Resistant OCD Research Articles

Combination of CBT and rTMS: what are the advantages?

IntroductionObsessive-Compulsive Disorder (OCD) and Major Depressive Disorder (MDD) are among the ten most disabling disorders, yet only 30-40% of people with the condition seek specialist care (WHO). Considered a relatively new tool in the treatment of OCD and MDD, repetitive transcranial magnetic stimulation (rTMS) was first used by our team 1 year ago. Based on current literature cognitive behavioural therapy (CBT) is effective in 60% of OCD cases, with MDD also having a good response rate of 50-60%. The efficacy of SSRI’s has been demonstrated, but side effects can have a negative impact on adherence in the long term. Prolonged use of certain drugs has adverse reactions that lead specifically to memory impairment, which compromises suitability for psychotherapy. The same problem applies to the use of electroconvulsive therapy (ECT) in a major depressive episode.ObjectivesOur aim was to study the efficacy of combining rTMS with CBT, to gather clinical experience on how these two different methods work in practice when combined.MethodsPatients diagnosed with therapy resistant MDD received rTMS treatment using 50Hz theta burst over 10 sessions. Therapy resistant OCD patients were treated by a 15 sessions rTMS using 1Hz single pulse. These rTMS sessions were combined with CBT, of which we would like to highlight two cases: one of them is a 34 years old woman, who has wide range of sexual, checking and contamination-related OCD symptoms and only received SSRI treatment so far. The other one is a 29 years old man, who suffers from religious obsessions, cleaning compulsions and other repetitive behaviours.Results The positive effects of rTMS treatment on working memory functions, attentional capacity and cooperative skills without significant additive effects suggest exciting possibilities for combining the two treatments, thus the combined treatment has been tested in clinical practice. In our own patient care, an important experience was that patients were committed to the therapy, felt safe and, unlike with medications, did not have to worry about side effects. While medication and ECT can make psychotherapy more difficult in the long term - mainly because of memory problems - rTMS facilitates it. Patients appreciate that we approach their problems in a complex way, and they perceive that the combination of the two very different methods reflects professionalism. Our poster attempts to present the experience of combining rTMS and CBT from the therapist’s perspective through two case studies.ConclusionsBased on our experiences it is an effective approach to combine rTMS with CBT in therapy resistant MDD and OCD patients. In the light of these results the revision of the existing guidelines are considerable.AcknowledgementsThis study has been supported by the Human Resource Development Operating Programme 5.2.6 grant.Disclosure of InterestNone Declared

Real world experience of Endoxifen augmentation therapy in a case of resistant OCD

About 40%–60% of obsessive-compulsive disorder patients do not achieve full remission even when treated with selective serotonin reuptake inhibitor and cognitive behavioural therapy. Here, we describe a case of a 30-year-old female suffering from OCD, who was not improved even after fluoxetine 80 mg per day and behavioural therapy and was successfully treated with low dose fluoxetine (60 mg/day) and Endoxifen (8 mg/day).

An update on the Pharmacological and Psychotherapeutic Management of Treatment Resistant OCD

AbstractAlthough the rates of response to first-line pharmacological treatments (serotonin reuptake inhibitors – SRIs) are generally twice that of placebo, only 40-60% of patients respond sufficiently or are able to tolerate traditional first-line pharmacotherapy. Augmentation with dopamine antagonist medications is associated with the strongest evidence, yet dopamine antagonists benefit only a minority of those who try them and carry elevated risks of adverse effects. Based on evolving pathophysiologic models of OCD, a variety of agents targeting serotonin, dopamine, norepinephrine, glutamate, and anti-inflammatory pathways have been explored as alternative or adjunctive therapies for treatment-resistant OCD and have at least preliminary evidence of efficacy. Similarly, approximately 50% of patients do not respond optimally to first psychotherapeutic treatments including cognitive behavioural therapy (CBT) and exposure and response prevention (ERP), even when combined with pharmacotherapy. The psychotherapy outcome literature is heterogeneous and very few psychological strategies have been developed specifically to treat treatment resistant OCD. However, a recent systematic review concluded that CBT improved treatment response in individuals with pharmacotherapy resistance. This presentation will present an update on the pharmacological and psychotherapeutic treatment of refractory OCD including novel strategies such as the use of psychedelics.Disclosure of InterestM. Van Ameringen Grant / Research support from: Elvium, CIHR,Hamilton Academic Health Sciences Organization, Consultant of: Abbvie, Bausch Health, Boehringer Ingelheim, Elvium, Jazz, Vistagen, Speakers bureau of: Abbvie, Elvium (Purdue), Lundbeck, Otsuka, Sunovion, and Takeda

