A randomized controlled study on the effect of intermittent theta burst stimulation on craving, mood, and cognitive function in alcohol-dependent patients during the withdrawal period

doi:10.3969/j.issn.1674-8115.2025.03.012

Abstract

Abstract:

Objective ·To explore the effect of intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex (DLPFC) on reducing craving in alcohol-dependent patients during the withdrawal period, as well as its impact on patients' emotions and cognitive functions. Methods ·A total of 41 inpatients with alcohol dependence in the withdrawal period were recruited from the Addiction Department of Mental Health Center, Shanghai Jiao Tong University School of Medicine, and randomly assigned to the experimental group (20 patients) and the control group (21 patients). Both groups received routine inpatient treatment for alcohol-dependence. The experimental group received real iTBS stimulation targeting the left DLPFC on the basis of routine inpatient treatment, while the control group received sham stimulation with the same parameters. The intervention course lasted for 2 weeks, with a total of 10 sessions. The Visual Analogue Scale (VAS), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were used to measure the craving, anxiety, and depression of the patients before and after the intervention. The behavioral tasks of the detection task (DET), identification task (IDN), two back task (TWOB), the Groton maze learning task (GML), and international shopping list task (ISL) in the CogState software package were used to assess the cognitive processing speed, attention/vigilance, working memory, spatial problem-solving/error monitoring ability, and verbal learning and memory of the patients before and after the intervention. Results ·Repeated measures ANOVA showed that the time effect [F=126.713, P<0.001, partial η² (η_p²)=0.765] and interaction effect (F=7.080, P=0.011, η_p²=0.154) of the VAS scores in the two groups of patients were statistically significant. The time effect (F=9.114, P=0.004, η_p²=0.189), group effect (F=5.557, P=0.024, η_p²=0.125), and interaction effect (F=4.977, P=0.032, η_p²=0.113) of the TWOB score were all statistically significant. Only the time effects of BDI (F=45.273, P<0.001, η_p²=0.578), BAI (F=31.432, P<0.001, η_p²=0.473), GML (F=8.993, P=0.005, η_p²=0.209), and ISL (F=26.657, P<0.001, η_p²=0.439) scores were statistically significant. There were no statistically significant effects of time, group, or interaction on the DET and IDN scores. Simple effect analysis showed that the VAS score of the real stimulation group was lower than that of the sham stimulation group after the intervention (F=8.805, P=0.005, η_p²=0.184), and the TWOB score of the real stimulation group was higher than that of the sham stimulation group (F=11.293, P=0.002, η_p²=0.225). Conclusion ·Combining iTBS with routine inpatient treatment can enhance the efficacy of reducing alcohol craving in alcohol-dependent patients during the withdrawal period, and improve their working memory.

Key words: repetitive transcranial magnetic stimulation (rTMS), intermittent theta burst stimulation (iTBS), alcohol dependence, craving, cognitive function

CLC Number:

R749

WANG Haihong, YUAN Chenxin, GAN Hong, JIANG Haifeng, ZHAO Yan, DU Jiang, ZHANG Yi. A randomized controlled study on the effect of intermittent theta burst stimulation on craving, mood, and cognitive function in alcohol-dependent patients during the withdrawal period[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(3): 349-356.

