Department of Psychiatry, University of Calgary, Alberta, Canada.
Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
JAMA Netw Open. 2021 Mar 1;4(3):e210963. doi: 10.1001/jamanetworkopen.2021.0963.
Major depressive episodes in bipolar disorder are common and debilitating. Repetitive transcranial magnetic stimulation is well established in the treatment of major depressive disorder, and the intermittent theta burst stimulation (iTBS) protocol is replacing conventional protocols because of noninferiority and reduced delivery time. However, iTBS has not been adequately studied in bipolar disorder and, therefore, its efficacy is uncertain.
To determine whether iTBS to the left dorsolateral prefrontal cortex (LDLPFC) is safe and efficacious in the treatment of acute bipolar depression.
DESIGN, SETTING, AND PARTICIPANTS: This study was a double-blind, 4-week, randomized clinical trial of iTBS targeting the LDLPFC. Two Canadian academic centers recruited patients between 2016 and 2020. Adults with bipolar disorder type I or type II experiencing an acute major depressive episode were eligible if they had not benefited from a first-line treatment for acute bipolar depression recommended by the Canadian Network for Mood and Anxiety Treatments and were currently treated with a mood stabilizer, an atypical antipsychotic, or their combination. Seventy-one participants were assessed for eligibility, and 37 were randomized to daily sham iTBS or active iTBS using a random number sequence, stratified according to current pharmacotherapy. Data analysis was performed from April to September 2020.
Four weeks of daily active iTBS (120% resting motor threshold) or sham iTBS to the LDLPFC. Nonresponders were eligible for 4 weeks of open-label iTBS.
The primary outcome was the change in score on the Montgomery-Asberg Depression Rating Scale from baseline to study end. Secondary outcomes included clinical response, remission, and treatment-emergent mania or hypomania.
The trial was terminated for futility after 37 participants (23 women [62%]; mean [SD] age, 43.86 [13.87] years; age range, 20-68 years) were randomized, 19 to sham iTBS and 18 to active iTBS. There were no significant differences in Montgomery-Asberg Depression Rating Scale score changes (least squares mean difference between groups, -1.36 [95% CI, -8.92 to 6.19; P = .91] in favor of sham iTBS), and rates of clinical response were low in both the double-blind phase (3 of 19 participants [15.8%] in the sham iTBS group and 3 of 18 participants [16.7%] in the active iTBS group) and open-label phase (5 of 21 participants [23.8%]). One active iTBS participant had a treatment emergent hypomania, and a second episode occurred during open-label treatment.
iTBS targeting the LDLPFC is not efficacious in the treatment of acute bipolar depression in patients receiving antimanic or mood stabilizing agents. Additional research is required to understand how transcranial magnetic stimulation treatment protocols differ in efficacy between unipolar and bipolar depression.
ClinicalTrials.gov Identifier: NCT02749006.
双相情感障碍中的重度抑郁发作很常见且使人虚弱。重复经颅磁刺激在重度抑郁障碍的治疗中已得到充分确立，由于非劣效性和减少的输送时间，间歇性 theta 爆发刺激（iTBS）方案正在取代传统方案。然而，iTBS 在双相情感障碍中的研究还不够充分，因此其疗效尚不确定。
确定左背外侧前额叶皮质（LDLPFC）的 iTBS 治疗急性双相抑郁是否安全有效。
设计、设置和参与者：这是一项针对 LDLPFC 的双盲、4 周、随机临床试验。加拿大的两个学术中心于 2016 年至 2020 年期间招募了患者。符合条件的患者为 I 型或 II 型双相情感障碍，目前正在服用心境稳定剂、非典型抗精神病药或两者联合治疗，正在经历急性重度抑郁发作，且对加拿大心境和焦虑治疗网络推荐的急性双相抑郁一线治疗没有反应。71 名参与者被评估是否符合条件，其中 37 名参与者根据当前的药物治疗情况，采用随机数序列，分层随机分配至每日假 iTBS 或活性 iTBS。数据分析于 2020 年 4 月至 9 月进行。
4 周的每日活性 iTBS（120%静息运动阈值）或 LDLPFC 的假 iTBS。无应答者有资格接受 4 周的开放标签 iTBS。
主要结局是从基线到研究结束时蒙哥马利-阿斯伯格抑郁评定量表（Montgomery-Asberg Depression Rating Scale）评分的变化。次要结局包括临床反应、缓解以及治疗引发的躁狂或轻躁狂。
在 37 名参与者（23 名女性[62%]；平均[SD]年龄 43.86 [13.87]岁；年龄范围 20-68 岁）被随机分配后，该试验因无效而终止，其中 19 名接受假 iTBS，18 名接受活性 iTBS。两组之间在蒙哥马利-阿斯伯格抑郁评定量表评分变化方面没有显著差异（组间最小二乘均值差异，假 iTBS 组为-1.36[95%CI，-8.92 至 6.19；P=0.91]），且在双盲阶段（假 iTBS 组 19 名参与者中有 3 名[15.8%]，活性 iTBS 组有 18 名参与者中有 3 名[16.7%]）和开放标签阶段（21 名参与者中有 5 名[23.8%]），临床反应率均较低。1 名活性 iTBS 参与者出现治疗性轻躁狂，第二次发作发生在开放标签治疗期间。
在接受抗躁狂或稳定情绪药物的患者中，靶向 LDLPFC 的 iTBS 对急性双相抑郁的治疗无效。需要进一步研究来了解经颅磁刺激治疗方案在单相和双相抑郁中的疗效差异。
ClinicalTrials.gov 标识符：NCT02749006。
