Repetitive transcranial magnetic stimulation over the orbitofrontal cortex for obsessive-compulsive disorder: a double-blind, crossover study

Abstract

This pilot study was designed to assess the efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the right orbitofrontal cortex (OFC) by means of a double-cone coil in patients suffering from obsessive-compulsive disorder. We hypothesized that low-frequency stimulation of the OFC would lead to a reduction in clinical symptoms, as measured on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). A randomized, double-blind, crossover design was implemented with two 1-week treatment periods (active stimulation versus sham stimulation) separated by a 1-month washout period. Concomitantly, a subgroup of patients underwent a positron emission tomography (PET) scan after each stimulation sequence. Statistical analyses compared the Y-BOCS scores at the end of each period. At day 7, we observed a significant decrease from baseline in the Y-BOCS scores, after both active (P<0.01) and sham stimulation (P=0.02). This decrease tended to be larger after active stimulation than after sham stimulation: -6 (-29, 0) points versus -2 (-20, 4) points (P=0.07). Active versus sham PET scan contrasts showed that stimulation was related to a bilateral decrease in the metabolism of the OFC. The OFC should definitely be regarded as a key neuroanatomical target for rTMS, as it is easier to reach than either the striatum or the subthalamic nucleus, structures favored in neurosurgical approaches.

Figure 1

Changes in OCD severity in 19 patients during the crossover study. Data are shown at the time of inclusion in the study (month 0), after the first period of active or sham stimulation (day 7), before (month 1) and after (day 7) the second period of active or sham stimulation and at the end of the study (month 2). (a) Shows the mean (s.d.) scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) for the active–sham group (lines) and sham–active group (dashed lines). (b) Shows the individual Y-BOCS scores for the active–sham and sham–active groups. The active stimulation period is shown in red and the sham stimulation period in orange. OCD, obsessive-compulsive disorder.

Figure 2

(a) Statistical parametric map showing decreased cerebral glucose metabolism in 10 OCD patients treated with rTMS, comparing active stimulation versus sham stimulation conditions. Areas with significant decreases (P<0.005, adjusted for multiple comparisons at cluster level) are shown on three telescoped orthogonal views. (b) Correlation between metabolic changes induced by rTMS and concomitant clinical improvement (Y-BOCS scores). Whole-brain analysis shows a significant cluster of correlation in the orbitofrontal cortex (Brodmann area 47) with the decrease in the Y-BOCS score.