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PubMed2002

Assessment of symptom exacerbations in a longitudinal study of children with Tourette's syndrome or obsessive-compulsive disorder.

OBJECTIVES: The severity of tic and obsessive-compulsive (OC) symptoms varies over time. Consequently, how do we, as clinicians, know when a change in symptom severity occurs that falls outside of the normal range of fluctuation? The goal of this study was to describe the level of symptom severity fluctuation over time and to establish an objective, prospective, and quantitative method for identifying symptom exacerbations in children with Tourette's syndrome, obsessive-compulsive disorder (OCD), or both. A second major aim was to assess whether fluctuations in tic and OC symptom severity covaried with one another. METHOD: Monthly consecutive Yale Global Tic Severity Scale and Children's Yale-Brown Obsessive Compulsive Scale scores were prospectively obtained in 64 children diagnosed with Tourette's syndrome and/or OCD for periods ranging from 3 to 39 months. Exacerbation thresholds were estimated by using state-of-the-art bootstrap methods. These thresholds were then independently evaluated by asking two expert clinicians to identify, retrospectively, clinically significant exacerbations based on a review of all available clinical and research records. RESULTS: The severity of tic and OC symptoms displayed a high degree of intrasubject variability. Exacerbation thresholds, which incorporated the change score from the previous month and the current symptom score, provided the best agreement with those of expert clinicians. When both tic and OC symptoms were present, they showed a significant degree of covariation. CONCLUSIONS: Evidence-based treatments are coming of age. The use of valid, clinician-rated severity scales will likely become a standard part of clinical practice. Bootstrapping methods may provide a quantitative and convenient way to obtain clinically valid thresholds to assess tic and OC symptom exacerbations. This method has the potential to be applied to other symptom domains where exacerbation thresholds are needed.

Adolescent↗
PubMed1996

Fluvoxamine versus clomipramine for obsessive-compulsive disorder: a double-blind comparison.

The efficacy and tolerability of fluvoxamine (100-300 mg/day) and clomipramine (100-250 mg/day) were compared in a randomized, double-blind, parallel-group study of 79 patients with obsessive-compulsive disorder (OCD) without coexisting major depression. After a 2-week placebo lead-in period, patients were randomized to fluvoxamine (37 patients) or clomipramine (42 patients) for 10 weeks. Efficacy was evaluated with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), the National Institute of Mental Health Obsessive-Compulsive scale, and Patient and Clinical Global Improvement scales. Hamilton Rating Scale for Depression scores and somatic symptoms were also assessed. Seventy-eight percent of fluvoxamine patients and 64% of clomipramine patients completed the study. At the end of treatment, 56% of fluvoxamine patients were classified as responders (> or = 25% decrease in Y-BOCS score), compared with 54% of clomipramine patients. Both groups showed steady improvement throughout the study; no statistically significant differences were observed between the groups for any efficacy variable at any time. A similar percentage of patients in both groups withdrew because of adverse events. No serious adverse events related to drug occurred with either drug. Insomnia, nervousness, and dyspepsia were more statistically frequent with fluvoxamine; dry mouth and postural hypotension were more frequent with clomipramine. In this study, fluvoxamine and clomipramine were equally effective in reducing OCD symptoms over a 10-week treatment period but displayed different side effect profiles.

Adolescent↗
PubMed1999

Placebo-controlled, multicenter study of sertraline treatment for obsessive-compulsive disorder.

The safety and efficacy of sertraline versus placebo were examined in a group of nondepressed outpatients with obsessive-compulsive disorder (OCD). Patients with moderate-to-severe OCD were recruited at 10 sites. After a 1-week placebo lead-in, patients were treated in a double-blind fashion for 12 weeks with sertraline or placebo. Sertraline was administered at a starting dose of 50 mg/day, with flexible titration up to 200 mg/day. The efficacy measures were the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH), and the Clinical Global Impression Scale (CGI) Severity of Illness and Improvement subscales. One hundred sixty-seven patients were randomly assigned and received at least one dose of double-blind medication: 86 received sertraline and 81 received placebo. All efficacy measures showed significantly greater improvement in the sertraline group from the end of week 8 until the end of week 12. Significantly greater improvement (p < 0.05) in the sertraline group first became apparent by the end of week 3 on the Y-BOCS and the CGI Improvement scale, and by the end of weeks 6 and 8, respectively, on the NIMH and CGI Severity scale. Sertraline was well tolerated, without serious adverse effects. In conclusion, sertraline was safe and effective in the treatment of patients with OCD.

