# Augmentative transcranial magnetic stimulation over the left orbitofrontal cortex in patients with treatment-resistant obsessive-compulsive disorder: An acute and follow-up study

## TL;DR

This study shows that transcranial magnetic stimulation over the left orbitofrontal cortex can reduce obsessive-compulsive and related symptoms in patients who do not respond to traditional treatments.

## Contribution

The study provides empirical evidence for the efficacy and tolerability of rTMS targeting the left OFC in treatment-resistant OCD.

## Key findings

- rTMS targeting the left OFC significantly reduced obsessive-compulsive, anxiety, and depressive symptoms in treatment-resistant OCD patients.
- About 30.8% of patients showed a clinically significant response to the treatment.
- The treatment was well tolerated, with only mild and transient headaches reported as a side effect.

## Abstract

Obsessive-compulsive disorder (OCD) is a disabling and chronic medical condition which impairs the overall functioning and the quality of life of affected individuals. At the current moment up to 60% of patients do not show a satisfactory response, and among alternative approaches for treatment-resistant OCD, repetitive transcranial magnetic stimulation (rTMS) showed promising results in terms of efficacy and tolerability. Despite this, stimulation parameters are still heterogeneous, and additional investigations are needed to support these data.

OCD patients with characteristic of treatment resistance were included in this open-label trial. The stimulation protocol consisted of one daily session, five days a week for three weeks, for a total of 15 sessions. The left orbitofrontal cortex (OFC) was the target, stimulated at 80% of the motor threshold, with a frequency of 1 Hz, 600 pulses per session. All patients maintained fixed medication doses during the trial. Primary outcome measures comprised the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the Hamilton Anxiety Rating Scale (HAM-A), the Hamilton Depression Rating Scale (HAM-D), the Sheehan Disability Scale (SDS), and the Clinical Global Impression Scale (CGI-S) scores, assessed at baseline (T0), at the end of the treatment (T1), and after a follow-up of one month (T2). We identified responders with a Y-BOCS reduction of ≥35% at T1. General linear model repeated measures were used to compare scores at psychometric scales, chi-squared test was used to compare variables between responders and non-responders.

Thirteen patients completed the psychometric assessment (males: 69.2%; females: 30.8%, mean age: 43.1 ± 10.2 years). We observed a significant reduction at the end of the treatment on the Y-BOCS (T0:23.4 ± 8.9 - T1:18.2 ± 7.2, p = 0.009), HAM-A (T0:13.8 ± 7.4-T1:8.6 ± 4, p = 0.006), HAM-D (T0:13.2 ± 5.8 - T1:9.5 ± 3.6, p = 0.014), SDS (T0:22.7 ± 6.2 - T1:18.3 ± 5.1, p = 0.008), and CGI-S scores (T0:4.8 ± 0.8 - T1:4.3 ± 0.9, p = 0.027). Among all timepoints, a trend of significance for reduction of Y-BOCS and HAM-A scores emerged (p = 0.075 and p = 0.077, respectively), while HAM-D scores were significantly reduced after one month (p = 0.047). Responders constituted 30.8% (N = 4) of the sample. Worse clinical variables were more frequently observed in non-responders compared to responders: a higher rate of psychiatric familiarity and a higher rate of lifetime suicidal ideation. The only side effect reported was mild and transient headache during stimulation (N = 1).

Our data support the efficacy and tolerability of rTMS over the left OFC on obsessive-compulsive, depressive, and anxious symptoms in treatment-resistant OCD, overall associated with a reduction of disability and functional impairment. Additionally, one third of patients showed a response and results suggest a maintenance of efficacy after one month follow-up.

•rTMS applied at 1 Hz to the OFC showed to ameliorate obsessive-compulsive symptoms in patients with treatment resistant OCD.•At the end of the treatment, also anxious and depressive symptoms decreased, and patients showed an overall reduction of disability and functional impairment.•The procedure was well tolerated, headache was the only side effect reported.

rTMS applied at 1 Hz to the OFC showed to ameliorate obsessive-compulsive symptoms in patients with treatment resistant OCD.

At the end of the treatment, also anxious and depressive symptoms decreased, and patients showed an overall reduction of disability and functional impairment.

The procedure was well tolerated, headache was the only side effect reported.