Biological therapies for obsessive-compulsive disorder

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.     

Paroxetine versus clomipramine in adolescents with severe major depression: a double-blind,randomized, multicenter trial

OBJECTIVE: To date, two randomized, double-blind trials of serotonin reuptake inhibitors (SRIs) have shown that antidepressant drugs are effective in treating adolescent depression. In contrast, tricyclic antidepressants (TCAs) are not superior to placebo. This has led to a serotonin hypothesis in this age group. This study explores this hypothesis and compares paroxetine, a specific SRI, with clomipramine, a TCA with SRI activity. METHOD: One hundred twenty-one adolescents (aged 12-20 years) with major depression were enrolled and randomized (stratified for age) to 20 or 40 mg of paroxetine or 75 mg or 150 mg of clomipramine for 8 weeks. Primary outcome measurements were the Clinical Global Impression (CGI) scale and the Montgomery and Asberg Depression Rating Scale (MADRS). RESULTS: Of the 121 patients, 58 received clomipramine and 63 paroxetine. Based on intent-to-treat analysis, both agents had similar efficacy, with no effect of age; 48.3% and 58.2% of the subjects receiving clomipramine and 65.1% and 59.3% of those receiving paroxetine were rated responders on the MADRS and CGI scales, respectively. Study withdrawals were frequent in both groups (41% and 31%, respectively), but side effects were significantly more frequent with clomipramine (69% versus 49.2%, respectively; p = .027). CONCLUSION: Paroxetine and clomipramine exhibit similar efficacy in adolescent depression. These data support the serotonin hypothesis but do not confirm it in the absence of a placebo arm. Given the adverse event profile of clomipramine, specific SRIs should be preferred. However, more placebo-controlled studies are needed to establish definitively the efficacy of SRIs in this age group.     

Cognitive-behavioral therapy as an adjunct to serotonin reuptake inhibitors in obsessive-compulsive disorder: an open trial.

BACKGROUND: We report the results of an open trial of cognitive-behavioral therapy (CBT) using exposure and ritual prevention as an adjunct to serotonin reuptake inhibitors (SRIs) in obsessive-compulsive disorder (OCD). We hypothesized that exposure and ritual prevention would significantly reduce OCD symptoms in patients who remained symptomatic despite an adequate trial of an SRI and enable patients to discontinue their medication. METHOD: OCD patients taking an adequate dose of an SRI > or = 12 weeks who remained symptomatic (i.e., a Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score > or = 16) were eligible. While taking a stable dose of an SRI, patients received 17 sessions of exposure and ritual prevention. For the intent-to-treat group, the paired t test was used to compare scores on the Y-BOCS, the National Institute of Mental Health (NIMH) Global OCD scale, the Clinical Global Impressions scale, and the Hamilton Rating Scale for Depression before and after exposure and ritual prevention. RESULTS: Six of 7 eligible patients entered the study, and 5 completed it. All 6 improved on all OCD measures. The mean +/- SD Y-BOCS score was 23.8 +/- 2.6 prior to exposure and ritual prevention and 12.2 +/- 4.3 after it (p < .001). The mean percentage decrease on the Y-BOCS was 49% (range, 26%-61%). Patients were rated by the therapist and rated themselves as much (N = 4) or very much (N = 2) improved. Blood drug levels did not change in most patients during exposure and ritual prevention; thus, the improvement was attributed to this type of therapy. No patients discontinued their medication. CONCLUSION: This open trial suggests that CBT using exposure and ritual prevention can lead to a significant reduction in OCD symptoms in patients who remain symptomatic despite an adequate trial of an SRI.     