Figures/Tables 2

TrendMD

References 28

1	FELTENSTEIN M W, SEE R E. The neurocircuitry of addiction: an overview[J]. Br J Pharmacol, 2008, 154(2): 261-274.
2	SHIELD K D, REHM J. Alcohol and the global burden of disease[J]. Lancet, 2019, 393(10189): 2390.
3	Word Health Organization. Global status report on alcohol and health 2018[R]. Geneva: WHO, 2018.
4	NUTT D, HAYES A, FONVILLE L, et al. Alcohol and the brain[J]. Nutrients, 2021, 13(11): 3938.
5	PETIT G, LUMINET O, DE SOUSA UVA M C, et al. Gender differences in affects and craving in alcohol-dependence: a study during alcohol detoxification[J]. Alcohol Clin Exp Res, 2017, 41(2): 421-431.
6	GREELEY J D, SWIFT W, PRESCOTT J, et al. Reactivity to alcohol-related cues in heavy and light drinkers[J]. J Stud Alcohol, 1993, 54(3): 359-368.
7	MYRICK H, ANTON R F, LI X B, et al. Differential brain activity in alcoholics and social drinkers to alcohol cues: relationship to craving[J]. Neuropsychopharmacology, 2004, 29(2): 393-402.
8	THORBERG F A, YOUNG R M, HASKING P, et al. Alexithymia and alcohol dependence: the roles of negative mood and alcohol craving[J]. Subst Use Misuse, 2019, 54(14): 2380-2386.
9	PAULINO S, POMBO S, ISMAIL F, et al. The role of affective temperament as a predictor of relapse in alcohol dependence[J]. Pers Ment Health, 2017, 11(4): 278-289.
10	SUZUKI S, MELL M M, O'MALLEY S S, et al. Regulation of craving and negative emotion in alcohol use disorder[J]. Biol Psychiatry Cogn Neurosci Neuroimaging, 2020, 5(2): 239-250.
11	CZAPLA M, SIMON J J, RICHTER B, et al. The impact of cognitive impairment and impulsivity on relapse of alcohol-dependent patients: implications for psychotherapeutic treatment[J]. Addict Biol, 2016, 21(4): 873-884.
12	MATSUSHITA S. Pharmacological treatment for alcohol dependence[J]. Brain Nerve, 2023, 75(5): 613-622.
13	MAKANI R, PRADHAN B, SHAH U, et al. Role of repetitive transcranial magnetic stimulation (rTMS) in treatment of addiction and related disorders: a systematic review[J]. Curr Drug Abuse Rev, 2017, 10(1): 31-43.
14	BENADHIRA R, THOMAS F, BOUAZIZ N, et al. A randomized, sham-controlled study of maintenance rTMS for treatment-resistant depression (TRD)[J]. Psychiatry Res, 2017, 258: 226-233.
15	RACHID F. Maintenance repetitive transcranial magnetic stimulation (rTMS) for relapse prevention in with depression: a review[J]. Psychiatry Res, 2018, 262: 363-372.
16	张淑婷, 沈悦娣, 刘兆宇. 重复经颅磁刺激对抑郁症病人认知功能影响的研究进展[J]. 护理研究, 2023, 37(21): 3886-3889.
	ZHANG S T, SHEN Y D, LIU Z Y. Research progress on effects of repetitive transcranial magnetic stimulation on cognitive function in patients with depression[J]. Chinese Nursing Research, 2023, 37(21): 3886-3889.
17	ZHANG Y, KU Y X, SUN J F, et al. Intermittent theta burst stimulation to the left dorsolateral prefrontal cortex improves working memory of subjects with methamphetamine use disorder[J]. Psychol Med, 2023, 53(6): 2427-2436.
18	ZHAO D, LI Y Q, LIU T, et al. Twice-daily theta burst stimulation of the dorsolateral prefrontal cortex reduces methamphetamine craving: a pilot study[J]. Front Neurosci, 2020, 14: 208.
19	钟娜, 赵敏. 计算机化认知测试CogState量表及其适用性[J]. 心理学通讯, 2019, 2(1): 67-70.
	ZHONG N, ZHAO M. The CogState computerized cognitive battery and its usability[J]. Psychological Communications, 2019, 2(1): 67-70.
20	MIKELLIDES G, MICHAEL P, PSALTA L, et al. Accelerated intermittent theta burst stimulation in smoking cessation: no differences between active and placebo stimulation when using advanced placebo coil technology. A double-blind follow-up study[J]. Int J Clin Health Psychol, 2023, 23(2): 100351.
21	STEELE V R, MAXWELL A M, ROSS T J, et al. Accelerated intermittent theta-burst stimulation as a treatment for cocaine use disorder: a proof-of-concept study[J]. Front Neurosci, 2019, 13: 1147.
22	HERREMANS S C, BAEKEN C, VANDERBRUGGEN N, et al. No influence of one right-sided prefrontal HF-rTMS session on alcohol craving in recently detoxified alcohol-dependent patients: results of a naturalistic study[J]. Drug Alcohol Depend, 2012, 120(1-3): 209-213.
23	闫美丽. 重复经颅磁刺激联合抗抑郁药物治疗伴焦虑痛苦症状抑郁症患者的疗效和安全性[J]. 湖北科技学院学报(医学版), 2023, 37(4): 332-334.
	YAN M L. Efficacy and safety of repeated transcranial magnetic stimulation combined with antidepressants in the treatment of depressed patients with anxiety-distressing symptoms[J]. Journal of Hubei University of Science and Technology (Medical Sciences), 2023, 37(4): 332-334.
24	ALVAREZ J A, EMORY E. Executive function and the frontal lobes: a meta-analytic review[J]. Neuropsychol Rev, 2006, 16(1): 17-42.
25	LE BERRE A P, FAMA R, SULLIVAN E V. Executive functions, memory, and social cognitive deficits and recovery in chronic alcoholism: a critical review to inform future research[J]. Alcohol Clin Exp Res, 2017, 41(8): 1432-1443.
26	FENG Z X, WU Q, WU L, et al. Effect of high-frequency repetitive transcranial magnetic stimulation on visual selective attention in male patients with alcohol use disorder after the acute withdrawal[J]. Front Psychiatry, 2022, 13: 869014.
27	DEL FELICE A, BELLAMOLI E, FORMAGGIO E, et al. Neurophysiological, psychological and behavioural correlates of rTMS treatment in alcohol dependence[J]. Drug Alcohol Depend, 2016, 158: 147-153.
28	SCHLUTER R S, VAN HOLST R J, GOUDRIAAN A E. Effects of ten sessions of high frequency repetitive transcranial magnetic stimulation (HF-rTMS) add-on treatment on impulsivity in alcohol use disorder[J]. Front Neurosci, 2019, 13: 1257.

