Deep Transcranial Magnetic Stimulation Combined with Escitalopram Oxalate in the Treatment of Depression: a Randomized Controlled Trial

doi:10.12114/j.issn.1007-9572.2023.0555

Abstract

Abstract:

Background

Depression is a common psychiatric disorder with limited treatment options. Deep transcranial magnetic stimulation (dTMS), as a new non-invasive neuromodulation technique, has been utilized in the treatment of major depressive disorder (MDD), but there is less evidence from clinical studies.

Objective

To explore the clinical efficacy of dTMS combined with escitalopram oxalate (Esc) in the treatment of depression, and provide further reliable data reference for dTMS in the treatment of depression patients.

Methods

A total of 73 patients with depression who attended Department of Psychiatry, Affiliated Hospital of Guizhou Medical University from December 2021 to January 2023 were selected as the study subjects and divided into the control group (n=35) and combined treatment group (n=38) according to the random number table. Patients in the control group were given Esc ( 10 mg per day in the first week and 20 mg per day from the second week for 2 consecutive weeks). The combined treatment group received the treatment of dTMS (left DLPFC as the stimulation target, 18 Hz, 120%MT, 1 980 times per day for 2 weeks, 10 times in total) based on the same treatment for the control group. The depressive symptoms and cognitive improvement of patients in the two groups were evaluated before and after the two weeks of treatments by Hamilton depression scale (HAMD), Beck Scale for Suicide Ideation (BSS), Montreal Cognitive Assessment Scale (MoCA) and the mean oxygenated hemoglobin (oxy-Hb) concentration in the prefrontal cortex measured by functional near-infrared spectroscopy (fNIRS) based on the verbal fluency text (VFT) task.

Results

The actual completion of the trial was 30 cases in the control group and 31 cases in the combined treatment group. After treatment, the HAMD and BSS scores of the combined treatment group were lower than those of the control group, and the MoCA score was higher than that of the control group (P<0.05). After treatment, the HAMD and BSS scores of patients in the two groups were lower than those before treatment, and the MoCA score was higher than that before treatment (P<0.05). There was no significant activation of the prefrontal cortex after treatment in both groups. The improvement of depression symptoms and cognitive function in the combined treatment group was better than that in the control group.

Conclusion

The combination of dTMS and Esc can improve the depressive symptoms and cognitive function better than Esc treatment alone in depression patients.

Key words: Depressive disorder, Deep transcranial magnetic stimulation, Near-infrared spectroscopy imaging, Cognitive function, Treatment outcome

摘要： 背景抑郁症是一种常见精神疾病，目前治疗手段有限，深部经颅磁刺激（dTMS）作为一种新型非侵入性神经调控技术，已经被运用于重度抑郁症（MDD）的治疗，但临床研究证据较少。目的探究dTMS联合草酸艾司西酞普兰（Esc）治疗抑郁症的临床疗效，为dTMS治疗抑郁症患者进一步提供可靠的数据参考。方法选取2021年12月—2023年1月就诊于贵州医科大学附属医院精神科的73例抑郁症患者为研究对象，按随机数字表法分为药物对照组35例、联合治疗组38例。药物对照组患者给予Esc（第1周10 mg/d，第2周起20 mg/d，连续2周），联合治疗组患者在药物对照组治疗基础上给予dTMS治疗[左侧背外侧前额叶（DLPFC）为刺激靶点，18 Hz，120%MT，1 980次/d，一共2周，总计10次]。分别于治疗开始前及治疗2周后应用汉密尔顿抑郁量表（HAMD）、贝克自杀意念量表（BSS）、蒙特利尔认知评估量表（MoCA）及基于言语流畅性任务（VFT）期间的功能性近红外光谱成像仪（fNIRS）测量的前额叶平均氧合血红蛋白（oxy-Hb）浓度变化对两组患者的抑郁症状及认知功能改善情况进行评定。结果实际完成试验的药物对照组30例、联合治疗组31例。联合治疗组患者治疗后HAMD、BSS评分低于药物对照组，MoCA评分高于药物对照组（P<0.05）。两组患者治疗后HAMD、BSS评分低于组内治疗前，MoCA评分高于组内治疗前（P<0.05）。两组患者治疗后前额叶皮质未见明显激活。联合治疗组患者治疗后抑郁症状及认知功能改善情况优于药物对照组。结论 dTMS联合Esc治疗较单独Esc治疗能更好地改善抑郁症患者抑郁症状及认知功能。

关键词: 抑郁症, 深部经颅磁刺激, 近红外光谱成像, 认知功能, 治疗结果

PANG Lan,LI Peifan,ZHU Xiaogang, et al. Deep Transcranial Magnetic Stimulation Combined with Escitalopram Oxalate in the Treatment of Depression: a Randomized Controlled Trial[J]. Chinese General Practice, 2024, 27(17): 2098-2103. DOI: 10.12114/j.issn.1007-9572.2023.0555.
庞兰,李佩璠,朱晓岗等. 深部经颅磁刺激联合草酸艾司西酞普兰治疗抑郁症的疗效：一项随机对照试验[J]. 中国全科医学, 2024, 27(17): 2098-2103. DOI: 10.12114/j.issn.1007-9572.2023.0555.