Pharmacological management of obsessive-compulsive disorder: a review for clinicians

Obsessive-compulsive disorder (OCD) has been treated pharmacologically with drugs that enhance availability of the neurotransmitter serotonin. This review summarizes the available literature on the pharmacological treatments of OCD. Numerous randomized controlled trials have attested to the efficacy of serotonin-reuptake inhibitors (SRIs) in treating this disorder, although a coherent model of serotonin dysfunction in OCD has not been established. Meta-analyses of randomized controlled trials have found better results with clomipramine than with other SRIs, but comparative studies have so far not replicated this finding. Aspects of the methodology in these studies that might explain this discrepancy are considered. Tolerability, side effects, dosing, and safety during pregnancy of the SRIs are discussed. Treatment of OCD with poor insight and of OCD comorbid with a tic disorder, augmentation strategies, and management of partial response to SRIs are reviewed. Finally, the available interventions for refractory OCD are considered.     

氯丙咪嗪合并利培酮治疗强迫症的对照研究

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。     

Pharmacotherapy of obsessive-compulsive disorder

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.     

Statistical choices can affect inferences about treatment efficacy: a case study from obsessive-compulsive disorder research

Longitudinal clinical trials in psychiatry have used various statistical methods to examine treatment effects. The validity of the inferences depends upon the different method's assumptions and whether a given study violates those assumptions. The objective of this paper was to elucidate these complex issues by comparing various methods for handling missing data (e.g., last observation carried forward [LOCF], completer analysis, propensity-adjusted multiple imputation) and for analyzing outcome (e.g., end-point analysis, repeated-measures analysis of variance [RM-ANOVA], mixed-effects models [MEMs]) using data from a multi-site randomized controlled trial in obsessive-compulsive disorder (OCD). The trial compared the effects of 12 weeks of exposure and ritual prevention (EX/RP), clomipramine (CMI), their combination (EX/RP&CMI) or pill placebo in 122 adults with OCD. The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale. For most comparisons, inferences about the relative efficacy of the different treatments were impervious to different methods for handling missing data and analyzing outcome. However, when EX/RP was compared to CMI and when CMI was compared to placebo, traditional methods (e.g., LOCF, RM-ANOVA) led to different inferences than currently recommended alternatives (e.g., multiple imputation based on estimation-maximization algorithm, MEMs). Thus, inferences about treatment efficacy can be affected by statistical choices. This is most likely when there are small but potentially clinically meaningful treatment differences and when sample sizes are modest. The use of appropriate statistical methods in psychiatric trials can advance public health by ensuring that valid inferences are made about treatment efficacy.     

Transcutaneous electrical acupoint stimulation as an adjunct therapy for obsessive-compulsive disorder: A randomized controlled study

BackgroundTranscutaneous electrical acupoint stimulation (TEAS) is thought to have potential to treat obsessive-compulsive disorder (OCD).ObjectiveThe purpose of this study was to determine whether adding TEAS to cognitive behavioral therapy (CBT) and clomipramine would improve the efficacy of these conventional treatments in OCD.MethodsIn this randomized controlled trial, 360 OCD patients were assigned to receive TEAS combined with CBT plus clomipramine (Group A, n = 120), TEAS combined with CBT plus placebo (Group B, n = 120), and simulated (placebo) TEAS combined with CBT plus clomipramine (Group C, n = 120) for 12 weeks. The primary outcome was measured using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS).ResultsOCD symptoms in all patients reduced over time, however Groups A and B had a significantly greater reduction in Y-BOCS total score and the subscale for obsession and compulsion between week 2 and week 12 compared to Group C. Groups A and B had similar scores on these measures. Both groups had significantly higher rates of clinical response than Group C (88.3% and 81.7% vs. 67.5%, respectively, p < 0.001); and higher rates of remission (30.0% and 22.5% vs. 9.2%, respectively, p < 0.001). Group B experienced fewer adverse events than the other two groups.ConclusionsTEAS enhances the efficacy of conventional OCD interventions and avoids the adverse effects associated with conventional pharmacological treatment. It can be considered as an effective adjunct intervention for OCD.     

