Search Results (225)

Background/Objectives: The Bergen 4-Day Treatment (B4DT) is a concentrated form of exposure and response prevention for patients with obsessive–compulsive disorder (OCD). Although response rates for the B4DT are generally high, a proportion of patients does not achieve clinically significant improvements. Quantitative measures can identify non-response, but offer limited insight into processes that may hinder change in highly structured, time-limited interventions. To identify factors potentially related to the lack of improvement, this study explored experiences of patients who had not benefitted from B4DT. Methods: B4DT participants were recruited from an uncontrolled German study. Of 32 patients assessed at three-month follow-up, 12 met the non-response criteria (<35% reduction on the Yale–Brown Obsessive Compulsive Scale), and eight completed semi-structured qualitative interviews 9–14 months after treatment. Interviews were analyzed using grounded theory methods. A brief quantitative comparison examined baseline differences between responders and non-responders. Results: Participants described benefits from B4DT, including improved understanding of OCD, supportive peer contact, and increased courage for exposure tasks. However, they consistently reported difficulties sustaining self-guided exposure after treatment. Within the B4DT framework, one possible interpretation is that the intended shift toward independently approaching anxiety had not yet been fully consolidated. Conclusions: Although quantitatively classified as non-responders, participants described meaningful psychological benefits from B4DT. The findings suggest that non-response may reflect incomplete consolidation of the intended shift from symptom control toward approaching anxiety in service of personally meaningful action, rather than an absence of change. Full article

Background/Objectives: Obsessive–compulsive disorder (OCD) is associated not only with obsessions and compulsions, but also with cognitive dysfunction involving inhibitory control, cognitive flexibility, working memory, attention, decision-making, feedback learning, and performance monitoring. Electroencephalography (EEG), event-related potentials (ERPs), quantitative EEG, and time–frequency analyses provide temporally precise methods for examining how these cognitive abnormalities unfold during information processing. This review aimed to synthesise electrophysiological evidence on the neural correlates of cognitive dysfunction in OCD. Methods: A systematic literature search was conducted in PubMed/MEDLINE, Scopus, Web of Science Core Collection, Embase, PsycINFO, and Google Scholar from database inception to 30 May 2026. Eligible studies included patients with OCD and used EEG, qEEG, spectral EEG, EEG connectivity, or ERP methods in relation to cognitive performance, cognitive task demands, or cognitive dysfunction. Studies were grouped according to electrophysiological modality and ERP component. Because of methodological heterogeneity, findings were synthesised narratively and mechanistically rather than by meta-analysis. Methodological quality was assessed using ROBINS-I. Results: The search identified 1321 records, of which 42 studies met the inclusion criteria. Most studies used task-based ERP paradigms, while fewer examined resting-state EEG, qEEG, or oscillatory activity. The most consistent findings concerned altered performance monitoring and cognitive control, especially ERN, N2/N200, Pe, Pc, and P3/P300 abnormalities. ERN findings suggested excessive early error monitoring, whereas N2/N200 and P3/P300 findings indicated task-dependent abnormalities in inhibition, conflict processing, attentional allocation, stimulus evaluation, and context updating. Earlier components, including P50, N1/N100, P2/P200, and N450, suggested abnormalities in sensory gating, early attentional selection, stimulus evaluation, and interference control, particularly under emotionally salient or OCD-relevant conditions. FRN findings indicated altered feedback processing and reinforcement learning, while limited P600 evidence suggested inefficient working-memory preparation. Plain EEG and time–frequency studies further implicated abnormal theta, alpha, beta, and delta activity in monitoring, inhibition, arousal, and network efficiency. Conclusions: EEG-based evidence suggests that cognitive dysfunction in OCD reflects a dysregulated control system rather than a general reduction in cognitive ability. The disorder appears to involve excessive performance monitoring, abnormal sensory and attentional gating, inefficient inhibition, altered feedback evaluation, and reduced cognitive flexibility. However, the current evidence is limited by heterogeneity in samples, paradigms, EEG methodology, medication status, and statistical approaches. Future studies should use larger, well-characterised samples, standardised EEG/ERP paradigms, direct brain–behaviour analyses, and longitudinal designs to clarify whether electrophysiological abnormalities represent trait markers, state-dependent effects, compensatory mechanisms, or clinically useful predictors of cognitive dysfunction in OCD. Full article

