Citrome Leslie
Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA.
Psychopharmacol Bull. 2003;37 Suppl 2:74-88.
Valproate (the active moiety of both valproic acid and divalproex sodium) is commonly used as an adjunctive agent for the treatment of schizophrenia. Among the anticonvulsants, valproate is the most extensively studied in patients with schizophrenia. Theoretical underpinnings for valproate in schizophrenia include its effect on voltage-gated ion channels and on the g-aminobutyric acid (GABA) system, thus modulating mesolimbic dopaminergic activity. Case reports, retrospective studies, and randomized clinical trials support the use of valproate combined with antipsychotics in managing schizophrenia. A recently completed 28-day, double-blind, randomized clinical trial of 249 patients with schizophrenia demonstrated faster improvement in psychopathology with a combination therapy of divalproex and risperidone or olanzapine, compared to monotherapy with risperidone or olanzapine. Additional research is needed to assess the utility of valproate in specialized populations such as those with treatment-refractory schizophrenia or agitation in schizophrenia. Regarding the latter, positive double-blind, randomized clinical trials have already been conducted in patients with borderline personality disorder, dementia, and with disruptive adolescents. It is anticipated that future research will focus on the new extended-release formulation of divalproex that can be administered on a once-daily basis.
丙戊酸盐（丙戊酸和丙戊酸钠的活性部分）通常用作治疗精神分裂症的辅助药物。在抗惊厥药物中，丙戊酸盐在精神分裂症患者中得到了最广泛的研究。丙戊酸盐治疗精神分裂症的理论基础包括其对电压门控离子通道和γ-氨基丁酸（GABA）系统的作用，从而调节中脑边缘多巴胺能活动。病例报告、回顾性研究和随机临床试验均支持丙戊酸盐与抗精神病药物联合使用治疗精神分裂症。最近一项针对249例精神分裂症患者的为期28天的双盲随机临床试验表明，与单独使用利培酮或奥氮平相比，丙戊酸与利培酮或奥氮平联合治疗能更快改善精神病理学症状。还需要进一步研究来评估丙戊酸盐在特殊人群中的效用，如难治性精神分裂症患者或精神分裂症伴激越患者。关于后者，已经在边缘型人格障碍患者、痴呆患者和有破坏行为的青少年中进行了阳性双盲随机临床试验。预计未来的研究将集中在可每日一次给药的新型丙戊酸缓释制剂上。
