Obsessive - Compulsive Disorder
Conditions
Keywords
tDCS
Brief summary
The goal of this clinical trial is to learn if symptom provocation before transcranial Direct Current Stimulation (tDCS) in Obsessive-Compulsive Disorder (OCD) patients. The main question it aims to answer is: Can symptom-provocation before tDCS improve therapeutic response in OCD patients ? Researchers will compare the clinical outcomes of OCD patients having received, in one arm, tDCS and, in the other arm, patients having received tDCS preceded by symptom provocation to see if therapeutic response and various other clinical variables differ.
Detailed description
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.
Interventions
PROCEDUREtDCS session
An active bifocal tDCS delivered through a CE-certified stimulator. The bifocal montage consists of an anodal electrode over the right orbitofrontal cortex (OFC) and a cathodal electrode over the supplementary motor area (SMA), with 5X5 cm electrod. Stimulation intensity is set at 2 mA, with a 30-minute session duration, including 30-second ramp-up and ramp-down periods.
BEHAVIORALsymptom provocation
A 3-5 minutes personalised symptom provocation procedure immediately before stimulation. This standardised clinical procedure induces brief activation of obsession-related distress without engaging in compulsions. It is delivered by a trained clinician health-care professional and does not constitute psychotherapeutic treatment.
Sponsors
Centre Hospitalier Henri Laborit
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Variation of Yale-Brown Obsessive-Compulsive Scale score | measured at baseline and 42 days after the start of the therapy | The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) is a clinician-administered assessment used to measure the severity of obsessive-compulsive disorder (OCD). Scores range from 0 to 40, with higher scores indicating more severe symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Persistence of variation of Yale-Brown Obsessive-Compulsive Scale score and Obsessive-Compulsive Inventory-Revised | measured between baseline, day 102 / day 162 | Assessment of the persistence of the therapeutic response at day 102 and 162 with the Y-BOCS and OCI-R scales. The Obsessive-Compulsive Inventory-Revised (OCI-R) is a self-report measure designed to assess the severity and type of obsessive-compulsive disorder (OCD) symptoms. It evaluates six symptom dimensions: washing, checking, ordering, hoarding, neutralizing, and obsessing. Each dimension is scored from 0 to 12, with higher scores indicating greater symptom severity. |
| Comparison of Clinical Global Impression Improvement between both groups | Scales assessed at baseline, day 42, 102 and 162 | The Clinical Global Impression (CGI) is a hetero-evaluation scale widely used in clinical studies to evaluate baseline severity and improvement in relation to treatment. |
| Assessment of the Montgomery and Asberg Depression Rating Scale | Scales assessed at baseline, day 42, day 102, day 162 | The Montgomery and Asberg Depression Rating Scale (MADRS) is a hetero-evaluation rating scale used to assess the severity of depressive symptoms. It consists of 10 items evaluating core dimensions of depression. Total scores range from 0 to 60, with higher scores indicating more severe depression. |
| Assessment of 36-Item Short Form Health Survey | baseline, day 102, and day 162 | The 36-Item Short Form Health Survey (SF-36) is a self-assessed scale to measure 8 dimensions of health and quality of life. Each dimension is graded on a score of 0 to 100, 0 being the poorest estimate of quality of life and 100 being the best. |
| Analysis of side effects and tolerance of tDCS | Assessed during treatment | Assessed with the Brunoni questionnaire |
| Analysis of complete response rate | between baseline and days 42 / day 102 / day 162 | 35% improvement of the Y-BOCS score. |
| Assessment of the Hospital Anxiety and Depression scale | baseline, day 42, day 102, day 162 | The Hospital Anxiety and Depression scale is a self-assessed scale yielding anxiety and depression scores ranging from 0 to 15 each (and a global score of 30), corresponding to higher depression or anxiety severities. |
| Assessment of insight with the Brown Assessment of Beliefs Scale | baseline, day 42, day 102, day 162 | The Brown Assessment of Beliefs scale is a clinician-assessed scale producing a score between 0 and 24. A higher score indicates a weaker insight. |
| "Echelle d'évaluation Globale du Fonctionnement": Assessment of psychological and socio-professional functioning | baseline, day 102, day 162 | The "Echelle d'évaluation Globale du Fonctionnement" (EGF) evaluates the psychological and socio-professional functioning. It is a clinican-graded scale giving a score of 1 - 100. A score of 100 corresponds to high functioning with absence of symptoms. |
Countries
France
Contacts
CONTACTGhina Harika-Germaneau, Dr.
Outcome results
None listed