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PubMed1998

Practice parameters for the assessment and treatment of children and adolescents with obsessive-compulsive disorder. AACAP.

These practice parameters describe the assessment and treatment of obsessive-compulsive disorder based on a detailed literature review and expert consultation. Obsessive-compulsive disorder is a disorder of heterogeneous origin characterized by intrusive thoughts or compulsive urges or behaviors that are distressing, time-consuming, or functionally impairing. In children and adolescents, the disorder often is accompanied by a wide range of comorbidity, including mood, anxiety, attentional, and learning difficulties, and/or tic disorder. These parameters describe the relevant areas of assessment, especially symptomatology, onset, and course, other associated psychopathology, and developmental, family, and medical history (including postinfectious onset or exacerbations). Two modalities have been systematically assessed and empirically shown to ameliorate core symptoms: cognitive-behavioral therapy (primarily exposure/response prevention) and serotonin reuptake inhibitor medication. Data regarding the indications, efficacy, and implementation of these modalities are reviewed. Because OCD frequently occurs in the context of other psychopathology and adaptive difficulties, additional individual and family psychotherapeutic, pharmacological, and educational interventions often are necessary. Treatment planning guidelines are provided.

Adolescent↗
PubMed1999

Paroxetine open-label treatment of pediatric outpatients with obsessive-compulsive disorder.

OBJECTIVE: Paroxetine is a selective serotonin reuptake inhibitor with demonstrated efficacy in treating obsessive-compulsive disorder (OCD) in adults. This study evaluates the safety and effectiveness of paroxetine in pediatric OCD patients. METHOD: In a 12-week, open-label trial of paroxetine, 20 OCD outpatients, aged 8 to 17 years, were treated for OCD with daily doses ranging from 10 to 60 mg. Target symptoms were rated at regular intervals with the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), the Children's Global Assessment Scale, the Clinical Global Impression Scale, the Hamilton Anxiety Rating Scale, and the Yale Global Tic Severity Scale. RESULTS: Paroxetine proved relatively safe in this brief trial with a small sample and appeared to be effective in patients with OCD; mean CY-BOCS scores decreased significantly (z = 3.49, p = .0005) from 30.6 +/- 3.5 to 21.6 +/- 6.8 on medication. The most common side effects (n > or = 2) were hyperactivity/behavioral activation, headache, insomnia, nausea, and anxiety. Paroxetine did not have to be discontinued in any of the patients because of side effects; the most serious side effects included hyperactivity/behavioral activation in 3 younger patients (< 10 years) necessitating dosage reduction but not discontinuation. CONCLUSIONS: Preliminary evidence suggests that short-term treatment of pediatric OCD outpatients with paroxetine may be relatively safe and effective.

Adolescent↗
PubMed1999

Case series: increased vulnerability to obsessive-compulsive symptoms with repeated episodes of Sydenham chorea.

The association between obsessive-compulsive symptoms (OCS) and Sydenham chorea (SC) supports the hypothesis of a common neuroimmunological dysfunction in basal ganglia associated with group A beta-hemolytic streptococcal infection underlying both conditions. Four children with 2 distinct SC episodes were evaluated to assess the course of OCS. All patients developed OCS during their second episodes (3 met criteria for obsessive-compulsive disorder [OCD]), but not in their first episodes (2 developed OCS and met criteria for OCD). These data suggest that the recurrence of SC episodes may result in a cumulative effect, thus increasing the risk of appearance and intensification of OCS.

Acute Disease↗
PubMed2000

Case study: suprasellar germinoma presenting with psychotic and obsessive-compulsive symptoms.

This case describes a 13-year-old boy who had a suprasellar germinoma involving the bilateral basal ganglia. His presenting symptoms included left-sided weakness, diabetes insipidus, a decline in academic functioning as well as psychotic and obsessive-compulsive symptoms. His neuroradiological findings and clinical symptoms lend support to the potential role of the basal ganglia in psychotic and obsessive-compulsive symptomatology.

Adolescent↗
PubMed2000

An open trial of plasma exchange in childhood-onset obsessive-compulsive disorder without poststreptococcal exacerbations.

