疾病中并无差异。
