Lamotrigine as add-on therapy in schizophrenia - Results of 2 placebo-controlled trials
Lamotrigine as add-on therapy in schizophrenia - Results of 2 placebo-controlled trials
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DOI：
10.1097/jcp.0b013e31815abf34
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发表时间：
2007-12-01
影响因子：
2.9
通讯作者：
Webster, Elizabeth L.
中科院分区：
文献类型：
--
作者：
Goff, Donald C.;Keefe, Richard;Webster, Elizabeth L.
目的：之前发现拉莫三嗪可以减轻氯胺酮引起的行为变化，并且在两项安慰剂对照试验中，当添加到抗精神病药物中时可以改善精神病。我们试图评估拉莫三嗪加强治疗对非典型抗精神病药物耐药的精神分裂症患者的潜在作用。方法：进行了两项多中心、随机、双盲、12周、平行组试验，以比较灵活剂量的拉莫三嗪（100-400 mg/d）与安慰剂作为附加治疗对具有稳定、残余精神病症状的精神分裂症患者的作用。主要终点在第12周时阳性和阴性症状量表总分发生变化。 结果：研究1入组了217名患者，研究2入组了212名患者；意向治疗样本的完成率分别为 71% 和 74%，并且治疗组之间没有差异。总体而言，两项研究的平均阳性和阴性症状量表总分均有所改善，并且治疗组之间没有差异。在研究 1 中，安慰剂组的阴性症状评估量表总分和临床总体印象比拉莫三嗪组改善更多；在研究2中，拉莫三嗪组的认知综合评分比安慰剂组改善更多。结论：这两项研究的结果不支持将拉莫三嗪作为难治性精神病患者的非典型抗精神病药物的辅助药物。目前还不清楚为什么之前的拉莫三嗪试验的积极结果没有被重复。一项试验显示拉莫三嗪对认知有积极作用，虽然意义不确定，但可能需要进一步研究。
Objective: Lamotrigine previously was found to attenuate ketamine-induced behavioral changes and, in 2 placebo-controlled trials, to improve psychosis when added to antipsychotic medication. We sought to evaluate the potential role of lamotrigine augmentation in schizophrenia patients resistant to atypical antipsychotic medication.Methods: Two multicenter, randomized, double-blind, 12-week, parallel-group trials were conducted to compare flexibly dosed lamotrigine (100-400 mg/d) with placebo as add-on treatment in schizophrenia patients with stable, residual psychotic symptoms. The primary end point was changed in Positive and Negative Syndrome Scale total score at week 12.Results: Two hundred seventeen patients were enrolled in study 1 and 212 in study 2; completion rates in the intent-to-treat samples were 71% and 74%, respectively, and did not differ between treatment groups. Overall, mean Positive and Negative Syndrome Scale total scores improved in both studies and did not differ between treatment groups. In study 1, the Scale for Assessment of Negative Symptoms total score and Clinical Global Impression improved more with placebo than with lamotrigine; in study 2, the cognitive composite score improved more with lamotrigine than with placebo.Conclusions: Results from these 2 studies do not support the use of lamotrigine as an adjunct to atypical antipsychotics in patients with refractory psychosis. It is unclear why positive results from previous lamotrigine trials were not replicated. The positive effect of lamotrigine on cognition in one trial, while of uncertain significance, may rnerit further study.