Transcranial Magnetic Stimulation (TMS) and Obsessive Compulsive Disorder (OCD)
Condition: Obsessive-Compulsive Disorder
MeSH terms: Compulsive Personality Disorder; Obsessive-Compulsive Disorder
Intervention: Repetitive Transcranial Magnetic Stimulation (rTMS); Sham
Intervention description: Stimulus train of 30 min duration, 1Hz frequency, and 110% of the motor threshold intensity given once a day, 5 days a week, for 4 weeks by Magstim SuperRapid Magnetic Stimulator.; Sham rTMS will be administered using the Magstim Sham coil which contains a mu-metal shield that diverts the majority of the magnetic flux such that a minimal (less than 3%) magnetic field is delivered to the cortex in order to provoke a subjective sensation similar to that obtained with the real stimulation but without inducing significant cortical stimulation.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: TMS, Supplementary Motor Area, Obsessive-Compulsive Disorder

Summary:

      This study will evaluate the clinical efficacy of functional Magnetic Resonance Imaging
      (fMRI) guided 1 Hz repetitive Transcranial Magnetic Stimulation (rTMS) applied to the
      Supplementary Motor Area (SMA) in OCD patients who have not fully responded to conventional
      therapies. The investigators will collect TMS measures of motor cortex excitability to test
      whether rTMS restores normal levels of intracortical inhibition found to be deficient in OCD.
      The investigators hypothesize that:

        1. Compared to sham (placebo), active rTMS will improve symptoms of OCD as assessed with
           the Yale Brown Obsessive Compulsive Scale (Y-BOCS) and Clinical Global Impression (CGI).

        2. Active (but not sham) rTMS will normalize levels of motor cortex excitability, as
           reflected by increased intracortical inhibition, motor threshold, and cortical silent
           period, and by decreased intracortical facilitation, relative to pre-treatment baseline.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Primary diagnosis of obsessive compulsive disorder, with residual OCD symptoms,
             defined as a total Y-BOCS score of ≥ 16, despite treatment with an adequate trial of a
             serotonin reuptake inhibitor (SRI), and a duration of the index episode of at least a
             year will be included. An adequate SRI trial is defined as treatment for at least 12
             weeks on the SRI, that meets or exceeds the recommended dosage level for OCD
             (fluoxetine 60 mg/d, sertraline 200 mg/d, paroxetine 50 mg/d, fluvoxamine 250 mg/d,
             citalopram 60 mg/d, escitalopram 30 mg/d).

          -  Individuals who cannot tolerate medications of class and dose at the specified
             duration as described above will also be included.

          -  Patients currently on OCD medication must be at the same stable dose(s) and must
             continue to be under the care of their treating psychiatrist who will be writing
             prescriptions for concomitant medications through the duration of the study.

        Exclusion Criteria:

          -  Refractory patients, where treatment refractoriness is defined as non-response to
             Clomipramine, at least 2 SSRIs at adequate dose and duration plus cognitive behavior
             therapy in the last year, will be excluded. An adequate trial of cognitive behavioral
             therapy is defined as at least once a week for 8 weeks with clear evidence of exposure
             during the sessions and homework given. Individuals diagnosed with major depressive
             disorder (current) of moderate or severe intensity (CGI ≥ 4), and those with bipolar
             disorder (lifetime), any psychotic disorder (lifetime), history of substance abuse or
             dependence within the past year (except nicotine and caffeine), and at significant
             acute suicide risk will also be excluded.

        Other exclusion criteria include those common to every TMS protocol:

          -  Individuals with a clinically defined neurological disorder, with an increased risk of
             seizure for any reason, with a history of treatment with TMS, deep brain stimulation
             for any disorder will be excluded.

          -  Patients with cardiac pacemakers, implanted medication pumps, intracardiac lines, or
             acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm clips,
             shunts, stimulators, cochlear implants, or electrodes) 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 will not be permitted.

          -  If participating in psychotherapy, patients must have been in stable treatment for at
             least three months prior to entry into the study, with no anticipation of change in
             frequency therapeutic sessions, or the therapeutic focus over the duration of the TMS
             trial.

          -  Finally, current significant laboratory abnormality, known or suspected pregnancy,
             women who are breast-feeding or women of childbearing potential not using a medically
             accepted form of contraception when engaging in sexual intercourse will also be
             excluded.