Treatment-refractory Obsessive-compulsive Disorder Research Articles

A clinical comparative study of venlafaxine and clomipramine in the treatment of refractory obsessive-compulsive disorder

目的 评价万拉法新与氯米帕明治疗难治性强迫症的疗效及安全性.方法符合CCMD-3强迫症诊断标准的难治性病人62例,随机分为两组,分别予万拉法新和氯米帕明治疗8周.采用Yale-Brown强迫量表(Y-BOCS)、副反应量表(TESS)和临床疗效评定疗效及副反应.结果万拉法新组显效14例,有效11例;氯米帕明组显效15例,有效10例.两组疗效相似,两组显效率与有效率经检验差异无显著性意义(P＞0.05).万拉法新副反应少于氯米帕明.结论万拉法新治疗难治性强迫症较安全有效。

P.3.043 Dopamine transporter density changes of basal ganglia with SSRI treatment i patients

Little data exist to inform the treatment of severe or treatment refractory obsessive–compulsive disorder (OCD) in an inpatient or residential setting. We aimed to determine effect size of inpatient, residential or day-patient program in people with OCD. Studies were selected if they were conducted in an inpatient, day-patient or residential setting; were using the Yale Brown Obsessive Compulsive Scale (Y-BOCS) as an outcome measure; treatment included cognitive behavior therapy; it involved adult patients; and had a sample size of at least 20. We identified 19 studies with a total of 2306 participants at admission. We extracted the mean and standard deviation pre-admission and at discharge. The overall reduction was 10.7 points (95% CI: 9.8–11.5, z=24.2 p<0.001) with an effect size, Hedges g, of 1.87. Being married or cohabiting consistently predicted better outcomes, and symptoms of hoarding or comorbid alcohol misuse consistently predicted worse outcomes. Clients with severe or treatment refractory OCD can make significant improvements with intensive residential or inpatient therapy but little is known either about its long term benefits or cost effectiveness compared with an alternative. Programs are offered internationally with a variety of inclusion criteria. We discuss how such programs might be optimized.

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.

Deep brain stimulation for treatment‐refractory obsessive‐compulsive disorder: psychopathological and neuropsychological outcome in three cases

Investigation of deep brain stimulation (DBS) as a last-resort treatment alternative to capsulotomy in treatment-refractory obsessive-compulsive disorder (OCD). Prospective single-case based design with evaluation of DBS impact on emotions, behaviour, personality traits and executive function in three patients with OCD. Two patients experienced sustained improvement of OCD symptoms with DBS. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) dropped 12 points and 23 points to baseline and Y-BOCS self-rating scale (Y-BOCS-SRS) and Profile of Mood States (POMS) for depression and tension decreased with increasing stimulation amplitude. Total Maladjustment Score on the Brief Psychiatric Rating Scale reduced with 44 and 59% to baseline. Reduction in psychopathology was sustained under continuous stimulation. No deleterious impact of DBS on neuropsychological testing or personality traits measured on a self-rated personality inventory was detected. These preliminary findings demonstrate that DBS may have important therapeutic benefits on psychopathology in OCD. No harmful side-effects were detected during follow-up (33/33/39 months, respectively).

Clomipramine use in obsessive–compulsive disorder

The serotonin reuptake inhibitor, clomipramine and newer selective serotonin reuptake inhibitors have become recognized as the most effective monotherapy for obsessive–compulsive disorder. Meta-analyses have suggested that clomipramine may be superior to other selective serotonin reuptake inhibitors in treating obsessive–compulsive disorder. Double-blind, direct comparisons of the selective serotonin reuptake inhibitors and clomipramine, have demonstrated equal efficacy, fewer side effects and lower medication discontinuation rates in selective serotonin reuptake inhibitor patients. However, clomipramine continues to play a vital role in the pharmacotherapy of obsessive–compulsive disorder, being used when two or more selective serotonin reuptake inhibitor trials have not been sufficiently effective, which can occur in up to a third of patients. Recent investigation suggests potential roles for intravenous clomipramine and the combination of oral clomipramine with selective serotonin reuptake inhibitors and other medications in treatment-refractory obsessive–compulsive disorder patients.

