Resistant Obsessive-compulsive Disorder Research Articles

Combining transcranial magnetic stimulation and cognitive-behavioral therapy in treatment resistant obsessive-compulsive disorder

Objective: A non-negligible percentage of patients with obsessive-compulsive disorder (OCD) do not respond satisfactorily to treatments. Inpatient cognitive-behavioral therapy (CBT) has provided some relief in even refractory and chronic patients. Repetitive transcranial magnetic stimulation (rTMS) has also provided promising results. However, no studies have combined these two strategies. Methods: Eighteen patients with treatment resistant and chronic OCD who had been hospitalized in order to receive pharmacotherapy, inpatient CBT and rTMS were evaluated on the Yale-Brown Obsession and Compulsion Scale (Y-BOCS) and the Hamilton Depression Rating Scale-17 (HDRS-17). rTMS was applied every day over the left dorsolateral prefrontal cortex for 5 days in a week with parameters of 25 Hz and 1000 pulses. Results: Y-BOCS scores decreased by 59.14%; from 30.72 ± 6.12 at admission to 12.55 ± 7.44 when discharged. HDRS-17 scores decreased by 56.80%; from 18.38 ± 3.94 at admission to 7.94 ± 5.70 at discharge. The mean numbers of rTMS and CBT sessions were 23.28 ± 6.78 and 17.17 ± 5.04 respectively. Discussion: The combination of pharmacotherapy, CBT and rTMS may be effective in treatment resistant and chronic OCD in the short term.

Amisulpride as add-on treatment for resistant obsessive-compulsive disorder: retrospective case series.

Obsessive-compulsive disorder (OCD) is one of the most common and disabling psychiatric disorders. Treatment with selective serotonin reuptake inhibitors (SSRIs) shows significant improvement; however, residual symptoms remain in most patients despite continued treatment. For partial or nonresponding patients to multiple SSRIs, augmentation strategies are usually recommended. Here we present a consecutive sample of patients with resistant OCD treated with amisulpride augmentation to SSRIs. We present 10 patients (5 males, 5 females) experiencing resistant OCD. Subjects were treated openly for 6 weeks with amisulpride 200 mg/d as add-on, excluding 1 patient who was treated with only 100 mg/d due to acute extrapyramidal adverse effect on a larger dose. Efficacy was assessed at baseline and after 6 weeks of treatment using the Yale-Brown Obsessive-Compulsive Scale, Clinical Global Impression-Severity, and Clinical Global Impression-Improvement. The treatment was generally well tolerated without serious events. In all patients, average Yale-Brown Obsessive-Compulsive Scale scores diminished from 25.3 ± 5.96 points at baseline to 12.2 ± 5.98 at the sixth week (P < 0.0005). Of 10 patients, 7 had significant and partial improvement, and 3 patients did not demonstrate any improvement. Treatment-resistant OCD patients positively responded and well tolerated amisulpride add-on to their ongoing regular pharmacotherapy. This case series demonstrates that amisulpride could be a promising optional therapy for patients who have resistant OCD. Further randomized controlled studies are necessary.

White matter lesions in patient with treatment resistant obsessive compulsive disorder: a case report

Neurobiological models of Obsessive compulsive disorder (OCD) suggest that there are structural and functional abnormalities in frontal-striatal-thalamic-cortical circuits. These cortical and subcortical microcircuits are physically and functionally connected through the white matter. Therefore, the disrupted white matter microstructure may be implicated in the pathophysiology of OCD. Neuroanatomical studies have reported various regional white matter abnormalities in patients with OCD. In this case, we present subcortical WMHs in a patient with treatment resistant OCD.

Atypical antipsychotic augmentation in SSRI treatment refractory obsessive-compulsive disorder: a systematic review and meta-analysis.

