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1.
OBJECTIVE: To examine the efficacy and tolerability of clomipramine compared with the selective serotonin reuptake inhibitors (SSRIs) in the treatment of obsessive-compulsive disorder (OCD), bearing in mind the recent Expert Consensus Guidelines recommendation to use clomipramine after 2 to 3 failed SSRI trials. METHOD: The literature on the pharmacotherapy of OCD was critically examined. RESULTS: The available research evidence is not conclusive but suggests that clomipramine possesses greater anti-obsessional efficacy than do the SSRIs. In addition, when clomipramine is presented to patients in a positive way, and properly used in small initial doses with gradual increases, it seems to be tolerated as well as the SSRIs. CONCLUSION: Recently expressed opinions that clomipramine should be used to treat OCD after 2 to 3 failed SSRI trials are not supported by research evidence. Both clomipramine and the SSRIs may be used as first-line treatments for OCD.  相似文献   

2.
OBJECTIVE: To critically review the antiobsessional properties of serotonin-norepinephrine reuptake inhibitors (SNRIs) (venlafaxine and clomipramine) in the treatment of obsessive-compulsive disorder (OCD) as an alternative to selective serotonin reuptake inhibitors (SSRIs), which are currently considered the first-line treatment of OCD. DATA SOURCES: A MEDLINE search was performed to identify clinical trials with the SNRIs venlafaxine and clomipramine published from 1996 to 2004 (keywords: SNRIs, venlafaxine, duloxetine, and clomipramine, each matched individually with the term OCD), focusing on the best-designed studies for inclusion. DATA SYNTHESIS: Much of the literature about SNRIs in OCD supports the efficacy of these compounds in the treatment of OCD. However, double-blind, placebo-controlled studies with venlafaxine are lacking, and the most relevant studies consist of active comparison trials between SNRIs and SSRIs. In these studies, SNRIs seem to be as effective as SSRIs in OCD; SNRIs might be preferred for patients with certain types of treatment-resistant OCD or those with particular comorbid conditions. A large number of placebo-controlled and active comparison trials with clomipramine document efficacy in OCD, and meta-analytic studies suggest a small superiority over SSRIs. Compared with clomipramine, the SNRI venlafaxine showed fewer side effects and better tolerability. CONCLUSION: The SNRIs may represent a valid alternative to the SSRIs, particularly in specific cases. Double-blind, placebo-controlled studies are, however, needed to confirm the positive findings reported by several studies with venlafaxine.  相似文献   

3.
OBJECTIVE: This study evaluates the clinical response to olanzapine used in association with selective serotonin reuptake inhibitors (SSRIs) or clomipramine in treatment-resistant obsessive-compulsive disorder (OCD). METHODS: We describe the cases of 9 patients with serotonin uptake inhibitor-resistant OCD who were given an open-label adjunctive treatment of olanzapine for a minimum of 6 weeks. The response was assessed by using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Clinical Global Impression Scale (CGI). RESULTS: Six patients showed improvement of symptoms after the augmentation with olanzapine. One patient (treated with clomipramine) discontinued olanzapine due to side effects, and another 2 did not respond. CONCLUSION: Olanzapine augmentation of SSRIs in treating OCD showed a good (two-thirds) response rate, and it could therefore be considered as a treatment option when conventional therapies have failed.  相似文献   

4.
SSRIs治疗强迫症对照分析   总被引:28,自引:4,他引:24  
目的:比较5羟色胺回收抑制剂(SSRIs)与氯丙咪嗪对强迫症的临床疗效及副反应。方法:对35例强迫症患者应用SSRIs(18例)与氯丙咪嗪(17例)进行对照分析。采用Yale-Brown强迫量表(Y-BOCS)、汉密尔顿抑郁量表(HAMD)、副反应量表(TESS)和临床疗效评定标准评定疗效及副反应。结果:SSRIs与氯丙咪嗪疗效相似,两组显效率和有效率无显著差异。SSRIs组副反应较氯丙咪嗪组少且  相似文献   

