Evaluation of Bilateral HF-rTMS on Abstinence in Alcohol Use Disorder Patients With Executive Dysfunction

High frequency repetitive transcranial magnetic stimulation (HF-rTMS) over dorsolateral prefrontal cortex (DLPFC) could correct defective executive functions over the hyperactive reward circuit through the meso-fronto-limbic connections. The restored cortical inhibitory control over compulsive alcohol use, could improve abstinence after withdrawal. The goal of this study is to evaluate the efficacy of HF-rTMS over DLPFC in AUD patients with executive dysfunction after withdrawal.

PARTICIPANTS:

Participants with AUD (moderate to mild according to Alcohol Dependance Scale) with executive dysfunctions will be randomized.

DESIGN:

This study is a multicenter pilot double blind randomized controlled trial. After at least seven days of alcohol residential detoxification, executive dysfunctions's participants will be tested. 64 of them with executive dysfunctions will be randomized either in the active rTMS group or in the sham rTMS group. TMS will be performed during hospitalisation over 10 days. rTMS are proposed as an add on to the usual treatment.

INTERVENTION:

20 rTMS (twice a day) will be performed 10 consecutive working days. The target of the rTMS will be the DLPFC (left side in the morning, right side in the afternoon). During each rTMS sessions (active and sham), alcohol related pictures from the Geneva Appetitive alcohol Pictures will be presented.In the active arm, rTMS will be performed with high frequency (20hz, 1500 pulses per session, 110% of motor threshold).In the control group, sham rTMS will be performed.

Participants will be follow up to three months after the end of rTMS treatment.

Eligibility Criteria:
Inclusion Criteria:

* Age between 18-75 years
* Alcohol use disorder according to DSM 5, moderate to mild according to ADS
* Residential stay for alcohol detoxofication

Exclusion Criteria:

* Cognitive deficits defined by MoCA \<25 (Montreal Cognitive Assessment) performed at least 7days after alcohol detoxification and after at least 12 hours after benzodiazepine cessation
* History of cerebral stroke
* DSM-5 substance use disorders other than nicotine and alcohol
* Contraindication for rTMS :

  * Pregnancy
  * History of epilepsy or seizure
  * Cochlear implants
  * Cardiac pacemaker or intracardiac lines, or metal in the body
* Clinical history of complicated withdrawal symptoms
* History of severe head trauma followed by loss of consciousness
* Actual major depressive episode, schizophrenia according to the MINI (Mini International Neuropsychiatric Interview)
* Breastfeeding women
* Actual or history of organic failure including cirrhosis
* Absence of health insurance; or patient with AME
* Legal protection (curatorship or tutorship)
* Deprive of freedom or security measure
* No adequate mastering of the French language or no ability to consent
* Major socio-economic problem: homelessness
* No written informed consent
* Participation in another interventional study

Secondary inclusion criteria (before randomization):

- Abnormal executive function defined as at least 3 impaired measurements among 19 measurements of 7 tests (Stroop test, Wisconsin test; Trail making test, verbal fluency, 6 elements, Brixton test, Dual task Baddeley test) from the Greffex battery. Each measure will be considered as impaired if it is below 1.65 SD. The procedure and the measurement are standardized. The neuropsychological evaluation will be performed at least seven days after alcohol detoxification and after at least 12 hours after benzodiazepine cessation.