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Damiaan Denys

Publications and source records attributed to Damiaan Denys.

18 recordsLinked to original sources
PubMed2005

Effects of paroxetine and venlafaxine on immune parameters in patients with obsessive compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) has been associated with an altered activity of the immune system. This study was carried out to investigate whether treatment with paroxetine and venlafaxine modifies the immune function in OCD and whether this modification is related to treatment outcome. METHODS: Ex vivo production of TNF-alpha, IL-4, IL-6, IL-10, and IFN-gamma in whole blood cultures, and NK-cell activity and peripheral blood NK-cell-, monocytes-, T-cell-, and B-cell- percentages were measured in 42 outpatients with OCD who participated in a 12-week, double-blind SRI trial. RESULTS: Paroxetine and venlafaxine treatment did not affect immune parameters and clinical response was not directly related to altered activity of the immune system. Responders, defined as having a >or=25% decrease on the Y-BOCS, differed from non-responders with regard to the change of TNF-alpha values. CONCLUSIONS: The present results suggest that paroxetine and venlafaxine do not affect immune parameters and that clinical response is not related to altered activity of the immune system in OCD. Nonetheless, our data yielded interesting preliminary results that warrant further discussion and investigation.

Adult↗
PubMed2005

Predictors of pharmacotherapy response in anxiety disorders.

Although treatment with different compounds such as tricyclic antidepressants, selective serotonin reuptake inhibitors, high-potency benzodiazepines, and monoamine oxidase inhibitors has been proven effective in anxiety disorders, 20% to 40% of patients are nonresponders. Given the limited efficacy, the delayed onset of response (it takes several weeks before a clinical effect can be seen for most of these drugs), and the occurrence of side effects associated with pharmacotherapy, predicting response in anxiety disorders would be immensely valuable. This review surveys the literature over the past years on predictors of response to pharmacotherapy in obsessive-compulsive disorder, social anxiety disorder, panic disorder, and posttraumatic stress disorder. Prediction of treatment response may be founded on demographic and clinical variables, neurochemical and electrophysiologic parameters, imaging studies, and genetic markers.

Alleles↗
PubMed2005

Bupropion for patients with obsessive-compulsive disorder: an open-label, fixed-dose study.

OBJECTIVE: In the present study, we examined the efficacy of bupropion for patients with obsessive-compulsive disorder (OCD). METHOD: Twelve patients with OCD according to DSM-IV criteria were included in an open trial with bupropion, maximum dosage 300 mg per day, during 8 weeks. The primary efficacy parameter was the Yale-Brown Obsessive Compulsive Scale (YBOCS). A responder was defined by a reduction in score on the YBOCS of > or = 25%. Data were collected from February 2003 to July 2003. RESULTS: An intent-to-treat analysis using the last observation carried forward demonstrated that bupropion had no mean effect on OCD symptoms (mean YBOCS decrease was 1.1 +/- 9.6). Four patients improved, with a mean decrease on the YBOCS of 31%, and 2 of them met responder rate criteria. Eight patients experienced an exacerbation of OCD symptoms, with a mean increase on the YBOCS of 21%. CONCLUSION: Bupropion is not an effective treatment for OCD, but the bimodal distribution of the effect supports the notion that dopamine might be involved in the pathophysiology of OCD.

Adult↗
PubMed2004

Use of factor analysis to detect potential phenotypes in obsessive-compulsive disorder.

This study aimed to identify symptom dimensions in obsessive-compulsive disorder (OCD) in order to reveal distinct clinical phenotypes. Factor analysis of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) checklist on item level was performed on data from 335 outpatients with primary OCD. The relationship of demographic and clinical characteristics to the resulting factor scores was examined. A principal component analysis identified the following five consistent symptom dimensions: (1) contamination and cleaning, (2) aggressive, sexual and religious obsessions, (3) somatic obsessions and checking, (4) symmetry and counting/arranging compulsions and (5) high-risk assessment and checking. We observed significant differences in sex distribution, age of onset, Y-BOCS scores and familial prevalence of OCD in relation to the symptom dimensions. These findings provide further evidence for distinct clinical phenotypes in OCD.

Adult↗
PubMed2004

Symptom dimensions in obsessive-compulsive disorder: factor analysis on a clinician-rated scale and a self-report measure.