Background: Deep brain stimulation (DBS) is a promising intervention for severe treatment-resistant OCD (TR-OCD), yet evidence of clinical efficacy remains inconsistent across heterogeneous study designs and anatomical target selection lacks standardization. Whether target choice influences clinical outcomes has not been systematically established, and prior meta-analyses have not characterized target-specific effects or predictors of response. Objectives: This systematic review and meta-analysis evaluated the efficacy of DBS versus sham stimulation in RCTs and its effectiveness in non-randomized studies, with OCD symptom severity, comorbid anxiety and depression, and global functioning as outcomes. Secondary objectives were to examine whether anatomical stimulation site influences therapeutic outcomes using systematic recategorization of reported targets, and to characterize the temporal dynamics of treatment response. Methods: Four databases (PubMed, Embase, Web of Science, CENTRAL) were searched through July 2025 following PRISMA 2020 guidelines. RCTs (active vs. sham DBS) and non-randomized studies reporting pre/post-DBS Y-BOCS scores were analyzed separately at three time points (≤12 months, >12 months, last follow-up). Stimulation targets were recategorized using active contact location and stereotactic coordinates. Random-effects models, meta-regression, RoB 2, ROBINS-I, and GRADE were applied. Results: Eight RCTs (n = 83) and 32 non-randomized studies (n = 321) were included. In RCTs, active DBS reduced Y-BOCS scores by 6.92 points (95% CI: 4.46–9.38; 18.3%; p < 0.001; I² = 62.93%) versus sham. Non-randomized studies demonstrated reductions of 13.83 points (95% CI: 11.01–16.52), 17.34 points (95% CI: 14.70–20.04), and 14.51 points (95% CI: 12.78–16.26; 43.5%; p < 0.001) at ≤12 months, >12 months, and last follow-up, respectively, with substantial heterogeneity (I² ≥ 89.79%). Responder and remission rates were 60.2% (95% CI: 52.8–67.2%; I² = 20.7%) and 36.4% (95% CI: 29.8–43.5%; I² = 12.1%), respectively. Anxiety (k = 7; d = 1.1; 95% CI: 0.72–1.56), depression (k = 24; d = 1.1; 95% CI: 0.80–1.26), and global functioning (k = 14; baseline GAF = 34.5; MD = 25.62; 95% CI: 22.18–29.03) improved significantly (all p < 0.001). In meta-regression, longer follow-up duration was the only significant predictor of Y-BOCS improvement (p = 0.042). Therapeutic effects varied substantially across anatomical stimulation sites. The anterior limb of the internal capsule (ALIC) and its ventral subdivision (vALIC) were most frequently stimulated. The inferior thalamic peduncle was associated with the largest mean Y-BOCS improvement (19.70 points; based on two trial arms only), nucleus accumbens stimulation did not reach the clinical response threshold (≥35% Y-BOCS reduction), and mediodorsal/ventral anterior thalamic stimulation showed no statistically significant benefit. Sensitivity analyses confirmed the robustness of primary estimates. Evidence quality was moderate (RCTs) and low (non-randomized studies). Conclusions: DBS significantly reduces OCD symptom severity in TR-OCD despite substantial heterogeneity, with greater improvements associated with longer follow-up duration and effects maintained for at least 30 months, alongside improvements in comorbid anxiety, depression, and global functioning. Not all anatomical stimulation sites are therapeutically equivalent, underscoring the importance of target selection. High-quality RCTs with standardized anatomical reporting are needed to consolidate the evidence base. Full article

