Psychometric Properties of the PANS 31-Item Symptom Rating Scale.

Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by sudden onset of obsessive-compulsive disorder and/or eating restriction with associated neuropsychiatric symptoms from at least two of seven categories. The PANS 31-Item Symptom Rating Scale (PANS Rating Scale) was developed to identify and measure the severity of PANS symptoms. The objective of this study was to define the psychometric properties of the PANS Rating Scale. Methods: Children with PANS (N = 135) and their parents participated. Parents completed the PANS Rating Scale and other scales on Research Electronic Data Capture. The PANS Rating Scale includes 31 items that are rated on a Likert scale from 0 = none to 4 = extreme. Pearson's correlations were run between the PANS Total score and scores on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Yale Global Tic Severity Scale (YGTSS), Modified Overt Aggression Scale (MOAS), Columbia Impairment Scale (CIS), PANS Global Impairment Score (GIS), and Children's Global Assessment Scale (CGAS). Results: Convergent validity was supported by significant correlations between the PANS Total and scores on the CY-BOCS, YGTSS, MOAS, CIS, GIS, and CGAS. The largest correlations were with measures of functional impairment: PANS Total and CIS (r = 0.81) and PANS Total and GIS (r = 0.74). Cronbach's alpha was 0.89 which demonstrates strong internal consistency of the 31 items. PANS Total score was significantly higher in children in a flare of their neuropsychiatric symptoms compared to children who were not in a flare. Conclusions: This study provides preliminary support for the PANS Rating Scale as a valid research instrument with good internal consistency. The PANS Rating Scale appears to be a useful measure for assessing children with PANS.

Brief youth self-report screener for tics: Can a subscale of the Motor tic, Obsession and compulsion, and Vocal tic Evaluation Survey (MOVES) identify tic disorders in youth?

Tics are unwanted, repetitive movements and sounds that frequently present during childhood. They are typically brief and purposeless, but can create significant distress for individuals, and often co-occur with other neuropsychiatric conditions. Thus, early identification of tics is warranted. Unfortunately, tics are often misdiagnosed, and because tics may wax and wane, identification can be difficult, especially in the context of routine clinical visits. There are limited tools that can be used to reliably identify tics in clinical practice, especially in non-specialty settings. The purpose of the current study was to evaluate the performance of the Motor tic, Obsession and compulsion, and Vocal tic Evaluation Survey (MOVES), a self-report scale with some support as a screening tool. In addition, the performance of a subset of questions (the MOVES-6) was evaluated for rapid screening. Participants were recruited across two study sites and included children and adolescents diagnosed with Tourette syndrome (n = 151) or another persistent tic disorder (n = 10) and community controls (n = 74). Results suggest both the MOVES and the MOVES-6 have high sensitivity (90% and 88%, respectively) and at least acceptable specificity (77% and 86%, respectively) compared with expert assessment of tic disorders, suggesting that both versions can identify tic disorders without high proportions of false negatives. Both versions were highly sensitive with acceptable specificity regardless of sex, race/ethnicity, and age. The MOVES and MOVES-6 show promise as a screener for tics or tic disorders, but additional research is needed, particularly in a general population setting.

Teacher Knowledge of Tourette Syndrome and Associated Factors.

BACKGROUND: Tourette syndrome (TS) is associated with learning disabilities and educational impairment. Teacher knowledge about TS may have a positive impact on students with TS, but factors associated with teacher knowledge of TS are not known. METHODS: In this cross-sectional study, teachers of youth with TS and of a community control group completed a Teacher Understanding of Tourette Syndrome Survey (TUTS), a pilot questionnaire enquiring about self-perceived understanding, teacher knowledge, and sources of information. We compared TUTS scores between TS and control groups and between those who did and did not use specific sources of information about TS using Wilcoxon rank-sum tests. Bivariate correlation analyses were used to evaluate associations between teacher knowledge and potential contributing factors. RESULTS: Data from 114 teachers of children with TS and 78 teachers of control subjects were included. Teachers of youth with TS had significantly more knowledge, had higher self-perceived understanding, and used more sources of information than teachers of the control group. Teachers who knew of the Tourette Association of America and who gathered information themselves had higher knowledge about TS than those who did not. CONCLUSION: Teachers of children with TS know more about TS and use more sources to learn about TS than teachers of children without TS.

