Resistant OCD Research Articles

Table of Contents

AbstractStudy of extended‐release guanfacine shows results for trauma symptomsGroundbreaking report shows increases in children's psychiatric disordersMedications, restraint still widely used for young inpatientsTORDIA update: Remission improves symptoms regardless of treatment typeReview study assesses atomoxetine efficacy globallyAripiprazole reduces prolactin serum levels in youthMinocycline for autism and regressive featuresVarenicline reduces alcohol consumption, cravingBlack box warning on prescription opioids — good or bad idea?Antipsychotic augmentation of SSRI in resistant tic‐related OCDApprovals

Family-focused treatment may help resistant OCD

Family-focused treatment may help resistant OCD

Neurobiology and Effectiveness of Antipsychotic Drugs in Resistant Obsessive-Compulsive Disorder: A Systematic Review

A systematic review of the literature was conducted using PRISMA criteria. The paradigm search was “obsessive compulsive disorder and antipsychotic agents”. Medline, Cochrane and Web of science databases were explored without date or language restriction. Case reports, open label studies and randomized double-blind controlled trials were included in the qualitative review. Unlike the classical serotonergic hypothesis, OCD may result from striatal dopaminergic hyperactivity, modulated in some patients by an underlying serotonergic hypo activity. In the treatment of resistant OCD, most studies report the effectiveness of first-generation antipsychotic (haloperidol, amisulpride) and some second-generation antipsychotics (risperidone, olanzapine, aripiprazole, quetiapine) in combination with an SSRI. Moreover, in case reports, recrudescence or onset of OCD symptoms in patients with schizophrenia have been described in a switch from first generation antipsychotic medication to olanzapine, risperidone, aripiprazole or clozapine, but not within a switch to amisulpride or quetiapine.

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.

Buprenorphine augmentation in the treatment of refractory obsessive–compulsive disorder

OCD is often refractory to treatment. There is a need for the development of new, non-invasive treatments for severe OCD. There is evidence that opiates can be a useful adjunctive treatment in OCD. We summarise our experience with sublingual buprenorphine augmentation of standard pharmacological management of severe OCD. Patients were recruited from a standard psychiatric outpatient clinic and gave their consent to the treatment trial. The severity of the OCD was rated with the Y-BOCS. The buprenorphine was introduced to their existing medication regime at a low dose and the dose increased according to response. In order to gauge the reproducibility of the response the buprenorphine was withdrawn and then reintroduced once symptoms had returned. 4 out of 7 patients with treatment resistant OCD showed a 30% reduction in the Y-BOCS score following buprenorphine augmentation. 3 of the responders were comorbid for other Axis 1 diagnoses. All of the responders had shown some improvement with SSRIs or clomipramine. Non-responders had not shown any improvement with either antidepressant or antipsychotic drugs. Typically improvement appeared within 2 days of initiating buprenorphine and waned within 1 to 2 days of its discontinuation. The dose of buprenorphine required varied between 400 µg and 600 µg a day. One responder managed on alternate day dosing. Reintroduction of buprenorphine resulted in symptom control within 2 to 3 days. The buprenorphine treatment was not associated with significant side-effects and the improvement was maintained without progressive dose escalation. Buprenorphine augmentation of standard treatment for OCD can result in clinically meaningful improvement in a proportion of refractory OCD cases. Further treatment trials are indicated.

Dopamine Pharmacological Agents in Resistant-OCD

The paper provides a brief summary of current preclinical and clinical evidences of dopaminergic system involvement in OCD pathophysiology. We also provide an overview of effectiveness and long-term safety of dopaminergic agents in the treatment of resistant OCD. Keywords: OCD, resistant-OCD, antipsychotics augmentation, dopamine agents, ondansetron, endogenous, placebo-controlled, quetiapine, olanzapine, aripiprazole, Haloperidol, risperidone augmentation, Sydenham's chorea, amphetamine, cocaine

AS28-01 - The role of DBS surgery in treatment refractory depression

Mental disorders carry heavy burden and come second only to cardiovascular disease. The disability adjusted life years, which is a measure for life years lost due to premature death, for mental disorders is about 15.4% compared to 18.6% for cardiovascular disease and 15% for all cancers put together. Fifteen to 25% of mental disorders become resistant or refractory to all conventional therapy including medications, behavioural therapy and ECT. Some of these patients might be helped by NMD. There are currently a number of surgical interventions that can be used to treat resistant and refractory OCD or MDD. Ablative neurosurgery includes bilateral anterior cingulotomy, bilateral anterior capsulotomy and subarcuate tractotomy. Neurostimulation for mental disorders is also used includes VNS and DBS. This symposium will cover the pros and cons of these interventions in detail including referral criteria, patient selection, referral pathways, outcome of these interventions, potential side effects and long term outcomes. There will be time to ask questions and discuss all aspects of NMD.

