Table 2.

Studies using rTMS as a tool to change alcohol consumption.

Study	Subjects	Study Design	Site and protocol of stimulation	Outcome measures	Results
Mishra et al., 2010	45 patients	Single blind, sham controlled study.	10 Hz, total 10 sessions over the right DLPFC.	Alcohol craving questionnaire.	Significant reduction in craving in the active group compared to sham. Moderate effect size.
De Ridder et al., 2011	1 patient with severe untractable craving.		1–35 Hz stimulations over 3 months targeting the dACC using a double coil.	EEG beta activity and functional connectivity (BOLD activity).	Craving was associated with EEG beta activity and connectivity between dACC and PCC that disappeared after successful rTMS. Cue-induced worsening of craving promoted activation ofACC,vmPFC,PCC, nucleus accumbens that disappeared on fMRI following successful rTMS. Relapseassociated with recurrence of ACC and PCC EEG activity in gamma band.
Höppner et al., 2011	19 female detoxified patients.	Blind sham controlled study.	10 sessions of HF (20 Hz) rTMS applied to the left DLPFC.	Obsessive Compulsive Drinking scale.	No significant differences between sham and active group.
Herremans et al., 2013	29 detoxified patients.	Single blind sham-controlled crossover study.	1 session of HF (20 Hz) rTMS applied to the right DLPFC.	Commission errors, mean reaction times, intra-individual reaction time variability during a Go-NoGo task. Obsessive Compulsive Drinking Scale.	Only the active stimulation reduced the intra individual reaction time variablity, suggesting that even one session stabilizes cognitive performance. No effects of stimulation on craving.
Ceccanti et al., 2015	18 patients	Randomized double blind sham controlled pilot study.	10 sessions of 20 Hz dTMS (H coil) applied to the mPFC.	Cortisolemia Prolactinemia. Craving visual analogic scale.	dTMS significantly reduced cortisolemia and prolactinemia suggesting a rebalancing of the dopamine-cortisol equilibrium during alcohol withdrawal. Craving decreased in treated patients, as well as mean number of drinks/per day.
Herremans et al., 2015	26 detoxified patients.	Open label study.	15 sessions of F rTMS applied to the right DLPFC HF-rTMS over 4 days.	Ten-point Likert scales (for cue-induced craving). Alcohol Urge Questionnaire the Obsessive Compulsive Drinking Scale (for general craving).	General craving significantly decreased after the 15 sessions. Cue-induced alcohol craving was not altered. The craving neurocircuit was not directly affected during an alcohol related exposure, but instead the attentional network was influenced.
Mishra et al., 2015	20 detoxified male patients	Single-blind, parallel-group, active-comparator rTMS study.	10 sessions of 10 Hz rTMS over either right or left DLPFC.	Alcohol Craving Questionnaire (ACQ-NOW).	Significant reduction in craving scores in patients receiving either right or left rTMS with large effect size. No difference in anticraving efficacy between the two groups.
Herremans et al., 2016	19 detoxified patients.	Open label study.	14 sessions of HF (20 Hz) rTMS applied to the right DLPFC spread over 3 days. Before and after stimulation, patients were confronted with a block and event related alcoholic cue exposure paradigm.	Relapse (consumption of any amount of alcohol within 4 weeks after the stimulation) functional connectivity (BOLD activation).	Abstainers (6) compared to patients who had relapsed (16) had higher dACC activation at baseline, but only during blocked cue-exposure paradigm suggesting higher baseline dACC as a protective factor for relpase. The lower the baseline dACC activation, the more dACC activity was increased after HF-rTMS treatment dACC (Rate dependent change in ACC).
Addolorato et al., 2017	11 male patients	Double blind sham controlled study.	12 dTMS sessions 10 Hz over bilateral DLPFC.	Dopamine transporter (DAT) availability by Single Photon Emission Computed Tomography (SPECT) in the striatum. Obsessive Compulsive Drinking Scale (OCDS).	After 1 month of rTMS sessions, striatal DAT availability decreased in the REAL group, being no longer different from HC, whereas it remained unchanged in SHAM patients a reduction of alcohol intake and an increase of the number of abstinence days was found only in the REAL rTMS. In particular alcohol craving decreased in both REAL and SHAM patients, although changes did not reach statistical significance.
Hanlon et al., 2017	24 patients	Single blind sham controlled crossover study.	1 session of real or sham cTBS over the left frontal pole.	Evoked BOLD signal.	Real cTBS significantly decreased evoked BOLD signal in OFC, insula, and lateral sensorimotor cortex.