Comparison of anticraving efficacy of right and left repetitive transcranial magnetic stimulation in alcohol dependence: a randomized double-blind study
Open accessAbstract
The objective of this study was to compare the anticraving efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the right versus left dorsolateral prefrontal cortex (DLPFC) in patients with alcohol dependence. Twenty patients with alcohol dependence syndrome were randomly allocated to receive either right or left rTMS over the right DLPFC (10 sessions at 10 Hz frequency; 20 trains per session; 4.9 seconds per train and intertrain interval 30 seconds) and were assessed on the Alcohol Craving Questionnaire (ACQ-NOW) to measure craving. Two-way repeated-measures analysis of variance for ACQ-NOW total score showed no main effect of group (F[1,18] = 0.0001 but significant main effect of time (F[1,18] = 185.91, p<0.0001, η(2) = 0.912). The interaction effect between group and time was not significant. There was significant reduction in craving scores in patients receiving either right or left rTMS with large effect size. However, there was no difference in anticraving efficacy between the two groups.
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The prefrontal cortical network, including DLPFC and OFC, supports inhibitory control, which is often impaired in SUD patients.
“these regions include the prefrontal cortical network including the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex [11,12] which have important functions in inhibitory control, a neurobehavioral output often impaired in patients with SUDs.”
TMS applications to investigate and modulate SUD-related networks have grown exponentially across alcohol, cocaine, methamphetamine, opioid, cannabis, and tobacco use disorders.
“there has been an exponential growth in the application of TMS to investigate and modulate these networks in populations with SUDs including alcohol, cocaine, methamphetamine, opioid, cannabis, and tobacco use disorder [11,12,25–29].”
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“There are presently no studies in the behavioral or substance addiction literature that have directly evaluated the combined effects of NIBS and pharmacotherapy, although several trials have enrolled patients with AD receiving pharmacological treatment (Klauss et al., 2014; Mishra et al., 2015; Del Felice et al., 2016…”
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“The main brain circuitry target for rTMS in the treatment of substance use disorders (SUD) is the prefrontal cortical network, specifically the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (Gorelick et al., 2014; Mishra et al., 2015).”
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“[258,259]”
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“in another study reported reduction in craving scores in patients receiving rTMS to either right or left DLPFC and reported no significant differences in between the groups.[5]”
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Repetitive transcranial magnetic stimulation: Re-wiring the alcoholic human brain
Diana, M., Bolloni, C., Antonelli, M., Giuda, D. D., Cocciolillo, F., Fattore, L., & Addolorato, G. (2018) · Alcohol · doi:10.1016/j.alcohol.2018.05.011 · Cited by 16 · see citing works
Spagnolo, P. A., Pérez, L. J. G., Terraneo, A., Gallimberti, L., & Bonci, A. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.14313 · Cited by 16 · see citing works
Tang, Z., Zhu, Z. A., & Xu, J. (2022) · Biological Research For Nursing · doi:10.1177/10998004221122522 · Cited by 15 · see citing works
“…same time, rTMS not only improves appetite in people with MA dependence, but also improves dependence on other substances such as cocaine (Camprodon et al., 2007; Politi et al., 2008; Terraneo et al., 2016), alcohol (Mishra et al., 2015) and nicotine (Amiaz et al., 2009; Dinur-Klein et al., 2014).”
