Stanley Center for Bipolar Research, Ministry of Health Mental Health Center, Faculty of Health Sciences, Department of Psychiatry, Ben Gurion University of the Negev, Beer Sheva, Israel.
Bipolar Disord. 2010 Jun;12(4):376-82. doi: 10.1111/j.1399-5618.2010.00828.x.
Valproic acid's well-known teratogenicity limits its use in women of childbearing age. Valnoctamide is an analog of valproate that does not undergo biotransformation to the corresponding free acid. In mice, valnoctamide has been shown to be distinctly less teratogenic than valproate. Valnoctamide is an anticonvulsant, and we hypothesized that valnoctamide is antimanic.
We performed a double-blind, five-week, add-on, controlled trial of valnoctamide in mania. Patients were treated with risperidone at doses of the physician's discretion. Valnoctamide or placebo was begun at doses of 600 mg/day and increased to 1200 mg after four days. Weekly ratings by a psychiatrist blind to the study drug were conducted using the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale (YMRS), and the Clinical Global Impression (CGI).
Fifteen valnoctamide patients and 17 placebo patients completed at least one post-baseline week and were included in data analysis. In all efficacy measures valnoctamide was more effective than placebo as an add-on to risperidone, using two-way analysis of variance (ANOVA) with time as the within-subject factor. Two-way ANOVA showed a significant effect of time (p < 0.001) and significant interaction between treatment and time (YMRS: p = 0.012; BPRS: p = 0.007; CGI: p = 0.003). Differences between valnoctamide and placebo were significant from week 3 to week 5.
Valnoctamide could be an important valproate substitute for women of childbearing age with bipolar disorder who may become pregnant.
丙戊酸具有众所周知的致畸性，限制了其在育龄妇女中的使用。瓦诺酰胺是丙戊酸的类似物，不会转化为相应的游离酸。在小鼠中，已证明瓦诺酰胺的致畸性明显低于丙戊酸。瓦诺酰胺是一种抗惊厥药，我们假设瓦诺酰胺具有抗躁狂作用。
我们进行了一项双盲、为期五周、附加、对照试验，评估瓦诺酰胺治疗躁狂症的效果。患者接受利培酮治疗，剂量由医生决定。瓦诺酰胺或安慰剂起始剂量为 600mg/天，四天后增加至 1200mg/天。由对研究药物盲态的精神科医生每周进行一次评估，使用简明精神病评定量表（BPRS）、躁狂量表（YMRS）和临床总体印象量表（CGI）。
15 名瓦诺酰胺患者和 17 名安慰剂患者至少完成了一次基线后周的治疗，并纳入数据分析。在所有疗效测量中，瓦诺酰胺作为利培酮的附加治疗，与安慰剂相比更有效，使用双向方差分析（ANOVA），时间作为受试者内因素。双向 ANOVA 显示时间有显著影响（p < 0.001），治疗和时间之间有显著交互作用（YMRS：p = 0.012；BPRS：p = 0.007；CGI：p = 0.003）。从第 3 周到第 5 周，瓦诺酰胺与安慰剂之间的差异有统计学意义。
瓦诺酰胺可能成为育龄期双相障碍女性的一种重要丙戊酸盐替代药物，这些女性可能怀孕。