Synergistic action of 5-HT2A antagonists and selective serotonin reuptake inhibitors in neuropsychiatric disorders.

Recently, the addition of drugs with prominent 5-HT(2) receptor antagonist properties (risperidone, olanzapine, mirtazapine, and mianserin) to selective serotonin reuptake inhibitors (SSRIs) has been shown to enhance therapeutic responses in patients with major depression and treatment-refractory obsessive-compulsive disorder (OCD). These 5-HT(2) antagonists may also be effective in ameliorating some symptoms associated with autism and other pervasive developmental disorders (PDDs). At the doses used, these drugs would be expected to saturate 5-HT(2A) receptors. These findings suggest that the simultaneous blockade of 5-HT(2A) receptors and activation of an unknown constellation of other 5-HT receptors indirectly as a result of 5-HT uptake inhibition might have greater therapeutic efficacy than either action alone. Animal studies have suggested that activation of 5-HT(1A) and 5-HT(2C) receptors may counteract the effects of activating 5-HT(2A) receptors. Additional 5-HT receptors, such as the 5-HT(1B/1D/5/7) receptors, may similarly counteract the effects of 5-HT(2A) receptor activation. These clinical and preclinical observations suggest that the combination of highly selective 5-HT(2A) antagonists and SSRIs, as well as strategies to combine high-potency 5-HT(2A) receptor and 5-HT transporter blockade in a single compound, offer the potential for therapeutic advances in a number of neuropsychiatric disorders.

Comorbid posttraumatic stress disorder: impact on treatment outcome for obsessive-compulsive disorder.

The study tested the effect of comorbid posttraumatic stress disorder (PTSD) on behavior therapy outcome for obsessive-compulsive disorder (OCD). Subjects were 15 patients with treatment-refractory OCD who were admitted consecutively to a short-term residential facility. Eight met DSM-IV criteria for comorbid PTSD. Patients participated in coached and self-directed behavior treatments of exposure and response prevention as well as in group treatments targeting specific OCD symptoms and related difficulties. Severity of OCD and depression were assessed at admission and exit. Patients with comorbid PTSD showed no significant improvements in OCD and depression symptoms. OCD and depression symptoms improved significantly more in patients without comorbid PTSD than in patients with comorbid PTSD. Behavioral treatment (with or without medication) of OCD may be adversely affected by the presence of comorbid PTSD.

Deep brain stimulation in severe treatment refractory OCD

Deep brain stimulation in severe treatment refractory OCD

Prospective long-term follow-up of 44 patients who received cingulotomy for treatment-refractory obsessive-compulsive disorder.

Long-term outcome associated with cingulotomy for obsessive-compulsive disorder (OCD) was prospectively assessed. Findings are reported for 18 patients previously described in 1995 and for 26 new patients. An open preoperative and follow-up assessment was conducted at multiple time points for 44 patients undergoing one or more cingulotomies for treatment-refractory OCD. The patients were assessed by using the Structured Clinical Interview for DSM-III-R preoperatively and with the Yale-Brown Obsessive Compulsive Scale, the Beck Depression Inventory, and the Sickness Impact Profile both preoperatively and at all follow-up assessments. The patients completed clinical global improvement scales at all follow-up assessments. At mean follow-up of 32 months after one or more cingulotomies, 14 patients (32%) met criteria for treatment response and six others (14%) were partial responders. Thus, 20 patients (45%) were at least partial responders at long-term follow-up after one or more cingulotomies. Few adverse effects were reported. Thirty-two percent to 45% of patients previously unresponsive to medication and behavioral treatments for OCD were at least partly improved after cingulotomy. Cingulotomy remains a viable treatment option for patients with severe treatment-refractory OCD.