BackgroundHu, X., Zhang, T., Ma, H., Zhou, X., Wang, H., Wang, X., Cheng, C., Li, Y., Duan, R., Zhang, B., et al. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.935491 · Cited by 15 · see citing works
Advances in neuroimaging studies of alcohol use disorder (AUD)
Xie, J.-Y., Li, R., Yuan, W., Du, J., Zhou, D., Cheng, Y., Xu, X.-M., Liu, H., & Yuan, T. (2022) · Psychoradiology · doi:10.1093/psyrad/kkac018 · Cited by 15 · see citing works
Tang, V. M., Foll, B. L., Blumberger, D. M., & Voineskos, D. (2021) · Brain Sciences · doi:10.3390/brainsci12010048 · Cited by 15 · see citing works
“MDD AUD rTMS Site/Frequency HF Left DLPFC [15,30,40] LF Right DLPFC [15,30,40] HF Bilateral PFC 1 [15,30,40] HF Right DLPFC [51,56,57] HF Bilateral PFC [62–65,70] rTMS Coil Figure-of-8 [15,30,40]Deep TMS [15,30,40] Figure-of-8 [51,56,57,61] Deep TMS [62–65,70] Adequate No. of Sessions 20–30 [15,30,40] ≥15 [56,63,64] T…”
BackgroundMethodInfluentialCerebral Hemodynamics With rTMS in Alcohol Dependence: A Randomized, Sham-Controlled Study
Mishra, B. R., Maiti, R., & Nizamie, S. H. (2016) · Journal of Neuropsychiatry · doi:10.1176/appi.neuropsych.15110381 · Cited by 14 · see citing works
Self-citationBrunelin, J., & Fecteau, S. (2014) · Brain stimulation · doi:10.1016/j.brs.2014.11.021 · Cited by 14 · see citing works
“Targeting to the other hemisphere, the right DLPFC, with rTMS can also alleviate symptoms in depression [32], substance use disorders [33], posttraumatic stress disorders [4], and panic disorders [34].”
BackgroundNoninvasive brain stimulation of addiction: one target for all?
Liu, Q., & Yuan, T. (2021) · Psychoradiology · doi:10.1093/psyrad/kkab016 · Cited by 13 · see citing works
“…for example, one study observed that only the right DLPFC stimulation reduced the cocaine craving (Camprodon et al. , 2007), and the craving score reduced significantly in patients receiving stimulation to either the right or the left side rTMS (Liu et al. , 2017; Mishra, Praharaj et al. , 2015).”
Brain Stimulation in Alcohol Use Disorders: Investigational and Therapeutic Tools
Loheswaran, G., Barr, M. S., Rajji, T. K., Zomorrodi, R., Foll, B. L., & Daskalakis, Z. J. (2015) · Biological Psychiatry Cognitive Neuroscience and Neuroimaging · doi:10.1016/j.bpsc.2015.09.005 · Cited by 13 · see citing works
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“[24] ADS A (Right vs Left) 10 - HF (10 Hz) RDLPFC 10 - HF (10 Hz) LDLPFC Pathak et al .”
Rewiring the Addicted Brain: Circuits-Based Treatment for Addiction.Preprint
Madeo, G., & Bonci, A. (2019) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2018.83.038158 · Cited by 10 · see citing works
“One study reported a reduction in craving following multiple sessions of rTMS (Mishra et al. 2015), whereas no anticraving effects were reported by another study (Herremans et al. 2015).”
ResultNardone, R., Sebastianelli, L., Versace, V., Ferrazzoli, D., Brigo, F., Schwenker, K., Saltuari, L., & Trinka, E. (2022) · Psychiatry Research · doi:10.1016/j.psychres.2022.114431 · Cited by 7 · see citing works
Wu, X.-Q., Ju, Y., Jiao, D., & Zhao, M. (2018) · Europe PMC (PubMed Central) · doi:10.11919/j.issn.1002-0829.218007 · Cited by 7 · see citing works
“And Mishra and colleagues found that rTMS (10 Hz) stimulating the right DLPFC reduced the craving for alcohol.([12]) Meanwhile, using rTMS (20 Hz) to stimulate the frontal cortex of morphine withdrawn rats increased the release of dopamine in the nucleus accumbens.”
