Treatment-resistant Obsessive-compulsive Disorder Research Articles

Joint anatomical, histological and imaging investigation of the midbrain target region for superolateral medial forebrain bundle (slMFB) DBS.

Deep Brain Stimulation (DBS) of the superolateral branch of the medial forebrain bundle (slMFB) is currently being researched in clinical trials and open case series as a therapeutic option for treatment resistant major depressive disorder (TR-MDD) and treatment resistant obsessive-compulsive disorder (TR-OCD). There are numerous publications describing stimulation in such proximity to the ventral tegmental area (VTA) and open questions remain concerning the stimulation target and its functional environment. As of right now, we are not aware of any publications that compare the typical electrode placements with the histologically supported tractographic depiction of the target structure. We used three cadaver midbrain samples with presumed unaltered anatomy. After fixation, staining and slicing, the histological samples were warped to the MNI (Montreal Neurological Institute) big brain environment. Utilizing a tractographic atlas, a qualitative analysis of the typical slMFB stimulation site in the lateral VTA utilizing a subset of clinically implanted DBS electrodes in n=12 patients, successfully implanted for TR-OCD was performed. A joint qualitative overlay analysis of predominantly tyrosine-hydroxylase stained histology at different resolutions in an anatomical common space was achieved. Localization of the DBS-lead bodies was found in the typical positions in front of the red nuclei in the lateral VTA. DBS lead tip region positions explained the oculomotor side effects of stimulation related to para-nigral or parabrachial pigmented sub-nuclei of the VTA, respectively. The location of active electrode contacts suggest downstream and antidromic effects on the greater VTA related medial forebrain bundle system. This is the first dedicated joint histopathological overlay analysis of DBS electrodes targeting the slMFB and lateral VTA in a common anatomical space. This analysis might serve to better understand the DBS target region for this procedure.

Twice-a-day low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over right dorsolateral prefrontal cortex in treatment-resistant obsessive–compulsive disorder: A case report

Twice-a-day low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over right dorsolateral prefrontal cortex in treatment-resistant obsessive–compulsive disorder: A case report

Long-term clinical outcome of a novel bilateral capsulotomy with focused ultrasound in refractory obsessive-compulsive disorder treatment.

Magnetic resonance-guided focused ultrasound (MRgFUS) capsulotomy is a promising treatment for refractory obsessive-compulsive disorder (OCD); however, long-term clinical outcome studies are lacking. We aimed to investigate the long-term efficacy and safety of MRgFUS capsulotomy in patients with refractory OCD. Ten of the eleven patients who underwent MRgFUS capsulotomy for treatment-resistant OCD between 2013 and 2014 were included in this study. Clinical outcomes were assessed after 10 years of follow-up post-MRgFUS capsulotomy using tools such as neuropsychological test, the Frontal Systems Behavior Scale (FrSBe), and a locally developed MRgFUS-patient-centered outcomes questionnaire. After 10 years of follow-up, there was a mean improvement of 52.3% in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score. Seven out of the ten participants responded fully (Y-BOCS reduction ≥35% + CGI-I 1 or 2) to the procedure, two of whom achieved remission (Y-BOCS score ≤12 and CGI-S 1 or 2). Obsessive-compulsive symptoms and overall functioning significantly reduced and improved, respectively (Y-BOCS = 20.7 after 2 years vs. 16.4 after 10 years, p = 0.012; Global Assessment of Functioning = 57.4 after 2 years vs. 69.0 after 10 years, p = 0.011). The patients experienced significantly improved frontal lobe-related functions (FrSBe Sum before 91.0 ± 17.6 vs. after 78.6 ± 17.7, p < 0.05). No adverse effects, including cases of suicide and neurological deficits, were reported. The majority of the respondents were generally satisfied with MRgFUS capsulotomy. MRgFUS capsulotomy is an effective and safe treatment option for the treatment of severe refractory OCD with sustained efficacy even after 10 years.