Cognitive Beliefs Across the Symptom Dimensions of Pediatric Obsessive-Compulsive Disorder: Type of Symptom Matters.

The cognitive model of obsessive-compulsive disorder (OCD) posits that dysfunctional cognitive beliefs are crucial to the onset and maintenance of OCD; however, the relationship between these cognitive beliefs and the heterogeneity of OCD symptoms in children and adolescents remains unknown. We examined how the major belief domains of the cognitive model (inflated responsibility/threat estimation, perfectionism/intolerance of uncertainty, importance/control of thoughts) and dysfunctional metacognitions were related to OCD symptoms across the following dimensions: doubting/checking, obsessing, hoarding, washing, ordering, and neutralization. Self-report ratings from 137 treatment-seeking youth with OCD were analyzed. When cognitive beliefs and symptom dimensions were analyzed in tandem, inflated responsibility/threat estimation and dysfunctional metacognitions were uniquely related to doubting/checking, obsessing, and hoarding and perfectionism/intolerance of uncertainty to ordering. Cognitive beliefs explained a large proportion of variation in doubting/checking (61%) and obsessing (46%), but much less so in ordering (15%), hoarding (14%), neutralization (8%), and washing (3%). Similar relations between cognitive beliefs and symptom dimensions were present in children and adolescents. Cognitive beliefs appear to be relevant for pediatric OCD related to harm, responsibility, and checking, but they do not map clearly onto contamination and symmetry-related symptoms. Implications for OCD etiology and treatment are discussed.

Irritability in Children and Adolescents With OCD.

Irritability is a common, impairing transdiagnostic symptom in childhood psychopathology, though it has not been comprehensively studied in pediatric obsessive-compulsive disorder (OCD). Further, the central cognitive behavioral treatment component for OCD, exposure and response prevention therapy (ERP), has been recently proposed as a treatment for irritability. This study aimed to evaluate whether certain clinical characteristics are associated with irritability in pediatric OCD and whether irritability reduces following ERP. Participants were 161 youth (ages 7-17) with OCD and a caregiver participating in a randomized controlled trial of D-cycloserine or pill placebo augmented ERP. Participants completed validated assessments during treatment. Irritability was significantly and positively associated with depressive symptoms, defiance, functional impairment, and family accommodation, but was not associated with pretreatment OCD severity, symptom dimensions, obsessive beliefs. Irritability significantly declined following treatment, with over half of youth with any pretreatment irritability experiencing clinically significant change, though this change was not related to OCD improvement. Results suggest that irritability may be a marker of psychiatric comorbidity, parental accommodation, and impairment in youth with OCD. Implications for the exposure-based treatment of irritability are discussed.

Age moderated-anxiety mediation for multimodal treatment outcome among children with obsessive-compulsive disorder: An evaluation with correspondence analysis.

INTRODUCTION: Anxiety expression varies by age in youth, and evaluation of putative mechanisms in treatment must consider both conjointly. Accordingly, age would moderate the mediation effect of anxiety in a youth obsessive-compulsive disorder (OCD) treatment trial. METHODS: Fifty-six children ages 7 - 17 participated in an RCT comparing three treatments: CBT with standard dosing of sertraline, CBT with slow dosing of sertraline, and CBT with placebo. To examine the moderated-mediation effects for OCD symptom improvement, we discretized the continuous anxiety and OCD measures into three symptom outcome categories, "improved", "unchanged", and "deteriorated". To evaluate the moderating effect of age, we further examined the association of age and anxiety with the "improved" OCD category. For analysis, the age groups used as rows were cross tabulated with discretized anxiety and OCD measures. To estimate category associations with correlations, we adopted correspondence analysis. RESULTS: The correlational results indicate that for all treatment conditions, age was a moderator of the mediation effect of physical anxiety symptoms for the improved OCD measures (outcomes). Specifically, age suppressed correlations with OCD outcomes, with Physical Symptoms as a mediator for the outcome measures. This moderated mediation effect was most evident for ages 8-10 in the CBT with placebo group. LIMITATIONS: The moderated mediation effect manifest in this single RCT-based study should be validated in other studies. DISCUSSION: Future research investigating a wider range of ages as a potential moderator of other symptom and emotion mediators of outcome is warranted, particularly in relation to individual symptom profiles of OCD.

