Treatment-resistant Obsessive-compulsive Disorder Patients Research Articles

Topiramate Augmentation in Resistant OCD: A Double-Blind Placebo-Controlled Clinical Trial.

Glutaminergic dysfunction has been shown to be related to the pathphysiology of obsessive-compulsive disorder (OCD). Topiramate is an antiepileptic that inhibits glutaminergic action. The aim of this study is to evaluate the efficacy of topiramate augmentation in patients with treatment resistant OCD. This augmentation trial was designed as a 12-week randomized, placebocontrolled, double-blind study. Forty-nine patients suffering from OCD who had failed to respond to at least 12 weeks of treatment of an adequate and stable dose of a selective serotonin reuptake inhibitor (SSRI) were randomly allocated to receive topiramate or placebo plus their current anti OCD treatment. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was the primary outcome measure. Treatment response was defined as 25 % or more decrease in scores of Y-BOCS. The mean dosage of topiramate was 180.15 mg/day (range 100-200 mg/day). Forty-one patients (20 of 24 in topiramate group; 21 of 25 in placebo group) completed the trial. The topiramate group showed significant improvement over the study period (mean Y-BOCS score at week 12 as compared with baseline: P=.000). Those receiving topiramate experienced a mean decrease of 32.0% in Y-BOCS score, compared with 2.4% decrease for those receiving placebo. Twelve patients in the topiramate group versus no patient in the placebo group were rated as responder. The results of our study demonstrated that topiramate may augment the therapeutic effect of SSRIs in treatment-resistant OCD patients. However, it should be noted that our study is preliminary and larger double-blind studies are needed to confirm these results.

Ondansetron Augmentation in Treatment-Resistant Obsessive-Compulsive Disorder

Serotonin and dopamine neuronal systems have been implicated in the modulation of obsessive-compulsive disorder (OCD) symptoms. About 40% of OCD patients do not respond to first-line selective serotonin reuptake inhibitor (SSRI) treatment; among those, dopamine blocker augmentation has been reported to improve the rate of response by an additional one-third. Given that serotonin 5-HT(3) receptors are indirect inhibitors of cortico-mesolimbic dopamine release, augmentation with the 5-HT(3) receptor antagonist ondansetron in combination with SSRIs and antipsychotics has potential efficacy in treatment-resistant OCD patients. To assess the efficacy and tolerability of ondansetron in combination with SSRIs and antipsychotics in patients with treatment-resistant OCD. In total, 14 patients with a DSM-IV diagnosis of OCD, who were treatment resistant and receiving stable treatment with SSRIs and antipsychotic augmentation, entered a 12-week, single-blind trial of ondansetron. The drug was initiated at a dosage of 0.25 mg twice daily for 6 weeks and was then titrated to 0.5 mg twice daily for 6 weeks. Of the 14 patients, nine (64.3%) experienced a treatment response (> or =25% reduction in the Yale-Brown Obsessive Compulsive Scale [YBOCS] score and a Clinical Global Impressions-Improvement [CGI-I] score of 1 or 2) at 12 weeks. The average reduction in YBOCS-rated symptoms for the whole group was 23.2%. None of the treated patients experienced symptom exacerbation or significant adverse effects. These results suggest that low-dose ondansetron may have promise as an augmentation strategy for some patients with OCD resistant to SSRIs and antipsychotic augmentation, but further controlled trials are required. Trial registration number (ClinicalTrials.gov): NCT00796497.

Aripiprazole augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive–compulsive disorder: a 12-week open-label preliminary study

One of the most studied and well-documented strategies for treatment-resistant obsessive-compulsive disorder (OCD) is the addition of antipsychotic drugs to the ongoing serotonin reuptake inhibitor (SRI) treatment. To date, there has been a paucity of data regarding the use of aripiprazole in OCD patients who failed to respond to SRIs. The aim of the present pilot study was to investigate the efficacy of flexible doses of aripiprazole as augmenting agent in the treatment of resistant OCD patients. Patients meeting the inclusion criteria of treatment-resistant OCD entered a 12-week, open-label, flexible-dose trial of aripiprazole addition to SRIs. Aripiprazole was started at 5 mg/day and increased up to a maximum of 20 mg/day. Twelve patients fulfilled entry criteria; nine patients took at least one dose of study medication and eight of them completed the study. The mean daily dosage of aripiprazole in completers was 11.2+/-5.2 mg/day. Patients showed a significant improvement over the 12-week study period (paired t-test for mean Yale-Brown Obsessive Compulsive Scale total score at week 12 as compared with baseline - all patients: t = 4.860, d.f. = 8, P = 0.001). The most common adverse event reported was inner unrest reported by four (44.4%) patients. Our study supports the notion that adding aripiprazole to SRIs could be a valid strategy for treatment-resistant OCD patients, and points towards the need of randomized, double-blind studies.