Safety and efficacy of targeting the supplementary motor area with double-cone deep transcranial magnetic stimulation vs figure-eight coil in treatment of obsessive-compulsive disorder with comorbid major depressive disorder

Background and objectiveThe Supplementary Motor Area (SMA), a relatively large brain structure predominantly located along the interhemispheric fissure, is an established target for repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Obsessive-Compulsive Disorder (OCD). We investigated the feasibility, safety, and efficacy of targeting SMA using a double-cone “deep” TMS coil compared to conventional figure-eight coil for treatment of OCD with comorbid Major Depressive Disorder (MDD). MethodsSixty-two patients with treatment-resistant OCD and comorbid MDD participated in the study. All patients received high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC) with a figure-eight coil (MagVenture B70), followed by 1 Hz rTMS over the bilateral SMA using either the B70 (N = 25) or double-cone deep coil (MagVenture DB80) (n = 23) for 36 treatment sessions. Weekly clinical assessments were conducted. ResultsSubjects overall had significant reductions in OCD and depressive symptom severity at the primary endpoint. Subjects stimulated at SMA with the double-cone deep coil had statistically significantly lesser reductions in overall OCD and depression symptom severity compared to the figure-eight group. The intensity of stimulation at SMA was significantly greater with the double-cone deep than figure-eight coil and e-field modeling showed that it affected broader regions beyond SMA (off-target stimulation). There was no significant difference in reported tolerability between groups. ConclusionsSMA stimulation using either a double-cone deep or conventional figure-of-eight coil was safe and was associated with a significant reduction in comorbid OCD and depression symptoms, but the higher intensities of stimulation with the double-cone deep coil used in this study were significantly less clinically beneficial than figure-eight coil stimulation.

Feasibility and Safety of Accelerated Sequential Theta Burst Stimulation for Adolescent Obsessive-compulsive Disorder: A Case Report

Repetitive transcranial magnetic stimulation (rTMS) has been shown to be effective for treatment-resistant obsessive-compulsive disorder (OCD) in adults; however, it has not yet been studied in adolescents with OCD. This report details the feasibility and safety of administering sequential accelerated theta burst stimulation (sequential aTBS) in an adolescent with treatment-resistant OCD. Despite completing 29 continuous TBS sessions over the right dorsolateral prefrontal cortex (DLPFC) and an additional 15 intermittent TBS sessions on the left DLPFC, our patient did not show any symptom improvement. This case represents the first documentation of the feasibility, safety, and tolerability of sequential aTBS in adolescents with OCD. The patient tolerated the aTBS sessions well, experiencing only mild tingling and local muscle twitches.

Deep Brain Stimulation for Childhood Treatment-Resistant Obsessive-Compulsive Disorder: Mental Health Clinician Views on Candidacy Factors

Introduction Deep brain stimulation (DBS) is approved under a humanitarian device exemption to manage treatment-resistant obsessive-compulsive disorder (TR-OCD) in adults. It is possible that DBS may be trialed or used clinically off-label in children and adolescents with TR-OCD in the future. DBS is already used to manage treatment-resistant childhood dystonia. Evidence suggests it is a safe and effective intervention for certain types of dystonia. Important questions remain unanswered about the use of DBS in children and adolescents with TR-OCD, including whether mental health clinicians would refer pediatric patients for DBS, and who would be a good candidate for DBS. Objectives To explore mental health clinicians’ views on what clinical and psychosocial factors they would consider when determining which children with OCD would be good DBS candidates. Materials and Methods In depth, semi-structured interviews were conducted with n = 25 mental health clinicians who treat pediatric patients with OCD. The interviews were transcribed, coded, and analyzed using thematic content analysis. Three questions focused on key, clinical, and psychosocial factors for assessing candidacy were analyzed to explore respondent views on candidacy factors. Our analysis details nine overarching themes expressed by clinicians, namely the patient’s previous OCD treatment, OCD severity, motivation to commit to treatment, presence of comorbid conditions, family environment, education on DBS, quality of life, accessibility to treatment, and patient age and maturity. Conclusions Clinicians generally saw considering DBS treatment in youth as a last resort and only for very specific cases. DBS referral was predominantly viewed as acceptable for children with severe TR-OCD who have undertaken intensive, appropriate treatment without success, whose OCD has significantly reduced their quality of life, and who exhibit strong motivation to continue treatment given the right environment. Appropriate safeguards, eligibility criteria, and procedures should be discussed and identified before DBS for childhood TR-OCD becomes practice.