P-811 - Rationale of use dopamine agonists in OCD

In OCD serotonin is considered as key neurotransmitter. However role of dopamine is not well understood. Dopamine antagonists are used as adjunct medicine in resistant type of OCD. Serotonin dampens feelings of over self consciousness in OCD. In diseases with high dopamine levels patients jettison self consciousness to enter into state of ecstasy. Enhanced dopaminergic activity can possibly alleviate painful feelings of over self consciousness in OCD. An electronic search was made to find out role of dopamine in OCD at various database website including medscape, and psychiatrist, com. Search only revealed results of use of antidopaminergic drugs in OCD. Dopamine agonists have not been tried in treatment of OCD. Increased dopamine levels tend to abate rigid conscious control of behavior. There are reports of increased incidences of impulse disorder in PD patients, using dopamine agonist. In BAD dopamine over activity make actions too spontaneous. In addiction dopamine action in NA produces euphoric feelings during which conscious control is minimized. Orgasm is highly euphoric phenomenon during which one feels like melting and loosing self-consciousness is mediated by dopamine. Thus pharmacological effects of dopamine inhere property of diminishing over self consciousness a hallmark of OCD. Low doses of antipsychotic have rather facilitatory effect on neurotransmission. Hence adding dopamine agonist to SSRI resistant OCD patient can have favorable effect. Drugs like bromocriptine or lasuride may be used in such patients. Adjunct use of dopaminergic drug can be beneficial in treatment of OCD.

P02-375 - Paliperidone augmentation for refractory obsessive-compulsive disorder: A case report

IntroductionDespite the substantial clinical improvements provided by the pharmacologic and cognitive-behavior therapies of OCD, it has been estimated that 40%–60% of patients still remains refractory to conventional treatment.ObjectivesMedication augmentation can be an effective and well-tolerated short-term treatment strategy for non-responders to first-line pharmacotherapy of obsessive-compulsive disorders.AimsTo investigate the efficacy of paliperidone as augmenting agent in the treatment of resistant OCD patient.MethodsIn the present case, we present a 6 months follow-up of an obsessive-compulsive patient treated with paliperidone ER and fluvoxamine. Paliperidone ER was started at 6 mg/day and increased up to a maximum of 12 mg/day. The clinical symptoms were measured by Y-BOCS and efficacy measures with CGI and PSP scale scores.ResultsWe found that obsessive-compulsive symptoms improved after 4weeks. Patient showed a significant improvement over the 6 months follow-up for Yale-Brown Obsessive Compulsive Scale total score at week 24 as compared with baseline (from a score of 34 to a score of 12). A significant improvement in the mean PSP scale score was also seen and “much improved” on the CGI score from baseline to end point. A mean bodyweight change of ≤2 kg over the 24-week study period observed, but there were no clinically meaningful changes in glucose, insulin and blood lipid levels. There was no adverse event reported after the augmentation with paliperidone.ConclusionsAdding paliperidone to SSRIs could be a valid strategy for treatment-resistant OCD patients and additional efficacy studies and randomized, double-blind studies are needed.

Table of Contents

AbstractParent Engagement in Child and Family Treatment: Considering the BarriersEngaging Families in Mental Healthcare From the Boardroom to the BedsidePsychiatric Symptoms in Bereaved vs. Nonbereaved YouthScreen Time and Psychological Difficulties in 10‐Year‐OldsBrief CB Depression Prevention for High‐Risk TeensPsychotic Disorders and Sexual Abuse in ChildhoodAdolescents With Chronic Pain and Family FunctioningAripiprazole Augmentation in Teens With Resistant OCDWhat's Behind the Bullying?

