Treating Refractory Obsessive Compulsive Disorder With rTMS
Condition: Obsessive Compulsive Disorder
MeSH terms: Compulsive Personality Disorder; Obsessive-Compulsive Disorder
Study type: Interventional

Summary: 
      Obsessive-compulsive disorder (OCD) is a severe psychiatric condition with only limited
      response to current first-line treatments, comprising pharmacotherapy and
      cognitive-behavioural therapy. Repetitive transcranial magnetic stimulation (rTMS) is a
      relatively new technique which has shown great promise in the treatment of refractory mood
      disorders, and schizophrenia, by alteration of brain activity. Previous work has demonstrated
      altered cortical excitability in OCD and preliminary studies have suggested that rTMS may
      have therapeutic potential in OCD. This pilot study will investigate the effectiveness of
      rTMS for treatment-refractory OCD, and establish appropriate treatment parameters. In
      addition, mechanisms whereby rTMS exerts its therapeutic effect will be explored using TMS to
      evaluate cortical inhibition and measures of cognitive biases and processing.
    

Detailed description: 
      Obsessive-compulsive disorder (OCD) is a severe and debilitating psychiatric illness
      characterized by intrusive unwanted thoughts (obsessions) and repetitive or ritualistic
      actions intended to reduce anxiety (compulsions). OCD is common with lifetime prevalence
      estimated at 2.5%, equally affecting both genders and all ethnic groups. It is also typically
      chronic in nature, resulting in substantial impact on quality of life. Functioning can be
      markedly impaired; it has been estimated that 20% of individuals with OCD should be
      considered severely affected. Although the pathophysiology is unclear, hyperactivity in the
      prefrontal orbital cortex has been consistently demonstrated, and normalizes with treatment.
      A decrease in cortical inhibition has been implicated in OCD utilizing a variety of methods,
      including paired-pulse TMS.

      First-line treatment typically consists of either cognitive-behavioural therapy and/or
      pharmacotherapy with serotonin reuptake inhibitors (SSRI's or clomipramine). Ordinarily only
      modest benefits are obtained with conventional pharmacotherapy, with the majority of patients
      considered nonresponsive or only partially responsive. The limited success of conventional
      treatment makes identifying alternative treatments a priority. Although psychosurgery is
      regarded as a valid alternative for severe and refractory individuals, the potential for
      serious and irreversible adverse consequences is significant, rendering this a treatment of
      'last resort' only. Repetitive TMS appears to represent a safe and effective alternative for
      severe sufferers.

      Repetitive TMS has been shown to be an effective therapeutic tool for the treatment of
      several neuropsychiatric disorders including MDD and schizophrenia, but investigations into
      its utility in OCD are very preliminary. In a study of 12 OCD patients single session
      stimulation of the right lateral prefrontal cortex (20 Hz, 80% motor threshold, for 20
      minutes) resulted in a decrease in compulsive urges for eight hours in contrast to the left
      prefrontal cortex which was associated with more modest response . Sachdev et al randomly
      assigned 12 individuals to receive right or left dorsolateral prefrontal stimulation (10
      Hz,110% resting motor threshold, 15 minutes 5 sessions/week for 2 weeks). Subjects showed
      significant improvement at two weeks and 1-month follow-up, regardless of lateralit. A
      randomized controlled trial comparing right prefrontal stimulation to sham treatment in 18
      OCD subjects was negative, however low frequency (1 Hz) stimulation was used in contrast to
      previous reports (110% motor threshold, 20 minutes 3 times/week for 6 weeks). Most recently a
      small study of 10 individuals with OCD and/or Tourette's syndrome found benefit with
      low-frequency stimulation of the supplementary motor area (1 Hz, 100% motor threshold, 20
      minutes 5 sessions/week for 2 weeks). Notably subjects were treatment-resistant in both this
      and the Sachdev study. Thus although this limited literature precludes any definitive
      conclusions, it suggests that rTMS may be of benefit in refractory OCD.

      In this study we propose to investigate the effectiveness of rTMS treatment in refractory
      OCD. Although ideal treatment parameters need to be established, the above literature
      suggests that high frequency stimulation of the dorsolateral prefrontal cortex is likely to
      be beneficial. Bilateral stimulation will be used; our previous work has demonstrated this
      method to be safe and well tolerated. Moreover patients will be assigned in randomized
      double-blind fashion to receive either active or sham TMS, allowing for more definitive
      conclusions to be drawn. We also propose to explore whether the induction of CI mediates the
      therapeutic effects of rTMS on OCD symptoms.
    

Intervention name(s): refractory transcranial magnetic stimulation (rTMS); Sham condition
Intervention type(s): Device; Device
Intervention description(s): Bilateral rTMS will be delivered according to the following protocol: high frequency left (HFL) stimulation will initially be applied at 20 Hz, in 25 trains of 1.5 second duration with a 30 second interval between trains and at 100% of the RMT for a total of 25 minutes of stimulation. Following this HFR stimulation will be applied at the same parameters. Therefore a total of 50 minutes of stimulation will be delivered.; Sham stimulation will be made at the site of active treatment but with only the side edge resting on the scalp. It will be administered as HFL and HFR for 50 minutes but with the coil angled 45-90 degrees away from the skull in a single-wing tilt position. This method produces sound and some somatic sensation (e.g., contraction of scalp muscles) similar to those with active stimulation but with minimal direct brain effects. Participants will be unable to see the stimulating coil and therefore will remain blind to the treatment condition.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: refractory transcranial magnetic stimulation; obsessive compulsive disorder; randomized; placebo-controlled; double-blind