Improvement In Obsessive-compulsive Symptoms Research Articles

EEG microstates are associated with the improvement of obsessive-compulsive symptoms after transcranial direct current stimulation

BackgroundTranscranial direct current stimulation (tDCS) is a safe, accessible, and promising therapeutic approach for obsessive-compulsive disorder (OCD). AimsThis study aimed to evaluate the effect of tDCS on electroencephalography (EEG) microstates and identify potential biomarkers to predict efficacy. MethodsA total of 24 individuals diagnosed with OCD underwent ten sessions of tDCS targeting the orbitofrontal cortex, while 27 healthy individuals were included as controls. Microstates A, B, C, and D were extracted before and after tDCS. A comparative analysis of microstate metrics was performed between the OCD and the healthy control groups, as well as within the OCD group before and after tDCS. Multiple linear regression analysis was performed to identify potential biomarkers of tDCS. ResultsComparison to healthy controls, the OCD group exhibited a significantly reduced duration of microstate A and increased occurrence of microstate D. The transition between microstates A and C was significantly different between patients with OCD and healthy controls and was no longer observed following tDCS. Multiple linear regression analysis revealed that the duration of microstate C was associated with an improvement OCD symptom after tDCS. ConclusionsThe results revealed an aberrant large-scale EEG brain network that could be modulated by tDCS. In particular, the duration of EEG microstate C may be a neurophysiological characteristic associated with the therapeutic effects of tDCS on OCD.

Stereotactic Surgery for Treating Intractable Tourette Syndrome: A Single-Center Pilot Study.

To evaluate the potential effect of radiofrequency ablation and deep brain stimulation in patients with treatment-refractory Tourette syndrome (TS), this study enrolled thirteen patients with TS who were admitted to our hospital between August 2002 and September 2018. Four patients received a single- or multi-target radiofrequency ablation after local, potentiated, or general anesthesia; eight patients underwent deep brain stimulation (DBS) surgery; and one patient underwent both ablation and DBS surgery. The severity of tics and obsessive compulsive disorder symptoms and the quality of life were evaluated using the Yale Global Tic Severity Scale (YGTSS), Yale–Brown Obsessive Compulsive Scale (YBOCS), and Gilles de la Tourette Syndrome Quality of Life scale (GTS-QOL), respectively, before surgery, one month after surgery, and at the final follow-up after surgery, which was conducted in December 2018. A paired-sample t test and a multiple linear regression analysis were performed to analyze the data. All patients underwent the operation successfully without any severe complications. Overall, the YGTSS total scores at one month post-surgery (44.1 ± 22.3) and at the final visit (35.1 ± 23.7) were significantly decreased compared with those at baseline (75.1 ± 6.2; both p < 0.05). Additionally, the YBOCS scores at one month post-surgery (16.5 ± 10.1) and at the final visit (12.0 ± 9.5) were significantly decreased compared with those at baseline (22.5 ± 13.1; both p < 0.05). Furthermore, the GTS-QOL scores at one month post-surgery (44.0 ± 12.8) and at the final visit (31.0 ± 17.8) were significantly decreased compared with those at baseline (58.4 ± 14.2; both p < 0.05). Results from a multiple linear regression analysis revealed that the improvement in the YGTSS total score was independently associated with the improvement in the GTS-QOL score at one month post-surgery (standardized β = 0.716, p = 0.023) and at the final visit (standardized β = 1.064, p = 0.000). Conversely, changes in YBOCS scores did not correlate with changes in GTS-QOL scores (p > 0.05). Our results demonstrate that tics, psychiatric symptoms, and the quality of life in patients with intractable TS may be relieved by stereotactic ablation surgery and deep brain stimulation. Furthermore, it appears that the improvement in tics contributes more to the post-operative quality of life of patients than does the improvement in obsessive compulsive symptoms.

Six-Nine Year Follow-Up of Deep Brain Stimulation for Obsessive-Compulsive Disorder.