Background: The global prevalence of anxiety and internalizing disorders in adolescence has increased epidemiologically over the past decade, compounded by the impact of the COVID-19 pandemic and the expansion of digital social networks. Despite the availability of empirically based interventions, their systematic implementation in Spanish educational settings—especially in socioeconomically vulnerable environments—remains insufficient. This study aimed to assess the emotional symptomatology profile in a sample of adolescents enrolled in the 2nd year of Compulsory Secondary Education (CSE) and to describe the changes in symptomatology observed after implementation of a multicomponent intervention program in an ordinary school setting. Methods: a quasi-experimental single-group repeated-measures design was used, with pretest–posttest measurements (T1–T2). The sample included 79 participants (age in completed years: M = 13.28 years, SD = 0.64; range: 12–15; 49.4% female, 44.3% male, 6.3% undisclosed), selected by convenience at IES Estuaria (Huelva). The assessment instrument was the Revised Child Anxiety and Depression Scale (RCADS-47), which measures total anxiety, total internalization, and six clinical subdimensions aligned with DSM-5: generalized anxiety disorder (GAD), major depressive disorder (MDD), panic disorder (PD), separation anxiety (SA), social phobia (SP), and obsessive–compulsive disorder (OCD). The intervention consisted of five multicomponent group workshops (45 min/session; three class groups) integrating emotional psychoeducation, receptive music therapy, cognitive–behavioral emotional regulation, assertive communication, and body expression/mindfulness. Results: At pretest, Social Phobia (SP) showed the highest clinical impairment, significantly affecting more females (66.67%) than males (20.00%). Generalized Anxiety Disorder (GAD) also presented high impairment in females. Significant correlations between pairs of subdimensions revealed a high comorbidity pattern. Following the intervention, reductions in clinically significant levels were observed across all dimensions. Matched-pairs Wilcoxon signed-rank tests confirmed statistically significant score reductions from T1 to T2 in Total Anxiety, Total Internalization, Social Phobia, and Generalized Anxiety Disorder (all p < 0.05), with the largest effect for Social Phobia (r = 0.46); no significant change was detected for Panic Disorder, Separation Anxiety, Major Depressive Disorder, or Obsessive–Compulsive Disorder, although the direction of change favored improvement in all cases. Conclusions: The multicomponent intervention program produced improvements in emotional symptomatology over the short-term follow-up period, although without achieving complete clinical remission in any subdimension. The persistent sex differences—with greater residual impairment in the female group after intervention—underscore the need to incorporate a gender perspective in the design of school emotional health programs. High comorbidity rates between subdimensions support the utility of transdiagnostic approaches. Implications for school nursing practice and future research are discussed. Full article

This study aimed to compare antisaccade performance among adolescents with obsessive–compulsive disorder (OCD), their unaffected siblings, and healthy controls, and to examine whether this performance may serve as a candidate familial-risk marker for OCD. The study included 48 adolescents aged 12–18 years with OCD, 35 unaffected siblings, and 39 healthy controls. Participants completed an antisaccade task using an eye-tracking device. Antisaccade correct response rate and latency were evaluated as the primary outcomes, whereas saccadic velocity was examined as an exploratory measure of oculomotor execution. The OCD group showed lower antisaccade correct response rate and longer latency compared with healthy controls, whereas the sibling group demonstrated intermediate performance. Exploratory analyses identified statistically significant group differences in mean saccadic velocity; however, this finding should be interpreted cautiously. Regression analyses indicated that both OCD diagnosis and sibling status were independently associated with antisaccade correct response rate and latency, whereas findings for saccadic velocity should be considered exploratory. These findings suggest that impairments in antisaccade performance may not be specific to OCD but may also be present, albeit to a milder extent, in unaffected siblings, providing preliminary evidence supporting antisaccade performance as a candidate familial-risk marker for OCD that warrants further investigation within an endophenotype framework. Full article

