Repetitive Transcranial Magnetic Stimulation in Obsessive Compulsive Disorder

Evaluate the therapeutic effect of a functional Magnetic Resonance Imaging (fMRI)-guided and robotized neuronavigated theta burst Transcranial Magnetic Stimulation (TMS) targeting right inferior frontal region in resistant obsessive compulsive disorder (OCD) in a double-blind, randomized, placebo-controlled, monocentric study.

This study evaluates the therapeutic effect of a fMRI-guided and robotized neuronavigated theta burst Transcranial Magnetic Stimulation (TMS) targeting right inferior frontal region in resistant obsessive compulsive disorder (OCD) in a double-blind, randomized, placebo-controlled, monocentric study. The study will also assess the interest of some clinical, neuropsychological, neuroimaging, electrophysiological variables in response prediction, besides physiopathological information.

There is an increasing interest in developping treatments for resistant OCD, which are not responding to the conventional treatment, represented by pharmacotherapy associated to cognitive behavioral therapy. Repetitive TMS represents a promising non invasive brain stimulation approach, but efficacy, best available brain target, optimal responder profile and stimulation parameters need to be further documented.

In this study, the included patients will be randomly assigned to an active (theta burst TMS) or sham-placebo treatment group. TMS will be added to their stable pharmacotherapy. The brain target, the right inferior frontal region, involved in the inhibition control brain network, will be defined in a personalized manner via a fMRI paradigm for each patient. TMS will be delivered daily for 2 successive weeks. Measures of different clinical, neuropsychological , electrophysiological (cortical excitability) variables will be performed at baseline, as well as at the end of the TMS course, and 1 week after. Other assessments are planned at 3 and 6 months, in order to highlight the evolution of the potential benefit.

Eligibility Criteria:
Inclusion Criteria:

* Volunteer subjects with Obsessive Compulsive Disorders (OCD) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM IV-TR) criteria and validated by an experimented clinician following instruments like SCID (Structured Clinical Interview for DSM IV) or MINI (Mini-International Neuropsychiatric Interview)
* with or without associated tics ("Gilles de la Tourette" Syndrome)
* Age \> 18 years old
* Y-BOCS score \> 20 and CGI (Clinical Global Impression Scale) score ≥ 4
* Resistant patients to standard treatments - where treatment resistance is defined by partial but insufficient response (Global Assessment of Functioning score GAF score \< 60 and/or reduction of Yale Brown Obsessions and Compulsion Scale score \< 35%) or lack of response to previous well conducted treatment including:

  * pharmacotherapy : optimal tolerated dose and adequate duration (\> 12 weeks) of at least 2 Serotonin Reuptake Inhibitors (selective serotonin reuptake inhibitors, clomipramine), and one augmentation strategy (adjunction of an antipsychotic - such as risperidone or olanzapine or aripiprazole - or lithium or buspirone) ;
  * psychotherapy (at least 6 months of cognitive and behavioral therapy)

Exclusion Criteria:

* other primary diagnosis than OCD (comorbid tics and depression are tolerated)
* comorbid diagnosis of schizophrenia/ psychotic disorder, bipolar disorder, substance abuse or dependance
* medical condition involving cognitive decline and affecting brain structures such as Parkinson disease, dementia, multiple sclerosis, HIV (human immunodeficiency virus) infection, lupus etc.
* Magnetic Resonance Imaging exclusion criteria (ferromagnetic implants etc)
* common TMS exclusion criteria (neurological condition with an increased risk of seizure, cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease, intracranial implants (e.g. cochlear implants, electrodes, aneurysm clips, stimulators... ) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed will be excluded
* Current use of any investigational drug
* pregnancy / breast feeding patients
* visual or auditive important deficit