Indicator	iTBS group (n=20)	Sham group (n=21)	χ²/t value	P value
Gender/n (%)			0.257	0.612
Male	16 (80.0)	19 (90.5)
Female	4 (20.0)	2 (9.5)
Age/year	38.15±8.88	38.71±6.73	0.230	0.819
Education/year	13.05±2.72	13.00±3.07	-0.055	0.956
Marital status/n (%)
Married	16 (80.0)	14 (66.7)
Unmarried	2 (10.0)	4 (19.0)	0.976	0.614
Divorced	2 (10.0)	3 (14.3)
Employment status/n (%)			0.197	0.657
Employed	13 (65.0)	16 (76.2)
Unemployed	7 (35.0)	5 (23.8)
Retired	0 (0)	0 (0)
Age of drinking for the first time/year	25.15±7.07	21.86±3.94	-1.829	0.078
Drinking/year	13.33±11.05	17.76±7.50	1.512	0.139
Alcohol consumption/standard unit	16.03±6.25	14.82±7.85	-0.542	0.591
CIWA-Ar/point	4.55±1.85	4.33±1.62	-0.399	0.692

Indicator	iTBS group (n=20)	Sham group (n=21)	χ²/t value	P value
Gender/n (%)			0.257	0.612
Male	16 (80.0)	19 (90.5)
Female	4 (20.0)	2 (9.5)
Age/year	38.15±8.88	38.71±6.73	0.230	0.819
Education/year	13.05±2.72	13.00±3.07	-0.055	0.956
Marital status/n (%)
Married	16 (80.0)	14 (66.7)
Unmarried	2 (10.0)	4 (19.0)	0.976	0.614
Divorced	2 (10.0)	3 (14.3)
Employment status/n (%)			0.197	0.657
Employed	13 (65.0)	16 (76.2)
Unemployed	7 (35.0)	5 (23.8)
Retired	0 (0)	0 (0)
Age of drinking for the first time/year	25.15±7.07	21.86±3.94	-1.829	0.078
Drinking/year	13.33±11.05	17.76±7.50	1.512	0.139
Alcohol consumption/standard unit	16.03±6.25	14.82±7.85	-0.542	0.591
CIWA-Ar/point	4.55±1.85	4.33±1.62	-0.399	0.692

Indicate	Time effect			Group effect			Time×Group interaction effect
Indicate	F	P	η²_p	F	P	η²_p	F	P	η²_p
VAS	126.713	<0.001	0.765	0.168	0.684	0.004	7.080	0.011	0.154
BDI	45.273	<0.001	0.578	0.261	0.613	0.008	2.059	0.161	0.059
BAI	31.432	<0.001	0.473	0.224	0.639	0.006	3.585	0.067	0.093
DET	1.089	0.305	0.033	0.131	0.720	0.004	1.351	0.254	0.041
IDN	0.907	0.348	0.028	0.638	0.430	0.020	0.454	0.505	0.014
TWOB	9.114	0.004	0.189	5.557	0.024	0.125	4.977	0.032	0.113
GML	8.993	0.005	0.209	0.007	0.932	<0.001	0.009	0.925	<0.001
ISL	26.657	<0.001	0.439	1.216	0.278	0.035	0.106	0.746	0.003

Indicate	Time effect			Group effect			Time×Group interaction effect
Indicate	F	P	η²_p	F	P	η²_p	F	P	η²_p
VAS	126.713	<0.001	0.765	0.168	0.684	0.004	7.080	0.011	0.154
BDI	45.273	<0.001	0.578	0.261	0.613	0.008	2.059	0.161	0.059
BAI	31.432	<0.001	0.473	0.224	0.639	0.006	3.585	0.067	0.093
DET	1.089	0.305	0.033	0.131	0.720	0.004	1.351	0.254	0.041
IDN	0.907	0.348	0.028	0.638	0.430	0.020	0.454	0.505	0.014
TWOB	9.114	0.004	0.189	5.557	0.024	0.125	4.977	0.032	0.113
GML	8.993	0.005	0.209	0.007	0.932	<0.001	0.009	0.925	<0.001
ISL	26.657	<0.001	0.439	1.216	0.278	0.035	0.106	0.746	0.003