A Long-Term Trial of the Effectiveness and Safety of Atypical Antipsychotic Agents in Augmenting SSRI-Refractory Obsessive-Compulsive Disorder

Although atypical antipsychotic agents have been found effective in the augmentation of serotonin reuptake inhibitors (SRIs) for treatment-resistant obsessive-compulsive disorder (OCD) in short-term trials, there are few data on the effectiveness and safety of these agents in clinical settings over the long term. Subjects (N = 46) who responded to selective SRIs (SSRIs) in an initial 12-week trial were continued on SSRI monotherapy plus cognitive-behavioral therapy (CBT) for 1 year. Subjects (N = 44) who failed to respond to SSRIs were randomly assigned to 1 of 3 atypical antipsychotics -- olanzapine, quetiapine, or risperidone -- and were consecutively treated using SSRI + atypical antipsychotics combined with CBT for 1 year. This study was conducted from January 2006 to November 2007 at Osaka City University Graduate School of Medicine Hospital, Japan. Augmentation with atypical antipsychotics reduced mean +/- SD Yale-Brown Obsessive Compulsive Scale (YBOCS) total scores in SSRI-refractory OCD patients (at initial assessment = 29.3 +/- 9.9, after 1 year = 19.3 +/- 6.8). However, compared to SSRI responders (at initial assessment = 25.8 +/- 11.4, after 1 year = 13.7 +/- 4.6), total YBOCS scores in those who required atypical antipsychotic augmentation were initially higher, and they remained at higher levels than those of SRI responders after 1 year of the treatments. Our work does not sufficiently support the long-term effectiveness of the atypical antipsychotics in the augmentation of SSRIs for treatment-resistant OCD patients. Even though this approach seems useful for some types of OCD patients, such as those with symmetry/ordering and hoarding symptoms, these data emphasize the limitations of the current pharmacotherapeutic options in treatment-refractory OCD, and their chronic use raises a number of safety concerns. (ClinicalTrials.gov) Identifier NCT00854919.

Effectiveness of Long-Term Augmentation with Citalopram to Clomipramine in Treatment-Resistant OCD Patients

The high percentage (between 40% and 60%) of resistance to first-line drugs, such as clomipramine or selective serotonin reuptake inhibitors, is a major problem in the pharmacologic management of obsessive-compulsive disorder (OCD). In these cases, different strategies have been employed with controversial outcomes. The meager information available on the association of two serotonergic drugs prompted us to explore the possible effectiveness and tolerability of citalopram+clomipramine in resistant OCD patients. Twenty outpatients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of OCD, who had failed to respond to at least two trials with a selective serotonin reuptake inhibitor and were currently taking clomipramine at different doses, were administered citalopram at a maximum dose of 60 mg/day. The clinical assessment was carried out at baseline (t0) and at the 4th (t1), 12th (t2), 24th (t3), 36th (t4), and 48th (t5) week by means of the Yale-Brown Obsessive Compulsive Scale, Hamilton Rating Scale for Depression, Clinical Global Impression scale, and the Dosage Record and Treatment Emergent Symptom Scale. The response was defined as a 35% decrease of the Yale-Brown Obsessive-Compulsive Scale total score. The results showed that approximately 50% of the patients improved significantly after 1 month of this regimen and after 1 year of treatment. This study, although carried out in a small sample and in an open fashion, represents one of the few experiences with the association of two serotonergic compounds in resistant OCD and confirms its potential usefulness and good tolerability profile. Controlled research on this association in OCD is recommended.