Patients with childhood-onset obsessive-compulsive disorder (OCD) with symptom exacerbations following streptococcal infections benefit from treatment with plasma exchange. In this study, 5 patients with treatment-refractory OCD without a history of streptococcus-related exacerbations underwent an open 2-week course of therapeutic plasma exchange. Behavioral ratings, completed at baseline and 4 weeks after the initial treatment, included the Clinical Global Impressions Scale and the Yale-Brown Obsessive Compulsive Scale. All 5 patients completed the trial with few side effects, but none showed significant improvement. Plasma exchange does not benefit children and adolescents with OCD who do not have streptococcus-related exacerbations.

Adolescent↗
PubMed2001

Fluvoxamine for children and adolescents with obsessive-compulsive disorder: a randomized, controlled, multicenter trial.

OBJECTIVE: To determine the safety and efficacy of fluvoxamine for the treatment of children and adolescents with obsessive-compulsive disorder (OCD) with a double-blind, placebo-controlled, multicenter study. METHOD: Subjects, aged 8 to 17 years, meeting DSM-III-R criteria for OCD were recruited from July 1991 to August 1994. After a 7- to 14-day single-blind, placebo washout/screening period, subjects were randomly assigned to fluvoxamine 50 to 200 mg/day or placebo for 10 weeks. Subjects who had not responded after 6 weeks could discontinue the double-blind phase of the study and enter a long-term, open-label trial of fluvoxamine. Analyses used an intent-to-treat sample with a last-observation-carried-forward method. RESULTS: Mean Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores with fluvoxamine were significantly (p < .05) different from those with placebo at weeks 1, 2, 3, 4, 6, and 10. Significant (p < .05) differences between fluvoxamine and placebo were observed for all secondary outcome measures at all visits. Based on a 25% reduction of CY-BOCS scores, 42% of subjects taking fluvoxamine were responders compared with 26% taking placebo. Forty-six (19 fluvoxamine, 27 placebo) of 120 randomized subjects discontinued early. Adverse events with a placebo-adjusted rate greater than 10% were insomnia and asthenia. CONCLUSIONS: Fluvoxamine has a rapid onset of action and is well tolerated and efficacious for the short-term treatment of pediatric OCD.

Adolescent↗
PubMed2001

Fluoxetine treatment for obsessive-compulsive disorder in children and adolescents: a placebo-controlled clinical trial.

OBJECTIVE: This study assesses the efficacy and tolerability of fluoxetine in the acute treatment of child and adolescent obsessive-compulsive disorder (OCD) during a 13-week, double-blind, placebo-controlled study. METHOD: Eligible patients aged 7 to 17 (N = 103) were randomized at a ratio of 2:1 to receive either fluoxetine or placebo. Dosing was initiated at 10 mg daily for 2 weeks, then increased to 20 mg daily. After 4 weeks of treatment, and again after 7 weeks of treatment, non-responders could have their dosage increased by 20 mg daily, for a maximum possible dosage of 60 mg daily. Primary measure of efficacy was improvement in OCD symptoms as measured by the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). All analyses were intent-to-treat. RESULTS: Fluoxetine was associated with significantly greater improvement in OCD as assessed by the CY-BOCS (p = .026) and other measures than was placebo. Fluoxetine was well tolerated and had a rate of discontinuation for adverse events similar to that of placebo (p = 1.00). CONCLUSIONS: Fluoxetine 20 to 60 mg daily was effective and well tolerated for treatment of OCD in this pediatric population.

Adolescent↗
PubMed2001

Manual-Driven group cognitive-behavioral therapy for adolescents with obsessive-compulsive disorder: a pilot study.

OBJECTIVE: Concerns about isolation, compromised development, partial pharmacotherapy response, therapist scarcity, and inadequate cognitive-behavioral therapy (CBT) adherence led the authors to adapt a CBT protocol to a group format for adolescents with obsessive-compulsive disorder (OCD). A naturalistic, open trial of group CBT for adolescent OCD is described. The authors predicted symptom improvement and format acceptability. METHOD: Over a 1 -year period, 18 adolescents aged 13 to 17 years with OCD received 14-week group CBT based on March and Mulle's OCD in Children and Adolescents: A Cognitive-Behavioral Treatment Manual in four consecutive sessions of five to nine patients. Eighty-three percent had undergone at least one medication trial, and 78% had previous CBT experience. RESULTS: OCD symptoms measured by the Children's Yale-Brown Obsessive Compulsive Scale improved significantly, both statistically and clinically. Adolescents consistently shared information and designed exposure interventions for themselves and others during sessions. Repeated self-report measures confirmed adolescents' satisfaction with therapy. CONCLUSIONS: This pilot study demonstrates that a manual-based treatment protocol may be exported for clinical use, adaptable for the end-user's needs, and palatable to adolescent patients. Clinical improvement and patient satisfaction justify further investigation in a controlled study.