MethodWalker, N. C., Philip, N. S., Kozel, F. A., Yesavage, J. A., & Madore, M. R. (2023) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2023.10.010 · Cited by 7 · see citing works
Soleimani, G., Souki, A., Honari, S., Baker, T. E., Brunoni, A. R., Ebrahimi, M., Garza‐Villarreal, E. A., George, T. P., Goldstein, R. Z., Jha, M. K., et al. (2025) · medRxiv · doi:10.1101/2025.09.21.25335559 · Cited by 4 · see citing works
Repetitive Transcranial Magnetic Stimulation for Wernicke-Korsakoff Syndrome: A Case Report
Chung, S. W., Park, S. W., Seo, Y. J., Kim, J. H., Lee, C. H., & Lim, J. Y. (2017) · Annals of Rehabilitation Medicine · doi:10.5535/arm.2017.41.1.162 · Cited by 3 · see citing works
“However, in a recent study comparing the anti-craving efficacy of rTMS over the right to the left DLPFC showed no significant difference and rTMS over the left DLPFC showed efficacy in severe cases of alcohol dependence compared to the right side [9].”
BackgroundMethodInfluentialMichel, A., Kang, D., Fillingim, R. B., Balderston, N. L., Bond, D. S., & Steele, V. R. (2025) · Current Addiction Reports · doi:10.1007/s40429-025-00620-3 · Cited by 2 · see citing works
Modulation of Alcohol Use Disorder by Brain Stimulation
Barnea‐Ygael, N., & Zangen, A. (2024) · Current topics in behavioral neurosciences · doi:10.1007/7854_2024_487 · Cited by 2 · see citing works
Biswas, T., Singh, G., Mishra, P., Mishra, B. R., & Parmar, A. (2024) · Indian Journal of Psychological Medicine · doi:10.1177/02537176241300195 · Cited by 2 · see citing works
Self-citationMahoney, J. J., Bryant, K. R., & Haut, M. W. (2019) · Springer eBooks · doi:10.1007/978-3-030-14895-9_32 · Cited by 2 · see citing works
Rak, M., Danek, M., & Dróżdż, W. (2023) · Current Problems of Psychiatry · doi:10.12923/2353-8627/2023-0019 · Cited by 1 · see citing works
“Kilka lat później, w 2015 roku, Mishra i wsp.[18] wykazali, że stymulacja po stronie lewej (przy zastosowaniu tego samego protokołu) miała porównywalną skuteczność, co po stronie prawej.”
BackgroundInfluentialYadav, T., Lokuge, B., Jackson, M. A., Austin, E. K., Fitzgerald, P. B., Brown, A. L., Paton, B. K., Sequeira, M. C., Nean, M., Mills, L., et al. (2024) · Pilot and Feasibility Studies · doi:10.1186/s40814-024-01498-0 · Cited by 1 · see citing works
“These regions include the pre-frontal cortical network including the dorsolateral pre-frontal cortex (DLPFC) and the orbitofrontal cortex (OFC) which have important functions in inhibitory control, a neurobehavioral output often impaired in patients with SUDs [13, 14].”
BackgroundTang, V. M., & Blumberger, D. M. (2024) · Expert Review of Medical Devices · doi:10.1080/17434440.2024.2404962 · Cited by 1 · see citing works
“One small study found that both left and right high frequency stimulation was effective for AUD [99].”
Fehring, D. J., Morrison-Ham, J., Cobden, A. L., Mahlberg, J., Gao, M., Kelly, C. E., Sangchooli, A., Stoliker, D., Giddens, E., Quinn, B., et al. (2025) · Contemporary Clinical Trials Communications · doi:10.1016/j.conctc.2025.101515 · Cited by 1 · see citing works
Li, G., Cao, Y. N., & Zhong, J. N. (2025) · ALPHA PSYCHIATRY · doi:10.31083/ap49374 · Cited by 1 · see citing works
“While the right DLPFC has been frequently targeted with promising results [10], some studies have explored the efficacy of left-sided or bilateral stimulation [41,52].”
