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
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
This study tests the efficacy of functional Magnetic Resonance Imaging (fMRI) guided
repetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of Obsessive Compulsive
Disorder (OCD). This study also examines measures of brain function that may inform us
about the brain basis underlying OCD.
Despite major advances in the study and treatment of OCD, patients often do not respond or
experience only partial remission from pharmacotherapy or cognitive behavioral therapy.
rTMS is a non-invasive procedure that allows stimulation of the brain using magnetic fields.
Some studies have reported that rTMS may be helpful in reducing obsessive and compulsive
symptoms. While promising, prior research has several limitations (e.g., relatively small
sample sizes, stimulation of sub-optimal target areas, relatively short durations of
treatment, and lack of sham (placebo) comparison).
This study addresses the drawbacks of prior work, and will provide data that will be
important in determining whether rTMS can be useful for OCD patients resistant to
conventional therapies. In this trial, 32 adult outpatients with OCD, that have been only
partially responsive to conventional therapies, will be randomly assigned to one of two
treatment groups (active low frequency (1 Hz) rTMS or sham-placebo) applied to the
Supplementary Motor Area (SMA) daily for up to four weeks. If rTMS will be added onto
ongoing pharmacotherapy, the doses must have been stable for 3 months prior to study entry.
The SMA was selected because of its connections with areas of the brain, especially motor
areas, implicated in OCD. Pilot work indicates that stimulation of SMA with low frequency
rTMS was beneficial in OCD patients. Low frequency rTMS has the added benefit of a better
safety profile (i.e. no risk of seizure) compared to high frequency rTMS.
Rating scales for symptom change will be obtained at baseline, during the rTMS course, and
at the end of 4 weeks of treatment. Patients who do not meet response criteria after four
weeks of sham and partial responders to either active or sham will be offered an open-label,
cross-over phase for an additional four weeks of daily active rTMS treatment. Patients who
meet response criteria in either the randomized phase or the cross-over phase will continue
routine clinical care under the supervision of their treating psychiatrist, and will be
invited back for a repeat assessment at 3 and 6 months to determine the persistence of
Measures of the excitability of the motor cortex have been reported to be abnormal in OCD,
and may relate to dysfunction in motor pathways related to OCD circuits. We will collect
measures of motor cortex excitability (performed with single pulse TMS) at baseline and
after treatment to determine whether changes in these measures may be correlated with
- 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.
- 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
- 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
- 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