The rapid integration of artificial intelligence (AI) into mental healthcare presents opportunities and ethical challenges, particularly for complex conditions like obsessive–compulsive disorder (OCD). In this perspective, we argue for a Dual Imperative: establishing safety architectures for AI-powered therapeutic tools to prevent algorithmic sycophancy (symptom accommodation), while mandating explainable AI (XAI) in prognostic models to ensure clinical auditability. In therapeutics, we propose a Guardian Angel architecture that utilizes patient-specific fear hierarchies and linguistic stance detection to distinguish compulsive reassurance-seeking from legitimate patient questions. This approach transforms potential therapeutic ruptures into opportunities for distress tolerance via the Digital Ulysses Pact, a patient-authorized, algorithmically enforced response prevention protocol. In diagnostics, we address the black box problem in precision psychiatry. We argue that as AI evolves from detection to high-stakes treatment selection, safety and accountability become a prerequisite for clinical application. Although distinct in implementation, these architectures form an integrated framework for aligning therapeutic and diagnostic AI. These architectures are not parallel tracks but a unified ecosystem: A patient’s XAI-audited profile can inform the Guardian Angel’s configuration, while the longitudinal data gathered during therapy enriches diagnostic precision. Grounded in ethical principles and best practices in OCD, this suggests a path toward AI that is auditable in its diagnostic logic, firm in its therapeutic boundaries, and enforceable through emerging regulatory frameworks. Full article

Background: Treatment-resistant obsessive–compulsive disorder (TR-OCD) remains a major therapeutic challenge. Although current guidelines recommend optimized serotonin reuptake inhibitor (SRI) therapy, clomipramine switching, exposure and response prevention, and antipsychotic augmentation, a substantial proportion of patients continue to experience severe and disabling symptoms. In such cases, clinicians may consider pharmacological intensification strategies beyond guideline-endorsed algorithms. Methods: This study combines a structured narrative synthesis of pharmacological strategies for TR-OCD with a retrospective observational case series from a tertiary OCD referral clinic. Treatment resistance was defined as failure to achieve at least a 35% reduction in Yale–Brown Obsessive Compulsive Scale (Y-BOCS) score after at least two adequate SRI trials, including clomipramine, and optimized exposure and response prevention when available. Five patients treated with pharmacological intensification strategies were included. The primary outcome was percentage change in Y-BOCS score at 12 weeks. Results: The case series illustrates five strategies used in highly refractory OCD: supratherapeutic SSRI dosing, SSRI plus mirtazapine augmentation, dual SSRI therapy, serotonergic intensification in a clozapine-treated patient, and glutamatergic/GABAergic augmentation with topiramate. Baseline Y-BOCS scores ranged from 28 to 32. At 12 weeks, symptom reduction ranged from 23% to 36%. One patient met criteria for response, three showed near-response, and one demonstrated partial improvement. No cases of serotonin toxicity or clinically significant cardiac complications occurred. Conclusions: These cases suggest that carefully monitored pharmacological intensification may be feasible in selected specialist settings, but efficacy and safety require confirmation in prospective controlled studies. Recommendations: Pharmacological intensification should be reserved for highly refractory patients managed in specialist services, implemented with gradual titration, structured serotonin toxicity and electrocardiographic monitoring, and explicit individualized risk–benefit discussion; dual SSRI therapy should be regarded as the most experimental and highest-risk serotonergic option; and prospective controlled studies incorporating standardized functional outcomes are needed to refine patient-selection criteria and clarify which patients may benefit. Full article

Obsessive–compulsive disorder (OCD) is a chronic and disabling psychiatric condition whose neurobiological underpinnings remain incompletely characterized. A growing body of evidence suggests that vitamin D, through its modulatory actions on neuroinflammation, serotonin synthesis, and cortico-striato-thalamo-cortical circuitry, may be implicated in its clinical expression. The present cross-sectional study examined the association between serum 25-hydroxyvitamin D levels and OCD severity in 306 adult outpatients with a diagnosis of OCD, of whom 173 had vitamin D measurements available. Symptom severity was assessed through the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS), and associations were examined using non-parametric tests, partial correlations and multivariable linear regression adjusted for age, gender, age at onset, and bipolar comorbidity. Mean vitamin D was 20.0 ± 13.1 ng/mL, with 60.1% of patients meeting criteria for deficiency. Lower vitamin D levels correlated inversely with Y-BOCS total score (ρ = −0.26, p = 0.001) and with both subscales, and deficient patients showed a mean Y-BOCS total approximately 5.5 points higher than non-deficient ones. In multivariable models, lower vitamin D (β = −0.253, p = 0.001) and earlier age at onset (β = −0.278, p = 0.001) independently predicted greater severity (R² = 0.133), while a history of suicide attempts neither predicted severity nor moderated the vitamin D association. These findings support vitamin D status as a biological correlate of OCD severity and warrant longitudinal and interventional investigation. Full article