5.
Cognitive-behavioral therapy (CBT) and pharmacological treatments are often applied in cases of pediatric obsessive-compulsive disorder (OCD). Especially in combination both methods are particularly efficacious; nonetheless, 40 % of all patients treated remain symptomatic. Exposure with response prevention, based on the principle of habituation, is the intervention with the best evidence. More recent cognitive and metacognitive treatments focus on modifying expectations and may have the potential to improve treatment efficacy. Selective serotonin reuptake inhibitors (SSRIs) are the first line of treatment in severe cases of OCD. With treatment resistance, the SSRI should be changed, or alternatively clomipramine can be employed. Augmentation strategies suggest the combination of two SSRIs, SSRI und clomipramin, or SSRI and (atypical) neuroleptics. Following successful treatment, medication should be reduced very slowly. Novel treatments in children and adolescent have been reported for antiglutamatergic agents as riluzole or D-cycloserine, a partial agonist of N-methyl-D-aspartic acid (NMDA).  相似文献   

6.
Two treatments have demonstrated efficacy in OCD, exposure and response (ritual) prevention (EX/RP) and pharmacotherapy with serotonin reuptake inhibitors (SRIs). In this article, which is the third in a three-part series, the authors present an overview of the role of biological treatments for OCD. The evidence for the efficacy of the serotonin reuptake inhibitors (clomipramine and the five selective serotonin reuptake inhibitors "SSRIs" fluvoxamine, fluoxetine, paroxetine, sertraline, and citalopram) as monotherapy for OCD is reviewed. The authors also discuss the rationale for choosing among these agents for specific patients. Research on other types of medication monotherapies for OCD is also discussed. The authors then cover strategies for treatment-resistant OCD, including combining EX/RP and SRI medication treatment, combining clomipramine and an SSRI, use of augmenting medications, and use of intravenous clomipramine. Findings concerning the use of other somatic therapies for treatment-resistant OCD, including electroconvulsive therapy, neurosurgery, plasma exchange/IV immunoglobulin/maintenance antibiotics, and transcranial magnetic stimulation, are also reviewed. Finally, the authors discuss what is known about matching treatments to patients with certain specific symptom clusters, how long to continue maintenance medication treatment, and how to terminate treatment.  相似文献   

7.
BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic illness associated with substantial morbidity; it often requires long-term medication. The best-studied therapeutic agent in the treatment of this disorder is the tricyclic antidepressant clomipramine. Since other tricyclic antidepressants appear to lack efficacy in OCD, that of clomipramine has been linked to its potent effects on serotonin. Consequently, agents that selectively inhibit serotonin reuptake have been the focus of several large-scale, placebo-controlled studies of OCD. Their efficacy in OCD is the focus of our review. DATA SOURCES: MEDLINE search (1966 to present) of OCD treatment with clomipramine or SSRI antidepressant medication using the key words obsessive-compulsive disorder, serotonin reuptake inhibitors, clomipramine, and pharmacology. STUDY FINDINGS: The selective serotonin reuptake inhibitors fluoxetine, sertraline, fluvoxamine, and paroxetine have, in separate multicenter trials, demonstrated efficacy and tolerability in the treatment of OCD. In contrast, clomipramine, though efficacious, is often associated with substantial adverse events, particularly anticholinergic side effects. While 2 recent meta-analyses support the superior efficacy of clomipramine over selective serotonin reuptake inhibitors in the treatment of OCD, 5 of 6 head-to-head comparisons of either fluoxetine or fluvoxamine versus clomipramine have found similar efficacy but a lower incidence of side effects with the selective serotonin reuptake inhibitor. A recently completed multicenter, 12-week, double-blind trial of paroxetine versus clomipramine versus placebo showed paroxetine to be as effective as clomipramine. With significantly fewer dropouts due to adverse effects than clomipramine, paroxetine was also associated with superior tolerability. CONCLUSION: The suggestion that selective serotonin reuptake inhibitors possess efficacy similar to that of clomipramine, but have a superior side effect profile, may have important implications for patients with OCD who require long-term treatment.  相似文献   