Sleep predicts the response to rTMS and CBT in patients with OCD: an open label effectiveness study

BackgroundAlthough many OCD patients benefit from repetitive transcranial magnetic stimulation (rTMS) as treatment, there is still a large group failing to achieve satisfactory response. Sleep problems have been considered transdiagnostic risk factors for psychiatric disorders, and prior work has shown comorbid sleep problems in OCD to be associated with non-response to rTMS in OCD. We therefore set out to investigate the utility of sleep problems in predicting response to rTMS in treatment resistant OCD. MethodA sample of 61 patients (treated with 1-Hz SMA or sequential 1-Hz SMA+DLPFC rTMS, combined with cognitive behavioral therapy) were included. Sleep disturbances were measured using the PSQI, HSDQ and actigraphy. Treatment response was defined as a decrease of at least 35% in symptom severity as measured with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Results32 of 61 patients (52.5%) responded to rTMS, and trajectories of response were similar for both rTMS protocols. Three PSQI items (Subjective Sleep Quality; Sleep Latency and Daytime Dysfunction) and the HSDQ-insomnia scale were found to predict TMS response. A discriminant model yielded a significant model, with an area under the curve of 0.813. ConclusionFuture replication of these predictors could aid in a more personalized treatment for OCD.

Treatment strategies for serotonin reuptake inhibitor-resistant obsessive-compulsive disorder: A network meta-analysis of randomised controlled trials

Objectives Treatment-resistant obsessive-compulsive disorder is a chronic debilitating illness. We conducted a network meta-analysis [NMA] to compare the efficacy of all interventions in SRI-resistant OCD from published Randomised controlled trials [RCT]. Methods We performed an NMA of RCTs in SRI resistant OCD from all modalities of treatments; pharmacological, psychological, neuromodulation, neurosurgery including deep brain stimulation. The design-by-treatment interaction inconsistency model within the frequentist framework was adopted with a change in Yale-Brown Obsessive-Compulsive Scale score as the primary outcome. We conducted sensitivity analyses excluding studies examining neurosurgical interventions, deep brain stimulation, studies in the paediatric population, and studies from a single geographical region. We also conducted analyses of interventions categorised into treatment groups. Results 55 RCTs examining 19 treatments or placebo involving 2011 participants were included in the NMA. Ondansetron [Standardised mean difference −2.01 (95% CI: −3.19, −0.83)], deep TMS [– 1.95 (−3.25, −0.65)], therapist administered Cognitive Behavioural Therapy [CBT-TA] [−1.46 (−2.93, 0.01)] and aripiprazole [−1.36 (−2.56, −0.17)] were ranked as the best four treatments on using the Surface Under the Cumulative Ranking [SUCRA] percentage values (85.4%, 83.2%, 80.3%, 67.9% respectively). While all four interventions had large effect sizes, CBT[TA] narrowly missed statistical significance in our analysis. In sensitivity analyses, deep TMS was ranked as the best treatment strategy for SRI-resistant OCD. The small number of subjects in individual studies, higher confidence interval limits, and wider prediction interval for most agents warrant a cautious interpretation. Conclusions Considering the principal analysis and sensitivity analyses together, deep TMS, ondansetron, CBT[TA], and aripiprazole may be considered a first-line intervention for SRI-resistant OCD in adults. Other This work was not funded. The NMA has been registered with PROSPERO, [Registration number: CRD42020173589]

