Transcranial electrical stimulation for the treatment of obsessive–compulsive disorder

Obsessive–compulsive disorder (OCD) imposes a substantial burden on mental health and is associated with substantial disability. While cognitive behavioral therapy and SSRI medication are considered first-line treatments for OCD, less than 40% of patients respond fully to these treatments.
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Obsessive–compulsive disorder (OCD) is a condition with substantial disability and subclinical obsessive–compulsive behaviors affect up to 1 billion people globally. Transcranial electrical stimulation (tES) is emerging as a potential treatment for OCD, yet its effectiveness is uncertain due to the limited number of randomized controlled trials conducted so far. In this analysis study, we applied 3 meta-analytic approaches to evaluate the pooled therapeutic effect size of included randomized controlled trials (ntDCS = 15, ntACS = 1) (pair-wise meta-analysis), compare the efficacy of various tES interventions (network meta-analysis), and explore how treatment effect size correlates with induced electrical field in the target brain regions (meta-modeling). With these 3 distinct meta-analytic approaches, we first show a significant moderate effect of tES interventions (standardized mean difference 0.61; 95% confidence interval [0.37 to 0.85]; P < 0.001) as a whole on reducing OCD severity, with larger therapeutic effects of twice-daily intervention, and with other stimulation parameters also moderating efficacy. Next, we identify specific tES interventions with superior indicated and estimated effects, including entraining alpha frequency alternating stimulation of the medial prefrontal cortex, excitability-diminishing cathodal stimulation over the supplementary motor area and orbitofrontal cortex, and excitability-enhancing anodal stimulation of the lateral prefrontal cortex. Finally, we show based on computational approaches that longer stimulation targeting the medial prefrontal and frontopolar cortices has greater therapeutic effects and suggest an optimized intervention accordingly.

Caa,b, Major findings of pairwise (a) and network (b) meta-analyses (for detailed results see Figs. 2 and 3). c, Model-estimated and suggested tES intervention based on computational modeling with atDCS over F2–F4 coupled with cathodal AF3–AF7. d, Proposed mechanisms of tES effects on reducing OCD severity by regulating glutamate/GABA levels, upregulating the prefrontal–striatum pathway, and downregulating the SMA–putamen and medial PFC–insula pathways. vmPFC, ventromedial prefrontal cortex; vlPFC, ventrolateral prefrontal cortex; DLPFC, dorsolateral prefrontal cortex; SMA, supplementary motor area; OFC, orbitofrontal cortex; tDCS, transcranial direct current stimulation; GABA, gamma‑aminobutyric acidption

We also discussed other potentially effective tES interventions according to the latest neurobiological theory of OCD. The results contribute to establishing the clinical efficacy of tES for OCD treatment while suggesting future studies to further evaluate current and future approaches to enhance the efficacy of interventions. This study is published in Nature Mental Health and is open access to readers: https://www.nature.com/articles/s44220-026-00590-z

OCD features a complex pathophysiology involving various cortical and subcortical regions that influence disease severity. Neuropsychological and cognitive deficits are integral to OCD psychopathology and closely linked to its pathophysiology. According to the latest framework about OCD psychopathology and pathophysiology92, several regions can be targeted by tES and other NIBS interventions. a, The VLPFC, an important region for the executive control system, is often hypoactive in OCD. This diminishes influence over the dorsal striatum and habit system, which can lead to compulsive behaviors. Enhancing VLPFC activity (for example, with atDCS) may benefit OCD by strengthening goal-directed behavior. b, The vmPFC is typically hyperactive in OCD. A downregulatory tES intervention targeting the medial PFC could alleviate negative feelings and urges to act by modulating the insula and caudate. c, The dorsal ACC, which is involved in action monitoring and interoceptive feelings through its connections to the insula, is also hyperactive in OCD. This hyperactivity can hinder action monitoring and amplify interoceptive urges, leading to compulsions. A downregulatory tES intervention on the dorsal ACC may help regulate these urges and improve action monitoring, potentially reducing compulsions. vmPFC, ventromedial prefrontal cortex; vlPFC, ventrolateral prefrontal cortex; ACC, anterior cingulate cortex; DLPFC, dorsolateral prefrontal cortex. Brain surface renderings are based on the MNI152 nonlinear 2009 (ICBM152) standard template.

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Brain Stimulation
Life Sciences > Biological Sciences > Neuroscience > Neurophysiology > Brain Stimulation
Psychiatry
Life Sciences > Health Sciences > Clinical Medicine > Psychiatry
Obsessive-Compulsive Disorder
Life Sciences > Health Sciences > Clinical Medicine > Diseases > Psychiatric Disorder > Obsessive-Compulsive Disorder
Cognitive Neuroscience
Life Sciences > Biological Sciences > Neuroscience > Cognitive Neuroscience