Hypothesis: High-frequency rTMS can significantly reduce craving for food in patients with BED just after the stimulation and also over the one month observation period.

Method: The study was designed as a randomized double blind and placebo controlled one. The active group was stimulated by high-frequency rTMS, with the following stimulation parameters: frequency 10 Hz, 1500 pulses, 107 s inter-train, 100% minimal motor threshold and 10 stimulation session. The control group was stimulated by a sham rTMS coil. The FCQ-S and the FCQ-T questionnaires were used to evaluate the food craving.

The study was realized at Department of Psychiatry First Faculty of Medicine Charles University in Prague and General University Hospital in Prague during 2013 - 2018. The study was approved by the Ethics committee General University Hospital in Prague by a decision dated 23.1.2014, number 1867/13 S-IV (individual research). The study was registered on clinicaltrials.gov.

Two psychiatrists examined each patient who signed up for the study, in order to set the diagnoses. The DSM-5 diagnostic criteria were used for the purpose of the study. The exclusion criteria were mainly based upon contraindications for rTMS such as: a history of epileptic seizure paroxysms, increased intracranial pressure, brain tumor, implanted metal devices in the cranium (except the oral cavity), and any implanted peacemaker or drug pump. Also, patients who were not able to complete 10 sessions of rTMS were excluded for non-compliance. Inclusion criteria were: having BED and being over the age of 18. The study did not account for the hemispherical laterality.

After signing an informed consent form, subjects were included into the study and randomly divided into two groups: one group stimulated by a real rTMS coil (group A - active), and the second (control group), stimulated by a sham rTMS coil (group P - placebo).

Patients were also offered to participate in cognitive behavioral group therapy (CBT) simultaneously with the rTMS treatment. However, the attendance in the CBT was voluntary, and it was not a condition for inclusion into the study.

The study was conceived as randomized double blind placebo controlled clinical study. The randomization was performed by statistics independent of study. The investigators group achieved the study´s double blind characteristics by dividing the roles of the researchers. One author provided the examinations of the patients, CBT, data collection and evaluations of the questionnaires, while a second author administered the stimulations. The control group was "blind" thanks to the use of the sham coil.

Collection of data and statistical analysis Subjects were asked to fill out the set of questionnaires consisting of the EDE-Q (Eating Disorder Examination - Questionnaire), as well as the FCQ-S, and the FCQ-T before the first stimulation session. The EDE-Q served to collect demographfic data, and to evaluate the severity of the disorder. On the day of the last stimulation, and one month after the last stimulation, subjects filled out the FCQ-S and the FCQ-T again.

Statistical package R, version 3.4.2 was used for the statistical processing of the data. The two-sample t-test method was used to compare the differences in cravings between subjects stimulated by the real and sham coils in all situations: before stimulation, directly after the last stimulation, and one month after the last stimulation. The paired t-test method was used to evaluate the changes of craving over time, meaning the difference in craving before the stimulation and on the last day of stimulation, and difference in craving on the last day of stimulation and one month after the last stimulation.

Parameters of stimulation A MAGSTIM Super Rapid 2 device with eight flat shaped coil was used to provide the rTMS. The control group was stimulated by a sham coil with similar side effects regarding sound and a pain perception on the scalp. The left DLPFC was chosen as the stimulation target. The coil placement for the DLPFC stimulation was 5 cm anterior in the same parasagital line from the place of maximum musculus abductor pollicis brevis response. The stimulation site was outlined on a cap, which was repositioned during each rTMS session.

The number of sessions was set on 10. Each stimulation session consisted of 15 trains of 10 s and 107 s intertrain, at a frequency of 10 Hz. That meant 1500 pulses applied during one session taking cca 20 minutes. The intensity of stimulation was 100% of minimal motor threshold (MMT). MMT was identified as the minimum magnetic field strength required to produce a motoric response of right thenar muscle, which was determined by visual control and controlled by EMG measurement. Stimulations were realized throughout a two week period, excepting weekends.

Inclusion Criteria:

• having binge eating disorder
• being over the age of 18

Exclusion Criteria:

• contraindications for rTMS such as: a history of epileptic seizur paroxysms, increased intracranial pressure, brain tumor, implanted metal devices in the cranium (except the oral cavity), and any implanted peacemaker or drug pump
• non-compliance - inability to complet 10 sessions of stimulation

The participants in control group were stimulated by sham repetitive transcranial magnetic stimulation coil. The investigator did not know if the participants were stimulated by real or sham coil. Stimulation was provided by other member of invetigation group.