Local field potentials in the BNST in patients with OCD: acute effects of DBS after symptom provocation

IntroductionObsessive-compulsive disorder (OCD) is a disabling psychiatric disorder that affects 2-3% of the population. Pharmacological or cognitive behavioral therapy can reduce symptoms. Deep brain stimulation is emerging for treatment-resistant patients.ObjectivesWe measured neuronal activity in two patients with treatment-resistant OCD, who had DBS electrodes implanted bilaterally in the BNST. Local field potentials were recorded directly from the BNST during and without symptom provocation and without electrical stimulation.MethodsIn two patients with a diagnosis of treatment resistant OCD (TR-OCD) local field potentials (LFP) were recorded as part of their clinical follow up post-implantation. In both patients, the diagnosis of TR-OCD was confirmed by a neuropsychiatric examination and a multidisciplinary committee comprising both experienced psychiatrists and neurosurgeons from different medical centers in Belgium. We used BrainSense recording technology in the Percept PC to record the LFPs. The LFP recordings in the first patient were acquired on the 15th day after DBS surgery. In the second patient, the interval between implantation and recording was 18 days. Symptom provocation was performed using the MOCCS image set, developed by Mataix-Cols.ResultsAt rest, relative power peaks in the BNST were highest in the theta (4-8 Hz) frequency band for both patients. In both patients switching DBS ON during provocation images appears to cause the LFP signal to closely resemble that recorded during neutral images.ConclusionsThe main finding of this pilot study is that switching stimulation ON in the BNST during provocation images causes the LFP signal to more closely resemble the LFP recorded during neutral images.DisclosureNo significant relationships.

Transcranial Magnetic Stimulation (TMS) Safety with Respect to Seizures: A Literature Review.

Transcranial magnetic stimulation is an increasingly popular FDA-approved treatment for resistant depression, migraines, and OCD. Research is also underway for its use in various other psychiatric and medical disorders. Although rare, seizures are a potential adverse event of TMS treatment. In this article, we discuss TMS-related seizures with the various coils used to deliver TMS, the risk factors associated with seizures, the differential diagnosis of its presentations, the effects of sleep deprivation and alcohol use on seizures, as well as seizure risks with protocols for traditional TMS, theta-burst stimulation, and accelerated TMS. A discussion is presented comparing the potential risk of seizures with various psychotropic medications versus TMS. Included are case reports of TMS seizures in the child/adolescent patient, bipolar disorder patients, patients with a history of a traumatic brain injury, and those with epilepsy. Reports are also shared on TMS use without seizures in patients with a history of head injuries and TMS’s continued use if patients have a seizure during their TMS treatment. Findings generated in this review suggest the following. Seizures, if present, are usually self-limiting. Most treatment recommendations for TMS-related seizures are supportive in nature. The risk of TMS-related seizures is <1% overall. TMS has successfully been used in patients with epilepsy, traumatic brain injuries, and those with a prior TMS-related seizure. The rate of TMS-related seizures is comparable to that of most psychotropic medications. While having a seizure is a rare but serious adverse effect of TMS, the benefits of treating refractory depression with TMS may outweigh the risk of suicidal ideation and other significant complications of depression.

Clinical utility of repeated intravenous ketamine treatment for resistant obsessive-compulsive disorder.

