Goldberg Joseph F, Calabrese Joseph R, Saville Benjamin R, Frye Mark A, Ketter Terence A, Suppes Trisha, Post Robert M, Goodwin Frederick K
Affective Disorders Program, Silver Hill Hospital, New Canaan, Connecticut, USA.
J Clin Psychiatry. 2009 Sep;70(9):1273-80. doi: 10.4088/JCP.08m04381. Epub 2009 Aug 11.
During post-acute phase pharmacotherapy for bipolar disorder, there has been little empirical study to establish when emerging mania symptoms (1) are of clinical significance and (2) reflect iatrogenic events versus the natural course of illness.
Secondary analyses were conducted in a previously studied group of bipolar I disorder (DSM-IV) outpatients randomly assigned to lamotrigine monotherapy (n=171) or placebo (n=121), and a larger prerandomization group (N=966) during open-label titration of lamotrigine, following an index depressive episode. Time until the emergence of mania symptoms, at varying severity thresholds, was examined over 6 months for lamotrigine versus placebo, while controlling for potential confounding factors in Cox proportional hazard models. Subject enrollment occurred between July 1997 and August 2001.
Rates of mood elevation during both acute open-label and randomized continuation phases of lamotrigine treatment were comparable to those seen with placebo during the randomized phase. The hazard ratio for the emergence of mania symptoms with lamotrigine was not significantly different from placebo (hazard ratio=0.79; 95% CI, 0.53 to 1.16), with an upper bound that suggests no meaningful increase in susceptibility toward mania with lamotrigine. By contrast, clinically meaningful rises in mania symptom severity were predicted by baseline residual manic symptoms prerandomization and by the number of manic, hypomanic, or mixed episodes in the past year.
Based on a composite definition of mood destabilization involving a range of severity thresholds for emerging signs of mania, lamotrigine confers no meaningful elevated risk relative to placebo for mood destabilization in bipolar I disorder. Rather, illness burden related to residual or lifetime mania features may hold greater importance for explaining mania relapses or breakthrough manic features during lamotrigine continuation pharmacotherapy.
在双相情感障碍的急性后期药物治疗期间，几乎没有实证研究来确定新出现的躁狂症状：（1）何时具有临床意义；（2）反映医源性事件还是疾病的自然病程。
对先前研究的一组双相I型障碍（DSM-IV）门诊患者进行二次分析，这些患者在索引抑郁发作后，被随机分配接受拉莫三嗪单药治疗（n = 171）或安慰剂治疗（n = 121），以及在拉莫三嗪开放标签滴定期间的一个更大的随机分组前组（N = 966）。在Cox比例风险模型中控制潜在混杂因素的同时，观察拉莫三嗪与安慰剂在6个月内出现不同严重程度阈值的躁狂症状的时间。受试者入组时间为1997年7月至2001年8月。
在拉莫三嗪治疗的急性开放标签和随机持续阶段，情绪升高的发生率与随机阶段安慰剂组相当。拉莫三嗪出现躁狂症状的风险比与安慰剂无显著差异（风险比 = 0.79；95%CI，0.53至1.16），上限表明拉莫三嗪对躁狂易感性无有意义的增加。相比之下，随机分组前的基线残留躁狂症状以及过去一年中躁狂、轻躁狂或混合发作的次数可预测躁狂症状严重程度的临床有意义升高。
基于涉及一系列躁狂新出现迹象严重程度阈值的情绪不稳定综合定义，拉莫三嗪相对于安慰剂在双相I型障碍中不会增加有意义的情绪不稳定风险。相反，与残留或终生躁狂特征相关的疾病负担对于解释拉莫三嗪持续药物治疗期间的躁狂复发或突破性躁狂特征可能更为重要。