Bilateral Anterior Capsulotomy for Treatment-Resistant Obsessive-Compulsive Disorder

Introduction: Ablative surgery is an intervention of last resort for treatment-resistant obsessive-compulsive disorder (TROCD). Our center has been using bilateral anterior capsulotomy (BAC) for the past 20 years for patients eligible for limbic surgery. This report details our experience with BAC for TROCD. Method: Five patients with OCD met eligibility criteria for BAC. Entry protocols were complex and took around 6 months to complete. Stereotactic radiofrequency was used to produce the capsulotomies. Lesion length varied between 5.7 and 16.9 mm in the coronal plane. Patients were followed between 4 and 20 years. Results: All 5 patients (100%) were responders as defined by the widely accepted criteria of a reduction of ≥35% in Yale-Brown Obsessive Compulsive Scale (YBOCS) score at 18-month follow-up. Four patients remained responders at the 48 months. One patient was lost to follow-up. Responder status when viewed from the perspective of the YBOCS was sustained over the 4- to 20-year follow-up with one relapse 19 years postsurgery when medications were discontinued. Real-world psychiatric outcomes were different as other vulnerabilities surfaced illustrating the multifactorial determinants of mental health. No patient had any significant long-term neurocognitive or physical side effects. Conclusion: BAC should remain an option of last resort for patients with severe OCD who remain unresponsive to all other interventions.

Long-Term Safety and Efficacy of Focused Ultrasound Capsulotomy for Obsessive-Compulsive Disorder and Major Depressive Disorder

BackgroundMagnetic resonance–guided focused ultrasound (MRgFUS) trials targeting the anterior limb of the internal capsule have shown promising results. We evaluated the long-term safety and efficacy of MRgFUS capsulotomy in patients with obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). MethodsThis phase 1, single-center, open-label study recruited patients with treatment-resistant OCD and MDD. Outcomes were measured 6 months, 12 months, and 18 to 24 months (long term) after MRgFUS capsulotomy. Neuropsychological testing and neuroimaging were conducted at baseline and 12 months postoperatively. The primary outcome was safety. The secondary outcome was clinical response, defined for OCD as a ≥35% improvement in Yale-Brown Obsessive Compulsive Scale scores and for MDD as a ≥50% reduction in Hamilton Depression Rating Scale scores compared with baseline. ResultsNo serious adverse effects were registered. In patients with OCD (n= 15), baseline Yale-Brown Obsessive Compulsive Scale scores (31.9 ± 1.2) were significantly reduced by 23% (p = .01) at 6 months and 35% (p < .0001) at 12 months. In patients with MDD (n = 12), a 26% and 25% nonsignificant reduction in Hamilton Depression Rating Scale scores (baseline 24.3 ± 1.2) was observed at 6 months and 12 months, respectively. Neuropsychological testing revealed no negative effects of capsulotomy. In the OCD and MDD cohorts, we found a correlation between clinical outcome and lesion laterality, with more medial left–placed lesions (OCD, p = .08) and more lateral right–placed lesions (MDD, p < .05) being respectively associated with a stronger response. In the MDD cohort, more ventral tracts appeared to be associated with a poorer response. ConclusionsMRgFUS capsulotomy is safe in patients with OCD and MDD and particularly effective in the former population.

Disruption of neural periodicity predicts clinical response after deep brain stimulation for obsessive-compulsive disorder

Recent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy (NCT05915741). We developed our neurobehavioral models based on continuous neural recordings in the region of the ventral striatum in an initial cohort of five patients and tested and validated them in a held-out cohort of seven additional patients. Before DBS activation, in the most symptomatic state, theta/alpha (9 Hz) power evidenced a prominent circadian pattern and a high degree of predictability. In patients with persistent symptoms (non-responders), predictability of the neural data remained consistently high. On the other hand, in patients who improved symptomatically (responders), predictability of the neural data was significantly diminished. This neural feature accurately classified clinical status even in patients with limited duration recordings, indicating generalizability that could facilitate therapeutic decision-making.