Although obsessive-compulsive disorder (OCD) is regarded as a unitary nosological entity, it encompasses a rich variety of heterogeneous mental and behavioural phenomena. The identification of clinical subtypes within this broad concept has been a focus of attention in recent years. In the present study, we administered a clinician-rated scale, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) with the Y-BOCS Symptom Checklist (Y-BOCS CL), as well as a self-report questionnaire, the Padua Inventory revised (PI-R), to 150 outpatients with OCD. A principal component analysis on the Y-BOCS CL, along with the PI-R, identified 6 consistent symptom clusters: (1) contamination obsessions and cleaning compulsions, (2) sexual/religious/somatic obsessions and checking, (3) high risk assessment and checking, (4) impulses and fear of loss of control, (5) need for symmetry and exactness, and ordering and counting compulsions, and finally (6) rumination. The Y-BOCS CL and PI-R showed great overlap and consistency regarding content and severity of the OCD symptoms. On inspection of items with identical content, only half of the items showed significant agreement. Both inventories have unique factors: rumination is represented solely in the PI-R, somatic obsessions and checking solely in the Y-BOCS CL. This means that the use of both clinician-administered and self-report measures is recommended, so that the entire spectrum of symptoms is represented.

Adult↗
PubMed2004

Low level of dopaminergic D2 receptor binding in obsessive-compulsive disorder.

BACKGROUND: Despite growing evidence for involvement of the dopaminergic system in obsessive-compulsive disorder (OCD), the functional anatomy of the dopaminergic system in the basal ganglia has been investigated sparsely. METHODS: Dopamine D(2) receptor binding was assessed in 10 medication-free OCD patients and 10 healthy control subjects, matched for age, gender, and handedness. The binding potential was measured with single photon emission computerized tomography (SPECT) and infusion of the D(2) receptor radiotracer [(123)I] iodobenzamide. With magnetic resonance imaging as reference, regions of interest (caudate and putamen) were delineated for each hemisphere and coregistered with the corresponding SPECT scans. RESULTS: Dopamine D(2) receptor binding in the left caudate nucleus was significantly lower in the patients with OCD than in healthy control subjects [F(1,18) = 7.0, p =.016]. In addition, an interhemispheric difference was observed in the patient sample. Both the D(2) receptor binding potential (df = 9, p =.012), and the volume (df = 9, p =.029) of the left caudate nucleus were statistically significantly reduced relative to the right caudate nucleus. CONCLUSIONS: This study provides in vivo evidence for abnormalities in the binding potential of the dopamine D(2) receptor, which suggest the direct involvement of the dopaminergic system in the pathophysiology of OCD.

Adolescent↗
PubMed2004

Synergistic dopamine increase in the rat prefrontal cortex with the combination of quetiapine and fluvoxamine.

RATIONALE: The combination of atypical antipsychotic drugs in addition to serotonin reuptake inhibitors has recently proven to be beneficial in a number of neuropsychiatric disorders, such as major depression, schizophrenia, and obsessive-compulsive disorder. OBJECTIVES: To investigate the effects of an atypical antipsychotic drug in combination with a serotonin reuptake inhibitor on extracellular serotonin [5-HT]ex, and dopamine levels [DA]ex in different brain areas. METHODS: The effects of quetiapine (10 mg/kg) with fluvoxamine (10 mg/kg) on [5-HT]ex and [DA]ex were compared in the rat dorsal striatum, prefrontal cortex, nucleus accumbens (core and shell), and thalamus by means of microdialysis coupled to HPLC with electrochemical detection. RESULTS: Quetiapine had no significant effect on [DA]ex and [5-HT]ex levels in the prefrontal cortex and thalamus, but increased [DA]ex and [5-HT]ex levels in the dorsal striatum. In the accumbens, quetiapine increased [DA]ex levels and decreased [5-HT]ex levels. Fluvoxamine increased [5-HT]ex levels in all brain areas, and also increased [DA]ex levels in the striatum. The combination of quetiapine with fluvoxamine increased [DA]ex and [5-HT]ex levels in all brain areas compared with baseline. Although neither quetiapine nor fluvoxamine in monotherapy affected [DA]ex levels in the prefrontal cortex and thalamus, the combination produced a significant increase of [DA]ex levels in these two brain areas. CONCLUSIONS: The combination of quetiapine with fluvoxamine causes a synergistic dopamine increase in the prefrontal cortex and the thalamus.

Animals↗
PubMed2004

Decreased TNF-alpha and NK activity in obsessive-compulsive disorder.

BACKGROUND: Accumulating evidence points towards the involvement of autoimmune mechanisms in the pathophysiology of some subgroups of obsessive-compulsive disorder (OCD). This study was carried out to investigate whether obsessive-compulsive disorder is associated with altered activity of the immune system, and whether these changes are related to particular clinical characteristics. METHODS: Ex vivo production of TNF-alpha, IL-4, IL-6, IL-10, and IFN-gamma in whole blood cultures, and NK-cell activity and peripheral blood NK cell-, monocytes-, T-cell-, and B-cell- percentages were measured in 50 medication-free outpatients with OCD and 25 controls. RESULTS: In OCD patients, we found a significant decrease in production of TNF-alpha (p < 0.0001) and NK-activity (p = 0.002) in comparison with controls. No significant differences were observed in the other immune variables. Patients with first-degree relatives with OCD had significant lower NK-activity than patients who had no relatives with OCD (p = 0.02), and patients with a childhood onset of OCD had significantly lower number of NK-cells than patients with a late onset (p= 0.003). CONCLUSIONS: Changes in TNF-alpha and NK activity suggest a potential role of altered immune function in the pathophysiology of obsessive-compulsive disorder.