8.
Obsessive-compulsive disorder (OCD) constitutes an etiologically heterogeneous set of conditions, including a subtype that seems etiologically related to Tourette syndrome (TS). In order to treat OCD patients optimally, the clinician needs to integrate educational, psychological and pharmacological approaches. The most effective psychological intervention is cognitive-behavior therapy (CBT). Drug treatment includes clomipramine and all selective serotonin reuptake inhibitors (SSRIs). A subgroup of OCD patients, however, shows no significant improvement. Few studies suggest that the presence of tics is associated to a worse treatment response to SSRIs and that such patients benefit from combined therapy of serotonin-reuptake inhibitors plus neuroleptics. Independently of the presence of tics, there are several different augmentation strategies for resistant cases with drugs that interfere in the dopamine, serotonin, opioid and gonadal hormone systems. In addition, new therapies are now being tested against presumed postinfectious autoimmune processes. Finally, new developments are promising in neural circuit-based therapies, including neurosurgery for refractory patients.  相似文献   

9.
Citalopram for treatment-resistant obsessive-compulsive disorder.   总被引:2,自引:0,他引:2  
We investigated the comparative efficacy of citalopram vs. citalopram administered with clomipramine, in treatment-resistant obsessive-compulsive disorder (OCD). Sixteen adult outpatients participated in a 90-day, randomized, open-label trial. Eligible patients were aged 18 to 45 years, had moderate to severe DSM-III-R OCD of >/= one year's duration, a baseline Yale-Brown scale (Y-BOCS) score of >/= 25 and no other active axis I diagnosis, and had failed adequate clomipramine and fluoxetine trials. The citalopram-plus-clomipramine group (n = 9) experienced a significantly larger percent decrease in mean Y-BOCS score by day 90 than the citalopram alone group (n = 7). Only one citalopram patient decreased her score by >/= 35%, and two by >/= 25%. All nine citalopram-plus-clomipramine patients experienced decreases of 35%. Side effects were mild to moderate in both groups. We also treated with citalopram six OCD patients who had not tolerated fluoxetine alone and clomipramine alone; three achieved Y-BOCS score decreases of >/= 35% at 90 days. Since citalopram does not significantly affect clomipramine metabolism, the improvement in the combined drug group is unlikely to have resulted from increased plasma clomipramine levels. Double-blind controlled trials are needed of citalopram in OCD, and of combining citalopram with clomipramine in treatment-resistant OCD.  相似文献   

10.
目的 比较帕罗西汀和氯米帕明治疗强迫症的疗效和安全性。方法 141例符合美国精神障碍诊断与统计手册第4版强迫症诊断标准的患者完成了研究,其中帕罗西汀治疗72例(帕罗西汀组),氯米帕明治疗69例(氯米帕明组),疗程均为10周。所有患者在入组前均服用安慰剂1周。帕罗西汀组第1周20mg/d;第2周30mg/d;第3周40mg/d;第4~10周低剂量组40mg/d,高剂量组50mg/d。氯米帕明组第1周50mg/d;第2周100mg/d;第3周150mg/d,第4~10周低剂量组150mg/d,高剂量组200mg/d。结果 帕罗西汀组痊愈率为21%,显效率为60%,总有效率为93%。氯米帕明组痊愈率为28%,显效率为57%,总有效率为90%。两组患者疗效的差异无显著性。帕罗西汀组不良反应发生率为18%,氯米帕明组不良反应发生率为43%,两组的差异有显著性(χ^2=10.54,P=0.00)。结论 帕罗西汀治疗强迫症的疗效与氯米帕明相当,但不良反应比帕罗西汀少而轻。  相似文献   