Glutamate modulators are used to treat OCD resistant to serotonin reuptake inhibitors (SRIs). Ketamine has shown some promise in treating OCD. Data on the use of ketamine in SRI-resistant OCD is limited, with no studies on the role of multiple ketamine infusions in this disorder. We report our experience of treating SRI- resistant OCD with multiple ketamine infusions. We reviewed the clinical charts of 14 adult inpatients with a diagnosis of SRI-resistant OCD and treated them with repeated ketamine infusions [mean (SD) = 5.4 (2.5)]. There was a significant reduction in the Yale-Brown Obsessive-Compulsive Scale (YBOCS) total score following intravenous ketamine infusions. One patient showed a dramatic response (a drop in the YBOCS to '0') and two patients showed a partial response (25-35 % reduction in the YBOCS). Eleven patients showed no clinical improvement. Ketamine may, therefore, be somewhat effective in a subset of OCD patients who are resistant to SRIs. Our findings suggest the need to examine the efficacy of ketamine in controlled studies with larger samples. It may be possible to identify predictors of response to ketamine in larger studies.

Uncovering Relationships Between Mood, Movement, and Neural Activity via Dense Longitudinal Data From an Obsessive-Compulsive Disorder Patient Undergoing Deep Brain Stimulation

Treatment resistant OCD is currently addressed with Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum. While this shows promise, clinical response is not reliable. To improve existing treatment, an experimental paradigm has been developed, with implants in Ventral Striatum and Supplementary Motor Area, driven at different frequencies to disrupt hyperconnectivity in Cortico-Striatal loops in OCD. Digital phenotyping is being employed alongside traditional clinical outcomes to evaluate this treatment.

Continuous theta burst stimulation over the supplementary motor area in refractory obsessive-compulsive disorder treatment: A randomized sham-controlled trial

BackgroundObsessive-compulsive disorder (OCD) is a complex disorder with 40 to 60 % of patients resistant to treatment. Theta burst transcranial magnetic stimulation (TBS) is a promising new technique that has been shown to induce potent and long lasting effects on cortical excitability. The present study evaluated for the first time therapeutic efficacy and tolerability of continuous TBS (cTBS) over the supplementary motor area (SMA) in treatment resistant OCD patients using a double blind, sham-controlled design. MethodsThirty treatment resistant OCD outpatients were randomized to receive either active cTBS or sham cTBS for 6 weeks (5 sessions per week). Each treatment session consisted of 600 stimuli at an intensity of 70% of resting motor threshold. Patients were evaluated at baseline, at the end of treatment (week 6), and follow-up (week 12). Response to treatment was defined as at least 25% decrease on the Yale-Brown Obsessive Compulsive Scale. ResultsThere was no significant difference between active and sham cTBS groups in treatment efficacy. Responder rates were not different between the two groups at week 6 (cTBS 28% versus sham 36%; p = 0.686) and week 12 (cTBS 28% versus sham 36%; p = 0.686). Depressive and anxious symptoms improvements were similar in the two groups. ConclusionThis study is the first controlled trial using cTBS in treatment resistant OCD patients. The use of cTBS over the SMA is safe but not sufficient to improve OCD symptoms. Further studies are needed to identify the optimal parameters to be used in OCD patients.

Clinical and electrophysiological outcomes of deep TMS over the medial prefrontal and anterior cingulate cortices in OCD patients

BackgroundObsessive Compulsive Disorder (OCD) is a chronic and disabling disorder with poor response to pharmacological treatments. Converging evidences suggest that OCD patients suffer from dysfunction of the cortico-striato-thalamo-cortical (CSTC) circuit, including in the medial prefrontal cortex (mPFC) and the anterior cingulate cortex (ACC). ObjectiveTo examine whether modulation of mPFC-ACC activity by deep transcranial magnetic stimulation (DTMS) affects OCD symptoms. MethodsTreatment resistant OCD participants were treated with either high-frequency (HF; 20 Hz), low-frequency (LF; 1 Hz), or sham DTMS of the mPFC and ACC for five weeks, in a double-blinded manner. All treatments were administered following symptoms provocation, and EEG measurements during a Stroop task were acquired to examine changes in error-related activity. Clinical response to treatment was determined using the Yale-Brown-Obsessive-Compulsive Scale (YBOCS). ResultsInterim analysis revealed that YBOCS scores were significantly improved following HF (n = 7), but not LF stimulation (n = 8), compared to sham (n = 8), and thus recruitment for the LF group was terminated. Following completion of the study, the response rate in the HF group (n = 18) was significantly higher than that of the sham group (n = 15) for at least one month following the end of the treatment. Notably, the clinical response in the HF group correlated with increased Error Related Negativity (ERN) in the Stroop task, an electrophysiological component that is attributed to ACC activity. ConclusionHF DTMS over the mPFC-ACC alleviates OCD symptoms and may be used as a novel therapeutic intervention. Notwithstanding alternative explanations, this may stem from DTMS ability to directly modify ACC activity.

