The Food and Drug Administration currently requires the package inserts of most psychostimulant medications to list the presence of a tic disorder as a contraindication to their use. Approximately ...half of children with Tourette's syndrome experience comorbid attention-deficit/hyperactivity disorder (ADHD). We sought to determine the relative efficacy of different medications in treating ADHD and tic symptoms in children with both Tourette's syndrome and ADHD.
We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of medications in the treatment of ADHD in the children with comorbid tics. We used a random effects meta-analysis with standardized mean difference as our primary outcome to estimate the effect size of pharmaceutical agents in the treatment of ADHD symptoms and tics.
Our meta-analysis included nine studies involving 477 subjects. We assessed the efficacy of six medications-dextroamphetamine, methylphenidate, alpha-2 agonists (clonidine and guanfacine), desipramine, atomoxetine, and deprenyl. Methylphenidate, alpha-2 agonists, desipramine, and atomoxetine demonstrated efficacy in improving ADHD symptoms in children with comorbid tics. Alpha-2 agonists and atomoxetine significantly improved comorbid tic symptoms. Although there was evidence that supratherapeutic doses of dextroamphetamine worsens tics, there was no evidence that methylphenidate worsened tic severity in the short term.
Methylphenidate seems to offer the greatest and most immediate improvement of ADHD symptoms and does not seem to worsen tic symptoms. Alpha-2 agonists offer the best combined improvement in both tic and ADHD symptoms. Atomoxetine and desipramine offer additional evidence-based treatments of ADHD in children with comorbid tics. Supratherapeutic doses of dextroamphetamine should be avoided.
Objective:
OCD is a clinically heterogeneous condition. This heterogeneity has the potential to reduce power in genetic, neuroimaging, and clinical trials. Despite a mounting number of studies, there ...remains debate regarding the exact factor structure of OCD symptoms. The authors conducted a meta-analysis to determine the factor structure of the Yale-Brown Obsessive Compulsive Scale Symptom Checklist.
Method:
Studies were included if they involved subjects with OCD and included an exploratory factor analysis of the 13 Yale-Brown Obsessive Compulsive Scale Symptom Checklist categories or the items therein. A varimax-rotation was conducted in SAS 9.1 using the PROC FACTOR CORR to extract factors from sample-size weighted co-occurrence matrices. Stratified meta-analysis was conducted to determine the factor structure of OCD in studies involving children and adults separately.
Results:
Twenty-one studies involving 5,124 participants were included. The four factors generated were 1) symmetry: symmetry obsessions and repeating, ordering, and counting compulsions; 2) forbidden thoughts: aggression, sexual, religious, and somatic obsessions and checking compulsions, 3) cleaning: cleaning and contamination, and 4) hoarding: hoarding obsessions and compulsions. Factor analysis of studies including adults yielded an identical factor structure compared to the overall meta-analysis. Factor analysis of child-only studies differed in that checking loaded highest on the symmetry factor and somatic obsessions, on the cleaning factor.
Conclusions:
A four-factor structure explained a large proportion of the heterogeneity in the clinical symptoms of OCD. Further item-level factor analyses are needed to determine the appropriate placement of miscellaneous somatic and checking OCD symptoms.
Background
Obsessive‐compulsive disorder (OCD) is a chronic condition that often produces lifelong morbidity, but few studies have examined long‐term outcome (greater than 5 years) in adult patients. ...Available studies suggest that 32–74% of adult OCD patients will experience clinical improvement over the long term. However, these studies were conducted before validated OCD rating scales were established and the development of evidence‐based treatments for OCD.
Methods
We investigated the 10–20 year outcome of 83 of 165 eligible subjects previously enrolled after participation in placebo‐controlled trials of serotonin reuptake inhibitor (SRI) medications for OCD. We examined the association between clinical characteristics at initial assessment and OCD symptom severity at follow‐up. We hypothesized that primary OCD symptom dimension and initial response to pharmacotherapy with serotonin reuptake inhibitors would be associated with later symptom severity.
