Beydler Emily M, Katzell Lauren, Schmidt Lauren, Carr Brent R, Holbert Richard C
College of Medicine, University of Florida, Gainesville, FL, United States.
Department of Psychiatry, University of Florida, Gainesville, FL, United States.
Front Psychiatry. 2023 Feb 9;14:1137055. doi: 10.3389/fpsyt.2023.1137055. eCollection 2023.
Bipolar major depressive episodes with mixed features are diagnosed in patients who meet the full criteria for a major depressive episode exhibiting three additional concurrent symptoms of hypomania or mania. Up to half of patients with bipolar disorder experience mixed episodes, which are more likely to be treatment-refractory than pure depression or mania/hypomania alone.
We present a 68-year-old female with Bipolar Type II Disorder with a four-month medication-refractory major depressive episode with mixed features referred for neuromodulation consultation. Previous failed medication trials over several years included lithium, valproate, lamotrigine, topiramate, and quetiapine. She had no history of treatment with neuromodulation. At the initial consultation, her baseline Montgomery-Asberg Depression Rating Scale (MADRS) was moderate in severity at 32. Her Young Mania Rating Scale (YMRS) was 22, with dysphoric hypomanic symptoms consisting of heightened irritability, verbosity and increased rate of speech, and decreased sleep. She declined electroconvulsive therapy but elected to receive repetitive transcranial magnetic stimulation (rTMS).
The patient underwent repetitive transcranial magnetic stimulation (rTMS) with a Neuronetics NeuroStar system, receiving nine daily sessions over the left dorsolateral prefrontal cortex (DLPFC). Standard settings of 120% MT, 10 Hz (4 sec on, 26 sec off), and 3,000 pulses/session were used. Her acute symptoms showed a brisk response, and at the final treatment, her repeat MADRS was 2, and YMRS was 0. The patient reported feeling "great," which she defined as feeling stable with minimal depression and hypomania for the first time in years.
Mixed episodes present a treatment challenge given their limited treatment options and diminished responses. Previous research has shown decreased efficacy of lithium and antipsychotics in mixed episodes with dysphoric mood such as the episode our patient experienced. One open-label study of low-frequency right-sided rTMS showed promising results in patients with treatment-refractory depression with mixed features, but the role of rTMS in the management of these episodes is largely unexplored. Given the concern for potential manic mood switches, further investigation into the laterality, frequency, anatomical target, and efficacy of rTMS for bipolar major depressive episodes with mixed features is warranted.
伴有混合特征的双相重度抑郁发作被诊断于符合重度抑郁发作全部标准且同时伴有另外三种轻躁狂或躁狂并发症状的患者。高达半数的双相情感障碍患者会经历混合发作，相较于单纯的抑郁或躁狂/轻躁狂发作，混合发作更有可能难治。
我们报告一名68岁患有II型双相情感障碍的女性，其患有持续四个月的药物难治性重度抑郁发作且伴有混合特征，前来接受神经调节咨询。过去数年中多种药物试验均告失败，这些药物包括锂盐、丙戊酸盐、拉莫三嗪、托吡酯和喹硫平。她既往没有神经调节治疗史。在初次咨询时，她的蒙哥马利-艾斯伯格抑郁评定量表（MADRS）基线严重程度为中度，得分为32分。她的杨氏躁狂评定量表（YMRS）为22分，伴有烦躁性轻躁狂症状，包括易怒加剧、言语增多、语速加快以及睡眠减少。她拒绝接受电休克治疗，但选择接受重复经颅磁刺激（rTMS）。
患者使用Neuronetics NeuroStar系统接受重复经颅磁刺激（rTMS），在左侧背外侧前额叶皮质（DLPFC）进行每日九次治疗。采用120%运动阈值（MT）、10赫兹（4秒开启，26秒关闭）以及每次治疗3000个脉冲的标准设置。她的急性症状迅速缓解，在最后一次治疗时，她的MADRS复测结果为2分，YMRS为0分。患者报告感觉“很棒”，她将其定义为多年来首次感觉稳定，抑郁和轻躁狂症状极少。
鉴于混合发作的治疗选择有限且反应减弱，其构成了一项治疗挑战。既往研究表明，锂盐和抗精神病药物在伴有烦躁情绪的混合发作（如我们患者所经历的发作）中的疗效降低。一项关于低频右侧rTMS的开放标签研究显示，在伴有混合特征的药物难治性抑郁患者中取得了有前景的结果，但rTMS在这些发作管理中的作用在很大程度上尚未得到探索。鉴于对潜在躁狂情绪转换的担忧，有必要进一步研究rTMS用于伴有混合特征的双相重度抑郁发作的刺激部位、频率、解剖靶点及疗效。