Figures/Tables 6

References 21

[1]	HERRMAN H, KIELING C, MCGORRY P，et al. Reducing the global burden of depression：a Lancet-World Psychiatric Association Commission[J]. Lancet，2019,393(10189):e42-43. DOI：10.1016/S0140-6736(18)32408-5.
[2]	HUANG Y Q, WANG Y, WANG H，et al. Prevalence of mental disorders in China：a cross-sectional epidemiological study[J]. Lancet Psychiatry，2019,6(3):211-224. DOI：10.1016/S2215-0366(18)30511-X.
[3]	MURPHY J A, SARRIS J, BYRNE G J. A review of the conceptualisation and risk factors associated with treatment-resistant depression[J]. Depress Res Treat，2017,2017:4176825. DOI：10.1155/2017/4176825.
[4]	LEVKOVITZ Y, ISSERLES M, PADBERG F，et al. Efficacy and safety of deep transcranial magnetic stimulation for major depression：a prospective multicenter randomized controlled trial[J]. World Psychiatry，2015,14(1):64-73. DOI：10.1002/wps.20199.
[5]	ROTH Y, PELL G S, CHISTYAKOV A V，et al. Motor cortex activation by H-coil and figure-8 coil at different depths. Combined motor threshold and electric field distribution study[J]. Clin Neurophysiol，2014,125(2):336-343. DOI：10.1016/j.clinph.2013.07.013.
[6]	TENDLER A, BARNEA YGAEL N, ROTH Y，et al. Deep transcranial magnetic stimulation （dTMS） - beyond depression[J]. Expert Rev Med Devices，2016,13(10):987-1000. DOI：10.1080/17434440.2016.1233812.
[7]	CHEN W L, WAGNER J, HEUGEL N，et al. Functional near-infrared spectroscopy and its clinical application in the field of neuroscience：advances and future directions[J]. Front Neurosci，2020,14:724. DOI：10.3389/fnins.2020.00724.
[8]	MARTINI M, ARIAS N. Near-infrared light spectroscopy and stimulation in cognitive neuroscience：the need for an integrative view?[J]. J Integr Neurosci，2021,20(4):1105-1109. DOI：10.31083/j.jin2004111.
[9]	KASTER T S, DASKALAKIS Z J, NODA Y，et al. Efficacy，tolerability，and cognitive effects of deep transcranial magnetic stimulation for late-life depression：a prospective randomized controlled trial[J]. Neuropsychopharmacology，2018,43(11):2231-2238. DOI：10.1038/s41386-018-0121-x.
[10]	MATSUDA Y, KITO S, IGARASHI Y，et al. Efficacy and safety of deep transcranial magnetic stimulation in office workers with treatment-resistant depression：a randomized，double-blind，sham-controlled trial[J]. Neuropsychobiology，2020,79(3):208-213. DOI：10.1159/000505405.
[11]	周杰，李佳美，胡瑞康，等. 重复经颅磁刺激治疗抑郁症的神经生物机制研究进展[J]. 临床精神医学杂志，2020,30(1):64-66. DOI：10.3969/j.issn.1005-3220.2020.01.023.
[12]	LISTON C, CHEN A C, ZEBLEY B D，et al. Default mode network mechanisms of transcranial magnetic stimulation in depression[J]. Biol Psychiatry，2014,76(7):517-526. DOI：10.1016/j.biopsych.2014.01.023.
[13]	LAN M J, CHHETRY B T, LISTON C，et al. Transcranial magnetic stimulation of left dorsolateral prefrontal cortex induces brain morphological changes in regions associated with a treatment resistant major depressive episode：an exploratory analysis[J]. Brain Stimul，2016,9(4):577-583. DOI：10.1016/j.brs.2016.02.011.
[14]	LIMA-OJEDA J M, RUPPRECHT R, BAGHAI T C. Neurobiology of depression：a neurodevelopmental approach[J]. World J Biol Psychiatry，2018,19(5):349-359. DOI：10.1080/15622975.2017.1289240.
[15]	LEVKOVITZ Y, HAREL E V, ROTH Y，et al. Deep transcranial magnetic stimulation over the prefrontal cortex：evaluation of antidepressant and cognitive effects in depressive patients[J]. Brain Stimul，2009,2(4):188-200. DOI：10.1016/j.brs.2009.08.002.
[16]	BAHUN I, IVEZIC E, ĐOGAS V V，et al. A pilot study of accelerated deep transcranial magnetic stimulation effects on cognitive functioning in patients diagnosed with treatment resistant major depressive disorder[J]. Psychiatry Res，2022,316:114750. DOI：10.1016/j.psychres.2022.114750.
[17]	LASKOV O, KLÍROVÁ M. Effects of deep transcranial magnetic stimulation （dTMS） on cognition[J]. Neurosci Lett，2021,755:135906. DOI：10.1016/j.neulet.2021.135906.
[18]	OKADA G, OKAMOTO Y, YAMASHITA H，et al. Attenuated prefrontal activation during a verbal fluency task in remitted major depression[J]. Psychiatry Clin Neurosci，2009,63(3):423-425. DOI：10.1111/j.1440-1819.2009.01952.x.
[19]	TOMIOKA H, YAMAGATA B, KAWASAKI S，et al. A longitudinal functional neuroimaging study in medication-naïve depression after antidepressant treatment[J]. PLoS One，2015,10(3):e0120828. DOI：10.1371/journal.pone.0120828.
[20]	TAKAMIYA A, HIRANO J, EBUCHI Y，et al. High-dose antidepressants affect near-infrared spectroscopy signals：a retrospective study[J]. Neuroimage Clin，2017,14:648-655. DOI：10.1016/j.nicl.2017.02.008.
[21]	KENNEDY S H, KONARSKI J Z, SEGAL Z V，et al. Differences in brain glucose metabolism between responders to CBT and venlafaxine in a 16-week randomized controlled trial[J]. Am J Psychiatry，2007,164(5):778-788. DOI：10.1176/ajp.2007.164.5.778.