Predicting outcome of treatment for severe, treatment resistant OCD in inpatient and community settings

Treatment of OCD is effective, even for the most chronic and severe cases. It has been difficult to identify predictors of treatment outcome, with little work aimed at predicting treatment outcome in severe OCD. We examined the ability of a range of demographic and psychopathology variables to predict treatment outcome in a cohort of 52 inpatients and a second group of 62 community outpatients with severe, treatment-refractory OCD. Despite both cohorts showing significant improvement in OCD symptoms, reliable predictors were difficult to identify, and were different in the two cohorts. In the inpatient group, marital status was a significant predictor, with those who were married or cohabiting showing better outcome that those not currently in a relationship. This relationship was not observed in the community treatment group. Initial symptom severity was also found to be a significant predictor, but only in the community treatment group, where higher initial severity was associated with greater reduction in symptoms during treatment. Further research examining a wider range of predictors may assist in identifying those factors which predict outcome in severe OCD.

P.4.c.001 Effectiveness of the combination of citalopram and clomipramine in resistant OCD patients

P.4.c.001 Effectiveness of the combination of citalopram and clomipramine in resistant OCD patients

Toc résistant : caractéristiques cliniques, facteurs prédictifs et influence des tempéraments affectifs

Despite significant advances in clinical research, Obsessive Compulsive Disorder, OCD represents a difficult to treat condition. The French Association of patients suffering from OCD, "AFTOC" is highly concerned by this issue. A new survey was implemented with the aim of exploring Resistant Obsessive Compulsive disorder "ROC". Patients with OCD and members of the "AFTOC" were included in the survey. A self-rated file was elaborated in order to get the maximum of information on the clinical and therapeutic aspects and conditions of OCD. The full version of "TEMPS-A" was also included for assessment of affective temperaments. Statistical analyses were performed for inter-group comparison between "ROC" (resistant OCD) and good responders. Logistic regression analyses with "ROC" method were used to search for independent predictive factors to "ROC". The new survey of "AFTOC", "TOC & ROC" selected a sample of 360 patients, who are members of the association. The rate of "ROC" was 44.2%, 25.3% of Good Responders (GR), and 30.5% in between. Inter-group comparisons ("ROC" versus GR) showed significant higher rates of psychiatric admissions (49% versus 28%), and suicide attempts (26% versus 13%), greater numbers of doctors consulted (5.5 versus. 3.2), compulsions (4.6 versus 3.4), and psychiatric comorbidity (2.8 disorders versus. 2.0; notably agoraphobia, social anxiety and worry about appearance) in the "ROC" group. Assessment by full "TEMPS-A" scale revealed, significantly higher rates of Cyclothymic Temperament (63% versus 43%; p: 0.0003), Depressive Temperament (72% versus 53%; p: 0.004), and Irritable Temperament (21% versus 9%; p: 0.02) in the ROC group. Moreover, the mean global score on each of these temperaments was significantly higher in the "ROC" group. No difference was obtained in the rate or the mean score on the hyperthymic temperament scale. The most predictive factors of "ROC" were represented by "slow continuous course", "worsening under SRI", "worry about appearance", current age above 40 years and psychiatric admission. Our data provides a more precise clinical picture of "ROC", which should be initially explored through baseline severity, compulsive dominance, hoarding, special comorbidity such as recurrent depression, obsession of appearance, agoraphobia, social anxiety, and complex mixture of unstable affective temperament (cyclothymic, irritable, and depressive), and course of illness. Furthermore, vigilance towards the notion of worsening linked to drug therapy, and the increased suicide risk is warranted in the clinical management of "ROC".

The effect of repetitive transcranial magnetic stimulation on symptoms in obsessive compulsive disorder

BACKGROUND Within a decade, the Repetitive Transcranial Magnetic Stimulation (rTMS) was being used to treat depression and schizophrenia. Antidepressant response has been reported in open and double-blind, sham-controlled studies of depression. Less is known about rTMS efficacy in the obsessive compulsive disorder. The general aim of our study was to evaluate the therapeutic effect of the low frequency rTMS in serotonin reuptake inhibitor (SRI) resistant OCD patients. Zero hypothesis was: lrTMS will have no impact on the symptomatology in the patients with OCD Alternative hypothesis was: rTMS will have significant impact on the symptomatology of OCD comparing with placebo aplication (sham).

