ImportanceBipolar disorder (BD) is chronic and disabling, with depression accounting for the majority of time with illness. Recent research demonstrated a transformative advance in the clinical efficacy of transcranial magnetic stimulation for treatment-resistant major depressive disorder (MDD) using an accelerated schedule of intermittent theta-burst stimulation (aiTBS), but the effectiveness of this treatment for treatment-refractory BD is unknown.ObjectiveTo evaluate the effectiveness of aiTBS for treatment-refractory BD.Design, Setting, and ParticipantsThis randomized clinical trial, conducted from March 2022 to February 2024, included individuals with treatment-resistant BD with moderate to severe depressive episodes referred from the Penn Bipolar outpatient clinic. Included patients had 2 or more prior failed antidepressant trials by Antidepressant Treatment History Form criteria and no other primary psychiatric diagnosis, were receiving a mood stabilizer for 4 or more weeks, and had a Montgomery-Åsberg Depression Rating Scale (MADRS) score of 20 or higher.InterventionPrior to treatment, resting-state functional magnetic resonance imaging was used to compute personalized left dorsolateral prefrontal cortex target by connectivity to subgenual anterior cingulate cortex. Patients were randomized 1:1 to 10 sessions per day of imaging-guided active or sham aiTBS for 5 days with 1 session per hour at 90% resting motor threshold for 90 000 pulses total.Main Outcome and MeasuresThe main outcome was repeated MADRS scores before and after treatment.ResultsA total of 24 participants (12 [50%] female; 12 [50%] male; mean [SD] age, 43.3 [16.9] years) were randomized to active (n = 12) or sham (n = 12) aiTBS. All participants completed treatment and 1-month follow-up. MADRS scores were significantly lower in the active group (mean [SD], 30.4 [4.8] at baseline; 10.5 [6.7] after treatment) than in the sham group (28.0 [5.4] at baseline; 25.3 [6.7] after treatment) at treatment end (estimated difference, –14.75; 95% CI, –19.73 to –9.77; P < .001; Cohen d, –2.19).Conclusion and RelevanceIn this randomized clinical trial, aiTBS was more effective than sham stimulation for depressive symptom reduction in patients with treatment-resistant BD. Further trials are needed to determine aiTBS durability and to compare with other treatments.Trial RegistrationClinicalTrials.gov Identifier: NCT05228457

中文翻译：

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加速间歇性 Theta 爆发刺激和治疗难治性双相抑郁症


重要性双相情感障碍 (BD) 是一种慢性且致残的疾病，患病期间大部分时间都是抑郁症。最近的研究表明，使用间歇性 theta 突发刺激 (aiTBS) 加速方案，经颅磁刺激治疗难治性重度抑郁症 (MDD) 的临床疗效取得了革命性进展，但这种治疗难治性 BD 的有效性尚不明确。未知。目的评估 aiTBS 对治疗难治性 BD 的有效性。设计、设置和参与者这项随机临床试验于 2022 年 3 月至 2024 年 2 月进行，纳入了来自宾夕法尼亚双相情感障碍中心转介的具有中度至重度抑郁发作的难治性 BD 患者门诊诊所。根据抗抑郁治疗史表标准，纳入的患者之前有 2 次或以上失败的抗抑郁试验，并且没有其他主要精神科诊断，正在接受情绪稳定剂 4 周或更长时间，并且蒙哥马利-阿斯伯格抑郁评定量表 (MADRS) 评分为 20 或干预在治疗之前，使用静息态功能磁共振成像通过与膝下前扣带皮层的连接来计算个性化的左背外侧前额叶皮层目标。患者按照每天 1:1 的比例随机接受影像引导的主动或假 aiTBS 治疗 5 天，每小时 1 次，在 90% 静息运动阈值下进行，总共 90 000 个脉冲。 主要结果和测量 主要结果是之前重复的 MADRS 评分结果 总共 24 名参与者（12 名 [50%] 女性；12 名 [50%] 男性；平均 [SD] 年龄，43.3 [16.9] 岁）被随机分为主动组 (n = 12) 或假组 (n = 12) aiTBS。所有参与者均完成治疗和 1 个月的随访。 活性组的 MADRS 评分（基线时平均 [SD] 30.4 [4.8]；治疗后 10.5 [6.7]）显着低于假手术组（基线时 28.0 [5.4]；治疗后 25.3 [6.7]）治疗结束（估计差异，–14.75；95% CI，–19.73 至 –9.77；P < .001；Cohen d，–2.19）。结论和相关性在这项随机临床试验中，aiTBS 比假刺激对抑郁症状更有效减少BD患者的治疗耐药性。需要进一步的试验来确定 aiTBS 的耐久性并与其他治疗进行比较。试验注册临床试验。政府标识符：NCT05228457