Results
Only 20% (17 of 83) of subjects had experienced a remission of their OCD symptoms at follow‐up (Y‐BOCS ≤ 8). Forty‐nine percent (41 of 83) of subjects were still experiencing clinically significant OCD symptoms. Response to initial SRI pharmacotherapy was significantly associated with long‐term outcome: 31% (13 of 42) of subjects who responded (CGI < 3) to initial SRI pharmacotherapy were remitted at follow‐up, compared to 12% (3 of 25) of partial responders and none of the 16 subjects who had no response to initial SRI pharmacotherapy. We did not find a significant association between long‐term clinical outcome and any of the OCD symptom dimensions.
Conclusion
Despite the introduction and dissemination of several evidence‐based treatments for OCD, most adult OCD patients do not achieve remission. Initial response to pharmacotherapy was strongly associated with long‐term outcome.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Autism spectrum disorders (ASDs) are a phenotypically and etiologically heterogeneous set of disorders that include obsessive–compulsive behaviors (OCB) that partially overlap with symptoms ...associated with obsessive–compulsive disorder (OCD). The OCB seen in ASD vary depending on the individual's mental and chronological age as well as the etiology of their ASD. Although progress has been made in the measurement of the OCB associated with ASD, more work is needed including the potential identification of heritable endophenotypes. Likewise, important progress toward the understanding of genetic influences in ASD has been made by greater refinement of relevant phenotypes using a broad range of study designs, including twin and family‐genetic studies, parametric and nonparametric linkage analyses, as well as candidate gene studies and the study of rare genetic variants. These genetic analyses could lead to the refinement of the OCB phenotypes as larger samples are studied and specific associations are replicated. Like ASD, OCB are likely to prove to be multidimensional and polygenic. Some of the vulnerability genes may prove to be generalist genes influencing the phenotypic expression of both ASD and OCD while others will be specific to subcomponents of the ASD phenotype. In order to discover molecular and genetic mechanisms, collaborative approaches need to generate shared samples, resources, novel genomic technologies, as well as more refined phenotypes and innovative statistical approaches. There is a growing need to identify the range of molecular pathways involved in OCB related to ASD in order to develop novel treatment interventions.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective: Neuropsychological functioning in children with Tourette syndrome (TS) has been characterized by subtle deficits in response inhibition, visual-motor integration, and fine-motor ...coordination. The association of these deficits with the tics of the TS versus co-occurring attention-deficit/hyperactivity disorder (ADHD) has not been well understood because of small sample sizes and lack of adequate control conditions. We examined neuropsychological functioning in relatively large and well-characterized samples of children categorized as TS, TS-plus-ADHD, ADHD, and unaffected controls. Method: A total of 56 children with TS-only, 45 with TS-plus-ADHD, 64 with ADHD, and 71 healthy community control subjects were assessed on a battery of neuropsychological measures including the Connors' Continuous Performance Test (CPT), the Stroop Color-Word Interference Test (Stroop), the Beery Visual-Motor Integration Test (VMI), and the Purdue Pegboard Test. Results: There were no differences between children with TS-only and unaffected controls on the measures of response inhibition and visual-motor integration. Boys with TS-only but not girls with TS-only were impaired in the dominant hand Purdue performance. Children with ADHD were impaired on all study measures. Children with TS-plus-ADHD revealed no deficits on the Stroop, VMI, and Purdue tests but were impaired on the sustained attention portion of the CPT. Conclusions: These results indicate that co-occurring ADHD may be responsible for the neuropsychological deficits, or at least those assessed in the present study, in children with TS. Explanations in terms of neurobiological mechanisms of co-occurring TS and ADHD, as well as possible compensatory mechanisms in children with TS, are discussed. (Contains 3 tables.)