11.
Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) with demonstrated efficacy in the treatment of major depressive episodes. Since 1985, it has been evaluated for the treatment of obsessive-compulsive disorder (OCD). The orbitofrontal cortex and caudate nucleus are cerebral structures believed to be involved in the pathogenesis of OCD, since hyperactivation of these territories in the basal state is corrected upon remission of symptoms induced by therapy with an SSRI or by behavioral psychotherapy. Furthermore, several studies have found abnormalities in serotoninergic transmission in the orbitofrontal cortex and SSRIs can increase serotonin release by desensitizing 5HTID autoreceptors. OCD is a severe, chronic psychiatric disorder frequently complicated by depressive episodes. Here we review the clinical trials of fluoxetine listed in the Medline and Embase computerized databases. Fluoxetine was found to be effective in OCD in all the published open-label studies as well as in placebo-controlled trials with an effective dose range of 40 to 60 mg daily. Clinical evaluation was carried out by using specific scales such as the Y-BOCS or NIMH-OC and improvement was observed after several weeks of therapy. These studies comprising an extended phase showed that efficacy was maintained--for three years in the longest study--resulting in a higher percentage of responders relative to the treatment initiation phase. A comparison of fluoxetine and clomipramine showed comparable efficacy and a superior safety profile, both in terms of anticholinergic side effects and cardiotoxicity or overdosage. The relapse rate was similar with both drugs. In the four meta-analyses appearing in the databases, two studies found similar efficacy for clomipramine and fluoxetine. There are few studies which directly compare the different SSRIs, apart from a comparison of fluoxetine and sertraline showing that both drugs have similar efficacy. With clomipramine, the SSRIs represent the first-line treatment recommended by the experts, in association with behavioral therapy to improve and maintain the clinical response over the long term. The guidelines recommend an optimal fluoxetine dose of 40 to 60 mg daily with a minimum treatment duration of 1 to 2 years. Efficacy should not be evaluated before 8 weeks to allow for onset of the therapeutic effects. Fluoxetine was found to have a good safety profile in these studies and the adverse effects described (insomnia, headache, diminished libido) rarely led to discontinuation of the treatment. Adverse effects such as nervousness or insomnia at the start of therapy were predictors of a good response to fluoxetine, as were the presence of remissions, the absence of prior pharmacologic therapy and a high impulsiveness score. A long history of the disorder, severity of the symptoms, collection obsessions, washing compulsions, obsessional slowness and comorbidity with a schizotypic personality or vocal or motor tics were associated with a poorer response. Fluoxetine also alleviates collateral depressive symptoms by significantly reducing suicidal ideation and impulsiveness in OCD patients. Our study indicates that fluoxetine is effective and well tolerated in OCD, placing it among the first-line treatments recommended by consensus conference guidelines.  相似文献   

12.
Obsessive-compulsive disorder (OCD) is a chronic and often incapacitating disorder that is frequently complicated by mood and additional anxiety diagnoses. Although appropriate pharmacotherapy is often of great benefit, full remission is rare. Separate multi-center, placebo-controlled trials of clomipramine, paroxetine, fluoxetine, sertraline and fluvoxamine, respectively, have established the unparalleled efficacy and safety of the serotonin reuptake inhibitors (SRIs) in the treatment of OCD. Direct comparisons of SRIs suggest similar efficacy, but reduced tolerability for clomipramine in comparison to fluoxetine, fluvoxamine, sertraline and paroxetine in patients with OCD. Although 60-80% of OCD patients will respond to SRI treatment, partial symptom reduction (mean improvement, 25-40% from baseline) remains the rule. Controlled trials of adjuvant lithium, buspirone, thyroid hormone or clonazepam added to ongoing SRI therapy have failed to demonstrate substantial further antiobsessive effects. The presence of comorbid conditions, specific OCD symptom content and various other clinical features have been investigated as potential predictors of medication response in patients with OCD, but consistent factors have not yet been identified. Clinical experience and preliminary data does suggest that a lack of response to one or more SRIs does not preclude response to another SRI. An overview of the pharmacotherapy of OCD, including first-line medication(s) and the comparative efficacy and pharmacological features of the different SRIs will be presented in this review, as well as potential strategies for OCD patients who fail to respond to conventional pharmacotherapeutic interventions.  相似文献   