Obsessive compulsive personality disorder and autism spectrum disorder traits in the obsessive-compulsive disorder clinic

IntroductionObsessive Compulsive Personality Disorder (OCPD) is a common, highly co-morbid disorder. Subjected to comparatively little research, OCPD shares aspects of phenomenology and neuropsychology with obsessive-compulsive spectrum disorders and neurodevelopmental disorders such as autism spectrum disorder (ASD). A greater understanding of this interrelationship would provide new insights into its diagnostic classification and generate new research and treatment heuristics.AimsTo investigate the distribution of OCPD traits within a cohort of OCD patients. To evaluate the clinical overlap between traits of OCPD, OCD and ASD, as well as level of insight and treatment resistance.MethodWe interviewed 73 consenting patients from a treatment seeking OCD Specialist Service. We evaluated the severity of OCPD traits (Compulsive Personality Assessment Scale; CPAS), OCD symptoms (Yale–Brown Obsessive Compulsive Scale; Y-BOCS), ASD traits (Adult Autism Spectrum Quotient; AQ) and insight (Brown Assessment of Beliefs Scale; BABS).ResultsOut of 67 patients, 24 (36%) met DSM-IV criteria for OCPD, defined using the CPAS. Using Pearson's test, CPAS scores significantly (P &lt; 0.01) correlated with total AQ and selected AQ domains but not with BABS. Borderline significant correlation was observed with Y-BOCS (P = 0.07). OCPD was not over-represented in a highly resistant OCD subgroup.ConclusionDisabling OCPD traits are common in the OCD clinic. They strongly associate with ASD traits, less strongly with OCD severity and do not appear related to poor insight or highly treatment-resistant OCD. The impact of OCPD on OCD treatment outcomes requires further research.Disclosure of interestThis work did not receive funding from external sources. Over the past few years, Dr. Fineberg has received financial support in various forms from the following: Shire, Otsuka, Lundbeck, Glaxo-SmithKline, Servier, Cephalon, Astra Zeneca, Jazz pharmaceuticals, Bristol Myers Squibb, Novartis, Medical Research Council (UK), National Institute for Health Research (UK), Wellcome Foundation, European College of Neuropsychopharmacology, UK College of Mental Health Pharmacists, British Association for Psychopharmacology, International College of Obsessive-Compulsive Spectrum Disorders, International Society for Behavioural Addiction, World Health Organization, Royal College of Psychiatrists.

Induced Obsessive Compulsive Symptoms (OCS) in schizophrenia patients under Atypical 2 Antipsychotics (AAPs): review and hypotheses.