[1]	HAN Rui, WU Qian, LIU Dan, CHENG Di, ZHANG Ying, NI Jiacheng, KANG Piao, CHEN Anran, YU Shujie, FANG Qichen, LI Huating. Alteration of cognitive function in overweight and obese adolescents and its relationship with serum FGF21 levels [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(1): 87-97.
[2]	SI Yuqi, LUO Ruyan, CHEN Tianzhen, WANG Lihui, ZHONG Na, JIANG Haifeng, ZHAO Min. Behavioral and eye movement study of attention bias to alcohol-related cues in male alcohol-dependent patients and correlation analysis of psychological factors [J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(6): 738-746.
[3]	Ruping LU, Hui GAO, Linna JIANG, Xiaoya CHEN, Hong PENG, Hui SHEN, Qing FAN. Effect of psychomotor therapy on negative symptoms and cognitive function of patients with stable schizophrenia [J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2022, 42(1): 77-81.
[4]	Yi WANG, Cheng CHENG, Hong-yan SHEN, Hong-yan GAO, Yue-ning DAI, Zheng-hui YI. Meta-analysis of efficacy of transcranial magnetic stimulation for the treatment of cognitive function and behavioral and psychological symptoms of dementia in patients with Alzheimer′s disease [J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(7): 931-941.
[5]	Guo-qin HU, Cheng-qing YANG, Qin-yu LÜ, Jing ZHAO, Ming-huan ZHU, Zheng-hui YI, Xin-hai DAI. Effects of computerized cognitive correction therapy on cognitive function of schizophrenia [J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(5): 622-627.
[6]	Wen-jun HUANG, Su-su JIANG, Min-fang TAO. Correlation between sleep quality and everyday cognitive function in perimenopausal and postmenopausal women [J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(4): 497-501.
[7]	Lin-jie SHEN, Yu-xin HUANG, Yong WANG, Hua JIN. Review of non-invasive brain stimulation for the treatment of somatic symptoms in major depressive disorder [J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2021, 41(11): 1535-1539.
[8]	ZHOU Shao-yu1, FENG Zhen-xiao1, YAO Xiao-ping2, WANG Wan1, ZHAO Jing3#, YI Zheng-hui4#. Effects of typical or atypical antipsychotics on cognitive symptoms of the patients with schizophrenia [J]. JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE), 2020, 40(8): 1075-1080.
[9]	HONG Bo, HE Hai-ning, LIU Yuan-yuan, SU Ning, YAN Feng, SHI Yan-chen, WANG Jing-hua, WANG Tao, XIAO Shi-fu. One year follow-up study of sleep duration and cognitive function changes in the elderly with normal cognitive function [J]. , 2019, 39(9): 1017-.
[10]	WANG Dan-dan, ZHANG Chen. Research progress of neuroimmune mechanisms of cognitive function in schizophrenia and effect of atypical antipsychotic drugs on it [J]. , 2019, 39(7): 795-.
[11]	XU Xiao-min, CHEN Tian-zhen, JIANG Hai-feng. Modulating neural circuits in substance addiction with repetitive transcranial magnetic stimulation [J]. , 2019, 39(6): 655-.
[12]	ZHU Jun-juan,ZHANG Tian-hong,ZHANG Ling,XU Li-hua,WEI Yan-yan,TANG Ying-ying,WANG Ji-jun. Effect of accelerated repetitive transcranial magnetic stimulation on suicide ideation in depressive patients [J]. , 2019, 39(5): 534-.
[13]	ZHU Li-na1, ZHANG Qiong2, CAI Jun1, ZHANG Wei-bo1, ZHU Hong-xia1. Effect of cerebellar vermal repetitive transcranial magnetic stimulation with theta burst stimulation paradigm on cognitive functions of patients with schizophrenia [J]. , 2019, 39(3): 282-.
[14]	LI Pu-yu, WANG Zhen. Application of repetitive transcranial magnetic stimulation in the treatment of obsessive-compulsive disorder [J]. , 2019, 39(12): 1477-.
[15]	Lü Wang-qiang, TANG Wei, CAI Jun, LU Wei-hong, YU Yue-guo, FAN Wei-xing, ZHANG Chen. Study on the effects of ANK3 gene on the development of cognitive impairment in patients with schizophrenia [J]. , 2016, 36(9): 1297-.