Background: Half of pediatric‐onset OCD cases remit by adulthood. Studies have demonstrated that initial response to pharmacotherapy, age of onset, prominent hoarding symptoms, and the presence of ...comorbid tic disorders are associated with long‐term outcome. Our goal was to examine the association between childhood performance on neuropsychological testing and persistence of OCD into adulthood.
Methods: Twenty‐four children with OCD were followed for an average of 7.5 years into early adulthood. Neuropsychological performance in childhood (<16 years) was measured. The battery included the Wechsler Intelligence Scale for Children (WISC‐III), the Purdue pegboard test, the Rey–Osterreith Complex Figure Task (RCFT) and the Beery–Buktenica test of Visual Motor Integration (VMI). We hypothesized that deficits in fine‐motor skills, visuospatial skills, and nonverbal memory as well as overall intelligence would be associated with adulthood outcome. We used a Cox proportional hazard model of survival analysis in which time to remission of OCD symptoms was the main outcome variable.
Results: Poor childhood performance on the Purdue pegboard task and the block design subscale of WISC‐III was associated with persistence of OCD symptoms into adulthood. IQ, VMI, and nonverbal memory performance did not predict significantly the persistence of OCD.
Conclusions: These results suggest that visuospatial and fine‐motor skill deficits are predictive of poor long‐term outcome in pediatric‐onset OCD. Future longitudinal studies are needed to chart the course of these deficits relative to the course of symptoms in OCD and to determine whether the association of these neuropsychiatric deficits with long‐term outcome is specific to pediatric‐onset OCD or generalizes to other psychiatric disorders.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Gilles de la Tourette syndrome (GTS) is a childhood onset neuropsychiatric disorder characterized by the presence of motor and vocal tics. The clinical spectrum of GTS is heterogeneous and varies ...from mild cases that do not require any medical attention to cases that are refractory to standard treatments. One of the unresolved issues is the definition of what constitutes treatment-refractory GTS. While for some other neuropsychiatric disorders, such as obsessive-compulsive disorder (OCD), a clear definition has been established, there is still no consensus with regard to GTS. One important issue is that many individuals with GTS also meet criteria for one or more other neurodevelopmental and neuropsychiatric disorders. In many individuals, the severity of these comorbid conditions contributes to the degree to which GTS is treatment refractory. The scope of this paper is to present the current state-of-the-art regarding refractory GTS and indicate possible approaches to define it. In closing, we discuss promising approaches to the treatment of individuals with refractory GTS.
Abstract Background Obsessive–compulsive disorder (OCD) is clinically heterogeneous. Previous studies have reported different patterns of treatment response to serotonin reuptake inhibitors (SRI) ...based on symptom dimension. Our objective was to replicate these results in OCD patients who participated in one of four randomized, placebo-controlled, clinical trials (RCT). Methods A total of 165 adult OCD subjects participated in one or more eight-week RCT with clomipramine, fluvoxamine, or fluoxetine. All subjects were classified as having major or minor symptoms in four specific OC symptom dimensions that were derived in a previous factor analytic study involving many of these same patients. Ordinal logistic regression was used to test the association between OC symptom dimensions and SRI response. Results We found a significant association between the symptom dimension involving sexual, religious and harm-related obsessions as well as checking compulsions (AGG/SR) and improved SRI response. This increased rate of SRI response was experienced primarily by individuals with harm-related obsessions. Over 60% of patients with AGG/SR OCD symptoms were rated as very much improved after SRI treatment. Limitations As some of the RCTs included were conducted prior to the development of the Yale–Brown Obsessive–Compulsive Scale (Y–BOCS), improvement in OCD severity was assessed using the Clinical Global Improvement (CGI) Scale. Data from the double-blind and open-label continuation phases of these trials was collapsed together to increase statistical power. Conclusions Patients with OCD vary in their response to SRIs. The presence of AGG/SR symptoms is associated with an initial positive response to SRIs. These data add to the growing body of work linking central serotonin systems with aggressive behavior.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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