Adult↗
PubMed2001

Clinical predictors of drug response in obsessive-compulsive disorder.

The aim of this study was to evaluate which clinical variables might influence the antiobsessional response to proserotonergic drugs in a sample of patients with obsessive-compulsive disorder (OCD). One hundred fifty-nine patients with DSM-IV OCD underwent a 12-week standardized treatment with fluvoxamine, clomipramine, citalopram, or paroxetine. According to treatment response, defined as a reduction of the Yale-Brown Obsessive Compulsive Scale total score >35%, patients were divided into two groups. Ninety patients (56.6%) responded to treatment and 69 (43.4%) did not. Responders had a significantly higher frequency of positive family history for OCD (FH-OCD) in their first-degree relatives, whereas nonresponders had an earlier onset and a higher frequency of "poor insight" subtype and somatic obsessions. The predictive value of all these variables was tested by a stepwise logistic regression analysis that confirmed poor insight and FH-OCD to be the best predictors of poor and good drug treatment response, respectively. These preliminary findings need additional investigations toward a better definition of the genetic and biological heterogeneity of patients with OCD, and they underlie the importance of collecting the insight score and family history for psychiatric disorders in the pretreatment assessment.

Adolescent↗
PubMed2002

Sertraline and fluoxetine treatment of obsessive-compulsive disorder: results of a double-blind, 6-month treatment study.

The purpose of this study was to evaluate the comparative efficacy and tolerability of sertraline and fluoxetine in the treatment of obsessive-compulsive disorder (OCD). Outpatients meeting DSM-IV criteria for OCD, with a Yale-Brown Obsessive-Compulsive (Y-BOCS) total score >or= 17, an NIMH Global Obsessive-Compulsive (NIMH-OC) scale score >or= 7, and a CGI-Severity score >or= 4 were randomized to 24 weeks of double-blind treatment with sertraline (N = 77) or fluoxetine (N = 73). Primary efficacy measures consisted of the Y-BOCS, the NIMH-OC scale, and the CGI-Severity (CGI-S) and Improvement (CGI-I) scales. Equivalent and significant (p < 0.001) improvement was found at week 24 in Y-BOCS and NIMH-OC scale scores for sertraline and fluoxetine. After 12 weeks, 49.2% of patients on sertraline were rated on the CGI-S scale as being mildly ill or not ill compared to 24.6% on fluoxetine (p < 0.01). A Cox analysis found patients on sertraline to have a statistically nonsignificant 42% greater likelihood of achieving a response by week 12 (CGI-I, much or very much improved; 95% CI, 0.85, 2.38; p = 0.18). Sertraline treatment also resulted in a higher proportion of remissions than fluoxetine (defined as a CGI-I <or= 2 and a Y-BOCS score <or= 11), both at week 12 (20% vs. 8%; chi2, 3.95; df 1; p = 0.047) and week 24 (36% vs. 22%; chi2, 3.18; df, 1; p = 0.075). Both medications were well-tolerated and demonstrated significant efficacy in the treatment of outpatients with moderate to severe OCD with the subjects treated with sertraline showing a greater likelihood of remission as well as an earlier improvement on some but not all efficacy measures

Adolescent↗
PubMed1992

Fluvoxamine in the treatment of obsessive compulsive disorder.

Obsessive compulsive disorder is a chronic, often severe condition that is associated with considerable long term morbidity and suffering. Potent serotonin reuptake inhibitors are now regarded as first line treatments and their efficacy has been established in a series of placebo-controlled studies. The first of these compounds to become available, clomipramine, has undesirable effects on a number of other receptor systems and is associated with marked anticholinergic side effects. Of the selective serotonin reuptake inhibitors fluvoxamine is the most widely studied, with three small positive placebo-controlled and two recent large multicentre studies. These two studies show that fluvoxamine is associated with significant improvement on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the National Institute of Mental Health Obsessive Compulsive Scale (NIMH-OC) and the Global Improvement item of the Clinical Global Impression (CGImp) Scale, compared with placebo.

