拉莫三嗪作为锂盐辅助治疗双相抑郁的疗效和安全性：一项多中心、双盲、安慰剂对照试验。

Efficacy and safety of lamotrigine as add-on treatment to lithium in bipolar depression: a multicenter, double-blind, placebo-controlled trial.

作者信息

van der Loos Marc L M, Mulder Paul G H, Hartong Erwin G Th M, Blom Marc B J, Vergouwen Anton C, de Keyzer Herman J U E M, Notten Peter J H, Luteijn Marijke L, Timmermans Manuela A, Vieta Eduard, Nolen Willem A

机构信息

Isala Klinieken, Lokatie Sophia, Department of Psychiatry, Dr van Heesweg 2, Zwolle, The Netherlands.

出版信息

J Clin Psychiatry. 2009 Feb;70(2):223-31. doi: 10.4088/jcp.08m04152. Epub 2008 Dec 30.

DOI:10.4088/jcp.08m04152

PMID:19200421

Abstract

OBJECTIVE

Lamotrigine is one of the pharmacologic options for the treatment of bipolar depression but has only been studied as monotherapy. This study compared the acute effects of lamotrigine and placebo as add-on therapy to ongoing treatment with lithium in patients with bipolar depression.

METHOD

Outpatients (N = 124) aged 18 years and older with a DSM-IV bipolar I or II disorder and a major depressive episode (Montgomery-Asberg Depression Rating Scale [MADRS] score > or = 18 and Clinical Global Impressions-Bipolar Version [CGI-BP] severity of depression score > or = 4) while receiving lithium treatment (0.6-1.2 mmol/L) were randomly assigned to 8 weeks of double-blind treatment with lamotrigine (titrated to 200 mg/d) or placebo. The primary outcome measure was mean change from baseline in total score on the MADRS at week 8. Secondary outcome measures were response (defined as a reduction of > or = 50% on the MADRS and/or change of depression score on the CGI-BP of "much improved" or "very much improved" compared to baseline) and switch to mania or hypomania (defined as a CGI-BP severity of mania score of at least mildly ill at any visit). Patients were included in the study between August 2002 (Spain started in October 2003) and May 2005.

RESULTS

Endpoint mean change from baseline MADRS total score was -15.38 (SE = 1.32) points for lamotrigine and -11.03 (SE = 1.36) points for placebo (t = -2.29, df = 104, p = .024). Significantly more patients responded to lamotrigine than to placebo on the MADRS (51.6% vs. 31.7%, p = .030), but not on the CGI-BP change of depression (64.1% vs. 49.2%, p = .105). Switch to mania or hypomania occurred in 5 patients (7.8%) receiving lamotrigine and 2 patients (3.3%) receiving placebo (p = .441).

CONCLUSION

Lamotrigine was found effective and safe as add-on treatment to lithium in the acute treatment of bipolar depression.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT00224510.

摘要

目的

拉莫三嗪是治疗双相情感障碍抑郁发作的药物选择之一，但此前仅作为单一疗法进行过研究。本研究比较了拉莫三嗪和安慰剂作为锂盐持续治疗的辅助疗法，对双相情感障碍抑郁发作患者的急性疗效。

方法

年龄在18岁及以上、患有DSM-IV双相I型或II型障碍且伴有重度抑郁发作（蒙哥马利-艾斯伯格抑郁量表[MADRS]评分≥18分，临床总体印象双相版[CGI-BP]抑郁严重程度评分≥4分）、同时接受锂盐治疗（0.6 - 1.2 mmol/L）的门诊患者（N = 124），被随机分配接受为期8周的双盲治疗，分别服用拉莫三嗪（滴定至200 mg/d）或安慰剂。主要结局指标为第8周时MADRS总分相对于基线的平均变化。次要结局指标包括缓解情况（定义为MADRS评分降低≥50%和/或CGI-BP抑郁评分相较于基线“明显改善”或“非常明显改善”）以及转为躁狂或轻躁狂（定义为在任何一次访视时CGI-BP躁狂严重程度评分为至少轻度患病）。患者于2002年8月（西班牙于2003年10月开始）至2005年5月纳入本研究。

结果

拉莫三嗪组从基线MADRS总分的终点平均变化为-15.38（标准误 = 1.32）分，安慰剂组为-11.03（标准误 = 1.36）分（t = -2.29，自由度 = 104，p = 0.024）。在MADRS量表上，对拉莫三嗪有反应的患者显著多于安慰剂组（51.6% 对 31.7%，p = 0.030），但在CGI-BP抑郁变化方面则不然（64.1% 对 49.2%，p = 0.105）。接受拉莫三嗪治疗的患者中有5例（7.8%）转为躁狂或轻躁狂，接受安慰剂治疗的患者中有2例（3.3%）出现这种情况（p = 0.441）。