Obsessive-Compulsive Hoarding

Compulsive hoarding and saving symptoms, found in many patients with obsessive-compulsive disorder (OCD), are part of a clinical syndrome that has been associated with poor response to medications and cognitive-behavioral therapy (CBT). We sought to determine whether patients with the compulsive hoarding syndrome had more severe symptoms and functional impairment than nonhoarding OCD patients and whether they would respond to intensive, multimodal treatment previously found to be effective for treatment-refractory OCD. We studied 190 consecutive patients with DSM-IV OCD treated openly for approximately 6 weeks with intensive CBT, medication, and psychosocial rehabilitation in a partial hospitalization program for severely ill OCD patients. Twenty of the 190 patients (11%) were identified as having the compulsive hoarding syndrome. All patients were assessed before and after treatment with the Yale-Brown Obsessive Compulsive Scale (YBOCS), Hamilton Rating Scale for Depression (HAM-D). Hamilton Rating Scale for Anxiety (HAM-A). and Global Assessment Scale (GAS). We compared the symptom severity and response to treatment of compulsive hoarders versus nonhoarding OCD patients. Compulsive hoarders were significantly older than nonhoarders (p < .001). Hoarders had significantly lower GAS scores and higher HAM-A scores than nonhoarders both before (p = .04) and after (p = .002) treatment, but had similar pretreatment YBOCS scores. Both groups improved significantly with treatment as assessed by YBOCS score (p < .001), but nonhoarders had significantly greater decreases in YBOCS scores than hoarders (p = .02). While the compulsive hoarding syndrome appears to be a distinct, more disabling, variant of OCD that does not respond as robustly to treatment, it may still improve significantly with intensive, multimodal treatment tailored to its specific features and associated deficits.

Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for obsessive compulsive disorder

Background: As interventions for severe, treatment-refractory obsessive compulsive disorder (OCD), neurosurgical procedures are associated with only modest efficacy. The purpose of this study was to identify cerebral metabolic correlates as potential predictors of treatment response to anterior cingulotomy for OCD. Methods: Clinical data were analyzed in the context of a retrospective design. Subjects were 11 patients who underwent stereotactic anterior cingulotomy for OCD. Symptom severity was measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) before and at approximately 6 months postoperative. Preoperative F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) data were available. Statistical parametric mapping methods were used to identify loci of significant correlation between preoperative regional cerebral metabolism and postoperative reduction in Y-BOCS scores. Results: One locus within right posterior cingulate cortex was identified, where preoperative metabolism was significantly correlated with improvement in OCD symptom severity following cingulotomy. Specifically, higher preoperative rates of metabolism at that locus were associated with better postoperative outcome. Conclusions: A possible predictor of treatment response was identified for patients with OCD undergoing anterior cingulotomy. Further research, utilizing a prospective design, is indicated to determine the validity and reliability of this finding. If confirmed, an index for noninvasively predicting response to cingulotomy for OCD would be of great value.

Surgical Treatment of Mental Illness: Impact of Imaging

Surgical Treatment of Mental Illness: Impact of Imaging

An Open Trial of Plasma Exchange in Childhood-Onset Obsessive-Compulsive Disorder Without Poststreptococcal Exacerbations

Patients with childhood-onset obsessive-compulsive disorder (OCD) with symptom exacerbations following streptococcal infections benefit from treatment with plasma exchange. In this study, 5 patients with treatment-refractory OCD without a history of streptococcus-related exacerbations underwent an open 2-week course of therapeutic plasma exchange. Behavioral ratings, completed at baseline and 4 weeks after the initial treatment, included the Clinical Global Impressions Scale and the Yale-Brown Obsessive Compulsive Scale. All 5 patients completed the trial with few side effects, but none showed significant improvement. Plasma exchange does not benefit children and adolescents with OCD who do not have streptococcus-related exacerbations.

NEUROANATOMICALLY BASED APPROACHES TO OBSESSIVE-COMPULSIVE DISORDER: Neurosurgery and TranscranialMagnetic Stimulation

Obsessive-compulsive disorder is a severe condition. Unfortunately, current medication and behavior therapies fail to adequately benefit some patients most severely affected. Advancing knowledge of brain circuit involvement has potential treatment implications. The neurosurgical techniques most often used in the United States for crippling, treatment-refractory obsessive-compulsive disorder are reviewed in the context of anatomic models of the illness. The use of transcranial magnetic stimulation to probe possible neuroanatomic and neurophysiologic substrates of this disorder is considered, and how the knowledge gained from such studies might advance treatment is presented.