Gambling disorder (GD) constitutes a worldwide social and economic burden and is associated with impaired functioning and reduced quality of life. GD shares important mechanistic substrates with obsessive–compulsive disorder (OCD), including dysfunction of cortico-striato-thalamo-cortical circuitry and dysregulation of serotonergic pathways involved in impulsivity, compulsivity, and impaired inhibitory control. On this basis, selective serotonin reuptake inhibitors (SSRIs), widely used in several psychiatric disorders, have been investigated as potential pharmacological treatments for GD. Evidence concerning fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, and escitalopram is heterogeneous and overall limited. Some early single-blind, randomized, and open-label studies have reported reductions in gambling urges, severity, and compulsive symptoms. However, larger and more rigorous placebo-controlled trials have frequently failed to demonstrate consistent superiority over placebo. Interpretation of these findings is further limited by small sample sizes, short observation periods, high dropout rates, heterogeneous outcome measures, and substantial placebo response. While SSRIs remain biologically plausible candidates for modulating the compulsive and impulsive dimensions of GD, current evidence does not support their routine use as first-line pharmacological treatment. Their role appears most justified in the presence of psychiatric comorbidity or within individualized, phenotype-oriented treatment strategies. Full article

The hypothesis that Group A beta-haemolytic Streptococcus (GAS) triggers an autoimmune cascade targeting basal ganglia dopaminergic circuits—producing obsessive–compulsive disorder (OCD), tic disorders, or chorea depending on the receptor subtype involved—is biologically compelling and supported by emerging molecular evidence. Yet PANDAS has remained a diagnostic conundrum since its original description in 1998, with ongoing uncertainty surrounding diagnostic criteria, the interpretation of streptococcal serology, and the distinction from primary neurodevelopmental disorders. This study aimed to review the diagnostic challenges of PANDAS, with focus on streptococcal serology interpretation, advances in dopamine receptor autoantibody biology, the genetic epidemiology of primary tic disorders, and the differential diagnosis of acute neuropsychiatric presentations in children. A structured narrative review was conducted using PubMed, MEDLINE, EMBASE, and the Cochrane Library for publications from 1998 to early 2025 addressing PANDAS, PANS, streptococcal antibodies, childhood movement disorders, autoimmune encephalitis, and the genetics of tic disorders. No currently available biomarker—including ASO, anti-DNase B, anti-basal-ganglia antibodies, or the Cunningham Panel—has demonstrated adequate individual-level diagnostic accuracy for PANDAS. Emerging molecular evidence identifies anti-D1R autoantibodies, acting via G protein-and beta-arrestin-mediated signalling, as candidate biomarkers for PANDAS/PANS neuropsychiatric phenotypes, and anti-D2R autoantibodies for Sydenham chorea movement phenotypes; independent replication in unselected populations is required. Primary tic disorders carry heritability estimates of 50–80% and first-degree familial risk ratios of approximately 18-fold in large population-based cohorts. Prospective blinded studies have not demonstrated a consistent population-level association between GAS infections and tic or OCD exacerbations: PANDAS and PANS remain diagnoses of exclusion. The high background prevalence of both GAS exposure and primary neurodevelopmental disorders in overlapping paediatric age ranges creates conditions for incidental temporal co-occurrence. In the absence of validated molecular biomarkers, diagnostic imprecision carries direct clinical consequences: children may be exposed to treatments with significant risk profiles—including IVIG, plasma exchange, and prolonged antibiotic prophylaxis—while evidence-based therapies are delayed. A stepwise diagnostic approach incorporating the full differential diagnosis is both an epistemological and a patient safety imperative. Full article