ObjectiveDeep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) region has shown promise as a neurosurgical intervention for adults with severe treatment-refractory obsessive-compulsive disorder (OCD). Pilot studies have revealed improvement in obsessive-compulsive symptoms and secondary outcomes following DBS. We sought to establish the long-term safety and effectiveness of DBS of the VC/VS for adults with OCD.Materials and MethodsA long term follow-up study (73–112 months) was conducted on the six patients who were enrolled in the original National Institute of Mental Health pilot study of DBS for OCD. Qualitative and quantitative data were collected.ResultsReduction in OCD symptoms mirrored the one-year follow-up data. The same four participants who were treatment responders after one year of treatment showed a consistent OCD response (greater than 35% reduction in Yale Brown Obsessive Compulsive Scale (YBOCS)). Another subject, classified as a non-responder, achieved a 26% reduction in YBOCS score at long term follow-up. The only patient who did not achieve a 25% or greater reduction in YBOCS was no longer receiving active DBS treatment. Secondary outcomes generally matched the one-year follow-up with the exception of depressive symptoms, which significantly increased over the follow-up period. Qualitative feedback indicated that DBS was well tolerated by the subjects.DiscussionThese data indicate that DBS was safe and conferred a long-term benefit in reduction of obsessive-compulsive symptoms. DBS of the VC/VS region did not reveal a sustained response for comorbid depressive symptoms in patients with a primary diagnosis of OCD.

Patient Rating of Therapeutic Factors and Response to Cognitive-Behavioral Group Therapy in Patients with Obsessive-Compulsive Disorder

Group therapy involves complex mechanisms that rely on certain therapeutic factors to promote improvement. The objective of this study was to assess patient rating of therapeutic factors during cognitive-behavioral group therapy (CBGT) and to investigate the correlation between patient rating and outcome of CBGT for the treatment of obsessive-compulsive disorder (OCD). In the present clinical trial, 15 patients participated in a 12-session CBGT protocol. Severity of symptoms was assessed before and after CBGT with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Clinical Global Impression (CGI), Hamilton Anxiety Scale (HAM-A), and Beck Depression Inventory (BDI). Yalom's Curative Factors Questionnaire was administered at the end of each session for patient rating of the usefulness of 12 therapeutic factors to treat OCD. There was a significant interaction between improvement in obsessive-compulsive symptoms and patient rating of altruism, universality, interpersonal learning input and output, family re-enactment, self-understanding, and existential factors over time. The results show that group therapeutic factors positively influence the response to CBGT in OCD patients.

Acceptance and Commitment Therapy, Selective Serotonin Reuptake Inhibitors, and Their Combination in the Improvement of Obsessive–Compulsive Symptoms and Experiential Avoidance in Patients With Obsessive–Compulsive Disorder

Background:: Selective serotonin reuptake inhibitors (SSRIs) and exposure with response prevention for treatment of obsessive-compulsive disorder (OCD) have demonstrated empirical support; however, a substantial number of patients remain with clinically significant OCD symptoms after such treatments. Objectives:: The aim of this study was to compare the effectiveness of acceptance and commitment therapy (ACT), selective serotonin reuptake inhibitors (SSRIs) and combination of ACT and SSRIs in the treatment of adults with obsessive-compulsive disorder (OCD). Patients and Methods:: Thirty-two outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for OCD were randomly assigned to one of the three treatment conditions: ACT, SSRIs and combined treatment. The Yale-Brown Obsessive-Compulsive Scale and Acceptance and Action Questionnaire were administered at pre-treatment and post-treatment. Twenty-seven patients completed the study. Data was analyzed using one-way analysis of variance (ANOVA) and one-way analysis of covariance (ANCOVA), clinically significant change (CSC) and complete remission status. Results:: ANCOVA revealed that patients treated with ACT and combined treatment experienced a significantly greater improvement in obsessive-compulsive (OC) symptoms and experiential avoidance (EA) at post-treatment compared to those treated with SSRIs alone. However, there were no significant differences between ACT and combined treatment on OC symptoms and EA. CSC and complete remission status results showed that unlike SSRI, ACT and combined treatment led to more improvement in OC symptoms. Conclusions:: ACT and combined treatment are more effective than SSRIs alone in treating OC symptoms and EA. However, it appears that adding SSRIs to ACT does not increase the effectiveness of ACT in the treatment of adults with OCD in the short-term.

Acceptance and Commitment Therapy, Selective Serotonin Reuptake Inhibitors and Their Combination in the Improvement of Obsessive-Compulsive Symptoms and Experiential Avoidance in Patients With Obsessive-Compulsive Disorder.