Therapeutic approaches to the treatment of refractory obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a debilitating condition that afflicts approximately 1% to 3% of the world population. The primary treatments are selective serotonin reuptake inhibitors and behavioral therapy. Despite therapy, approximately 30% to 40% of patients continue to suffer from disabling OCD symptoms. This article addresses the range of treatment options for patients with refractory OCD, focusing upon novel strategies and the most recent research.

Issues and Strategies in Treating Refractory Obsessive-Compulsive Disorder

The World Health Organization has determined that obsessive-compulsive disorder (OCD) is the 10th leading medical cause of disability across the globe. Unfortunately, a substantial proportion of patients with OCD fail to respond to medication trials. In the pivotal double-blind, placebo-controlled trials that established the efficacy of clomipramine and the selective serotonin reuptake inhibitors (SSRIs), 40% to 60% of patients were nonresponders to a given drug. Moreover, patients who do not respond to their first medication trial may be less likely than treatment-naive patients to respond to subsequent trials. For example, only 33% of patients participating in double-blind trials who had failed trials of one or more serotonin reuptake inhibitors (SRIs) benefited from a subsequent trial of sertra-line, compared with 53% of those who were treatment naive (Rasmussen, Baer, Eisen, and Shera, unpublished data, 15th Annual Meeting, American Psychiatric Association, May 17-22, 1997).At the Fourth International Obsessive-Compulsive Disorder Conference, held in February 2000 in St. Thomas, US Virgin Islands, an afternoon panel was devoted to considering issues and strategies related to treatment-refractory OCD. The panel presentations were divided into three groups: time to response and outcome after long-term followup; pharmacologic strategies for nonresponders; and new data concerning nonpharmacologic interventions.

Serotonergic drugs in the treatment of depressive and anxiety disorders.

Serotonergic dysfunction has been implicated in the aetiology of several psychiatric conditions, including depressive and anxiety disorders. Much of the evidence for the role of serotonin (5-HT) in these disorders comes from treatment studies with serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs), 5-HT(1A) agonists and 5-HT antagonists. This review considers the place of these drugs in the treatment of panic disorder, obsessive-compulsive disorder (OCD), social phobia, and generalized anxiety disorder (GAD). Among these agents, the SSRIs stand out with proven efficacy in the treatment of a spectrum of disorders, such as depression, panic disorder, OCD and social phobia. They may also be a suitable treatment for GAD. 5-HT(1A) agonists have been used extensively for the treatment of depression and GAD but evidence of their efficacy in other anxiety disorders is equivocal. 5-HT antagonists are the least well studied of these agents: while they may have activity in depression, their efficacy has not been fully investigated in anxiety disorders. However, preliminary reports suggest that they may be useful as adjuvants to SSRIs in treatment-refractory OCD. The high incidence of comorbidity amongst psychiatric disorders means that pharmacotherapy that is effective against a range of disorders, such as the SSRIs, is of considerable use to clinicians. Future research into the biological mechanisms underlying such disorders is likely to further enhance pharmacotherapy. Copyright 2000 John Wiley & Sons, Ltd.

Neurosurgical treatment of obsessive-compulsive disorder

Case reports suggest that neurosurgical operations can improve symptoms in patients with severe treatment-refractory obsessive-compulsive disorder (OCD). However, it is unclear which procedure is best and which may produce the most side-effects. I review the literature on the efficacy and complications of four frequently used neurosurgical procedures (cingulotomy, capsulotomy, limbic leucotomy and subcaudate tractotomy) that are used to treat refractory OCD. Since the vast majority of patients who underwent surgery were severely and chronically disabled, it is likely that these procedures were of assistance in alleviating some of their symptoms. It is currently impossible to determine which surgical procedure is the best for a particular patient. Despite a lack of controlled data and inconsistencies in the literature, it appears that when non-surgical treatments have failed to improve OCD symptoms significantly in severely ill patients, at least partial relief can be obtained by some people with OCD by neurosurgery. Results of cumulative studies strongly support the need for continued research in this area.

Open-label pilot study of tramadol hydrochloride in treatment-refractory obsessive-compulsive disorder

Open-label pilot study of tramadol hydrochloride in treatment-refractory obsessive-compulsive disorder