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.

Inclusion criteria

• Diagnosis of Obsessive-Compulsive Disorder (OCD) according to DSM-5, with a duration ≥ 2 years.
• Good insight, defined as a BABS score ≤ 18.
• Chronic OCD, with either a Y-BOCS total score > 20 or a subscale score > 15.
• Treatment-resistant OCD, defined as:

• failure of ≥ two adequate trials of SSRIs, or
• failure of one SSRI plus augmentation with an atypical antipsychotic,
• and/or insufficient response after ≥ one year of cognitive-behavioural therapy.
• Stable pharmacological treatment (fixed antidepressant dose) for at least 12 weeks prior to inclusion, with no significant improvement during this period.
• Age 18 to 70 years.
• Ability to provide informed written consent.
• Affiliation with the French social security system.

Exclusion criteria

• Women of childbearing potential without effective contraception, or those unwilling to maintain abstinence or contraception.
• Pregnancy or breastfeeding.
• Compulsory psychiatric hospitalisation.
• Legal guardianship or curatorship.
• Current DSM-5 Axis I disorder other than OCD (schizophrenia spectrum, bipolar disorder, substance use).
• Current major depressive episode (MADRS > 21).
• Suicide risk (MADRS item 10 > 3).
• Dermatological lesions at electrode placement sites.
• History of traumatic brain injury.
• Presence of intracranial metal, pacemaker, or epilepsy.
• Emergency situations or inability to provide informed consent.