BackgroundIn 2006, the National Institute of Clinical and Health Excellence (NICE) guidelines for Obsessive Compulsive Disorder (OCD) recommended anti-psychotics as a class for SSRI treatment resistant OCD. The article aims to systematically review and conduct a meta-analysis on the clinical effectiveness of atypical anti-psychotics augmenting an SSRI.MethodsStudies that were double-blind randomized controlled trials of an atypical antipsychotic against a placebo, for a minimum of 4 weeks, in adults with OCD, were included. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores were the primary outcome measure. Inclusion criteria included Y-BOCS score of 16 or more and at least one adequate trial of a SSRI or clomipramine for at least 8 weeks prior to randomization. Data sources included Medline, Embase, PsycINFO, Cochrane Database of Systematic Reviews (CDSR), trial registries and pharmaceutical databases and manufacturers up to September 2013. Forest-plots were drawn to display differences between drug and placebo on the Y-BOCS.ResultsTwo studies found aripiprazole to be effective in the short-term. There was a small effect-size for risperidone or anti-psychotics in general in the short-term. We found no evidence for the effectiveness of quetiapine or olanzapine in comparison to placebo.ConclusionsRisperidone and aripiprazole can be used cautiously at a low dose as an augmentation agent in non-responders to SSRIs and CBT but should be monitored at 4 weeks to determine efficacy.

Troubles anxieux résistants : revue des stratégies de traitements médicamenteux

Anxiety disorders are widespread psychiatric conditions with significant social and professional disability, poor quality of life, an increased risk of suicide, and frequent attendance of medical services. Serotonin reuptake inhibitors (SRI) and serotonin and norepinephrine reuptake inhibitors (SNRI) have demonstrated a rather robust efficacy for the treatment of most of anxiety disorders. Nevertheless a substantial number of patients are resistant or still suffer from residual symptoms despite this first line treatment. The objective of our paper is to review relevant studies for the pharmacologic management of anxiety disorders resistant to the first line treatment. For this purpose, we conducted a pubmed/medline search for double-blind placebo-controlled trials of treatment-resistant anxiety disorders. An adequate trial for a SRI in the treatment of obsessive-compulsive disorder (OCD) should continue for at least 12 weeks. Special considerations of the comorbidities and symptom profile could help in the choice of an appropriate pharmacotherapy. Several trials have highlighted the efficacy of antipsychotics as an add-on to SRI in treatment-resistant OCD such as haloperidol more so when comorbid with a tic disorder, or risperidone that can reduce OCD as well as depressive symptoms. Aripiprazole has been shown efficacious in two placebo-controlled double-blind trials, while the efficacy of quetiapine and olanzapine remains controversial. Other trials showed some efficacy of anticonvulsants (lamotrigine, topiramate), pindolol, memantin and N-acetylcystein as an adjunctive treatment to SRI for resistant OCD. Few trials have investigated selective serotonin reuptake inhibitors (SSRI) or SNRI resistant generalized anxiety disorder showing a failure of adjunctive therapy with olanzapine, quetiapine, ziprasidone and risperidone. These studies were underpowered and very limited in number. Adjunctive risperidone for resistant post-traumatic stress disorder (PTSD) showed benefit in some but not all trials. Olanzapine was beneficial for the reduction of the CAPS score in addition to the improvement of sleep disturbances. Furthermore, prazosin was efficacious by reducing PTSD symptoms, sleep disturbances, nightmares, and psychological distress. One double-blind placebo-controlled study was conducted to investigate treatment-resistant social phobia showing no benefit of pindolol add-on paroxetine. Our results demonstrate that the pharmacological management of treatment-resistant anxiety disorders is not sufficiently investigated in double-blind placebo-controlled trials, despite a growing evidence in favor of antipsychotics and some other pharmacological agents in resistant OCD and, to a lesser extent, PTSD. Hence, there is a crucial need for larger double-blind placebo-controlled trials for resistant anxiety disorders. Finally, being out of the scope of our review, we omitted studies of non-pharmacologic therapies.

Closed loop deep brain stimulation: an evolving technology.

Deep brain stimulation is an effective and safe medical treatment for a variety of neurological and psychiatric disorders including Parkinson's disease, essential tremor, dystonia, and treatment resistant obsessive compulsive disorder. A closed loop deep brain stimulation (CLDBS) system automatically adjusts stimulation parameters by the brain response in real time. The CLDBS continues to evolve due to the advancement in the brain stimulation technologies. This paper provides a study on the existing systems developed for CLDBS. It highlights the issues associated with CLDBS systems including feedback signal recording and processing, stimulation parameters setting, control algorithm, wireless telemetry, size, and power consumption. The benefits and limitations of the existing CLDBS systems are also presented. Whilst robust clinical proof of the benefits of the technology remains to be achieved, it has the potential to offer several advantages over open loop DBS. The CLDBS can improve efficiency and efficacy of therapy, eliminate lengthy start-up period for programming and adjustment, provide a personalized treatment, and make parameters setting automatic and adaptive.

