tDCS and Symptom Provocation in Treatment-Resistant OCD

Obsessive-compulsive disorder (OCD) is a chronic and disabling condition affecting 2-3% of the population. Despite evidence-based interventions-cognitive behavioural therapy with exposure and response prevention (ERP) and serotonergic antidepressants, 40-60% of patients exhibit insufficient improvement, highlighting a substantial need for more effective therapeutic strategies.

Neuroimaging and neurophysiological studies consistently implicate dysfunction within cortico-striato-thalamo-cortical circuits, particularly the supplementary motor area (SMA) and orbitofrontal cortex (OFC). These findings have guided the development of neuromodulation interventions targeting these regions. Among them, transcranial direct current stimulation (tDCS) has emerged as a safe, accessible, and potentially effective approach for modulating aberrant neural activity in OCD.

Our research group has previously investigated a bifocal tDCS montage combining cathodal SMA stimulation with anodal right OFC stimulation. In an open-label study of 21 patients, this protocol produced clinically meaningful improvement in 15% of participants and was well tolerated. A subsequent multicentre randomised controlled trial confirmed the feasibility, safety, and potential therapeutic value of this montage, although overall effects remained modest. These findings underscore the need to optimise neuromodulatory strategies in OCD.

One promising direction is to enhance neuromodulation by manipulating the pre-stimulation neural state. Evidence suggests that the impact of tDCS depends on ongoing cortical activity, raising the possibility that activating symptom-relevant circuits immediately before stimulation could potentiate its effects. Pre-stimulation symptom provocation-also referred to as paired associative cognitive stimulation-has shown encouraging results when combined with rTMS in depression, addiction, and post-traumatic stress disorder (PTSD). In PTSD, for example, brief reactivation of traumatic memories prior to stimulation enhanced symptom reduction compared with stimulation alone.

This approach is grounded in the theory of memory, which posits that reactivated memories enter a transiently labile state during which their emotional intensity can be modified. Experimental and clinical studies have demonstrated that targeted interventions delivered during this window can weaken maladaptive emotional memories. In OCD, intrusive thoughts typically accompanied by fear, disgust, or distress may therefore constitute ideal targets for reconsolidation-based modulation.

Symptom provocation is widely used in neuroimaging research to activate OCD-related circuits and forms part of ERP-based treatment strategies. More recently, introduced its use before rTMS in OCD, reporting significant symptom reduction, although the specific contribution of provocation could not be isolated as all participants received it. Despite the fact that the specific contribution of symptom provocation could not be isolated in the initial trial, its continued use in clinical research has been supported by the excellent results reported in subsequent studies, as well as by its good acceptability among patients. The same research group recently published a standardized symptom-provocation protocol to ensure strong reproducibility and methodological reliability. This intervention requires only basic clinical skills and does not involve the use of complex psychotherapeutic techniques such as cognitive restructuring or symptom interpretation. To date, no study has evaluated symptom provocation combined with tDCS.

Given the safety, accessibility, and potential for home-based use of tDCS, identifying strategies that enhance its effectiveness is of clinical relevance. Brief activation of symptom-triggering cues prior to stimulation may allow tDCS to more effectively modulate targeted neural networks.

Objective This multicentre randomised controlled trial aims to determine whether personalised symptom provocation combined with bifocal tDCS (anodal right OFC, cathodal SMA) produces greater clinical improvement than tDCS alone in adults with severe, treatment-resistant OCD.

This study is a multicentre, randomised, controlled, single-blind clinical trial conducted across six french psychiatric centres in France (Poitiers, Nantes, Rennes, Limoges, Thouars and Angoulême). Eligible participants with severe, treatment-resistant OCD will be randomly allocated (1:1) to one of two parallel groups:

* Active tDCS alone * Active tDCS combined with personalised symptom provocation. Both study arms will receive identical tDCS stimulation parameters. The intervention consists of 10 sessions of 30 minutes, delivered over two consecutive weeks (five sessions per week), followed by a 5-month follow-up period. The total study duration is 41 months, including 36 months of enrollment.

• Persistence of variation of Yale-Brown Obsessive-Compulsive Scale score and Obsessive-Compulsive Inventory-Revised [Time frame: measured between baseline, day 102 / day 162]
• Comparison of Clinical Global Impression Improvement between both groups [Time frame: Scales assessed at baseline, day 42, 102 and 162]
• Assessment of the Montgomery and Asberg Depression Rating Scale [Time frame: Scales assessed at baseline, day 42, day 102, day 162]
• Assessment of 36-Item Short Form Health Survey [Time frame: baseline, day 102, and day 162]
• Analysis of side effects and tolerance of tDCS [Time frame: Assessed during treatment]
• Analysis of complete response rate [Time frame: between baseline and days 42 / day 102 / day 162]
• Assessment of the Hospital Anxiety and Depression scale [Time frame: baseline, day 42, day 102, day 162]
• Assessment of insight with the Brown Assessment of Beliefs Scale [Time frame: baseline, day 42, day 102, day 162]
• "Echelle d'évaluation Globale du Fonctionnement": Assessment of psychological and socio-professional functioning [Time frame: baseline, day 102, day 162]