Pediatric Treatment-Resistant Obsessive Compulsive Disorder: Treatment Options and Challenges.

Pediatric obsessive-compulsive disorder (OCD) is a chronic, potentially debilitating psychiatric condition. Although effective treatments exist, at least 10% of youth do not achieve remission despite receiving first-line treatments. This article reviews the extant, albeit limited, evidence supporting treatment approaches for youth with treatment-resistant OCD. A literature search for articles addressing pediatric treatment-resistant OCD was conducted through April 11, 2024. These results were augmented by searching for treatment-resistant OCD in adults; treatment strategies discovered for the adult population were then searched in the context of children and adolescents. In general, intensive treatment programs and antipsychotic augmentation of an antidepressant had the most substantial and consistent evidence base for treatment-resistant youth with OCD, although studies were limited and of relatively poor methodological quality (i.e., open trials, naturalistic studies). Several pharmacological approaches (clomipramine, antipsychotics [e.g., aripiprazole, risperidone], riluzole, ketamine, D-cycloserine, memantine, topiramate, N-acetylcysteine, ondansetron), largely based on supporting data among adults, have received varying levels of investigation and support. There is nascent support for how to treat pediatric treatment-resistant OCD. Future treatment studies need to consider how to manage the significant minority of youth who fail to benefit from first-line treatment approaches.

Serotonin reuptake inhibitors augmentation with cariprazine in patients with treatment-resistant obsessive-compulsive disorder: a retrospective observational study.

Serotonin reuptake inhibitors augmentation with cariprazine in patients with treatment-resistant obsessive-compulsive disorder: a retrospective observational study.

Supra-Therapeutic Selective Serotonin Reuptake Inhibitor (Ssri) Dosesfor Refractory Obsessive-Compulsive Disorder: A Case Report

Supra-Therapeutic Selective Serotonin Reuptake Inhibitor (Ssri) Dosesfor Refractory Obsessive-Compulsive Disorder: A Case Report

Genomics of severe and treatment-resistant obsessive-compulsive disorder treated with deep brain stimulation: A preliminary investigation.

Individuals with severe and treatment-resistant obsessive-compulsive disorder (trOCD) represent a small but severely disabled group of patients. Since trOCD cases eligible for deep brain stimulation (DBS) probably comprise the most severe end of the OCD spectrum, we hypothesize that they may be more likely to have a strong genetic contribution to their disorder. Therefore, while the worldwide population of DBS-treated cases may be small (~300), screening these individuals with modern genomic methods may accelerate gene discovery in OCD. As such, we have begun to collect DNA from trOCD cases who qualify for DBS, and here we report results from whole exome sequencing and microarray genotyping of our first five cases. All participants had previously received DBS in the bed nucleus of stria terminalis (BNST), with two patients responding to the surgery and one showing a partial response. Our analyses focused on gene-disruptive rare variants (GDRVs; rare, predicted-deleterious single-nucleotide variants or copy number variants overlapping protein-coding genes). Three of the five cases carried a GDRV, including a missense variant in the ion transporter domain of KCNB1, a deletion at 15q11.2, and a duplication at 15q26.1. The KCNB1 variant (hg19 chr20-47991077-C-T, NM_004975.3:c.1020G>A, p.Met340Ile) causes substitution of methionine for isoleucine in the trans-membrane region of neuronal potassium voltage-gated ion channel KV2.1. This KCNB1 substitution (Met340Ile) is located in a highly constrained region of the protein where other rare missense variants have previously been associated with neurodevelopmental disorders. The patient carrying the Met340Ile variant responded to DBS, which suggests that genetic factors could potentially be predictors of treatment response in DBS for OCD. In sum, we have established a protocol for recruiting and genomically characterizing trOCD cases. Preliminary results suggest that this will be an informative strategy for finding risk genes in OCD.