Reduction in Obsessive-Compulsive and Depressive Symptoms Following Bilateral Repetitive Transcranial Magnetic Stimulation (rTMS): Case Series

s / Brain Stimulation 7 (2014) e17ee26 e21 Objective: We sought to examine the time course of rTMS augmentation of medication in 54 psychiatric outpatients with treatment resistant depression. Methods: rTMS was administered with the Neurostar device. The standard protocol was 3000 pulses at 10 or 20 Hz at 120% motor threshold (MT) on the left dorsolateral prefrontal cortex (DLPFC) for the treatment of depression. A subset of patients (n1⁄433) also received 2000 pulses at 1 Hz at 80% MT on the right DLPFC for the treatment of anxiety. A retrospective chart review was preformed to assess progress after both ten and twenty treatments using the Beck Depression Inventory-II (BDI-II) and the Beck Anxiety Inventory (BAI). Results: Mean BDI-II scores were 25.6 (SD1⁄411.2) at baseline, 14.6 (SD1⁄411.7) after 10 treatments, and 11.0 (SD1⁄410.3) after 20 treatments. Scores were significantly reduced on the BDI-II, t(53)1⁄4 8.05, p < 0.001 between baseline and 10 treatments and between baseline and 20 treatments BDI-II t(31)1⁄48.40, p < 0.001. Mean scores on the BAI were 18.8 (SD1⁄411.2) at baseline, 10.2 (SD1⁄49.8) after 10 treatments, and 8.2 (SD1⁄48.4) after 20 treatments. Significant differences emerged on the BAI between baseline and 10 treatments, t(51)1⁄4 6.36, p < 0.001 and between baseline and 20 treatments BAI t(30)1⁄4 6.78, p < 0.001. Conclusions: Our research suggests that most patients experienced a significant reduction in anxiety and depression in as little at 10 treatments. Supported by a grant from Neuronetics, Inc. Clinical trial posted on www.clinicaltrials.gov, listing number NCT 01114477 13 Reduction in Obsessive-Compulsive and Depressive Symptoms Following Bilateral Repetitive Transcranial Magnetic Stimulation (rTMS): Case Series Veronica Holland LaSalle-Ricci PhD , Elyssa Sisko BA , Laura DeLuca MD , Mark DeLuca MD , Heather Allsup AAS , Kristie DeBlasio PhD , Aron Tendler MD C.BSM a,c Advanced Mental Health Care Inc b Private Practice c Presenting Author Background: High frequency rTMS to the left dorsolateral prefrontal cortex (DLPFC) has demonstrated efficacy and is FDA approved for depression. Low frequency rTMS to the right DLPFC has antidepressant activity in a subset of patients, and is immediately anxiolytic though this effect has not been shown to be sustainable. Objective: We combined high frequency rTMS to the left DLPFC with low frequency rTMS to the right DLPFC in 12 patients diagnosed with comorbid treatment resistant depression and obsessive-compulsive disorder (OCD) as an augmentation to medication. Methods: rTMS was administered with the Neurostar device. Patients first received 2000 pulses at 1 Hz at 80% motor threshold (MT) on the right DLPFC followed by 3000 pulses at 10 or 20 Hz at 120% MT on the left DLPFC. Patients were assessed at baseline, 10 treatments, and 20 treatments using the Yale-Brown ObsessiveCompulsive Inventory (YBOCS) and the Beck Depression InventoryII (BDI-II). Results: Patients experienced a decline in BDI-II scores from baseline (mean1⁄429.0, SD1⁄411.7), to 10 treatments (mean1⁄417.0, SD1⁄414.7), and to 20 treatments (mean1⁄410.8, SD1⁄413.5). Scores were significantly reduced on the BDI-II between baseline and 10 treatments (BDI-II t(12)1⁄44.6, p<0.001), as well as between baseline and 20 treatments (BDI-II t(10)1⁄48.4, p< 0.001). YBOCS scores also decreased from baseline (mean1⁄420.8, SD1⁄48.9), to 10 treatments (mean1⁄417.6, SD1⁄4 6.9), and to 20 treatments (mean1⁄411.1, SD1⁄47.6). No significant difference occurred between baseline and 10 treatments (t(12)1⁄41.3, p1⁄40.1), but significant differences emerged between baseline and 20 treatments (t(10)1⁄43.5, p1⁄40.004). Conclusions: Bilateral rTMS may be an effective treatment for patients with comorbid depression and OCD.