13.
The cornerstone of pharmacotherapy for OCD is serotonin reuptake inhibition, either with clomipramine or with selective serotonin reuptake inhibitors (SSRIs). In spite of the success of serotonin reuptake inhibiting drugs, nearly half of OCD patients do not respond to treatment. Treatment response may be affected by genetic polymorphisms of the P450 metabolic system. The four most common enzyme-activity reducing polymorphisms of the P450 CYP2D6 enzyme were determined in 91 outpatients with primary OCD according to DSM-IV criteria, receiving dosages titrated upward to 300 mg/day of venlafaxine or 60 mg/day of paroxetine, using a fixed dosing schedule. Our results show that the investigated CYP2D6 polymorphisms are not a decisive factor in the response to paroxetine and venlafaxine treatment in OCD in spite of their highly significant effect on the blood levels of these medicines.  相似文献   

14.
Knowledge of pharmacotherapeutic treatment options in obsessive-compulsive disorder (OCD) has grown considerably over the past 40 years. Serotonergic antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and clomipramine, are the established pharmacologic first-line treatment of OCD. Medium to large dosages and acute treatment for at least 3 months are recommended until efficacy is assessed. In case of significant improvement, maintenance treatment is necessary. Unfortunately, about half of the patients do not respond sufficiently to oral serotonergic antidepressants; augmentation with atypical antipsychotics is an established second-line drug treatment strategy. Alternatives include intravenous serotonergic antidepressants and combination with or switch to cognitive behavioral psychotherapy. Remarkably, a considerable proportion of OCD patients still do not receive rational drug treatment. Novel research approaches, such as preliminary treatment studies with glutamatergic substances, and trials with further drugs, as well as needed aspects of future research, are reviewed.  相似文献   

15.
Biological markers in obsessive-compulsive and affective disorders   总被引:2,自引:0,他引:2  
To explore the relationship between obsessive-compulsive disorder (OCD) and affective disorder, patients with OCD were studied using a series of biological markers which have been previously reported to be abnormal in patients with affective illness. These “markers” included the dexamethasone suppression test, sleep electroencephalography, the plasma growth hormone response to clonidine, and platelet 3H-imipramine binding. Results from each of these studies suggested similarities between patients with obsessional disorder and those with affective illness. Many of these biological abnormalities were evident in obsessional patients who did not manifest depressive symptoms. As a tricyclic antidepressant, clomipramine, has been found to reduce obsessional symptoms, the relationship between these “affective-like” laboratory findings and the clinical response to clomipramine was studied in a subgroup of OCD patients. Preliminary results suggest that none of the markers studied predict clomipramine response.  相似文献   

16.
西酞普兰合并氯丙咪嗪治疗难治性强迫症   总被引:4,自引:2,他引:2  
目的探讨西酞普兰以及西酞普兰合并氯丙咪嗪治疗难治性强迫症的疗效和不良反应。方法将16例难治性强迫症患者随机分为2组(n=8),分别给予西酞普兰,西酞普兰合并氯丙咪嗪治疗。采用耶鲁布朗强迫症量表(YBOCS)和副反应量表(TESS)评定疗效和副反应。结果西酞普兰合并氯丙咪嗪组的所有病人的YBOCS减分率均大于35%,有6例出现副反应。西酞普兰组仅有一例患者的YBOCS减分率大于35%,有3例出现副反应。结论西酞普兰合并氯丙咪嗪治疗难治性强迫症的疗效优于单用西酞普兰,但副反应明显多于西酞普兰组。  相似文献   

17.
Even though selective serotonin reuptake inhibitors (SSRIs) are the mainstay of pharamacological treatment for obsessive-compulsive disorder (OCD), as many as 40% of patients do not have an adequate response to these medications. For such SSRI-refractory patients, the augmentation of SSRIs with new-generation antipsychotics that modulate both 5-HT and DA systems has recently been proven effective in controlled augmentation studies. The benzisothiazole derivative perospirone is a new serotonin 5-HT2 and dopamine D2 antagonist available in Japan for the treatment of schizophrenia. As its unique property, perospirone also exhibits 5-HT1A agonistic action. We present two SSRI-refractory OCD patients who showed little improvement with adequate trials of SSRI monotherapy, but exhibited significant improvement in their OCD symptoms after the addition of perospirone to ongoing SSRI treatment. The cases suggest that perospirone augmentation may be an effective and well-tolerated strategy for SSRI-refractory OCD patients. Controlled studies are required to further confirm the efficacy and tolerability of perospirone augmentation for treatment-resistant OCD.  相似文献   