480 Effect of Chronic DBS on Ventral Capsule Ventral Striatum-Specific Circadian Rhythm in Refractory Obsessive-Compulsive Disorder

INTRODUCTION: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) improves symptoms in ∼66% of patients with treatment-resistant obsessive-compulsive disorder (OCD). However, a common adverse effect of VC/VS DBS is hypomania, marked by decreased need for sleep and increased risk-taking behaviors. Modern DBS devices have enabled 24-hour collection of neural data, allowing for tracking of circadian rhythms reflected by VC/VS local field potentials (LFPs). METHODS: We implanted six patients with treatment-resistant OCD with a DBS device configured for constant VC/VS stimulation and recording. Spectral power in the 9 ± 2.5 Hz band was estimated onboard the device every 10 minutes for a median of 249 days (range 77-608). We assessed the rhythmicity of power in this spectral band by fitting 7-day retrospective rolling windows of per-day normalized LFP power to cosine functions using least-squared regression. Output metrics included acrophase (time of peak activity), amplitude, and fit significance. We quantified trends in acrophase over time using Pearson correlation. RESULTS: All six patients demonstrated consistent 24-hour cyclic LFP activity bilaterally. Two of the six had diurnal peaks which shifted significantly earlier across the study period. The remaining four patients had nocturnal peaks, all shifting significantly later over time. Notably, a patient in the latter group experienced three days of hypomania after DBS initiation associated with circadian disruptions even after clinical symptom resolution. Only after clinical DBS adjustment 2 weeks later did circadian rhythm rapidly return to pre-hypomanic levels. CONCLUSIONS: Study patients demonstrated evolving circadian VC/VS LFP activity across the course of DBS therapy, usually independent of cyclic whole-brain activity (i.e. sleep). Conversely, disruptions to these circadian patterns, as observed here during hypomania, may serve as biomarkers of region-specific stimulation side effects.

A Low-Intensity Transcranial Focused Ultrasound Parameter Exploration Study of the Ventral Capsule/Ventral Striatum

ObjectivesDeep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is effective for treatment-resistant obsessive-compulsive disorder (OCD); however, DBS is associated with neurosurgical risks. Transcranial focused ultrasound (tFUS) is a newer form of noninvasive (ie, nonsurgical) stimulation that can modulate deeper regions, such as the VC/VS. tFUS parameters have just begun to be studied and have often not been compared in the same participants. We explored the effects of three VC/VS tFUS protocols and an entorhinal cortex (ErC) tFUS session on the VC/VS and cortico-striato-thalamo-cortical circuit (CSTC) in healthy individuals for later application to patients with OCD. Materials and MethodsTwelve individuals participated in a total of 48 sessions of tFUS in this exploratory multisite, within-subject parameter study. We collected resting-state, reward task, and arterial spin-labeled (ASL) magnetic resonance imaging scans before and after ErC tFUS and three VC/VS tFUS sessions with different pulse repetition frequencies (PRFs), pulse widths (PWs), and duty cycles (DCs). ResultsVC/VS protocol A (PRF = 10 Hz, PW = 5 ms, 5% DC) was associated with increased putamen activation during a reward task (p = 0.003), and increased VC/VS resting-state functional connectivity (rsFC) with the anterior cingulate cortex (p = 0.022) and orbitofrontal cortex (p = 0.004). VC/VS protocol C (PRF = 125 Hz, PW = 4 ms, 50% DC) was associated with decreased VC/VS rsFC with the putamen (p = 0.017), and increased VC/VS rsFC with the globus pallidus (p = 0.008). VC/VS protocol B (PRF = 125 Hz, PW = 0.4 ms, 5% DC) was not associated with changes in task-related CSTC activation or rsFC. None of the protocols affected CSTC ASL perfusion. ConclusionsThis study began to explore the multidimensional parameter space of an emerging form of noninvasive brain stimulation, tFUS. Our preliminary findings in a small sample suggest that VC/VS tFUS should continue to be investigated for future noninvasive treatment of OCD.