Adolescent↗
PubMed2004

Relative contribution of attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and tic severity to social and behavioral problems in tic disorders.

The aim of this study was to investigate social and behavioral problems related to attention-deficit hyperactivity disorder (ADHD), obsessions and compulsions, and tic severity in children with a tic disorder. Parents of 58 children with a tic disorder with and without different forms of ADHD completed the Child Behavior Checklist (CBCL) and the Children's Social Behavior Questionnaire. Patients with a tic disorder with primarily hyperactive-impulsive ADHD had the highest questionnaire scores, patients with primarily inattentive ADHD had medium scores, and patients without ADHD had the lowest scores. On most subscales, significant part correlations with ADHD severity, but not tic severity, were obtained. Severity of obsessions and compulsions was independently correlated with the CBCL Thought Problems subscale but not with most other subscales. There was no significant correlation between tic severity and ADHD severity. Thus, in patients with a tic disorder, the presence and severity of ADHD are the main predictors of associated behavioral and social problems.

Adolescent↗
PubMed1996

Relationship between early side effects and therapeutic effects of clomipramine therapy in obsessive-compulsive disorder.

Early adverse effects of a drug may be a manifestation of individual differences in drug metabolism or of different pathologic processes. These differences may influence therapeutic responsiveness. Using data from Ciba-Geigy's multicenter 10-week clinical trial, we studied the relationship between early side effects and subsequent therapeutic response to clomipramine (CMI) in obsessive-compulsive disorder. We used tabular analyses and multiple regression to evaluate associations between early complaints and change in score on the Yale-Brown Obsessive-Compulsive Scale. We also evaluated whether early complaints were drug related (i.e., true side effects). It appeared that dry mouth, constipation, dizziness, insomnia, male impotence, nervousness, palpitation, and tremor reported during the first 4 weeks were predictive of good response to CMI. Myoclonus and tinnitus appeared weakly associated with treatment success. Most of these complaints were reported more by the CMI group than the placebo group, and more during CMI treatment than before. The more common complaints may reflect an individual's ability to metabolize CMI appropriately so that adequate therapeutic blood levels are attained. The less common complaints may reflect a sensitivity to CMI's serotonergic actions.

Adult↗
PubMed1999

Side effects as predictors of drug response in obsessive-compulsive disorder.

Differences between the side effect profiles of clomipramine (CMI) and the selective serotonin reuptake inhibitors may be important factors in both treatment outcome and patient selection in obsessive-compulsive disorder (OCD). Safety and efficacy data from an industry-sponsored, multicenter clinical trial of CMI were analyzed previously using tabular and multiple regression methods. Good response, defined as at least a 35% drop in final scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), was associated with a later age of OCD onset and certain early side effects that may reflect a sensitivity of responders to CMI's serotonergic actions. The authors conducted a similar analysis of data from an industry-sponsored clinical trial of fluoxetine in OCD. Fluoxetine response did not seem to be associated with age of OCD onset. Good response to both drugs was associated with initial nervousness and sexual complaints. The common side effects of fluoxetine (headache, nausea, and gastrointestinal complaints) did not seem to be associated with treatment response. Slight differences in the protocols of the two clinical trials yielded patient populations that were different in factors found to be associated with treatment outcome: subjects in the fluoxetine study had lower scores on the Y-BOCS, higher scores on the Hamilton Rating Scale for Depression, and an earlier age of OCD onset.

Adolescent↗
PubMed2001

Long-term treatment of obsessive-compulsive disorder after an acute response: a comparison of fluoxetine versus placebo.