The prevalence of OCS and OCD is higher in schizophrenic patients than in the general population. These disorders are sometimes induced by AAPs. There is higher frequency of OCS and greater severity in patients treated with antipsychotics with predominant anti-serotoninergic profiles opposed to those with predominant dopaminergic blockade. Induced OCS may be due to complex neuromodulation involving many serotonin, dopamine and glutamate receptors and several subtypes. Concerning connectivity, AAPs differentially influence the BOLD signal, depending on the intensity of D2 receptor blockade. The OFC could play a significant role, on account of its involvement in inhibitory control. There is a paradox: AAPs are efficient as augmentation to SSRI in treatment resistant OCD, some of them such as risperidone or aripiprazole have favourable effects in schizoptypic OCD, but AAPs cause induced OCS in schizophrenic patients. When prescribing AAPs, we should inform patients about this potential side effect and assess systematically OCS with Y-BOCS assessment after 1 month of treatment. Afterwards there are different strategies: Aripiprazole in combination can reduce OCS induced by clozapine, SSRI are slightly effective and CBT shows a few encouraging results. OCS are sometimes dose-dependent, so we also recommend prescribing the minimum effective dose and gradual introduction.

Emotional support, depressive symptoms and age-related alterations in male body composition

The prevalence of OCS and OCD is higher in schizophrenic patients than in the general population. These disorders are sometimes induced by AAPs. There is higher frequency of OCS and greater severity in patients treated with antipsychotics with predominant anti-serotoninergic profiles opposed to those with predominant dopaminergic blockade. Induced OCS may be due to complex neuromodulation involving many serotonin, dopamine and glutamate receptors and several subtypes. Concerning connectivity, AAPs differentially influence the BOLD signal, depending on the intensity of D2 receptor blockade. The OFC could play a significant role, on account of its involvement in inhibitory control. There is a paradox: AAPs are efficient as augmentation to SSRI in treatment resistant OCD, some of them such as risperidone or aripiprazole have favourable effects in schizoptypic OCD, but AAPs cause induced OCS in schizophrenic patients. When prescribing AAPs, we should inform patients about this potential side effect and assess systematically OCS with Y-BOCS assessment after 1 month of treatment. Afterwards there are different strategies: Aripiprazole in combination can reduce OCS induced by clozapine, SSRI are slightly effective and CBT shows a few encouraging results. OCS are sometimes dose-dependent, so we also recommend prescribing the minimum effective dose and gradual introduction.

Dual target repetitive transcranial magnetic stimulation in the treatment of comorbid obsessive-compulsive disorder in patients with anorexia nervosa: Preliminary results of two case reports

IntroductionObsessive-compulsive disorder (OCD) is a frequently reported comorbid disorder (20–30%) in patients with anorexia nervosa (AN). Increasing evidence suggests that repetitive transcranial magnetic stimulation (r-TMS) may be effective in the treatment of refractory OCD and to a lesser extent in AN. Hereby, different target areas: supplemental motor area (SMA) and orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex in AN. We report two patients with enduring AN and comorbid treatment resistant OCD treated with r-TMS.MethodsBoth female patients (34 and 26 years respectively) were hospitalized at the Eating Disorder Unit at the Ghent University Hospital. Treatment responses were evaluated with Yale Brown Obsessive Compulsive Scale (Y-BOCS) and weight gain. Inhibitory continuous thetaburst stimulation (cTBS) of the SMA followed by cTBS of the OFC was conducted during 20 sessions, 5 sessions a week, during 4 weeks. Stimulation intensity was respectively 100% and 80% of the motor treshold.ResultsAfter cTBS treatment Y-BOCS score of both patients decreased (31 to 24 and 31 to 23 respectively). Only one patient showed a 10% increase of weight. The treatment was well tolerated. No significant side effects were reported.ConclusionTreatment resistant comorbid OCD in patients with AN may be succesfully treated with cTBS.Disclosure of interestThe authors have not supplied their declaration of competing interest.