Estimulación cerebral para el trastorno obsesivo-compulsivo resistente a tratamiento médico

Approximately 10% of patients with obsessive-compulsive disorder have very disabling chronic forms of the disease, which are resistant to all current conservative therapies. These patients experience a significant deterioration in their quality of life and high rates of suicide. The development of new effective neurosurgical treatments has led to an improvement in a significant percentage of patients that would otherwise have remained severely disabled.We comprehensively review remission rates, adverse effects and fundamental methodological aspects of the current neurosurgical techniques for medication resistant obsessive-compulsive disorder. The making of small lesions in specific targets of the limbic circuit, such as cingulotomy, capsulotomy, limbic leucotomy and subcaudate tractotomy, is being replaced by deep brain stimulation through electrodes located in these targets, which is reversible and adaptable to every patient's need. Furthermore, the development of neuroimaging techniques and a better understanding of brain circuits in the last decades, have allowed the identification of new targets for neurostimulation in this disorder, with good results.Research must continue in order to help in the treatment of medication-resistant obsessive-compulsive disorder.

“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.

Atypical antipsychotic augmentation in SSRI treatment refractory obsessive-compulsive disorder: a systematic review and meta-analysis

BackgroundIn 2006, the National Institute of Clinical and Health Excellence (NICE) guidelines for Obsessive Compulsive Disorder (OCD) recommended anti-psychotics as a class for SSRI treatment resistant OCD. The article aims to systematically review and conduct a meta-analysis on the clinical effectiveness of atypical anti-psychotics augmenting an SSRI.MethodsStudies that were double-blind randomized controlled trials of an atypical antipsychotic against a placebo, for a minimum of 4 weeks, in adults with OCD, were included. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores were the primary outcome measure. Inclusion criteria included Y-BOCS score of 16 or more and at least one adequate trial of a SSRI or clomipramine for at least 8 weeks prior to randomization. Data sources included Medline, Embase, PsycINFO, Cochrane Database of Systematic Reviews (CDSR), trial registries and pharmaceutical databases and manufacturers up to September 2013. Forest-plots were drawn to display differences between drug and placebo on the Y-BOCS.ResultsTwo studies found aripiprazole to be effective in the short-term. There was a small effect-size for risperidone or anti-psychotics in general in the short-term. We found no evidence for the effectiveness of quetiapine or olanzapine in comparison to placebo.ConclusionsRisperidone and aripiprazole can be used cautiously at a low dose as an augmentation agent in non-responders to SSRIs and CBT but should be monitored at 4 weeks to determine efficacy.

Microstructural abnormality in left nucleus accumbens predicts dysfunctional beliefs in treatment-resistant obsessive-compulsive disorder.

BackgroundThe aim of this study was to determine whether dysfunctional beliefs might predict treatment-resistance and to examine the relationship between fractional anisotropy (FA) in diffusion tensor imaging (DTI) and cognitive biases for optimal treatment choice.Material/MethodsWe recruited 11 non-resistant obsessive-compulsive disorder (OCD) patients, 11 resistant OCD patients, and 11 healthy subjects.ResultsOCD patients had higher Obsessive Beliefs Questionnaire (OBQ-87) subscale scores than subjects in non-resistant and resistant groups. A significant difference was found between non-resistant and resistant OCD patients in R-Scale and I-Scale. A significant decrease in FA was found in left dorsal frontal gyrus and left inferior parietal lobule in the non-resistant group as compared to the control group. FA also decreased significantly in left anterior cingulate cortex, putamen, and nucleus accumbens in the resistant group as compared to the control group. There was a significant decrease in FA in nucleus accumbens in the resistant group as compared to the non-resistant group. Reduced FA in left nucleus accumbens was negatively associated with OBQ-87 factor R and I and the total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS).ConclusionsAbnormalities in cortical-striatal white matter networks may contribute to the dysfunctional beliefs in patients with treatment-resistant OCD, and the left nucleus accumbens may be an important and promising target for the treatment of OCD.