Increases in functional connectivity between the default mode network and sensorimotor network correlate with symptomatic improvement after transcranial direct current stimulation for obsessive-compulsive disorder

BackgroundNon-invasive neuromodulation is a promising intervention for obsessive-compulsive disorder (OCD), although its neurobiological mechanisms of action are still poorly understood. Recent evidence suggests that abnormalities in the connectivity of the default mode network (DMN) and the supplementary motor area (SMA) with other brain regions and networks are involved in OCD pathophysiology. We examined if transcranial direct current stimulation (tDCS) alters these connectivity patterns and if they correlate with symptom improvement in treatment-resistant OCD. MethodsIn 23 patients from a larger clinical trial (comparing active tDCS to sham) who underwent pre- and post-treatment MRI scans, we assessed resting-state functional MRI (rs-fMRI) data. The treatment involved 30-minute daily tDCS sessions for four weeks (weekdays only), with the cathode over the SMA and the anode over the left deltoid. We conducted whole-brain connectivity analysis comparing active tDCS-treated to sham-treated patients. ResultsWe found that active tDCS, but not sham, led to connectivity increasing between the DMN and the bilateral pre/postcentral gyri (p = 0.004, FDR corrected) and temporal-auditory areas plus the SMA (p = 0.028, FDR corrected). Also, symptom improvement was directly associated with connectivity increasing between the left lateral sensorimotor network and the left precuneus (r = 0.589, p = 0.034). LimitationsLimited sample size (23 participants with resting-state neuroimaging), inability to analyze specific OCD symptom dimensions (e.g., harm, sexual/religious, symmetry/checking, cleaning/contamination). ConclusionsThese data offer novel information concerning functional connectivity changes associated with non-invasive neuromodulation interventions in OCD and can guide new brain stimulation interventions in the framework of personalized interventions.

Mindfulness-based cognitive therapy neurobiology in treatment-resistant obsessive-compulsive disorder: A domain-related resting-state networks approach

Mindfulness-based cognitive therapy (MBCT) stands out as a promising augmentation psychological therapy for patients with obsessive-compulsive disorder (OCD). To identify potential predictive and response biomarkers, this study examines the relationship between clinical domains and resting-state network connectivity in OCD patients undergoing a 3-month MBCT programme. Twelve OCD patients underwent two resting-state functional magnetic resonance imaging sessions at baseline and after the MBCT programme. We assessed four clinical domains: positive affect, negative affect, anxiety sensitivity, and rumination. Independent component analysis characterised resting-state networks (RSNs), and multiple regression analyses evaluated brain-clinical associations. At baseline, distinct network connectivity patterns were found for each clinical domain: parietal-subcortical, lateral prefrontal, medial prefrontal, and frontal-occipital. Predictive and response biomarkers revealed significant brain-clinical associations within two main RSNs: the ventral default mode network (vDMN) and the frontostriatal network (FSN). Key brain nodes —the precuneus and the frontopolar cortex— were identified within these networks. MBCT may modulate vDMN and FSN connectivity in OCD patients, possibly reducing symptoms across clinical domains. Each clinical domain had a unique baseline brain connectivity pattern, suggesting potential symptom-based biomarkers. Using these RSNs as predictors could enable personalised treatments and the identification of patients who would benefit most from MBCT.

Treatment-resistant obsessive-compulsive disorders

Obsessive-compulsive disorders (OCD) are mainly treated with disorder-specific cognitive behavioral therapy using exposure and response management and/or selective serotonin reuptake inhibitors; however, asignificant subgroup of patients does not sufficiently benefit from this approach. This article provides an overview of treatment-resistant OCD. In this narrative review the definition, causes, diagnostic and therapeutic approaches to treatment-resistant OCD are addressed. Treatment resistance can be assumed in the absence of clinically relevant improvement under therapy, in the sense of areduction of < 25% on the Yale-Brown obsessive-compulsive scale and ascore of 4(no change) on the clinical global impression-improvement scale. The number of unsuccessful treatment attempts required to establish treatment resistance is defined differently. Causative factors include misdiagnosis, a high severity, comorbid disorders, substance use, specific symptom constellations, organic causes, environmental factors, and aggravating factors in psychotherapy and pharmacotherapy. Suggestions for diagnostic and therapeutic approaches based on the GermanS3 guideline on OCD are presented. For patients with treatment resistance to first-line therapy, useful diagnostic and therapeutic recommendations are available (psychotherapeutic, psychopharmacological and neurostimulation procedures).