Few controlled studies have evaluated the long-term continuation of pharmacotherapy for relapse prevention in patients with obsessive-compulsive disorder (OCD). This study assessed efficacy and safety of fluoxetine versus placebo in preventing relapse of OCD during a 52-week period in responders to short-term administration of fluoxetine. Patients who met DSM-IV criteria for OCD and had a Yale-Brown Obsessive Compulsive Scale score > or = 19 were treated with single-blind fluoxetine 20, 40, or 60 mg/day (based on physician assessment of response and tolerability). After 20 weeks, responders were randomly assigned to receive continued treatment with fluoxetine or placebo and were monitored for relapse for up to 52 weeks. Of 130 patients who entered the study, 71 (55%) were randomly assigned to receive fluoxetine (N = 36) or placebo (N = 35). Patients who received fluoxetine had numerically lower relapse rates compared with those who received placebo, although the difference was not significant (Kaplan-Meier 1-year relapse rates: fluoxetine, 20.6%; placebo, 31.9%; one-tailed p value = 0.137). In additional analyses evaluating patients on the basis of fluoxetine dose at randomization, patients who continued treatment with fluoxetine 60 mg/day (N = 52) had significantly lower rates of relapse than those who were switched to placebo (Kaplan-Meier 1-year relapse rates: fluoxetine, 17.5%; placebo, 38.0%; one-tailed p value = 0.041). Those who responded to the acute treatment phase with 40 (N = 18) or 20 (N = 1) mg/day had low overall rates of relapse, and the difference between continued fluoxetine and placebo treatment for these patients was not significant. For responders to the 60 mg/day dosage, those patients who continued treatment with fluoxetine were provided greater protection against relapse than those patients switched to placebo.

Adolescent↗
PubMed2002

Multivariate meta-analysis of controlled drug studies for obsessive-compulsive disorder.

Meta-analytic reviews of placebo-controlled studies for obsessive-compulsive disorder have found that clomipramine is more effective than drugs with more selective actions on serotonin reuptake, whereas in most direct comparisons, clomipramine's superiority has been less obvious. The authors used metaregression to identify sources of he-terogeneity in placebo-controlled trials of clomipramine, fluvoxamine, sertraline, and paroxetine. They evaluated such patient characteristics as age, gender, age of obsessive-compulsive disorder (OCD) onset, and baseline severity of OCD and depression, and such study characteristics as exclusion or inclusion criteria, length of single-blind prerandomization period, length of trial, number of subjects, and publication year. We found considerable heterogeneity across studies that was associated, in part, with publication year, length of single-blind prerandomization period, length of trial, and severity of patients' OCD. The apparent superiority of clomipramine persisted after controlling for these factors. The authors also confirmed previous reports that placebo response is higher in more recent studies. Meta-analyses can help characterize responders and nonresponders. The authors urge investigators to provide summaries of patient characteristics, especially baseline severity, age at onset, and duration of OCD, by patients' response.

Clomipramine↗
PubMed1996

Sequential administration of augmentation strategies in treatment-resistant obsessive-compulsive disorder: preliminary findings.

Given that an important proportion of patients with obsessive-compulsive disorder (OCD) fail to respond adequately to serotonin (5-HT) reuptake inhibitors (SRI), augmentation strategies aimed at enhancing further 5-HT transmission by different mechanisms were attempted sequentially in 13 SRI-resistant patients. Addition of the 5-HT1A l beta-adrenergic antagonist pindolol did not alter OCD symptomatology but produced a rapid improvement of depressive symptoms. The 5-HT1A agonist buspirone as well as 5-hydroxytryptophan, the immediate precursor of 5-HT, added to the SRI-pindolol regimen, were not effective in attenuating the intensity of OCD. Tryptophan, added to the SRI-pindolol regimen, produced a significant improvement after 4 weeks, with further amelioration after 6 weeks (36% decrease of the Yale-Brown Obsessive Compulsive Score), which was maintained with treatment prolongation.

Adrenergic beta-Antagonists↗
PubMed1996

Antidepressant-induced hypomania in obsessive-compulsive disorder.

Out of ten consecutive patients with DSM-III-R obsessive-compulsive disorder without any previous history of bipolarity, three patients showed antidepressant-induced hypomania (clomipramine, one patient; fluvoxamine, two patients) within the first 5 to 8 weeks of the drug treatment. These data support the previous results on a strong association between obsessive-compulsive disorder and bipolar affective illness.

Adolescent↗
PubMed1997

A 2-year study of sertraline in the treatment of obsessive-compulsive disorder.