Background:Selective serotonin reuptake inhibitors (SSRIs) and exposure with response prevention for treatment of obsessive-compulsive disorder (OCD) have demonstrated empirical support; however, a substantial number of patients remain with clinically significant OCD symptoms after such treatments. Objectives:The aim of this study was to compare the effectiveness of acceptance and commitment therapy (ACT), selective serotonin reuptake inhibitors (SSRIs) and combination of ACT and SSRIs in the treatment of adults with obsessive-compulsive disorder (OCD).Patients and Methods:Thirty-two outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for OCD were randomly assigned to one of the three treatment conditions: ACT, SSRIs and combined treatment. The Yale-Brown Obsessive-Compulsive Scale and Acceptance and Action Questionnaire were administered at pre-treatment and post-treatment. Twenty-seven patients completed the study. Data was analyzed using one-way analysis of variance (ANOVA) and one-way analysis of covariance (ANCOVA), clinically significant change (CSC) and complete remission status.Results:ANCOVA revealed that patients treated with ACT and combined treatment experienced a significantly greater improvement in obsessive-compulsive (OC) symptoms and experiential avoidance (EA) at post-treatment compared to those treated with SSRIs alone. However, there were no significant differences between ACT and combined treatment on OC symptoms and EA. CSC and complete remission status results showed that unlike SSRI, ACT and combined treatment led to more improvement in OC symptoms.Conclusions:ACT and combined treatment are more effective than SSRIs alone in treating OC symptoms and EA. However, it appears that adding SSRIs to ACT does not increase the effectiveness of ACT in the treatment of adults with OCD in the short-term.

Aripirazole augmentation in clozapine-associated obsessive-compulsive symptoms in schizophrenia

ObjectivePatients with schizophrenia often experience comorbid obsessive-compulsive symptoms. Within these patients, a significant subgroup developed secondary obsessive-compulsive symptoms during treatment with clozapine.MethodIn this paper, we report on four cases in which adjunctive therapy with aripiprazole was tested to alleviate obsessive-compulsive symptoms in schizophrenia.ResultsAll four patients had a significant improvement in obsessive-compulsive symptoms. The combination of clozapine and aripiprazole was well tolerated.ConclusionThis case series demonstrates the clinical efficacy of aripiprazole adjunctive therapy with clozapine in schizophrenic patients with comorbid obsessive-compulsive symptoms. Larger-sampled and controlled studies are required in order to test and confirm these observations.

The Effects of Pharmacological Treatment on Functional Brain Connectome in Obsessive-Compulsive Disorder

Previous neuroimaging studies of obsessive-compulsive disorder (OCD) have reported both baseline functional alterations and pharmacological changes in localized brain regions and connections; however, the effects of selective serotonin reuptake inhibitor (SSRI) treatment on the whole-brain functional network have not yet been elucidated. Twenty-five drug-free OCD patients underwent resting-state functional magnetic resonance imaging. After 16-weeks, seventeen patients who received SSRI treatment were rescanned. Twenty-three matched healthy control subjects were examined at baseline for comparison, and 21 of them were rescanned after 16 weeks. Topological properties of brain networks (including small-world, efficiency, modularity, and connectivity degree) were analyzed cross-sectionally and longitudinally with graph-theory approach. At baseline, OCD patients relative to healthy control subjects showed decreased small-world efficiency (including local clustering coefficient, local efficiency, and small-worldness) and functional association between default-mode and frontoparietal modules as well as widespread altered connectivity degrees in many brain areas. We observed clinical improvement in OCD patients after 16 weeks of SSRI treatment, which was accompanied by significantly elevated small-world efficiency, modular organization, and connectivity degree. Improvement of obsessive-compulsive symptoms was significantly correlated with changes in connectivity degree in right ventral frontal cortex in OCD patients after treatment. This is first study to use graph-theory approach for investigating valuable biomarkers for the effects of SSRI on neuronal circuitries of OCD patients. Our findings suggest that OCD phenomenology might be the outcome of disrupted optimal balance in the brain networks and that reinstating this balance after SSRI treatment accompanies significant symptom improvement.