18.
OBJECTIVE: The authors conducted a meta-analysis of published randomized, controlled medication trials in children and adolescents with obsessive-compulsive disorder (OCD) to assess evidence for differential efficacy based on type of drug, study design, and outcome measure. METHOD: A systematic literature search was performed for articles pertaining to the pharmacological treatment of pediatric and/or adolescent OCD. All baseline, posttreatment, and change scores with standard deviations reported in each study were included in the analyses. Effect sizes for dependent measures were expressed as standardized mean differences. The analysis included data on efficacy for four selective serotonin reuptake inhibitors (SSRIs) (paroxetine, fluoxetine, fluvoxamine, and sertraline) and clomipramine, four study designs, four dependent outcome measures, and two types of outcome scores (change and posttreatment scores). Multivariate regression was performed to assess the degree to which the effect sizes varied with the methodological features of each study. RESULTS: Twelve studies with a total of 1,044 participants met all inclusion criteria for the analysis. The pooled standardized mean difference for the results of all studies was 0.46 and showed a highly significant difference between drug and placebo treatment. Only one of the four outcome measures evaluated was not sensitive to change with treatment. A multivariate regression analysis of drug effect with other variables controlled showed that clomipramine was significantly superior to each of the SSRIs but that the SSRIs were comparably effective. CONCLUSIONS: Although highly significant, the overall effect sizes for medication were modest. Similarities and differences between the variables studied that emerged in the meta-analysis may have implications for both clinical care and future research.  相似文献   

19.
OBJECTIVE: The purpose of the study was to test the relative and combined efficacy of clomipramine and exposure and ritual prevention in the treatment of obsessive-compulsive disorder (OCD) in adults. Serotonin reuptake inhibitors (SRIs) and cognitive behavior therapy by exposure and ritual prevention are both established treatments for OCD, yet their relative and combined efficacy have not been demonstrated conclusively. METHOD: A double-blind, randomized, placebo-controlled trial comparing exposure and ritual prevention, clomipramine, their combination (exposure and ritual prevention plus clomipramine), and pill placebo was conducted at one center expert in pharmacotherapy, another with expertise in exposure and ritual prevention, and a third with expertise in both modalities. Participants were adult outpatients (N=122 entrants) with OCD. Interventions included intensive exposure and ritual prevention for 4 weeks, followed by eight weekly maintenance sessions, and/or clomipramine administered for 12 weeks, with a maximum dose of 250 mg/day. The main outcome measures were the Yale-Brown Obsessive Compulsive Scale total score and response rates determined by the Clinical Global Impression improvement scale. RESULTS: At week 12, the effects of all active treatments were superior to placebo. The effect of exposure and ritual prevention did not differ from that of exposure and ritual prevention plus clomipramine, and both were superior to clomipramine only. Treated and completer response rates were, respectively, 62% and 86% for exposure and ritual prevention, 42% and 48% for clomipramine, 70% and 79% for exposure and ritual prevention plus clomipramine, and 8% and 10% for placebo. CONCLUSIONS: Clomipramine, exposure and ritual prevention, and their combination are all efficacious treatments for OCD. Intensive exposure and ritual prevention may be superior to clomipramine and, by implication, to monotherapy with the other SRIs.  相似文献   

20.
目的探讨利培酮对于氯丙咪嗪治疗强迫症的增效作用。方法将70例强迫症随机分为2组,氯丙咪嗪同时合并利培酮和单独使用氯丙咪嗪治疗,治疗8周。采用强迫症量表(Y-BOCS)、汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)评定疗效。结果合并利培酮组有31例完成试验,氯丙咪嗪组有32例完成试验。治疗8周后,两组Y-BOCS平均总分有明显下降,合并利培酮组优于氯丙咪嗪组,两组无显著性差异(P<0.05);HAMA、HAMD的评分均显著下降,两组无显著性差异(P>0.05)。结论合并利培酮对于氯丙咪嗪治疗强迫症有增效作用。  相似文献   

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