Cognitive behavioral therapy of obsessive-compulsive disorder

Until the mid-1960s, obsessive-compulsive disorder (OCD) was considered to be treatment-resistant, as both psychodynamic psychotherapy and medication had been unsuccessful in significantly reducing OCD symptoms. The first real breakthrough came in 1966 with the introduction of exposure and ritual prevention. This paper will discuss the cognitive behavioral conceptualizations that influenced the development of cognitive behavioral treatments for OCD. There will be a brief discussion of the use of psychodynamic psychotherapy and early behavioral therapy, neither of which produced successful outcomes with OCD. The main part of the paper will be devoted to current cognitive behavioral therapy (CBT) with an emphasis on variants of exposure and ritual or response prevention (EX/RP) treatments, the therapy that has shown the most empirical evidence of its efficacy.     

Effects of imipramine on depression and obsessive-compulsive symptoms

Most of the controlled studies on the efficacy of medical treatments of obsessive-compulsive disorder (OCD) have involved clomipramine, a tricyclic antidepressant reputed to have anti-obsessional properties. To test the possibility that the drug's antidepressant action mediates the reduction of obsessive-compulsive symptoms, we treated 37 OCD patients with imipramine (mean dose = 233 mg/day) or placebo for 6 weeks and assessed improvement on both obsessive-compulsive and depressive symptoms. Imipramine reduced depression in highly depressed OCD patients, but did not affect obsessive-compulsive symptoms in these or in less depressed patients.     

Pharmacotherapy for obsessive-compulsive disorder.

SSRIs and the tricyclic antidepressant clomipramine are the first-line therapies for patients with OCD, with the side-effect profile of SSRIs being more favorable than that of clomipramine. As many as 40% to 60% of patients with OCD may not respond to adequate trials of SRIs. Not all patients tolerate SSRIs, and delays in full therapeutic responses often occur. Thus, other pharmacologic approaches to treating patients with OCD have been investigated. Augmentation and monotherapy have been explored with serotonergic enhancers, dopamine and 5-HT antagonists, enhancers of second-messenger systems, and GABAergic agents with varying efficacy.     

Response versus remission in obsessive-compulsive disorder

OBJECTIVE: To investigate rates of response and remission in adults with obsessive-compulsive disorder (OCD) after 12 weeks of evidence-based treatment. METHOD: Post hoc analyses of response and remission were conducted using data from a multisite, randomized, controlled trial comparing the effects of 12 weeks of exposure and ritual prevention (EX/RP), clomipramine (CMI), their combination (EX/RP+CMI), or pill placebo (PBO) in 122 adults with OCD (DSM-III-R or DSM-IV criteria). Response was defined as a decrease in symptoms; remission was defined as minimal symptoms after treatment. Different response and remission definitions were constructed based on criteria used in prior studies. For each definition, the proportion of responders or remitters in each treatment group was then compared. RESULTS: There were significant differences (p<.05) among the 4 treatment groups in the proportion of responders and remitters. In pairwise comparisons, EX/RP+CMI and EX/RP each produced significantly more responders and remitters than PBO; CMI produced significantly more responders and remitters than PBO for some definitions but not for others. When remission was defined as a Yale-Brown Obsessive Compulsive Scale (YBOCS) score of 12 or less, significantly more EX/RP+CMI (18/31 [58%]) and EX/RP (15/29 [52%]) patients entering treatment achieved remission than either CMI (9/36 [25%]) or PBO (0/26 [0%]) patients. However, even in treatment completers, many CMI and some EX/RP+CMI and EX/RP patients did not achieve remission (remission rates for YBOCS相似文献   

A double-blind, randomized, placebo-controlled trial of quetiapine addition in patients with obsessive-compulsive disorder refractory to serotonin reuptake inhibitors