726 – Improvement of obsessive-compulsive symptoms in schizophrenia patients after switching from typical or atypical antipsychotics to amisulpride

Background Obsessive-compulsive symptoms (OCSs) are frequently comorbid with schizophrenia. Various atypical antipsychotics induce OCSs by 5-HT2A receptor inhibition. Amisulpride causes only minimal inhibition of the 5-HT2A receptor, and therefore, should not induce or exacerbate OCSs in patients with schizophrenia. Objective To evaluate the efficacy and tolerability of amisulpride on OCSs in patients with schizophrenia who were taking typical or atypical antipsychotics. Method 21 patients, aged 18-65 years, with schizophrenia and OCSs (DSM-4 criteria) with a score of 16 or higher on YBOCS and taking a single antipsychotic were enrolled to a 12-week prospective open trial of amisulpride (400-1200 mg/d). Changes in YBOCS, PANSS,CGI,GAF QLS -18, extrapyramidal symptoms, adverse events, and body-weight changes were evaluated 12 weeks after the antipsychotics were switched to amisulpride. Results All 19 patients who completed the trial had an improvement on the YBOCS,PANSS,CGI,GAF AND QLS-18. At week 12,the mean YBOCS total score decreased significantly (26.579 ± 5.124 vs.14.631± 5.479; p Conclusions These results indicate that switch to amisulpiride is very effective for OCSs, psychotic symptoms and global functioning in patients with schizophrenia.However, changes in OCSs and psychotic symptoms were independent. Further studies with amisulpiride under controlled conditions are needed for these patients.

A Double-Blind Placebo-Controlled Trial of Fluoxetine for Repetitive Behaviors and Global Severity in Adult Autism Spectrum Disorders

The effects of fluoxetine and placebo on repetitive behaviors and global severity were compared in adults with autism spectrum disorders (ASDs). Adults with ASDs were enrolled in a 12-week double-blind placebo-controlled fluoxetine trial. Thirty-seven were randomly assigned to fluoxetine (N=22) or placebo (N=15). Dosage followed a fixed schedule, starting at 10 mg/day and increasing as tolerated up to 80 mg/day. Repetitive behaviors were measured with the compulsion subscale of the Yale-Brown Obsessive Compulsive Scale; the Clinical Global Impression (CGI) improvement scale was used to rate improvement in obsessive-compulsive symptoms and overall severity. There was a significant treatment-by-time interaction indicating a significantly greater reduction in repetitive behaviors across time for fluoxetine than for placebo. With overall response defined as a CGI global improvement score of 2 or less, there were significantly more responders at week 12 in the fluoxetine group than in the placebo group. The risk ratio was 1.5 for CGI global improvement (responders: fluoxetine, 35%; placebo, 0%) and 1.8 for CGI-rated improvement in obsessive-compulsive symptoms (responders: fluoxetine, 50%; placebo, 8%). Only mild and moderate side effects were observed. Fluoxetine treatment, compared to placebo, resulted in significantly greater improvement in repetitive behaviors, according to both the Yale-Brown compulsion subscale and CGI rating of obsessive-compulsive symptoms, as well as on the CGI overall improvement rating. Fluoxetine appeared to be well tolerated. These findings stand in contrast to findings in a trial of citalopram for childhood autism.

Altered Brain Activation in Ventral Frontal-Striatal Regions Following a 16-week Pharmacotherapy in Unmedicated Obsessive-Compulsive Disorder

Recent studies have reported that cognitive inflexibility associated with impairments in a frontal-striatal circuit and parietal region is a core cognitive deficit of obsessive-compulsive disorder (OCD). However, few studies have examined progressive changes in these regions following clinical improvement in obsessive-compulsive symptoms. To determine if treatment changes the aberrant activation pattern associated with task switching in OCD, we examined the activation patterns in brain areas after treatment. The study was conducted on 10 unmedicated OCD patients and 20 matched controls using event-related functional magnetic resonance imaging. Treatment improved the clinical symptoms measured by the Yale-Brown Obsessive Compulsive Scale and behavioral flexibility indicated by the switching cost. At baseline, OCD showed significantly less activation in the dorsal and ventral frontal-striatal circuit and parietal regions under the task-switch minus task-repeat condition compared with controls. After treatment, the neural responses in the ventral frontal-striatal circuit in OCD were partially normalized, whereas the activation deficit in dorsal frontoparietal regions that mediate shifting attention or behavioral flexibility persisted. It is suggested that altered brain activation in ventral frontal-striatal regions in OCD patients is associated with their cognitive flexibility and changes in these regions may underlie the pathophysiology of OCD.