Combined Modality Therapy↗
PubMed2000

Risperidone augmentation in refractory obsessive-compulsive disorder: an open-label study.

Risperidone, an atypical neuroleptic, has been proposed for augmentation strategies in resistant obsessive-compulsive disorder (OCD). We report the results of an open-label trial on the use of the combination of serotonin reuptake inhibitors (SRIs) with risperidone in 20 refractory OCD outpatients. All patients had been suffering from OCD, according to DSM-IV criteria, for at least 2 years and had various comorbid disorders. All had been treated with a SRI at adequate dosages for at least 6 months, but had failed to respond. Therefore, risperidone was added and the dosage titrated up to the mean dose of 3 mg/day over 8 weeks. After 2 months of this regimen, all patients had shown a reduction in obsessive-compulsive symptoms, as assessed by the decrease in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score, particularly those with a lifetime comorbidity with bipolar disorder; only three patients reported mild sedation and postural hypotension, two mild extrapyramidal side-effects (tremors and akatysia) and two an increased appetite. All these effects were well tolerated and no patient halted the treatment. The addition of risperidone would appear to be a useful strategy for augmenting SRI effectiveness in refractory OCD patients.

Adult↗
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↗
PubMed1983

Tricyclic antidepressants in obsessive-compulsive disorder. Antiobsessional or antidepressant agents?

The response to tricyclic antidepressants of eight obsessive-compulsive patients was assessed at pretreatment and at 4, 8, and 12 weeks of treatment, with the aim of delineating differential rates of improvement, or desynchrony, between the various symptoms. Change in obsessive-compulsive symptoms paralleled change in depression and anxiety, suggesting a global beneficial effect of the drugs. The analysis of individual data also revealed this synchronous pattern of change, with significant improvement, in responders, occurring within the first 4 weeks of treatment. Furthermore, responders had higher initial Hamilton depression ratings compared to nonresponders. These results do not lend support to the claim that tricyclics possess specific antiobsessional effect which is independent of their antidepressant effect. The limitations of a purely symptomatic approach in exploring the mode of action of antidepressants in obsessive-compulsive disorder is briefly discussed.

Adolescent↗
PubMed1990

Absence of placebo response in obsessive-compulsive disorder.

Analyses in 30 patients with a diagnosis of obsessive-compulsive disorder given single-blind placebo over a 2-week period and of 12 of these patients who continued treatment on double-blind placebo for an additional 10 weeks revealed virtual absence of improvement on both clinician and self-rating scales of obsessions, compulsions, phobias, depression, and anxiety. This result would imply that the contribution of the placebo effect to the pharmacotherapy of patients with obsessive-compulsive disorder is negligible although considerable effort and work is still required to reliably identify one of four panic disorder with agoraphobia patients who respond to placebo. The placebo response thus presents a clear distinction between these two phenomenologically complex anxiety disorders.

Adolescent↗
PubMed1995

Does neurosurgery for obsessive-compulsive disorder produce personality change?

Seventeen patients suffering from intractable obsessive-compulsive disorder treated with neurosurgery were assessed before surgery and a mean 10 +/- 5.1 years after surgery. Change in personality was assessed using a special 34-item schedule on patients and informants. The majority of subjects had not noted any significant changes in personality. The subjects were rated by themselves and their informants to have improved overall in the following characteristics: they were less obsessional, cried less, demonstrated a greater depth of feelings, laughed more, were more sociable, and were less anxious or dependent. Six subjects were judged by informants to have improved in their degree of obsessionality, which was distinguishable from the impact on obsessive-compulsive symptoms. The traits that showed an overall negative change were initiative/drive and energy level. Four subjects (2/4 open and 2/13 stereotactic surgery) were judged to have a negative personality change. Ratings of neuroticism, anxiety, depression, and capacity for pleasure showed significant improvement. We conclude that while most obsessive-compulsive disorder patients treated with stereotactic surgery do not experience a personality change, a small proportion report a positive or negative impact. Of note is the improvement in obsessionality in some patients, and an adverse personality change of the "frontal lobe type" in a few patients.