组别	例数	性别（男/女）	年龄[M（P₂₅，P₇₅），岁]	受教育年限[M（P₂₅，P₇₅），年]	病程[M（P₂₅，P₇₅），月]	发病年龄[M（P₂₅，P₇₅），岁]
药物对照组	30	9/21	20.5（18.0，24.5）	12.5（12.0，16.0）	19.0（2.8，33.0）	18.5（16.0，24.5）
联合治疗组	31	11/20	21.0（19.0，24.0）	14.0（12.0，16.0）	24.0（8.0，37.0）	19.0（17.0，22.0）
Z（χ²）值		0.208^a	-0.944	-0.588	-0.224	-0.615
P值		0.648	0.345	0.557	0.823	0.538

组别	例数	性别（男/女）	年龄[M（P₂₅，P₇₅），岁]	受教育年限[M（P₂₅，P₇₅），年]	病程[M（P₂₅，P₇₅），月]	发病年龄[M（P₂₅，P₇₅），岁]
药物对照组	30	9/21	20.5（18.0，24.5）	12.5（12.0，16.0）	19.0（2.8，33.0）	18.5（16.0，24.5）
联合治疗组	31	11/20	21.0（19.0，24.0）	14.0（12.0，16.0）	24.0（8.0，37.0）	19.0（17.0，22.0）
Z（χ²）值		0.208^a	-0.944	-0.588	-0.224	-0.615
P值		0.648	0.345	0.557	0.823	0.538

组别	例数	HAMD评分				BSS评分				MoCA评分
组别	例数	治疗前	治疗后	t_配对值	P值	治疗前	治疗后	t_配对值	P值	治疗前	治疗后	t_配对值	P值
药物对照组	30	27.5±3.7	19.5±4.8	15.360	<0.001	19.8±7.7	13.0±8.7	6.959	<0.001	23.8±1.6	26.6±1.8	-8.445	<0.001
联合治疗组	31	27.7±4.1	16.9±4.0	19.505	<0.001	18.7±7.7	7.4±7.4	8.430	<0.001	23.7±1.3	27.9±1.0	-18.432	<0.001
t值		0.177	-2.259			-0.553	-2.733			-0.417	3.698
P值		0.860	0.028			0.583	0.008			0.678	0.001

组别	例数	HAMD评分				BSS评分				MoCA评分
组别	例数	治疗前	治疗后	t_配对值	P值	治疗前	治疗后	t_配对值	P值	治疗前	治疗后	t_配对值	P值
药物对照组	30	27.5±3.7	19.5±4.8	15.360	<0.001	19.8±7.7	13.0±8.7	6.959	<0.001	23.8±1.6	26.6±1.8	-8.445	<0.001
联合治疗组	31	27.7±4.1	16.9±4.0	19.505	<0.001	18.7±7.7	7.4±7.4	8.430	<0.001	23.7±1.3	27.9±1.0	-18.432	<0.001
t值		0.177	-2.259			-0.553	-2.733			-0.417	3.698
P值		0.860	0.028			0.583	0.008			0.678	0.001

组别	例数	HAMD评分变化值	BSS评分变化值	MoCA评分变化值
药物对照组	30	8.0±2.9	6.8±5.4	2.8±1.8
联合治疗组	31	10.7±3.1	11.4±7.5	4.3±1.3
t值		3.576	2.737	3.811
P值		0.001	0.008	<0.001