Neuropsychological Outcome of Ventral Capsular/Ventral Striatal Gamma Capsulotomy for Refractory Obsessive-Compulsive Disorder: A Pilot Study

Neuropsychological Outcome of Ventral Capsular/Ventral Striatal Gamma Capsulotomy for Refractory Obsessive-Compulsive Disorder: A Pilot Study

Thalamic deep brain stimulation for treatment-refractory Tourette syndrome

Eighteen patients with severe and refractory Tourette syndrome (TS) underwent bilateral thalamic deep brain stimulation (DBS). To assess the long-term outcome on tics, behavioral symptoms, and cognitive functions in the largest case series of thalamic DBS for TS to date. In this prospective cohort study, 15 of the original 18 patients were evaluated before and after surgery according to a standardized protocol that included both neuropsychiatric and neuropsychological assessments. In addition to marked reduction in tic severity (p = 0.001), 24-month follow-up ratings showed improvement in obsessive-compulsive symptoms (p = 0.009), anxiety symptoms (p = 0.001), depressive symptoms (p = 0.001), and subjective perception of social functioning/quality of life (p = 0.002) in 15 of 18 patients. There were no substantial differences on measures of cognitive functions before and after DBS. At 24-month follow-up, tic severity was improved in patients with intractable Tourette syndrome (TS) who underwent bilateral thalamic deep brain stimulation. Available data from 15 of 18 patients also showed that neuropsychiatric symptoms were improved and cognitive performances were not disadvantaged. Controlled studies on larger cohorts with blinded protocols are needed to verify that this procedure is effective and safe for selected patients with TS. This study provides class IV evidence that bilateral thalamic deep brain stimulation reduces global tic severity measured 24 months after implantation in patients with severe intractable Tourette syndrome.

Gabapentin Reduces Alcohol Consumption and Craving

This study examined the efficacy of a 28-day gabapentin treatment in reducing alcohol consumption and craving. A randomized, double-blind, placebo-controlled trial was performed in a Brazilian public outpatient drug treatment center, with 60 male alcohol-dependent subjects with a mean age of 44 years and an average of 27 years of alcohol use, who consumed 17 drinks per day (165-170 g/day) over the past 90 days before baseline and had no other significant medical or psychiatric condition. Subjects were recruited between July 8, 2004, and February 24, 2005. Following screening, 60 subjects were selected and received diazepam and vitamins as treatment for acute withdrawal for at least 7 days. After the detoxification treatment, 30 subjects were randomly assigned to receive gabapentin (300 mg twice daily) for 4 weeks, and 30 subjects, with similar baseline characteristics, were randomly assigned to receive matching placebo tablets for the same period. After 28 days of treatment, the gabapentin group showed a significant reduction in both number of drinks per day and mean percentage of heavy drinking days (p = .02 for both), and an increase in the percentage of days of abstinence (p = .008), compared to the placebo group. Additionally, some improvement in obsessive-compulsive symptoms was noted in both groups after the treatment, but it resulted in a more pronounced decrease in automaticity of drinking and aspects of craving in the gabapentin group than in the placebo group. Gabapentin reduces alcohol consumption and craving, which may help patients to maintain abstinence. These results, together with the virtual absence of side effects and a favorable safety profile, support gabapentin as a potential drug for the treatment of alcohol withdrawal and dependence.

Behavior Therapy Augments Response of Patients With Obsessive-Compulsive Disorder Responding to Drug Treatment

In many patients with obsessive-compulsive disorder (OCD), residual symptoms persist despite a clinically meaningful response. The objective of this study was to examine whether addition of behavior therapy would augment treatment outcome in these patients. Ninety-six patients with DSM-IV OCD who had responded to 3 months of drug treatment were randomly assigned to either receive addition of behavior therapy or continue on drug treatment alone for 6 months. Patients who continued on drug treatment alone eventually received addition of behavior therapy for 6 months. Data were gathered from October 1998 to June 2002. OCD patients who received addition of behavior therapy showed a greater improvement in obsessive-compulsive symptoms (Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score change = -3.9 in the completers sample) than those who continued on drug treatment alone (Y-BOCS score change = +3.9 for completers). Significantly more patients who received addition of behavior therapy were in remission compared with those who continued on drug treatment alone (p < .0001 for completers). Patients who received behavior therapy after 6 months of drug treatment alone showed a nonsignificant decline in obsessive-compulsive symptoms (Y-BOCS score change = -2.7 for completers); however, the remission rate found in this group was comparable to the remission rate found in the group of patients receiving addition of behavior therapy directly after responding to drug treatment. The results indicate that addition of behavior therapy is beneficial for patients who have responded to drug treatment. The data also suggest that the effect is greater when behavior therapy is added immediately after attainment of the drug response.

