Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin.
J Clin Psychiatry. 2014 Feb;75(2):162-8. doi: 10.4088/JCP.12m08305.
Suboptimal availability of circulating thyroid hormones may contribute to the high rate of treatment failures in bipolar disorder. This study tested the efficacy of adjunctive treatment with supraphysiologic doses of levothyroxine in patients with bipolar depression and the hypothesis that women would display a better outcome compared to men.
The aims of this multicenter, 6-week, double-blind, randomized, placebo-controlled fixed-dose (300 μg/d) trial conducted from 2004 to 2009 were to assess efficacy and tolerability of levothyroxine adjunctive to continuing treatment with mood stabilizer and/or antidepressant medication for patients with bipolar I or II disorder, currently depressed (DSM-IV), and to investigate gender differences in treatment response. The primary efficacy variable was mean change in Hamilton Depression Rating Scale (HDRS) score.
Of 74 patients enrolled in the study, 62 (35 with bipolar I; mean age = 44.9 years) were randomized. Mean change in HDRS score from randomization to week 6 was larger in the levothyroxine group compared to the placebo group, with a 2.7-point difference (decline of -7.8 [38.3%] vs -5.1 [25.5%]; last-observation-carried-forward analysis). The course of HDRS scores over time from randomization to week 6 was significantly different between groups at week 4 (P = .046) but not at the end of the placebo-controlled phase (P = .198). The secondary analysis of women (n = 32) revealed a significant difference between groups in mean change in HDRS score (-16.6% placebo vs -42.4% levothyroxine, P = .018). A mixed-effects model for repeated-measures analysis showed a significant between-group difference in HDRS score (6.8, P = .012) for women. High thyroid-stimulating hormone levels, indicating suboptimal levels of circulating thyroid hormones, were predictive for positive treatment outcome in women treated with levothyroxine in a linear regression model (F3 = 3.47; P = .05).
This trial demonstrated that patients treated with levothyroxine did numerically better than those treated with placebo; however, the study failed to detect a statistically significant difference between the 2 groups in the primary outcome measure due to a high placebo response rate. Previous findings that women show better improvement in depression scores with levothyroxine compared to men were confirmed.
ClinicalTrials.gov identifier: NCT01528839.
循环甲状腺激素的供应不足可能导致双相情感障碍的治疗失败率居高不下。本研究测试了在双相情感障碍抑郁患者中添加超生理剂量左甲状腺素的辅助治疗的疗效，以及女性的治疗效果是否优于男性。
这是一项 2004 年至 2009 年进行的、多中心、6 周、双盲、随机、安慰剂对照固定剂量（300μg/d）试验，旨在评估左甲状腺素辅助治疗心境稳定剂和/或抗抑郁药治疗的双相 I 或 II 型障碍、当前抑郁（DSM-IV）患者的疗效和耐受性，并研究治疗反应中的性别差异。主要疗效变量是汉密尔顿抑郁评定量表（HDRS）评分的平均变化。
在这项研究中，共有 74 名患者入组，其中 62 名（35 名患有双相 I；平均年龄=44.9 岁）被随机分配。与安慰剂组相比，左甲状腺素组从随机分组到第 6 周时 HDRS 评分的平均变化更大，差值为 2.7 分（下降 7.8[38.3%] vs 5.1[25.5%]；最后观察值结转分析）。从随机分组到第 6 周，HDRS 评分随时间的变化在第 4 周时组间差异具有统计学意义（P=0.046），但在安慰剂对照阶段结束时无统计学意义（P=0.198）。对女性（n=32）的二次分析显示，两组间 HDRS 评分的平均变化有显著差异（安慰剂组-16.6%，左甲状腺素组-42.4%，P=0.018）。重复测量混合效应模型分析显示，HDRS 评分在组间有显著差异（6.8，P=0.012）。线性回归模型显示，高促甲状腺激素水平（提示循环甲状腺激素水平不足）预示着接受左甲状腺素治疗的女性有积极的治疗效果（F3=3.47；P=0.05）。
本试验表明，接受左甲状腺素治疗的患者在数值上比接受安慰剂治疗的患者效果更好；然而，由于安慰剂组的反应率较高，该研究未能检测到两组在主要终点测量上的统计学差异。之前的研究发现，与男性相比，女性服用左甲状腺素后抑郁评分的改善更好，这一发现得到了证实。
ClinicalTrials.gov 标识符：NCT01528839。