Adolescent↗
PubMed1998

Obsessions and compulsions as a distinct cluster of symptoms in schizophrenia: a neuropsychological study.

Using neurocognitive testing, the present study assessed whether obsessions and compulsions could represent a distinct cluster of symptoms in schizophrenia. We formulated our hypothesis based on data from nonschizophrenic patients, expecting to find that schizophrenic patients with obsessive-compulsive (OC) symptoms would experience more difficulties in the same cognitive areas as nonschizophrenic patients with obsessive-compulsive disorder (OCD). Patients had separate psychiatric and cognitive evaluations. The OC and non-OC schizophrenic subjects did not differ significantly on the positive and negative symptom scores. However, compared with non-OC schizophrenic patients, those with OC symptoms performed worse on cognitive areas thought to be impaired (i.e., visual-spatial skills, delayed nonverbal memory, and cognitive shifting abilities). In addition, the severity of OC scores correlated with poor performance in these areas of cognition. Our results support our hypothesis, specifically that OC symptoms may constitute a distinct cluster separate from psychosis in schizophrenia and raise the possibility of a distinct subtype of schizophrenia. The theoretical and clinical implications of these findings are discussed.

Cognition Disorders↗
PubMed1998

Incidence of obsessive-compulsive disorder in adults.

This study addressed the incidence of obsessive-compulsive disorder (OCD) in adults in the general population. The Baltimore cohort of 3481 subjects, originally sampled during the 1981 multisite Epidemiologic Catchment Area Study, was traced. From 1993 to 1996, 1920 people were reinterviewed using the Diagnostic Interview Schedule. The incidence of DSM-III-R obsessive-compulsive disorder in adults was estimated at .55 per 1000 person-years. There was a relatively high rate of new cases in elderly women. It appeared that there were two peaks of onset of OCD over the life span, both of which occur later in female subjects. Subjects with adult incidence OCD often presented for psychiatric treatment, though they did not specify obsessive-compulsive symptoms as the reason. The difference in diagnostic criteria between DSM-III and DSM-III-R substantially influenced the threshold for new case identification.

Adolescent↗
PubMed1999

Lesion topography and outcome after thermocapsulotomy or gamma knife capsulotomy for obsessive-compulsive disorder: relevance of the right hemisphere.

OBJECTIVES: Obsessive-compulsive disorder is a common mental disorder, notorious for its chronicity and intractability. Stereotactic lesions within the anterior limb of the internal capsule have been shown to provide symptomatic relief in such refractory cases, but only few systematic evaluations have correlated anatomic lesion location with individual postoperative outcome. PATIENTS AND METHODS: Between 1976 and 1989, extremely disabled and otherwise intractable patients with a chronic deteriorating clinical course of obsessive-compulsive disorder underwent bilateral thermocapsulotomy (n = 22) or radiosurgical gamma knife capsulotomy (n = 13) at the Karolinska Hospital, Stockholm. Clinical morbidity was monitored prospectively pre- and postoperatively by using standardized psychiatric rating scales. In 29 patients (thermocapsulotomy, n = 19; gamma knife capsulotomy, n = 10), both psychiatric and magnetic resonance imaging follow-up data (median, 8.4 yr) were available. RESULTS: A right-sided anatomically defined lesion volume was identified in all successfully treated patients. This common topographic denominator was defined in the approximate middle of the anterior limb of the internal capsule on the plane parallel to the anterior commissure-posterior commissure line at the level of the foramen of Monro and 4 mm above on the plane defined by the internal cerebral vein. This region was unaffected in patients with poor outcomes. On the left side, no particular lesion topography was associated with clinical outcome. Topographic differences of lesion overlap between good and poor outcome groups were significant for the right side (Fisher's exact test, P < 0.005). CONCLUSION: The current anatomic long-term analysis after thermocapsulotomy or gamma knife capsulotomy for obsessive-compulsive disorder reveals common topographic features within the right-sided anterior limb of the internal capsule independent of treatment modality.