Background: Treatment-resistant obsessive–compulsive disorder (OCD) is a heterogeneous and clinically challenging condition. Growing evidence suggests alterations in glutamatergic signaling within cortico–striatal–thalamo–cortical circuits, including those involving medium spiny neurons (MSNs), as well as genetic factors affecting synaptic organization, although the biological mechanisms underlying differential treatment response remain incompletely understood. Methods: This multicenter study presents a translational research framework aimed at investigating potential molecular and cellular correlates of treatment response in a cohort of patients with OCD, stratified according to their response to pharmacological treatments and transcranial magnetic stimulation (TMS). Peripheral blood mononuclear cells from clinically defined subgroups are reprogrammed into human induced pluripotent stem cells and differentiated into MSN-enriched neuronal cultures, enabling in vitro investigation of morphological, biochemical, and transcriptomic features associated with different clinical profiles. Optogenetic and pharmacological stimulation paradigms are applied to probe selected aspects of neuronal activation in vitro, providing a controlled and simplified experimental framework to explore cellular responses under different treatment conditions. By integrating clinical phenotyping with patient-derived cellular models, this study establishes a translational platform for hypothesis generation in the investigation of treatment response in OCD. Results and Conclusions: Preliminary clinical observations from an initial cohort undergoing neuromodulation are also reported to document feasibility and early clinical implementation of the study, providing an initial characterization of the cohort. Full article

Background: Obsessive–compulsive disorder (OCD) frequently co-occurs with autism spectrum disorder (ASD), but the prevalence and clinical correlates of this comorbidity remain incompletely understood. Methods: We examined a clinical sample of 603 patients with a primary diagnosis of OCD, of whom 149 (24.7%) presented with comorbid ASD. Sociodemographic variables, clinical characteristics, comorbidities, and obsessive–compulsive symptom dimensions were compared between patients with and without ASD. Results: Patients with OCD + ASD reported an earlier onset of both obsessive–compulsive symptoms and full-blown disorder. While overall symptom severity (Y-BOCS, HAM-D, and HAM-A) was comparable, OCD + ASD patients were characterized by a higher exposure to stressful and traumatic life events, including severe trauma (e.g., death of a close family member, sexual abuse, physical violence, serious illness, and bullying). Severe traumatic events, in particular, were independently associated with ASD comorbidity in our OCD cohort (exploratory model). Comorbidities were also distinct: onychophagia (66.4% vs. 0.4%) and trichotillomania (8.7% vs. 0%) were markedly more prevalent in the OCD + ASD group. Phenomenologically, OCD + ASD patients more often exhibited religious and somatic obsessions, as well as repetition compulsions. Specifically, somatic obsessions were independently associated with ASD in our regression analysis. Conclusions: OCD with comorbid ASD represents a clinically distinct subgroup, characterized by greater vulnerability to trauma, earlier onset, unique symptom profiles, and specific comorbidities. Recognition of these features, and in particular a history of severe traumatic experiences and the presence of somatic obsessions, may support earlier consideration of ASD comorbidity during OCD assessment and may inform personalized treatment planning. Full article

Background/Objectives: Although obsessive–compulsive disorder (OCD) is clinically heterogeneous, it is unclear whether specific metacognitive belief domains are differentially associated with particular symptom dimensions in adults with confirmed OCD. This systematic review synthesised the available clinical evidence and explored its implications for dimension-informed case formulation and treatment planning. Methods: In March 2026, PubMed/MEDLINE, Scopus, Cochrane CENTRAL and Google Scholar were searched without date or language restrictions. Eligible studies enrolled adults with a confirmed diagnosis of OCD, administered at least one validated metacognitive instrument (MCQ-30/65, TFI, TAF, BARI, SSQ or OBQ-based subscales) and reported associations with validated dimensional OCD measures. The review was preregistered on PROSPERO (CRD420261338178). Due to methodological heterogeneity, the findings were synthesised narratively in accordance with SWiM guidance. Results: Ten studies, including 1320 adults with OCD, were included. These studies were conducted across five countries between 2010 and 2025. Negative beliefs about thought uncontrollability and danger (MCQ-30 NB) showed the broadest associations across the synthesis, particularly with the checking/harm avoidance and the unacceptable thought dimensions. Thought-fusion constructs (TAF/TFI) were most consistently associated with checking/harm avoidance and unacceptable thought presentations. Beliefs about rituals and stop-signal criteria (BARI/SSQ) were most relevant to symmetry/ordering. In contrast, contamination/washing and hoarding exhibited weaker and less consistent metacognitive profiles. Conclusions: The available evidence suggests that metacognitive belief profiles in OCD are not dimensionally uniform. Harm-relevant metacognitions appear to be the most salient factor in the checking and unacceptable thought dimensions, whereas ritual-regulation metacognitions appear to be more relevant to the symmetry/ordering dimension. While these findings may inform dimension-sensitive case formulation and generate testable hypotheses for future metacognitive and exposure-based treatment research, they do not yet justify prescriptive, dimension-specific treatment algorithms. The evidence base remains predominantly cross-sectional and methodologically diverse. Full article