The Efficacy of Fluvoxamine in Obsessive-Compulsive Disorder

This retrospective case-controlled analysis evaluated treatment response to the serotonin reuptake inhibitor fluvoxamine in patients with obsessive-compulsive disorder (OCD), with or without a comorbid chronic tic disorder. Thirty-three fluvoxamine-treated OCD patients with a concurrent chronic tic disorder were compared with 33 age- and sex-matched OCD patients without chronic tics who had received fluvoxamine treatment in the same setting during the same period of time and in a similar manner. Although both groups of patients demonstrated statistically significant reductions in obsessive-compulsive, depressive, and anxiety symptoms with fluvoxamine treatment, the frequency and magnitude of response of obsessive-compulsive symptoms was significantly different between the two groups. A clinically meaningful improvement in obsessive-compulsive symptoms occurred in only 21% of OCD patients with comorbid chronic tics compared with a 52% response rate in OCD patients without chronic tics. Moreover, OCD patients with a concurrent chronic tic disorder showed only a 17% reduction in Yale-Brown Obsessive-Compulsive Scale scores compared with a 32% decrease in the severity of obsessive-compulsive symptoms in those OCD patients without chronic tics. These results suggest that serotonin reuptake inhibitor monotherapy may be less efficacious for improving obsessive-compulsive symptoms in OCD patients with than without tics. Combined with differences in the clinical phenomenology between these two groups, these treatment response data support the hypothesis that OCD patients with a comorbid chronic tic disorder may be a clinically meaningful subtype.

A Controlled Trial of Lithium Augmentation in Fluvoxamine-Refractory Obsessive-Compulsive Disorder

Two- and 4-week double-blind placebo-controlled trials of lithium augmentation of ongoing fluvoxamine treatment trials were conducted in 20 and 10 patients, respectively, with primary obsessive-compulsive disorder (OCD) who had failed to respond to fluvoxamine alone. Although 2 weeks of double-blind lithium augmentation produced a small but statistically significant reduction in obsessive-compulsive symptoms, most patients did not have a clinically meaningful response. Furthermore, there was no statistical or clinical improvement in obsessive-compulsive symptoms during the subsequent 4-week double-blind, placebo-controlled trial of lithium augmentation. On the basis of treatment response criteria, only 18% and 0% of the patients responded to lithium augmentation of fluvoxamine during the 2- and 4-week treatment trials, respectively. In light of the previously reported 44% response rate to lithium augmentation in treatment-resistant depressed patients on fluvoxamine, the results of this study suggest that pathophysiological differences may exist between OCD and depression. The routine use of lithium augmentation in the management of patients with OCD who are refractory to serotonin reuptake inhibitors is not supported by these findings.

Local Cerebral Glucose Metabolic Rates in Obsessive-Compulsive Disorder

In a recent study, we reported abnormal local cerebral glucose metabolic rates in the orbital frontal cortex of patients with obsessive-compulsive disorder. Eight patients with obsessive-compulsive disorder scanned previously were scanned again during treatment with the tricyclic antidepressant clomipramine hydrochloride. Comparisons of local cerebral glucose metabolic rates for both groups showed a relative decrease in regions of the orbital frontal cortex and the left caudate, and an increase in other areas of the basal ganglia, including the right anterior putamen. When comparing patients who responded well to clomipramine with those who were either poor or partial responders, we found significant decreases only in the left caudate of patients who responded well to the drug. The present study suggests that clomipramine-induced improvement in obsessive-compulsive symptoms is associated with a return of regional brain metabolism to a more normal level in regions of the orbital frontal cortex and the caudate nucleus.

A controlled trial of fluvoxamine in obsessive-compulsive disorder: implications for a serotonergic theory

Thirty-eight patients with primary obsessive-compulsive disorder participated in a 10-week, double-blind, placebo-controlled trial of the potent, selective serotonin reuptake inhibitor fluvoxamine. Fluvoxamine was significantly better than placebo on two of three measures of improvement in obsessive-compulsive symptoms. The authors also compared studies of the serotonergic agents fluvoxamine, sertraline, fluoxetine, and clomipramine and found that a greater effect size was associated with less serotonergic specificity and that some ability to affect other neurotransmitter systems may be a necessary but not sufficient requirement for antiobsessional activity. These data lend only partial support to a serotonin hypothesis of obsessive-compulsive disorder.