Troubles obsessionnels compulsifs résistants et antipsychotiques : données neurobiologiques et thérapeutiques actuelles

IntroductionForty to sixty percent of patients with obsessive compulsive disorder (OCD) are resistant to well conducted treatment with selective serotonin reuptake inhibitors (SSRIs) over 8 weeks. The data concerning effectiveness of the addition of antipsychotics in this indication is controversial. Aims of the studyTo synthesize the neurobiological mechanisms at work in order to understand the action of pharmacological treatments in this disease and to propose a systematic review of the literature on effectiveness of different antipsychotic drugs according to their pharmacological profiles, in monotherapy or in combination with SSRIs in OCD. MethodWe conducted a systematic review of the literature using the criteria according to the PRISMA research paradigm “obsessive compulsive disorder AND antipsychotic agents”. Research bases MEDLINE, Cochrane and Web of science have been explored. ResultsUnlike the classical serotonergic hypothesis, OCD may result from striatal dopaminergic hyperactivity, modulated in some patients by an underlying serotonergic hypoactivity. Most studies report effectiveness of first-generation antipsychotics (amisulpride and haloperidol) and some second-generation antipsychotics (risperidone, olanzapine, aripiprazole, quetiapine) in combination with an SSRI in the treatment of resistant OCD. Recrudescence or onset of OCD in patients with schizophrenia have been described in a relay from first generation antipsychotic to olanzapine, risperidone, aripiprazole or clozapine in case reports, but not amisulpride and quetiapine.

Does time-intensive ERP attenuate the negative impact of comorbid personality disorders on the outcome of treatment-resistant OCD?

Background and objectivesThere is growing interest regarding patients with obsessive-compulsive disorder (OCD) who do not fully respond to cognitive-behavioural therapy (CBT). Limited data are available on the role of Comorbid Personality Disorders (CPDs) in the outcome of treatment-resistant obsessive-compulsive disorder (OCD), despite the fact that CPDs are considered a predictor of a poorer outcome. This study investigated whether a time-intensive scheduling of treatment could be an effective strategy aimed at attenuating the negative influence of CPDs on outcome in a sample of 49 inpatients with a primary diagnosis of treatment-resistant OCD. Method38 inpatients completed the five-week individual treatment consisting of daily and prolonged sessions of exposure with response prevention (ERP) delivered for 2 h in the morning and 2 h in the afternoon. 44% of the sample received a full diagnosis of one or more CPDs. Following a pre-post-test design, outcome measures included the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI). ResultsData showed that the treatment was effective and indicated that CPDs were not a significant predictor of treatment failure. LimitationsFuture larger studies should evaluate the role of specific clusters of CPDs on the outcome of resistant OCD. ConclusionsThese findings suggest that an intensive treatment could be effective for severely ill patients who have not responded to weekly outpatient sessions and could also attenuate the negative impact of CPDs on outcome, evidencing the importance of a tailored therapeutic approach for patients who need a rapid reduction in OCD-related impairment.

3029 – Bridging the gap between physio- and psychopathology: the example of deep brain stimulation in human-repetitive behaviours

Deep brain stimulation (DBS) is able to target with precision specific cerebral networks, thus offering hope for severe and treatment refractory illnesses, as well as to investigate in the detail the subcortical bases. In obsessive-compulsive disorder (OCD), DBS is being tested at several nodes of a prefrontal-subcortical circuit, including the subthalamic nucleus (STN). Functional imaging studies of OCD patients have shown abnormal metabolic activity of the orbito-frontal and cingulate cortices, as well as of the anterior part of the striatum. In animal and human studies, these structures have been associated with performance-monitoring and more generally metacognitive processes, thus suggesting that metacognitive dysfunctions might be central to OCD leading to pathological doubt. In this conceptual framework of hyperactive distrust metacognitive mechanism in OCD, checking behaviour can be regarded as an ill-founded metacognitive strategy designed to restore confidence in the outcome of one's actions. Within the basal ganglia network, the STN could act a crucial part in this process regarding its role in the inhibitory control of behaviour. Moreover, anatomy and neuro-computational models of the basal ganglia show that this nucleus is in the position to implement cortical metacognitive control by increasing the threshold for decision. This framework has the advantage of providing a theoretical basis to the promising clinical results obtained for STN-DBS in severe resistant OCD. Bearing in mind this model, it can be postulated that DBS, by its action on STN, positively interferes with the neural mechanism underlying compulsive behaviour.