Background: Severe, treatment-resistant Obsessive–Compulsive Disorder (OCD) remains a major clinical challenge. When conventional pharmacological and psychotherapeutic strategies fail, neuromodulatory interventions such as repetitive transcranial magnetic stimulation (rTMS) and psychosurgical approaches are increasingly considered. Although both modalities target nodes within the cortico-striato-thalamo-cortical (CSTC) circuit, their relative effectiveness has not been examined within a unified analytical framework. Objective: We aimed to compare responder rates between rTMS and psychosurgical interventions in adults with treatment-resistant OCD through a systematic review and meta-analysis. Methods: A PRISMA-guided search of PubMed and Scopus (2015–2025) identified clinical studies reporting treatment response. Pooled responder rates were estimated separately for each modality using random-effects models. Between-study heterogeneity and publication bias were systematically assessed. Results: Fourteen studies met inclusion criteria, including 10 rTMS studies (416 participants) and four lesion-based psychosurgical studies (142 participants). Both modalities demonstrated clinically meaningful responder rates. Pooled analyses suggested higher responder proportions in psychosurgical cohorts (RR = 3.06, 95% CI 1.43–6.54); however, this finding was accompanied by substantial heterogeneity (I² = 63%) and signals of publication bias. Follow-up duration differed markedly between modalities (mean 2.4 months for rTMS vs. 33.0 months for psychosurgery), reflecting fundamentally different study designs and outcome assessment timepoints. Conclusions: Differences in pooled responder rates should be interpreted as exploratory rather than as evidence of comparative efficacy. The lack of a shared comparator, differences in patient selection, and large discrepancies in follow-up limit direct comparisons between modalities. These findings support a stepped-care framework for neuromodulation in treatment-resistant OCD and highlight the need for methodologically harmonized studies to better define the role of each intervention across distinct clinical profiles of treatment resistance. Full article

Background/Objective: A substantial proportion of patients with obsessive–compulsive disorder (OCD) does not respond adequately to first-line treatments such as selective serotonin reuptake inhibitors and cognitive-behavioral therapy. OCD has traditionally been conceptualized as a serotonergic disorder. However, emerging evidence suggests that glutamatergic dysfunction plays an important role. Ketamine and esketamine are NMDA receptor antagonists with rapid antidepressant effects and have therefore attracted interest as potential treatments for OCD. This scoping review aims to map and synthesize the existing preclinical and clinical evidence regarding the therapeutic potential of ketamine and esketamine in OCD. Methods: A scoping review methodology based on the Arksey and O’Malley framework and Joanna Briggs Institute guidance was applied. Searches were conducted in PubMed, Scopus, and Web of Science. Studies that examined ketamine or esketamine in OCD populations or relevant experimental models were included. Results: Twenty-one studies met the inclusion criteria, of which five were preclinical studies and sixteen were clinical investigations. Preclinical evidence suggests that ketamine and esketamine improve compulsive-like behaviors. Clinical studies suggest that ketamine can produce rapid reductions in obsessive symptoms, though results remain inconsistent. Most trials evaluated single administrations, while limited evidence suggests that repeated dosing strategies may provide greater clinical benefit. Conclusions: Ketamine and esketamine show promise as rapid acting interventions for OCD, particularly in treatment refractory cases. However, current evidence remains preliminary and heterogeneous. Future research should prioritize adequately powered randomized trials and investigation of repeated administration protocols with longer follow-up periods to determine efficacy and optimal clinical implementation. Full article