P.4.d.006 Serotonin reuptake inhibitor augmentation with n-acetylcysteine in treatment resistant ocd: a double-blind randomized controlled trial

P.4.d.006 Serotonin reuptake inhibitor augmentation with n-acetylcysteine in treatment resistant ocd: a double-blind randomized controlled trial

Transcranial Direct Current Stimulation of Pre-Supplementary Motor Area for SSRI resistant OCD

Transcranial Direct Current Stimulation of Pre-Supplementary Motor Area for SSRI resistant OCD

Treatment Resistant OCD: Conceptualization and Treatment

Obsessive compulsive disorder is a severe disorder that is heterogeneous in nature and often challenging to treat. Exposure and response prevention is the leading treatment for OCD and has proven efficacious, with 75% long term improvement in symptoms. However, many patients do not respond optimally to treatment. In fact, many remain treatment resistant. The purpose of the current paper is to discuss factors contributing to treatment resistance as well as treatment planning strategies. Keywords: Cognitive behavioral therapy, comorbid disorders, OCD, Overvalued ideation, TIB, treatment resistance.

Low frequency bilateral rTMS in resistant OCD subjects: does the effect last?

s / Brain Stimulation 7 (2014) e17ee26 e22 study investigates a 25-session 20Hz treatment protocol modeled after a 12-session 20Hz protocol for migraine treatment. Methods: Six adults, diagnosed using the ICHD-II, with chronic migraine, migraine with aura, or migraine without aura, were tracked over seven months. Patients received 25 sessions of interventional rTMS therapy using a Neurostar device beginning at month 3. 1600 pulses per session were administered to the left DLPFC at 90%motor-threshold in 20Hz 2-second trains separated by 30-second rests. Primary endpoints of migraine frequency and severity were measured using a MIGSEV scale integrated into a migraine log format. Secondary endpoints of disability and quality of life were rated on MIDAS and QVM scales respectively. Results: Results comparing baseline to post-treatment measurements indicate that 5 of 6 patients experienced a 44% average reduction in migraine frequency, 4 of 6 patients experienced a 36% average reduction in migraine severity, 4 of 6 patients experienced a 75% average decrease in their disability, and 4 of 6 patients experienced a 46% average increase in their quality of life. Conclusions: These results confirm that a 25-session 20Hz rTMS protocol reduces migraine frequency, severity, and disability, while increasing quality of life.

“Tackling Trauma to Overcome OCD Resistance” (The TTOOR Florence trial) Efficacy of EMDR plus CBT versus CBT Alone for Inpatients with Resistant Obsessive Compulsive Disorder. Protocol for a Randomized Comparative Outcome Trial.

Researchers and clinicians have recently highlighted the usefulness of integrating additional therapeutic approaches into standard intensive cognitive behavioural treatments (CBT) with the aim to improve clinical outcomes for patients with severe resistant OCD. To date, there is still a limited amount of knowledge on the effectiveness of third-wave CBT techniques for OCD, despite such techniques seemed to be effective for a wide range of mental disorders. The Eyes Movement Desensitization Reprocessing (EMDR) is a treatment approach, based on the Adaptive Information Processing model, which conceptualizes psychological disorders as manifestations of unresolved traumatic or distressing memories. EMDR has been conceived as an integrative approach, aimed at facilitating resolution of memories, desensitizing stimuli that trigger present distress as a consequence of second-order conditioning, and incorporating adaptive attitudes and behaviours for better functioning. The present paper describes a research protocol for a randomized comparative outcome trial on inpatients with treatment-resistant OCD in a tertiary inpatient clinic in Italy. The study will aim to: (a) examine the effectiveness of EMDR with intensive brief CBT (EMDR+CBT) compared to intensive brief CBT alone on primary outcomes (OCD symptoms, obsessive beliefs, depression, and anxiety) at immediate post-treatment, one-, six-month-, and one-year-follow-up; (b) compare feasibility and acceptability of EMDR+CBT protocol versus intensive brief CBT alone (in terms of attrition and treatment satisfaction); (c) examine the effectiveness of EMDR+CBT versus intensive brief CBT alone on secondary outcomes (disgust propensity and sensitivity, emotion dysregulation, and dissociative experiences and symptoms). Inclusion/exclusion criteria of participants, outcomes, time scheduling, rationale, and therapeutic components of the treatments will be presented.