P.4.b.006 Clinical profiles of obsessive compulsive symptoms in schizophrenic patients

Obsessive-compulsive disorder (OCD) is a severely distressing disorder represented by obsessions and compulsions. A significant proportion of OCD patients fail to improve with conventional treatment methods. Repetitive transcranial magnetic stimulation (rTMS) has been proposed as an alternative for OCD treatment. Functional neuroimaging studies indicate that OCD is associated with increased activity in the supplementary motor area (SMA), a region that plays an important role in the pathophysiology of this disorder. In this study, we assessed the efficacy of augmentation with 1 Hz rTMS over the SMA in treatment-resistant OCD patients. The participants received 1 Hz rTMS over the SMA in 20 daily sessions for 4 weeks. We observed significant reduction in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score at the 4th week of the treatment. Reduction in compulsion contributed to the reduction of global Y-BOCS whereas there was no significant reduction in obsession. Clinical global impression-global improvement also showed significant change at the 2nd and 4th week of the treatment. No additional significant changes or significant adverse effects were seen. These findings suggest that 1 Hz rTMS over the SMA can be an efficient and safe add-on therapeutic method in treatment-resistant patients with OCD. Further controlled studies in larger samples are required to confirm the effect of 1 Hz rTMS over the SMA in OCD.

P.4.b.010 Tryptophan depletion in females with generalised anxiety disorder

This study aimed to evaluate the long-term course of obsessive–compulsive disorder (OCD) in patients treated with serotonin reuptake inhibitors (SRIs) and to identify predictors of clinical outcome. Seventy-nine patients fulfilling DSM-IV criteria for OCD were followed prospectively for 3 years. Baseline information was collected on demographic and clinical characteristics, using standardized instruments. During the follow-up period, the clinical status of each patient was evaluated monthly in the first year and bimonthly thereafter by means of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Hamilton Rating Scale for Depression (HDRS). The cumulative probability of achieving at least partial remission from obsessive–compulsive (OC) symptoms during the 3-year period was 65%. The probability of full remission was 38%. For subjects who achieved at least partial remission, the probability of subsequent relapse was 60%. Significant predictors of poor outcome included a longer duration of illness, a greater severity of OC symptoms at intake, and the presence of comorbid schizotypal personality disorder. The findings confirm that the course of illness in OCD is usually continuous with fluctuations in the intensity of OC symptoms. Despite adequate SRI therapy, relatively few patients achieve a completely asymptomatic state, and of those who achieve at least a partial remission, a substantial proportion subsequently relapse. One third of OCD patients is treatment-resistant. Further studies with large samples are required to adequately identify predictors of long-term outcome of OCD in order to optimize the choice among the existing treatment modalities. The development of alternative strategies is needed to improve the treatment approaches for treatment-resistant OCD patients.

Obsessive–compulsive disorder: A 3-year prospective follow-up study of patients treated with serotonin reuptake inhibitors: OCD follow-up study

This study aimed to evaluate the long-term course of obsessive–compulsive disorder (OCD) in patients treated with serotonin reuptake inhibitors (SRIs) and to identify predictors of clinical outcome. Seventy-nine patients fulfilling DSM-IV criteria for OCD were followed prospectively for 3 years. Baseline information was collected on demographic and clinical characteristics, using standardized instruments. During the follow-up period, the clinical status of each patient was evaluated monthly in the first year and bimonthly thereafter by means of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Hamilton Rating Scale for Depression (HDRS). The cumulative probability of achieving at least partial remission from obsessive–compulsive (OC) symptoms during the 3-year period was 65%. The probability of full remission was 38%. For subjects who achieved at least partial remission, the probability of subsequent relapse was 60%. Significant predictors of poor outcome included a longer duration of illness, a greater severity of OC symptoms at intake, and the presence of comorbid schizotypal personality disorder. The findings confirm that the course of illness in OCD is usually continuous with fluctuations in the intensity of OC symptoms. Despite adequate SRI therapy, relatively few patients achieve a completely asymptomatic state, and of those who achieve at least a partial remission, a substantial proportion subsequently relapse. One third of OCD patients is treatment-resistant. Further studies with large samples are required to adequately identify predictors of long-term outcome of OCD in order to optimize the choice among the existing treatment modalities. The development of alternative strategies is needed to improve the treatment approaches for treatment-resistant OCD patients.

Riluzole Augmentation in Treatment-Resistant Obsessive–Compulsive Disorder: An Open-Label Trial

Most patients with obsessive-compulsive disorder (OCD) show only partial reduction of symptoms with standard therapy. Recent imaging data suggests glutamatergic dysfunction in the corticostriatal pathway in OCD. We investigated the efficacy of augmentation therapy with riluzole, a glutamate-modulating agent, in treatment-resistant OCD. Thirteen patients aged between 18 and 65 years with a primary diagnosis of OCD that had proven resistant to standard treatment were treated with the addition of riluzole to their existing pharmacotherapy. Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Depression Inventory (HAM-D), and Hamilton Anxiety Inventory (HAM-A) scores were obtained weekly. Thirteen treatment-resistant OCD patients received riluzole 50 mg twice a day. Y-BOCS scores improved significantly over time. Of 13 patients, 7 (54%) demonstrated a >35% reduction in Y-BOCS scores, and 5 (39%) were categorized as treatment responders. HAM-D and HAM-A scores for the group also significantly improved over time. Riluzole was well tolerated with no serious adverse effects noted. Riluzole appears to have significant antiobsessional, antidepressant, and antianxiety properties. The addition of this agent may be of practical clinical benefit in patients with OCD.