How Does Deep Brain Stimulation Work?

s p t s D eep brain stimulation (DBS) presents the promise of effective treatment for central nervous system disorders that are resistant to other available treatments. Deep brain stimulation has been reported to be effective in Parkinson’s disease, essential tremor, pain syndromes, and medication resistant obsessivecompulsive disorder (OCD). Deep brain stimulation has also been reported to exert a remarkably large antidepressant effect in openlabel, single blind lead-in, and long-term follow-up studies, even in patients in whom aggressive medication strategies and electroconvulsive therapy have failed (1). This is notable, given the expected low placebo response in such refractory patients. However, expectancy of benefit from invasive procedures such as DBS can be high, and the results of a sham-controlled randomized trial have yet to be published, although a large-scale trial is presently underway. Amidst the excitement about this exciting treatment that permits the translation of knowledge with regard to pathological circuits into a focal therapeutic circuit modulation, there looms a vexing and as yet unanswered question: How does it work? If indeed DBS for depression is more effective than other available treatments and is able to achieve remission when all else has failed, then answering this question of mechanism is of great importance to advancing understanding of the causes of severe neuropsychiatric disorders and could shed light on their effective treatment and, hopefully, ultimately their cure. Historical explanatory models for the mechanism of action of DBS for depression as a virtual lesion have since been replaced with a more nuanced understanding of the impact of patterned electrical stimulation on neurocircuit functioning. For example, computational modeling of the impact of electric fields on subcompartments of neurons suggests that, dependent upon neuronal orientation relative to the field and intensity of stimulation, soma might be hyperpolarized whereas axons might be depolarized, resulting in a decoupling of cell body and axonal effects (2). This might in part explain observations of local inhibition coupled with increased axonal firing in response to DBS. Mechanisms of action of DBS can be approached from multiple levels of analysis (molecular, cellular, and circuit), each of which can be expected to be important to a comprehensive understanding of how DBS exerts its clinical effects. At the cellular level, attention has been mostly focused on neuronal effects (local neurons, afferent inputs, and fibers of passage), but recent reports suggest that glia might also play a role. At the circuit level, consideration has been paid mostly to the topography of effects on connected brain regions within distributed mood regulatory networks, as revealed via diffusion tensor tractography (3). Recent work in Parkinson’s disease DBS mechanisms has emphasized not just the spatial topography of circuit effects but also the temporal components of circuit

N-acetylcysteine augmentation in treatment resistant obsessive compulsive disorder: A case series

BackgroundEvidence-based, first-line treatments for obsessive compulsive disorder, (OCD) include the serotonin reuptake inhibitors (SRI), however, 40–60% of OCD patients do not respond. A wide variety of agents have been examined as adjuncts to standard SRI treatment in cases of treatment resistance, however, no gold-standard approach has been identified. Glutamate dysfunction is now thought to have a role in OCD, and use of glutamatergic treatment agents may hold promise. N-acetylcysteine (NAC) is an amino acid derivative of cysteine, available as a health supplement. It has shown efficacy in OCD-spectrum disorders and in 1 case report of treatment resistant OCD. MethodA retrospective chart review of 6 treatment resistant OCD patients, who had been treated with NAC for 6–12 weeks. Symptom severity was evaluated at regular clinic visits. ResultsFive of 6 patients took NAC for 12 weeks. The mean endpoint dose was 2833.3±408.2mg/day. Only 1/6 patients responded to treatment with NAC; two patients reported a worsening of symptoms; no patients reported adverse events. ConclusionsNAC was not effective in this sample of treatment-refractory OCD patients. Whether this result was a function of the mechanism of action of NAC or of the pathophysiology of treatment refractory OCD, remains unclear.

EFFECTS OF ARIPIPRAZOLE AUGMENTATION IN TREATMENT-RESISTANT OBSESSIVE-COMPULSIVE DISORDER (A DOUBLE BLIND CLINICAL TRIAL)

Obsessive-compulsive disorder (OCD) is a chronic disorder with unknown etiology. Failure in OCD treatmentcompulsive is common and finding effective augmentations in treatment of OCD will benefit patients. Antipsychotic augmentation is a common strategy for treatment resistant OCD. This trial evaluated the efficacy of adding aripiprazole in patients whose OCD was insufficiently responsive to an adequate SSRI treatment. Thirty-nine adult outpatients, who met the DSM-IV-TR criteria for OCD and had treatment resistant OCD were evaluated in a double-blind randomized clinical trial. The patients received either aripiprazole 10 mg/day or placebo, for 12 weeks. Data were analyzed using intention-to-treat analysis with last observation carried forward. All statistical tests were two-sided, and were considered statistically significant at P < 0.05. A significant reduction in total scores of Y-BOCS (P < 0.0001) was found in the aripiprazole group. Aripiprazole was generally well tolerated. There was no significant difference between the two groups in terms of observed side effects. Results of the present study indicate that aripiprazole could be an effective augmentation medicine in treatment resistant OCD.