Adult↗
PubMed2004

Axis I and II comorbidity in a large sample of patients with obsessive-compulsive disorder.

BACKGROUND: No study has reported yet on the prevalence of both comorbid DSM-IV axis I and personality disorders in a large cohort of OCD patients, and little is known about differences in clinical characteristics between OCD patients with and without comorbid symptoms. OBJECTIVE: To examine the cross-sectional prevalence of comorbid DSM-IV axis I, and personality disorders in a population of patients with primary obsessive-compulsive disorder (OCD). METHOD: 420 outpatients with OCD were evaluated for comorbid pathology, demographic, and clinical characteristics. RESULTS: Forty-six percent of the patients were diagnosed with a comorbid disorder. Twenty-seven percent met the criteria for at least one comorbid axis I disorder, 15.6 percent for a comorbid personality disorder, and 20.4 percent for both a comorbid axis I disorder and a personality disorder. LIMITATIONS: A limitation of the current study is that the sample was drawn from a psychiatric department specialised in anxiety disorders, which might have underestimated the rate of comorbid diagnoses. CONCLUSION: Comorbid diagnoses occur less frequently than would be expected on the basis of comparable comorbidity studies in OCD. Associated axis I comorbidity did not affect clinical severity of OCD, but was related to higher levels of depression and anxiety, whereas axis II comorbidity impaired to a higher extent the overall functioning.

Adult↗
PubMed2004

A double-blind switch study of paroxetine and venlafaxine in obsessive-compulsive disorder.

BACKGROUND: The treatment guidelines for obsessive-compulsive disorder (OCD) propose to switch serotonin reuptake inhibitors (SRIs) in case of refractoriness. However, no controlled research has been published yet that prospectively examined the effects of changing SRIs. This article describes the first double-blind switch study of 2 SRIs in patients with OCD. METHOD: 150 patients with primary OCD, according to DSM-IV criteria, were randomly assigned in a 12-week, double-blind trial to receive dosages titrated upward to 300 mg/day of venlafaxine (N = 75) or 60 mg/day of paroxetine (N = 75). Primary efficacy was assessed by the change from baseline on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and nonresponse was defined as less than 25% reduction on the Y-BOCS. After a 4-week tapering phase, 43 nonresponders were switched to 12 additional weeks of the alternate antidepressant, of which 16 patients received venlafaxine and 27 received paroxetine. RESULTS: Eighteen of 43 patients benefited from a switch to the alternate SRI with a mean +/- SD decrease of at least 25% on the Y-BOCS. At the end of 12 weeks, responder rates were 56% for paroxetine (15/27) and 19% for venlafaxine (3/16). An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean decrease on the Y-BOCS of 1.8 +/- 3.5 in the venlafaxine group and 6.5 +/- 7.1 in the paroxetine group. After 2 consecutive SRI trials, 109 of 150 patients (73%) achieved a Y-BOCS decrease of at least 25%. CONCLUSION: The results of the current study show that 42% of the nonresponders benefited from a crossover to the other SRI, and that paroxetine was more efficacious than venlafaxine in the treatment of nonresponders to a previous SRI trial. Switching SRIs in case of refractoriness may be considered a useful strategy for patients with OCD.

Administration, Oral↗
PubMed2004

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.

Adolescent↗
PubMed2004

The role of dopamine in obsessive-compulsive disorder: preclinical and clinical evidence.

Obsessive-compulsive disorder (OCD) is a frequent and chronic psychiatric disorder that has been linked closely to the serotonin system mainly because of the antiobsessional efficacy of selective serotonin reuptake inhibitors (SSRIs). A limitation of the serotonin hypothesis of OCD is that a substantial number of the patients with OCD show no significant improvement after an adequate trial with SSRIs. There is substantial evidence that these patients may benefit from addition of antipsychotics to their ongoing SSRI treatment, suggesting that dopamine also might play a role in the pathophysiology of OCD. In this review, the preclinical and clinical evidence on the role of dopamine in OCD is summarized.

Animals↗
PubMed2003

A score for predicting response to pharmacotherapy in obsessive-compulsive disorder.