Adding quetiapine to SRI in treatment-resistant obsessive???compulsive disorder: a randomized controlled treatment study

This study aimed to determine the efficacy and tolerability of adding quetiapine to a serotonin reuptake inhibitor in treatment-resistant obsessive-compulsive disorder (OCD). Twenty-one adult treatment-resistant OCD patients were randomized to 16 weeks of augmentation with either quetiapine (n = 11) or placebo (n = 10). Patients with significant comorbidities, including tic-spectrum disorders, were not included. The treatment was well tolerated, with only one premature dropout in each treatment-group. The primary analysis showed that individuals in the quetiapine-treated group showed a 14% mean improvement in baseline Yale-Brown Obsessive-Compulsive Scale scores at study endpoint compared with a 6% improvement in those treated with placebo, but this difference did not reach statistical significance (F<1). Three patients treated with quetiapine met criteria for clinical response, compared to one patient who was treated with placebo. Larger studies are needed to explore the efficacy of second generation antipsychotics, such as quetiapine, when used as adjunct treatment in resistant OCD.

Bipolar Disorder With Comorbid Cluster B Personality Disorder Features

Because of their overlapping phenomenology and mutually chronic, persistent nature, distinctions between bipolar disorder and cluster B personality disorders remain a source of unresolved clinical controversy. The extent to which comorbid personality disorders impact course and outcome for bipolar patients also has received little systematic study. One hundred DSM-IV bipolar I (N = 73) or II (N = 27) patients consecutively underwent diagnostic evaluations with structured clinical interviews for DSM-IV Axis I and cluster B Axis II disorders, along with assessments of histories of childhood trauma or abuse. Cluster B diagnostic comorbidity was examined relative to lifetime substance abuse, suicide attempt histories, and other clinical features. Thirty percent of subjects met DSM-IV criteria for a cluster B personality disorder (17% borderline, 6% antisocial, 5% histrionic, 8% narcissistic). Cluster B diagnoses were significantly linked with histories of childhood emotional abuse (p = .009), physical abuse (p = .014), and emotional neglect (p = .022), but not sexual abuse or physical neglect. Cluster B comorbidity was associated with significantly more lifetime suicide attempts and current depression. Lifetime suicide attempts were significantly associated with cluster B comorbidity (OR = 3.195, 95% CI = 1.124 to 9.088), controlling for current depression severity, lifetime substance abuse, and past sexual or emotional abuse. Cluster B personality disorders are prevalent comorbid conditions identifiable in a substantial number of individuals with bipolar disorder, making an independent contribution to increased lifetime suicide risk.

Double-Blind Treatment With Oral Morphine in Treatment-Resistant Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) often responds inadequately to serotonin reuptake inhibitors (SRIs). A case series reported substantial response to once-weekly oral morphine. We conducted a placebo-controlled, double-blind trial to investigate whether once-weekly oral morphine is effective in SRI-resistant OCD. Subjects with DSM-IV-defined OCD for > or =3 years who had failed > or =2 adequate SRI trials and had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of > or =20 were recruited. Current medications were continued. Subjects were randomly assigned to random-order, 2-week blocks of once-weekly morphine, lorazepam, and placebo. Week 2 dosage was increased, decreased, or maintained depending on response and side effects. We enrolled 23 subjects, who had failed 2 to 6 SRI trials. The median screening Y-BOCS score was 29. The median Y-BOCS score after morphine (highest dose) was 25 (median decrease = 13%). Seven subjects (30%) were responders (Y-BOCS decreases > or =25%). The median Y-BOCS score after lorazepam (highest dose) was 27 (median decrease = 6%). Four subjects (17%) responded to lorazepam; 1 was a morphine responder. The median Y-BOCS score after placebo (highest dose) was 27 (median decrease = 7%), and no subject responded. Responses differed significantly among the 3 conditions (Friedman 2-way analysis of variance, chir(2) = 13.92, df = 2, p = .01). Wilcoxon matched-pairs signed-rank tests (T = 56.5, p = .05) showed significance for morphine versus placebo but not lorazepam versus placebo. Our results support the hypothesis that once-weekly oral morphine can reduce symptoms in some treatment-resistant OCD patients. The mechanism of action is unknown. Further studies of mu-agonists and glutamate antagonists are warranted.