The present study investigated the tolerability, safety profile, and anti-obsessional efficacy of sertraline, a selective serotonin reuptake inhibitor, during long-term treatment of patients with obsessive-compulsive disorder (OCD). Fifty-nine OCD patients who had completed a 1 year double-blind, fixed dose study comparing sertraline and placebo subsequently entered a 1-year open extension. Among the 51 patients who had been treated with sertraline during the double-blind phase, the mean total duration of sertraline treatment was 690 days. Only treatment responders who completed the 52-week double-blind treatment phase were permitted to enter the open extension. The higher rate (p < 0.02) of sertraline patients (51 out of 241) than of placebo patients (eight out of 84), who responded to treatment and entered the open-label phase is therefore consistent with the greater mean improvement observed in the sertraline group during double-blind treatment. Placebo responders differed from sertraline responders in that they were less impaired at baseline of the double-blind study [Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) of 18.5 versus 23.4] and they exhibited less improvement during double-blind treatment (-6.1 versus -11.4). In the open-label phase all patients received sertraline at a starting dose of 50 mg once a day, titrated in 50 mg increments to a maximum dose of 200 mg according to clinical response. At end-point the mean Y-BOCS score for all patients decreased by a further 3.6 points. Patients previously treated with placebo showed greater improvement after being switched to sertraline than those who received continued sertraline treatment. Patients who completed the study and received 2 full years of sertraline treatment (n = 38) exhibited a mean improvement of 15.6 points using the Y-BOCS. Sertraline was well tolerated during both the double-blind phase and the open extension, and the incidence of adverse experiences was generally reduced during the second year of treatment. Three patients discontinued open treatment because of adverse experiences. Long-term sertraline treatment did not appear to be associated with the emergence, increased incidence, or increased severity of adverse experiences or clinically significant abnormalities in laboratory tests, vital signs, or the electrocardiogram. The study supports the long-term safety and tolerability of sertraline over a 2-year treatment course and the sustained efficacy of sertraline in patients with OCD.

1-Naphthylamine↗
PubMed1999

Inositol augmentation of serotonin reuptake inhibitors in treatment-refractory obsessive-compulsive disorder: an open trial.

Inositol, an isomer of glucose and precursor in the phosphatidylinositol cycle, may be effective in a number of psychiatric disorders, including obsessive-compulsive disorder (OCD). There is little data, however, on inositol as an augmenting agent of serotonin reuptake inhibitors (SRIs) in treatment-refractory patients. Ten OCD patients who had failed to respond to current and previous trials of serotonin reuptake inhibitors participated in open-label trial of inositol (18 gm/day) [corrected] augmentation for 6 weeks. Symptoms were rated at 2-weekly intervals using the Yale-Brown Obsessive-Compulsive Scale, the Montgomery-Asberg Depression Rating Scale, and the Clinical Global Impressions (CGI) Scale. The majority of patients (n = 7) did not respond to treatment with inositol augmentation on the CGI improvement item. However, a small number of patients (n = 3) did report a clinically significant response on the CGI improvement item. OCD patients who fail to respond to a number of trials of SRIs may be a particularly treatment-refractory group of subjects. Unfortunately, inositol augmentation of a SRI did not lead to significant improvement in the majority of such cases. Nevertheless, further research on the mechanism of inositol efficacy in some patients with anxiety and mood disorders is warranted.

Adolescent↗
PubMed2001

Relapses after discontinuation of drug associated with increased resistance to treatment in obsessive-compulsive disorder.

The aim of the present study was to determine whether obsessive-compulsive disorder (OCD) patients whose symptoms recur after drug discontinuation respond again when the same drug at the same daily dosage is reinstituted. Eighty-one patients who were responders to a previous 6-month, open-label, noncomparative, acute treatment phase with fixed doses of selective reuptake inhibitors (SRIs) and who relapsed within 6 months of drug discontinuation had the drug to which they responded in the acute phase reinstated at the same daily dose. The reinstitution trial lasted 24 weeks with monthly evaluations (Yale-Brown Obsessive-Compulsive Scale and Clinical Global Improvement). Data obtained in the reinstitution phase were analysed using Pearson's chi-squared test or Fisher's exact test when appropriate. The cumulative percentages of patients who responded in the second trial were compared to those of patients who responded in the acute treatment phase (for each treatment and for all SRIs together) across all evaluation times. When considering all patients together, a lower percentage of responders resulted when SRIs were reinstated: the difference in the cumulative percentage of responders appeared at month 4 and increased at months 5 and 6 (Pearson chi-squared, P = 0.028, P = 0.009 and P < 0.001, respectively). When considering the patients separately according to the SRI used, no differences in the percentages of responders were found at any time. Our results indicate that patients whose symptoms recur after drug discontinuation respond again when the same drug used previously (at the same dosage used in the acute phase) is reinstated, but at a lower degree with respect to the acute treatment. Findings from our study, together with literature data indicating high relapse rates when discontinuing the treatment after the acute phase, support the idea of continuing the treatment in OCD over the long term.

Acute Disease↗