Dhungana, A., McCalley, D. M., Heath, A. M., Kraybill, E. P., Mojabi, F. S., Morales, J. M., Morningstar, A. R., Davis, A., Padula, C. B., Giardino, W. J., et al. (2025) · Transcranial magnetic stimulation . · doi:10.1016/j.transm.2025.100098 · Cited by 1 · see citing works
“However, a number of reports have demonstrated little to no change in alcohol drinking following rTMS (Hoppner et al., 2011; Herremans et al., 2015; Mishra et al., 2015, 2010).”
InfluentialTranscranial Direct Current Stimulation-Psychiatric Application and Its Current Status
Pyungkyu, K., & Kim, D. (2017) · Saengmul jeongsin euihag/Saengmul jeongsin uihak · doi:10.22857/kjbp.2017.24.4.002 · Cited by 1 · see citing works
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Substanzgebundene Abhängigkeitserkrankungen und bulimische Essstörungen
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Trans-cranial Magnetic Stimulation in Treatment of Alcohol Use Disorder: A Meta-analysis
Kaleem, M. I., & Bokhari, S. M. A. (2022) · Exploratory Research and Hypothesis in Medicine · doi:10.14218/erhm.2022.00096
Brain Stimulation Methods for Substance Use Disorders
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Transcranial Magnetic Stimulation in Addiction Therapies
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The Future of Alcohol Use Disorder Treatment and Research
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Role of Non-Invasive Brain Stimulation in Alcohol Use Disorder: A Systematic Review
Kumar, A., Mishra, S., Singh, Y. C., Eashwar, S., Kumar, N., & Shukla, R. (2025) · Current Behavioral Neuroscience Reports · doi:10.1007/s40473-025-00302-4
“In another Indian study, Mishra et al. 2015 [35] compared the effect of HF-rTMS over right and left DLPFC by randomly allocating 20 patients to receive either right or left DLPFC (10 Hz; 20 trains per session; 4.9 s per train and intertrain interval of 30 s) and were assessed on the Alcohol Craving…”
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“Furthermore, the same rTMS protocol to the left or right DLPFC significantly ( P .05) reduced alcohol craving for people with AUD alone, with no effect size differences between sites [41].”
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“Application of TMS to the DLPFC has been shown to reduce alcohol craving [46, 47], alcohol consumption [1, 5], and self-reported obsessive compulsive drinking scale (OCDS) scores [5, 24, 52].”
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- Authors
- Mishra, B. R., Praharaj, S. K., Katshu, M. Z. U. H., Sarkar, S., & Nizamie, S. H.
- Affiliations
- Mahatma Gandhi Medical College and Research Institute (IN)
- Venue
- The Journal of Neuropsychiatry and Clinical Neurosciences
- Published
- 2015-01
- Volume
- 27
- Issue
- 1
- Pages
- e54-e59
- ISSN
- 0895-0172 (ISSN-L)
- 1545-7222
- OpenAlex
- W2154108980
- Cited by
- 89
- References
- 32
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 7 · 2023: 7 · 2022: 7 · 2021: 11 · 2020: 8 · 2019: 7 · 2018: 9 · 2017: 5 · 2016: 6 · 2015: 5 · 2014: 2
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by
- Locations
- Journal of Neuropsychiatry (publishedVersion)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Repository@Nottingham (University of Nottingham) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Keywords
- alcoholism, repetitive transcranial magnetic stimulation, dorsolateral prefrontal cortex, alcohol craving, craving reduction, high-frequency rTMS, hemispheric lateralization
- MeSH terms
- Adult, Alcoholism, Analysis of Variance, Double-Blind Method, Electroencephalography, Female, Humans, Functional Laterality, Male, Middle Aged, Psychiatric Status Rating Scales, Surveys and Questionnaires, Retrospective Studies, Prefrontal Cortex, Evoked Potentials, Motor, Transcranial Magnetic Stimulation, Craving
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