Andrade Chittaranjan, Jyothi Subramanian Arun, Renitha Thampi, Anuroopa K P, Dona Baiju, Basila T, Nimmy George
Department of Clinical Psychopharmacology and Neurotoxicology, National Institute of Mental Health and Neurosciences, Bangalore, India.
Corresponding author: Chittaranjan Andrade, MD, Department of Clinical Psychopharmacology and Neurotoxicology, National Institute of Mental Health and Neurosciences, Bangalore 560 029, India (
J Clin Psychiatry. 2021 Nov 23;83(1):21m14023. doi: 10.4088/JCP.21m14023.
Gestational exposure to valproate is associated with an unacceptably high risk of major congenital malformations, neurodevelopmental disorders, and other adverse outcomes. Prescription of valproate to reproductive-age women is therefore strongly discouraged in many parts of the world. To our knowledge, there is no pharmacoepidemiologic study of the prescription of valproate to women in a developing country. During September to November 2019, we examined the prescriptions of 10,001 consecutive outpatients issued by about 250 medical professionals from the Departments of Psychiatry, Neurology, and Neurosurgery at the National Institute of Mental Health and Neurosciences, Bangalore, India (this is a large, tertiary care referral center and a designated institute of national importance, the largest of its kind in the country). We examined the prescriptions for inclusion of any formulation of valproate in women and men separately. For comparison purposes, we also extracted data on the prescription of carbamazepine. A large proportion of women (647/3,837; 16.9%) received a prescription that included valproate (mean dose = 898 mg/d); the age band 15-45 years accounted for 460 (71.1%) of these prescriptions. In comparison, 403 (10.5%) of 3,837 women received a prescription that included carbamazepine, and 289 (71.7%) of these were in the 15-to-45-year age band. Women were more likely to receive a prescription for valproate in the Departments of Neurology and Neurosurgery than in the Department of Psychiatry (29.1% vs 14.4%, respectively). Female outpatients of childbearing age who consulted for disorders related to psychiatry, neurology, and neurosurgery were found to have a high exposure to valproate. If these findings can be generalized to other practices in the country, and to other developing countries, they suggest a pressing need for regulatory guidance regarding the avoidance of prescription of valproate to women of childbearing age. This is a public health matter of global importance.
孕期接触丙戊酸盐与严重先天性畸形、神经发育障碍及其他不良后果的风险高得令人难以接受有关。因此，世界上许多地方都强烈不鼓励给育龄妇女开具丙戊酸盐处方。据我们所知，在发展中国家，尚未有关于丙戊酸盐在女性中处方情况的药物流行病学研究。2019年9月至11月，我们检查了印度班加罗尔国家心理健康和神经科学研究所精神病学、神经病学和神经外科约250名医学专业人员开出的10001例连续门诊患者的处方（这是一家大型三级医疗转诊中心，也是具有国家重要意义的指定机构，是该国同类机构中最大的）。我们分别检查了女性和男性包含任何丙戊酸盐制剂的处方。为作比较，我们还提取了卡马西平的处方数据。很大一部分女性（647/3837；16.9%）收到了包含丙戊酸盐的处方（平均剂量 = 898毫克/天）；其中15至45岁年龄组占这些处方的460例（71.1%）。相比之下，3837名女性中有403例（10.5%）收到了包含卡马西平的处方，其中289例（71.7%）在15至45岁年龄组。与精神病学部门相比，神经病学和神经外科部门的女性更有可能收到丙戊酸盐处方（分别为29.1%和14.4%）。发现咨询精神病学、神经病学和神经外科相关疾病的育龄女性门诊患者丙戊酸盐暴露率很高。如果这些发现能够推广到该国的其他医疗机构以及其他发展中国家，那么这表明迫切需要有关避免给育龄女性开具丙戊酸盐处方的监管指导。这是一个具有全球重要性的公共卫生问题。
