Long-term effects of subthalamic stimulation in Obsessive-Compulsive Disorder: Follow-up of a randomized controlled trial

Abstract

Obsessive-Compulsive Disorder (OCD) is characterized by intrusive, anxious thoughts with repetitive, ritualized behaviors, and has negative impacts on family relationships and social life. Its lifetime prevalence is estimated to be 2-3% [1]. Cognitive and behavioral therapy and selective serotonin reuptake inhibitors are the standard treatments for OCD; nevertheless, despite these treatments, between 25 and 40% of patients display persistent symptoms leading to severe functional disability [2]. Neurosurgical treatment targeting different parts of the orbito-fronto-striato-thalamo-cortical circuit has been proposed for the most severe and refractory forms, including both gamma knife non-invasive stereotactic lesions and invasive deep brain stimulation (DBS) [3] (Supplementary Information). However, the longterm efficacy (> 3 years) and safety of DBS for OCD is not fully reported. We prospectively followed 14 OCD patients treated with subthalamic DBS (STN-DBS, STOC study) for 46 months [4] (ClinicalTrials.gov Number: NCT00169377) (Supplementary Information). The primary outcome was the change in the total Yale Brown Obsessive Compulsive Scale (Y-BOCS) score between inclusion (baseline) and month 46 with STN-DBS, or month 34 in the case of missing data at month 46 (Supplementary Figure 1). We also assessed others psychiatric symptoms, global functioning and tolerance (Supplementary Information) [4].Twelve patients completed the follow-up study ( Supplementary Figure 1). The Y-BOCS total score between inclusion (baseline) and the end of the follow up period showed a median decrease of 15.5 points (IQR=-31 to -6), with a median change of 50% (IQR=-86.1 to -19.4%, Table 1). At the final follow-up, 11 patients (92%) were considered at least partial responders (>25% of Y-BOCS decrease) and 9 (75%) full responders (>35% of Y-BOCS decrease) ( Table 1). The Y-BOCS score was also significantly improved at month 46 compared to month 16 (Table 1) and decreased by an average of 1 (SE=.04) point per year between month 16 and month 46 (Time effect p=0.027, Supplementary Figure 2). At the end 4 of the follow-up period (month 46), the compulsion, obsession, anxiety and depression scores, but also global functioning and social and family life subscores were significantly improved ( Supplementary Table 1). We found a significant positive relationship between the severity of OCD at month 46 and the age at onset (r=0.61, p=0.045, Supplementary Figure 3) with early onset patients having fewer OCD symptoms with STN stimulation. During the follow-up, the medication had not changed significantly (not shown) but stimulation voltage was significantly increased (p=0.042, Supplementary Table 2). Twenty-three serious adverse events occurred, 5 being transient and related to STN-DBS (hypomania, impulsivity, dysarthria or fall) and 18 related to the disease (increased anxiety and obsessive and compulsive symptoms, and major depressive episodes with suicide attempts, Supplementary Table 3). Our results show that STN-DBS can effectively treat OCD...

Deep brain stimulation of the subthalamic nucleus in obsessive–compulsives disorders: long-term follow-up of an open, prospective, observational cohort

“…This paper reinforces the previous study of STN-DBS for OCD, which was recently updated at the long-term follow-up. 23 Despite being the first randomised controlled study in psychosurgery, and despite publication in one of the highest-ranking journals, the STOC study did not have a relevant impact in psychiatry up to now. We were however highly impressed by the outcomes of our first patients, more so than in STN-DBS in PD as patients with OCD are younger, have a more severe impairment in quality of life than PD patients.…”

“…Our results Neurosurgery confirm the favourable long-term outcome reported by Mallet et al who showed that 9 out of 14 patients were full responders at the last follow-up, with a median improvement of 50%. 23 Up to now, only one paper from our group has reported the outcome at a very long-term follow-up of an OCD case as a comorbidity in Gilles de la Tourette syndrome treated by noM-STN-DBS 27 that illustrated the long-term efficacy of this technique applied on a new target, the noM-STN. In the present study, the same target located in the anteromedial STN was used in all patients and parameter settings were similar to those usually used in patients with PD.…”

Deep Brain Stimulation for Refractory Obsessive-Compulsive Disorder: Towards an Individualized Approach

“…The anteromedial subthalamic nucleus DBS (amSTN-DBS) is another therapeutic option to treat severe and refractory OCD and has the strongest evidence in the literature. To our knowledge, amSTN-DBS is associated with the best response rates in randomized and controlled trials, with best long-term outcomes (75% full responders and 53% decrease in OCD severity at 3 years post-surgery) and improvement in global functioning, social, and familial disabilities (96).…”

“…A recent meta-analysis found that 44% of patients could be considered responders to STN-DBS (7). Interestingly, it has been shown recently that amSTN-DBS decreases OCD symptoms for up to 3 years, with a 53% decrease in OCD severity and 92% of patients being considered responders at the final assessment (12 patients in total at 3 years) (96). They also report a positive effect on social activities with a significant improvement in social adjustment (SAS-SR) and work, social, and familial disabilities (SDS).…”

“…Finally, the high rate of suicidal attempts (23%) is in agreement with those encountered in the general population of patients with refractory OCD. DBS may not be the cause since these patients display concomitant increase of impulsivity, anxiety, or depression (96).…”