BACKGROUND: Although serotonin reuptake inhibitors (SRIs) are the most effective pharmacologic treatment currently available for patients with obsessive-compulsive disorder (OCD), 40% to 60% of patients do not respond to this treatment. This study was conducted to evaluate the efficacy and tolerability of quetiapine in addition to an SRI for treatment-refractory patients with OCD. METHOD: Forty patients (10 men/30 women, mean +/- SD age = 35.2 +/- 12.1 years; range, 18-60 years) with primary OCD according to DSM-IV criteria who were recruited between February 2001 and December 2002 were randomly assigned in an 8-week, double-blind, placebo-controlled trial to receive dosages titrated upward to 300 mg/day of quetiapine (N = 20) or placebo (N = 20) in addition to their SRI treatment. At entry, all patients were unresponsive to courses of treatment with at least 2 different SRIs at a maximum tolerated dose for 8 weeks. During the study, primary efficacy was assessed according to change from baseline on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). A responder was defined as having a final Clinical Global Impressions-Improvement scale rating of "very much improved" or "much improved" and a decrease of > or = 35% in Y-BOCS score. RESULTS: An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean +/- SD decrease in Y-BOCS score of 9.0 +/- 7.0 (31%) in the quetiapine group and 1.8 +/- 3.4 (7%) in the placebo group (F=16.99, df=1,38; p <.001). Eight (40%) of 20 patients in the quetiapine group and 2 (10%) of 20 patients in the placebo group were responders (chi2=4.8, df=1, p=.028). The most common side effects in the quetiapine group were somnolence, dry mouth, weight gain, and dizziness. CONCLUSION: The results of this study show that quetiapine in addition to an SRI is beneficial for patients with OCD who do not respond to SRI treatment alone.     

Use of factor-analyzed symptom dimensions to predict outcome with serotonin reuptake inhibitors and placebo in the treatment of obsessive-compulsive disorder.

OBJECTIVE: No consistent predictors of outcome have been identified for the pharmaco-therapy of obsessive-compulsive disorder (OCD). Recent factor analytic studies have identified meaningful symptom dimensions that may be related to response to serotonin reuptake inhibitors and other treatments. METHOD: A total of 354 outpatients with primary OCD were administered the Yale-Brown Obsessive Compulsive Scale Symptom Checklist, and its 13 main symptom categories were factor analyzed by using principal components analysis. The identified symptom dimensions were then entered into multiple regression models as outcome predictors of response to serotonin reuptake inhibitors and placebo response in a group of 150 nondepressed subjects who completed six double-blind, placebo-controlled trials with a serotonin reuptake inhibitor (clomipramine, fluvoxamine, fluoxetine, sertraline, and paroxetine). Eighty-four patients received a serotonin reuptake inhibitor and 66, placebo. RESULTS: The principal components analysis identified five factors that explained 65.5% of variance in outcome: symmetry/ordering, hoarding, contamination/cleaning, aggressive/checking, and sexual/religious obsessions. Serotonin reuptake inhibitors were significantly superior to placebo on all outcome measures. Initial severity of OCD was related to greater posttreatment severity of OCD. Higher scores on the hoarding dimension predicted poorer outcome following treatment with serotonin reuptake inhibitors, after control for baseline severity. No predictors of placebo response were identified. Exclusion of clomipramine did not modify the overall results, suggesting a cross-serotonin reuptake inhibitor effect. CONCLUSIONS: The identified symptom dimensions are largely congruent with those identified in earlier reports. Patients with OCD vary in their response to treatment with serotonin reuptake inhibitors. The presence of hoarding obsessions and compulsions is associated with poorer response to serotonin reuptake inhibitors.     

Clomipramine and imipramine in obsessive-compulsive disorder

Twenty-three outpatients with primary obsessive-compulsive disorder (OCD) were started in a 12-week double-blind clinical trial of clomipramine (CLI) (n = 11) and imipramine (IMI) (n = 12). There was no placebo and no crossover. After 6 weeks of treatment, data on 19 subjects (9 CLI, 10 IMI) were available. After week 12, the sample was reduced to 16 patients (8 CLI, 8 IMI). At both time points, OCD symptoms showed modest reductions (in comparison with the pretreatment baseline) in both CLI and IMI groups. Both drugs showed a major antidepressant effect. Analyses accounting for the differences in the baseline levels indicated a somewhat superior effect of CLI over IMI on OCD as well as depression. The effect of CLI and IMI on OCD was independent of the initial severity of depression. There were no clear differences in the safety of the treatments.     