Antipsychotics in Obsessive-Compulsive Disorder

Drug treatment of OCD entails serotonin re-uptake inhibitors as first-line interventions. However, many patients with OCD do not benefit from standard treatments with SRIs; this proportion of patients may be approximately estimated between 40 and 50 percent of all subjects who are initially treated with these agents. One of the most studied approaches for treatment-resistant patients is antipsychotic augmentation, which consists in adding to the ongoing SRI an antipsychotic. Good results have been obtained when the augmentation was made with a low-dose first generation antipsychotic (haloperidol, for which a double-blind study exists, and pimozide). Given the side-effects profile of first generation antipsychotics, researchers have, in the last years, tried second generation ones as augmentation drugs. Risperidone, olanzapine and, more recently, quetiapine at low doses have been proved to be effective in a series of open label reports and in double-blind studies. The present paper will review all available studies concerning the use of antipsychotics in OCD, pointing toward benefits and potential side effects of this augmentation strategy. All of the studies that evaluated the addition of an antipsychotic in resistant OCD lasted 6-12 weeks; only a preliminary study lasted 16 weeks. A question that remains unresolved to date is then how long should a clinician maintain the antipsychotic augmentation in patients who responded to this strategy. In other words, is antipsychotic at low doses only necessary in order to elicit a response or is it also necessary in order to maintain it? Another way of looking at the problem is to examine whether the discontinuation of the antipsychotic in patients who responded to this strategy is associated with a worsening of obsessive-compulsive symptoms. We will present data on relapse rates in patients who responded to the addition of the antipsychotic and then discontinued it without discontinuing the SSRI. Keywords: obsessive-compulsive disorder, anthipsychotics, treatment-resistance, olanzapine, risperidone, quetiapine

Risperidone Augmentation in the Treatment of Severe Adolescent OCD in SSRI-refractory Cases: A Case-series

The adverse effects and potential clinical value of risperidone as augmentation to selective serotonin reuptake inhibitor (SSRI) treatment in treatment resistant severe adolescent OCD patients were examined in 17 adolescents (15-19 years old, 8 males and 9 females) in an open label trial of risperidone 1-2 mg daily. After 12 weeks of augmenting treatment, statistically significant improvements were reflected in OCD symptom ratings (mean total Y-BOCS/CY-BOCS scores after treatment with second SSRI 24.2 +/- 2.6 versus 19.9 +/- 2.9, p < 0.001) and global assessment scores (mean CGAS, 69.4 +/- 11.4 versus 74.7 +/- 9.6, p < 0.001). Four patients had moderate improvement of more than 25% reduction in Y-BOCS scores in OCD symptoms. Further 10 patients had a reduction of 10-25% in total score, indicating slight improvement. One patient (6%) dropped from clinical OCD to a subclinical level of OCD (Y-BOCS total score < 15). No patient was found to have worsened during augmentation treatment. Eight cases had weight gain and sedation was reported in four cases. These preliminary findings suggest that augmentation with risperidone in dosages up to 2 mg daily might be efficient in adolescents with treatment resistant OCD.

Bipolarité cachée dans le trouble obsessionnel compulsif : enquête collaborative avec l’Association française des personnes souffrant de TOC (AFTOC)

Background : Clinical data is largely focused on depressive comorbidity in OCD. However in practice, treating resistant or severe OCD sufferers revealed many cases who seem to have an authentic OCD with a hidden comorbid bipolar disorder. Methods : The rate of bipolar comorbidity in OCD was analyzed in a epidemiological survey which we undertook among the members of the French Association of patients suffering from OCD (AFTOC in French). To explore mood comorbidity, we used structured self-rated questionnaires for major depression, hypomania and mania (DSM-IV criteria) and self-rated Angst’s checklist of Hypomania and Cyclothymic Temperament (developped by Akiskal and Hantouche). From a total sample of 780, 453 files (58 %) were returned and analyzed : 76 % had suffered from a major depression (83 % recurrent) and 17 % had attempted suicide. Results : According to DSM-IV definitions of hypomania/mania, 11 % of the total sample were classified as bipolar (3 % as BP-I and 8 % as BP-II). However, 20 % had been recognized as bipolar or cyclothymic before the survey and treated with mood stabilizers. Furthermore, the Hypomania Checklist of Angst showed that 30 % obtained a cut-off score = 10. Analysis on the self-rated questionnaire for Cyclothymic Temperament showed that 50 % scored = 10, and so classified as BPII1/2. Both thresholds for self-rated hypomania and cyclothymia were previously validated by Hantouche et al. (1998). Finally, our analyses showed that anger attacks and suicide behavior were mainly linked to comorbid bipolarity. Conclusion : These data extend clinical research on “bipolar OCD” entity which is largely under-recognized in clinical practice. Also, they implicate cyclothymia in hostility and suicide risk in this population.

Treatment of resistant OCD

Treatment of resistant OCD