Delusional Misidentification Syndromes in Obsessive–Compulsive Disorder

Delusional misidentification syndromes (DMS) have been rarely reported in patients with conditions other than schizophrenia-related disorders, diffuse brain disease (dementia) and focal neurological illness. In this report, we describe DMS (i.e. Capgras and Fregoli syndromes) in two patients with severe and treatment resistant obsessive-compulsive disorder (OCD), one with paranoid personality disorder (PPD) and the other with a pervasive developmental disorder (PDD) not otherwise specified. While our findings highlight an interesting phenomenon (the occurrence of DMS in OCD), it is presently unclear whether this association is rare or underreported. Misidentification syndromes might be the ultimate result of a combination of obsessive fears and preexisting cognitive bias/deficits, such as mistrustfulness (in PPD) or poor theory of mind (in PDD).

When the Problem is Beneath the Surface in OCD: The Cognitive Treatment of a Case of Pure Mental Contamination

Mental contamination is a phenomenon whereby people experience feelings of contamination from a non-physical contaminant. Rachman (2006) proposes that standard cognitive behavioural treatments (CBT) need to be adapted here and there is a developing empirical grounding supporting the concept, although suggestions on adapting treatment have yet to be tested. A single case study is presented of a man with a 20-year history of severe treatment resistant Obsessive Compulsive Disorder (OCD) characterized by mental contamination following the experience of "betrayal". He was offered two consecutive treatments: standard CBT and then (following disengagement with this) a cognitive therapy variant adapted for mental contamination. Clinician and patient rated OCD severity was measured at baseline and the start and end of both interventions. Six sessions of high quality CBT were initially attended before refusal to engage with further sessions. There were no changes in OCD severity ratings across these sessions. A second course of cognitive therapy adapted for mental contamination was then offered and all 14 sessions and follow-ups were attended. OCD severity fell from the severe to non-clinical range across these sessions. The need to consider adapting standard treatments for mental contamination is suggested. Limitations and implications are discussed.

Aripiprazole Augmentation in Patients with Resistant Obsessive Compulsive Disorder: a Pilot Study

Background:Antipsychotic augmentation is an effective treatment intervention for Obsessive Compulsive Disorder (OCD) patients resistant to Selective Serotonin Reuptake Inhibitors (SSRI) agents. This pilot study was conducted to evaluate the effectiveness and tolerability of Aripiprazole for the augmentation of standard treatments in patients with resistant OCD.Methods:Twenty patients diagnosed with OCD according to DSM-IV TR criteria and having a history of resistance to standard pharmacological treatment were included in the study. Aripiprazole was added to ongoing SSRI or clomipramine treatment with a starting dose of 5 mg/day and titrated up to a maximum of 20 mg/day (mean dose 12.62 mg ± 4.25). Efficacy was assessed with the Yale-Brown obsessive compulsive scale (Y-BOCS) and the Clinical Global Improvement-severity scale (CGI-S) at baseline and at week 12 of Aripiprazole augmentation. Side effects were monitored by the Udvalg for Kliniske Undersogelser (UKU) side effect rating scale.Results:All 20 subjects enrolled in our study completed the full 12-week course of treatment. A significant improvement over the 12-week study period was observed (paired t-test for mean Y-BOCS total score at week 12 as compared with baseline – all patients: t = 13.146, d.f. = 19, p= 0.0001). Aripiprazole was generally well tolerated and no changes were observed in vital signs. The most commonly observed side effects after the introduction of the augmenting agent included: akathysia, nausea/vomiting, hyperkinesia, tension/inner unrest, tremors, asthenia/lassitude/increased fatiguability. Conclusions:Although results of this pilot study are preliminary and require confirmation in randomized controlled trials, our experience suggested that Aripiprazole is effective and well-tolerated as an augmenting agent in patients with treatment resistant OCD.