A review of the efficacy of selective serotonin reuptake inhibitors in obsessive-compulsive disorder

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.     

Post-treatment effects of exposure therapy and clomipramine in obsessive-compulsive disorder

We sought to determine whether adults with obsessive-compulsive disorder (OCD) who respond to intensive exposure and response (ritual) prevention (EX/RP) with or without clomipramine (CMI) fare better 12 weeks after treatment discontinuation than responders receiving CMI alone. After receiving 12 weeks of treatment (EX/RP, CMI, EX/RP+CMI, or pill placebo [PBO] in a randomized clinical trial conducted at three outpatient research centers), 46 adults with OCD who responded to treatment (18 EX/RP, 11 CMI, 15 EX/RP+CMI, 2 PBO) were followed after treatment discontinuation for 12 weeks. Patients were assessed every 4 weeks with the Yale-Brown Obsessive-Compulsive Scale, the National Institutes of Health Global Obsessive-Compulsive Scale, and the Clinical Global Impressions scale by an evaluator who was blind to original treatment assignment. The primary hypothesis was that EX/RP and EX/RP+CMI responders would be less likely to relapse 12 weeks after treatment discontinuation than responders to CMI alone. Twelve weeks after treatment discontinuation, EX/RP and EX/RP+CMI responders, compared to CMI responders, had a significantly lower relapse rate (4/33 = 12% versus 5/11 = 45%) and a significantly longer time to relapse. The CMI relapse rate was lower than previously reported. Nonetheless, responders receiving intensive EX/RP with or without CMI fared significantly better 12 weeks after treatment discontinuation than responders receiving CMI alone.     

Venlafaxine versus clomipramine in the treatment of obsessive-compulsive disorder: a preliminary single-blind, 12-week,controlled study

BACKGROUND: The objective of this study was to investigate, in a single-blind manner over a period of 12 weeks, the efficacy and tolerability of venlafaxine versus clomipramine in the treatment of obsessive-compulsive disorder (OCD). METHOD: Patients with a DSM-IV diagnosis of OCD and a Yale-Brown Obsessive Compulsive Scale (YBOCS) score >/= 16 were randomly assigned to receive venlafaxine, 225 to 350 mg/day (26 patients), or clomipramine, 150 to 225 mg/day (47 patients), for 12 weeks, with dosage adjustments according to tolerability and response to treatment. All patients were medication-free from at least 2 months prior to study enrollment. Efficacy measures were the YBOCS and the Clinical Global Impressions scale (CGI), which were completed at baseline and every 4 weeks.We defined responders as patients who had an improvement from baseline in YBOCS score of >/= 35% and a CGI score 相似文献   

帕罗西汀与氯米帕明治疗强迫症的多中心、随机、双盲、平行对照研究

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。     

Urinary free cortisol levels in obsessive-compulsive disorder

Seventeen obsessive-compulsive disorder (OCD) patients and 25 normal control subjects submitted 24-hour urine samples for measurement of urinary free cortisol (UFC). Thirteen of the 17 OCD patients submitted a second 24-hour urine collection after a 10-week trial of either clomipramine (n = 6) or placebo (n = 7). At baseline, the OCD patients had significantly higher UFC levels than the control group. After 10 weeks of clomipramine or placebo, however, the UFC levels for both OCD groups decreased and were comparable with those of the control group. Obsessive-compulsive symptomatology, as assessed by the Yale-Brown and the NIMH Global Obsessive-Compulsive Scales, improved in the clomipramine group but did not improve in the placebo group. There was a relationship between UFC levels and depressive symptoms.