Adult↗
PubMed1994

Pharmacologic management of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is an intriguing, difficult problem characterized by anxiety-producing intrusive thoughts and performance of anxiety-reducing rituals. Current evidence suggests that OCD may be associated with dysregulation of serotonin and dopamine neurotransmission. Numerous early studies involving the serotonin-specific reuptake inhibitor clomipramine led to the formulation of this hypothesis. Positive results with clomipramine initiated further research with other serotonin-specific reuptake inhibitors, such as fluoxetine, fluvoxamine, sertraline, and serotonergic agents such as buspirone and trazodone. Findings from a number of clinical trials suggest that drugs that inhibit serotonin reuptake or affect serotonergic transmission in other ways are of clear benefit in the treatment of OCD. These drugs may be more effective for obsessive thoughts than for compulsive rituals. Effective pharmacotherapy can dramatically decrease obsessive-compulsive symptoms and improve the patient's quality of life.

1-Naphthylamine↗
PubMed1993

Obsessive compulsive disorder in children and adolescents.

During 1992, further progress has been made in determining the incidence of obsessive compulsive disorder and change in symptoms over time. Advances have been made in determining what category of mood disorder obsessive compulsive disorders belong to; contributions have been made in the theoretic understanding of the cause of obsessive compulsive disorder, and why it may be associated with trichotillomania and Tourette's syndrome. Finally, the treatment of children with both medication and behavior therapy has been explored.

Adolescent↗
PubMed2003

Orienting attention in obsessive-compulsive disorder.

OBJECTIVES AND BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by recurrent obsessions and/or compulsions that affect daily functioning. This study aimed to ascertain whether OCD patients have problems in orienting attention, via the use of a vibrotactile choice reaction time task. METHODS: Participants were required to depress a button in response to a vibration delivered to the index finger of either the right or left hand. Prior to the stimulus, one of three precues was administered: valid (precue delivered to the same hand as stimulus), invalid (precue delivered to opposite hand to stimulus), or neutral (precue delivered simultaneously to both hands). RESULTS: Obsessive-compulsive disorder participants were overall slower and less accurate than controls. Contrary to our predictions, OCD participants did not show increased costs or benefits. However, unlike controls, patients did not show the normal pattern of faster reaction times on neutral compared with invalid precues, which may reflect a problem in inhibiting irrelevant information. CONCLUSIONS: Both patients and controls may benefit from the provision of directed attention in tactile tasks when difficulty levels are maximal. OCD patients may have problems with inhibitory control.

Adult↗
PubMed2005

Investigating the structure of craving using structural equation modeling in analysis of the obsessive-compulsive drinking scale: a multinational study.

BACKGROUND: Currently, there is no agreement among researchers on the definition of craving and its underlying theoretical model. The Obsessive-Compulsive Drinking Scale (OCDS) seems to measure certain aspects of craving, but its theoretical basis remains unclear. The aim of this study was to investigate the structure of alcohol craving, using OCDS data. METHODS: OCDS data from four studies were pooled to obtain a large and heterogeneous sample of 505 participants. All participants were treatment-seeking alcoholics meeting DSM-IV criteria for alcohol dependence. The factor structures of the OCDS previously found were evaluated using confirmatory factor analyses. The goodness of fit of these solutions was compared with those of alternative causal models: an obsessive-compulsive disorder model, an inhibition model, and a cognitive-behavioral model. These alternative models were based on modern theories about craving and were tested in the OCDS data, using structural equation modeling. In this way, the current study replaced simple correlational analysis by a more sophisticated causal way of analyzing the underlying structure of the OCDS items. The best fitting model was selected by comparing the mean discrepancy between the implied and observed matrices of the models. RESULTS: The data showed that the previously reported factor structures had to be rejected. Also, the inhibition model and obsessive-compulsive disorder model did not fit the data. The cognitive-behavioral model showed encouraging fit. Optimizing strategies were applied to further improve the fit of this model, which resulted in a model with close fit to the data. CONCLUSIONS: The causal cognitive-behavioral model proved to be superior. It showed that the OCDS contains many items that do not represent the core concept of craving but instead are indicators for the consequences of craving. From this model, it seems that craving, in a narrow sense, can be reliably assessed with only five items of the OCDS.

Adult↗