Lack of efficacy of low doses of quetiapine addition in refractory obsessive-compulsive disorder.

Some studies have shown that low dose of neuroleptic addition to ongoing antiobsessive treatment might be effective in treatment resistant obsessive-compulsive disorder (OCD). The primary purpose of this study was to evaluate the efficacy of low-dose quetiapine in clomipramine and serotonin reuptake inhibitor-refractory obsessive-compulsive disorder patients. Eight obsessive-compulsive disorder patients who were resistant to treatment after 2 or more inadequate trials with clomipramine or serotonin reuptake inhibitor were admitted to the study. The patients were administrated on open trial of quetiapine at daily dose of 150 mg. Treatment response was assessed using the Yale-Brown Compulsive Scale and the Clinical Global Impressions Scale. Only 2 patients were partial responders, with Yale-Brown Compulsive Scale score decreases of 28% and 29%. The results of this preliminary open trial suggest that low dose of quetiapine may not be effective in treatment-resistant obsessive-compulsive disorder patients. Larger placebo-controlled trials are needed to investigate the clinical efficacy of quetiapine addition at low doses to antiobsessive treatment in treatment-refractory obsessive-compulsive disorder.

Lack of Efficacy of Low Doses of Quetiapine Addition in Refractory Obsessive-Compulsive Disorder

Background Some studies have shown that low dose of neuroleptic addition to ongoing antiobsessive treatment might be effective in treatment resistant obsessive-compulsive disorder (OCD). The primary purpose of this study was to evaluate the efficacy of low-dose quetiapine in clomipramine and serotonin reuptake inhibitor-refractory obsessive-compulsive disorder patients. Method Eight obsessive-compulsive disorder patients who were resistant to treatment after 2 or more inadequate trials with clomipramine or serotonin reuptake inhibitor were admitted to the study. The patients were administrated on open trial of quetiapine at daily dose of 150 mg. Treatment response was assessed using the Yale-Brown Compulsive Scale and the Clinical Global Impressions Scale. Results Only 2 patients were partial responders, with Yale-Brown Compulsive Scale score decreases of 28% and 29%. Conclusion The results of this preliminary open trial suggest that low dose of quetiapine may not be effective in treatment-resistant obsessive-compulsive disorder patients. Larger placebo-controlled trials are needed to investigate the clinical efficacy of quetiapine addition at low doses to antiobsessive treatment in treatment-refractory obsessive-compulsive disorder.

Citalopram Treatment of Compulsive Shopping

Article AbstractBackground: Treatment with intravenous clomipramine is rapidly effective in some obsessive-compulsive disorder (OCD) patients unresponsive to orally administered serotonin reuptake inhibitors (SRIs). The selective serotonin reuptake inhibitor citalopram is effective for OCD when administered orally. We investigated whether intravenous citalopram would rapidly benefit OCD patients unresponsive to orally administered SRIs. Method: Thirty-nine adult outpatients participated in a 3-week open-label trial of intravenous citalopram. Eligible patients had moderate-to-severe DSM-IV OCD of >=1 year's duration, a baseline Yale-Brown Obsessive Compulsive Scale (YBOCS) score >=25, and no other active Axis I diagnosis and had failed at least 2 adequate oral SRI trials, excluding citalopram. Intravenous citalopram was administered daily for 21 days, followed by oral citalopram until treatment day 84. Intravenous citalopram was started at 20 mg/day and was increased to 40 to 80 mg/day as tolerated. Results: Intravenous citalopram was well tolerated even at higher doses (dropout rate=2.6%). At day 21, 23 (59%) of the 39 patients had YBOCS score decreases of >=25%, of whom 4 had decreases of >=35%. Twenty-seven patients with YBOCS score decreases of >=20% were allowed to continue on treatment with oral citalopram, and by day 84, all had substantial further improvement. All 27 patients also showed significant improvement in several dimensions of quality of life. Conclusion: Intravenous citalopram was safe and rapidly effective in a group of treatment-resistant OCD patients. The early onset of response suggests a means of accelerating OCD symptom relief and predicting response to oral citalopram treatment. Double-blind, double-dummy, placebo-controlled trials of intravenous versus oral citalopram in patients with treatment-resistant OCD are indicated.