Benefits of stereotactic radiosurgical anterior capsulotomy for obsessive-compulsive disorder: a meta-analysis.

Anterior capsulotomy (AC) is a therapeutic option for patients with severe, treatment-resistant obsessive-compulsive disorder (OCD). The procedure can be performed via multiple techniques, with stereotactic radiosurgery (SRS) gaining popularity because of its minimally invasive nature. The risk-benefit profile of AC performed specifically with SRS has not been well characterized. Therefore, the primary objective of this study was to characterize outcomes following stereotactic radiosurgical AC in OCD patients. Studies assessing mean Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores before and after stereotactic radiosurgical AC for OCD were included in this analysis. Inverse-variance fixed-effect modeling was used for pooling, and random-effects estimate of the ratio of means and standard mean differences were calculated at 6 months, 12 months, and the last follow-up for Y-BOCS scores, as well as the last follow-up for the Beck Depression Inventory (BDI)/BDI-II scores. A generalized linear mixed model was used to generate fixed- and random-effects models for categorical outcomes. Univariate random-effects meta-regression was used to evaluate associations between postoperative Y-BOCS scores and study covariates. Adverse events were summed across studies. Publication bias was assessed with Begg's test. Eleven studies with 180 patients were eligible for inclusion. The mean Y-BOCS score decreased from 33.28 to 17.45 at the last-follow up (p < 0.001). Sixty percent of patients were classified as responders and 10% as partial responders, 18% experienced remission, and 4% had worsened Y-BOCS scores. The degree of improvement in the Y-BOCS score correlated with time since surgery (p = 0.046). In the random-effects model, the mean BDI at the last follow-up was not significantly different from that preoperatively. However, in an analysis performed with available paired pre- and postoperative BDI/BDI-II scores, there was significant improvement in the BDI/BDI-II scores postoperatively. Adverse events numbered 235, with headaches, weight change, mood changes, worsened depression/anxiety, and apathy occurring most commonly. Stereotactic radiosurgical AC is an effective technique for treating OCD. Its efficacy is similar to that of AC performed via other lesioning techniques.

Transcranial Magnetic Stimulation of Dorsolateral Prefrontal Cortex in Treatment-Resistant Obsessive Compulsive Disorder: A Mini-Review

Introduction: Approximately two-thirds of patients with Obsessive-Compulsive Disorder (OCD) exhibit inadequate responses to current standard therapies. A previous meta-analysis has shown the potential benefit of repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (dlPFC) area in patients with OCD. However, the analysis also included patients who had not previously failed first-line treatments. This mini-review aims to explore the therapeutic effects of rTMS applied to the dlPFC area in patients with treatment-resistant OCD. Methods: We conducted a comprehensive search for randomized controlled trials (RCTs) and observational studies across various databases (PubMed, EMBASE, Ebsco, Web of Science, and Cochrane Central). Eligible studies encompassed rTMS administered to the dlPFC area in cases of treatment-resistant OCD. Studies that did not focus on using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) to assess the efficacy of rTMS were excluded. Quality assessments were conducted based on the Cochrane risk-of-bias tool. Results: Our review identified five RCTs involving 132 patients that met the established criteria. The application of high-frequency (HF) and low-frequency (LF) rTMS to the dlPFC region yielded controversial post-treatment Y-BOCS findings due to factors such as small sample sizes, short-term study durations, variations in rTMS protocols, and four studies exhibiting a high risk of bias. Discussion: The available data is constrained by a scarcity of high-quality, large-scale trials with extended follow-up periods and optimized protocols. Further research is warranted to establish the efficacy of rTMS administered to the dlPFC in this patient population.