Although there have been many attempts to find predictors of therapeutic response to antidepressant treatment of obsessive-compulsive disorder (OCD), few reports have evaluated the joint predictive value of a number of clinical characteristics. This study aimed to identify clinical predictors of outcome in OCD, and to develop an easily applicable method to predict response to drug treatment. One hundred and fifty patients with primary OCD according to DSM-IV criteria were randomly assigned in a 12-week, double-blind, comparison trial with a selective serotonin reuptake inhibitor (paroxetine), and a serotonin-noradrenaline reuptake inhibitor (venlafaxine). The primary efficacy parameter was the Yale-Brown obsessive-compulsive scale (Y-BOCS) score, and response to treatment was prospectively defined as a >/= 35% decrease from the beginning. A stepwise multivariate analysis was used to identify predictors. The absence of previous therapies, moderate baseline severity of obsessive-compulsive symptoms (Y-BOCS score < 23), and low Hamilton Depressive Rating Scale scores (6-15) were found to be prognostic determinants of good response to pharmacotherapy. The prognostic ability of the prediction model to discriminate between responders and non-responders was quantified as the area under the receiver operating/operator characteristic curve (ROC area), which was 0.71 (95% confidence interval 0.63-0.8), demonstrating a reasonable discriminatory power. This study is the first to present a model that can estimate by the use of prediction rules the probability of treatment response to antidepressants in patients with OCD.

Adolescent↗
PubMed2003

A double blind comparison of venlafaxine and paroxetine in obsessive-compulsive disorder.

SUMMARY: While the usefulness of clomipramine and selective serotonin reuptake inhibitors (SSRIs) in obsessive-compulsive disorder (OCD) has been established, the efficacy of serotonin-norepinephrine reuptake inhibitors remains to be determined. This report describes the first randomized double-blind comparison study of an SNRI in patients with obsessive-compulsive disorder. The current study compares the efficacy and tolerability of venlafaxine with paroxetine. One hundred and fifty patients with primary OCD according to DSM-IV criteria were randomly assigned in a 12-week double-blind trial to receive dosages titrated upward to 300 mg/d of venlafaxine (n = 75) or 60 mg/d of paroxetine (n = 75). Primary efficacy was assessed by the change from baseline on the Yale-Brown obsessive-compulsive scale (Y-BOCS). Other assessments throughout the trial included the Hamilton depression rating scale, and the Hamilton anxiety rating scale. An intent-to-treat, last-observation-carried-forward analysis demonstrated a mean decrease on the Y-BOCS of 7.2 +/- 7.5 in the venlafaxine group and of 7.8 +/- 5.4 in the paroxetine group. In both treatment groups, a responder rate (decrease > 35% on the Y-BOCS) of approximately 40% was found. There were no significant differences between venlafaxine and paroxetine with regard to response or responder rates. The incidence of adverse events for venlafaxine and paroxetine was comparable. The most common side effects for venlafaxine were somnolence, insomnia, a dry mouth, and sweating; and for paroxetine somnolence, sweating, nausea, and headache. These results show that venlafaxine was equally effective to paroxetine in treating patients with OCD. Venlafaxine may be a useful therapy for obsessive-compulsive patients, but is not superior to SSRIs.

Adolescent↗
PubMed2003

Emerging skin-picking behaviour after serotonin reuptake inhibitor-treatment in patients with obsessive-compulsive disorder: possible mechanisms and implications for clinical care.

Pathological skin-picking is a self-injurious, impulsive behaviour with repetitive, and ritualistic characteristics. A number of studies show that selective serotonin reuptake inhibitors (SSRIs) may be efficacious in reducing skin-picking behaviour. Two case reports are presented demonstrating that SSRI-treatment may induce or aggravate pathological skin-picking behaviour. Possible mechanisms of SSRI-induced pathological skin-picking and implications for clinical care are discussed.

Adult↗
PubMed2002

Quetiapine addition to serotonin reuptake inhibitor treatment in patients with treatment-refractory obsessive-compulsive disorder: an open-label study.

OBJECTIVE: Although patients with obsessive-compulsive disorder (OCD) benefit from treatment with serotonin reuptake inhibitors (SRIs), it is estimated that 40% to 60% of the patients remain unimproved. The objective of this study was to examine whether addition of the atypical antipsychotic quetiapine to SRIs is useful for patients with OCD who do not respond to SRI monotherapy. METHOD: Ten patients with OCD (DSM-IV criteria) who had not responded to at least 3 previous treatments with an SRI at maximum dose and duration were assigned to receive quetiapine in addition to an SRI for 8 weeks. Treatment response was assessed using the Yale-Brown Obessive-Compulsive Scale (YBOCS). RESULTS: Seven of 10 patients responded to the quetiapine addition. The mean +/- SD baseline YBOCS score of 31.4 +/- 7.8 dropped to a mean of 20.8 +/- 8.4 at endpoint with a mean reduction of 35.4%. CONCLUSION: This is the first study to show that treatment-refractory OCD patients may benefit from addition of quetiapine to ongoing SRI therapy.

Adult↗