Defining tic severity and tic impairment in Tourette Disorder.

OBJECTIVE: Treatment guidelines for Tourette's Disorder (TD) are based on patients' degree of tic severity and impairment. However, clear benchmarks for determining tic severity and impairment have not been established. This study examined benchmarks of tic severity and tic impairment using the Yale Global Tic Severity Scale (YGTSS) and the Clinical Global Impression of Severity (CGI-S). METHOD: Individuals with TD or another Tic Disorder (N = 519) recruited across nine sites were administered a diagnostic interview, the YGTSS, and the CGI-S. Correlations and trend analyses contrasted YGTSS scores across CGI-S ratings. A logistic regression model examined predictive benchmarks for tic severity, tic impairment, and global severity. Model classifications were compared against CGI-S ratings, and agreement was examined using kappa. RESULTS: Spearman correlations between the CGI-S and YGTSS scores ranged from 0.54 to 0.63 (p < 0.001). Greater CGI-S ratings were associated with a linear stepwise increase in YGTSS Total Tic scores, Impairment scores, and Global Severity scores. Despite moderate-to-strong associations (ρ = 0.45-0.56, p < 0.001) between the CGI-S and predictive logistical regression models, only fair agreement was achieved when applying classification benchmarks (κ = 0.21-0.32, p < 0.001). CONCLUSIONS: CGI-S ratings are useful to characterize benchmarks for tic severity, tic impairment, and global severity on the YGTSS. Logistic regression model benchmarks had only fair agreement with the CGI-S and underscore the heterogeneity of TD symptoms. Collectively, findings offer guidance on the delineation of tic severity categorizations to apply evidence-based treatment recommendations.

Anxiety Symptoms Differ in Youth With and Without Tic Disorders.

We compared anxiety symptoms in youth with and without tic disorders by comparing scores on the Multidimensional Anxiety Scale for Children (MASC) in youth with tic disorders to those in a concurrent community control group and in a group of treatment-seeking anxious youth from the Child/Adolescent Anxiety Multimodal Study (CAMS). Data from 176 youth with tic disorders, 93 control subjects, and 488 CAMS participants were included. Compared to youth with tic disorders, controls had lower total MASC scores (p < 0.0001) and CAMS participants had similar total MASC scores (p = 0.13). Separation Anxiety (p = 0.0003) and Physical Symptom (p < 0.0001) subscale scores were higher in youth with tic disorders than in CAMS participants. We conclude that the anxiety symptom profile differs in youth with and without tic disorders, which may have important implications for targeting treatment of anxiety in youth with tic disorders.

Urge Intolerance and Impairment Among Youth with Tourette's and Chronic Tic Disorders.

Individuals with Tourette's Disorder and Persistent Tic Disorders (TD) often experience premonitory urges-aversive sensations that precede tics and are relieved by tic expression. Given its role in the neurobehavioral model of TD, understanding factors that influence premonitory urges and associated relief can advance understanding of urge phenomenology and optimize treatments for individuals with TD. This study examined whether the novel construct of urge intolerance-difficulty tolerating premonitory urges-predicted tic severity and tic-related disability. Participants included 75 youth with TD and their caregivers. Assessments characterized tic severity, premonitory urge, distress tolerance, internalizing symptoms, and tic-related disability. Structural equation modeling revealed that higher levels of urge intolerance predicted greater levels of tic-related disability. Furthermore, the relationship between urge intolerance and tic-related disability was more robust for youth with clinically-elevated levels of internalizing symptoms. While further investigation is needed, urge intolerance represents a promising treatment target to improve tic-related disability in youth with TD.

Temporal precedence of the change in obsessive-compulsive symptoms and change in depressive symptoms during exposure and response prevention for pediatric obsessive-compulsive disorders.

The current study examined the temporal precedence of change in obsessive-compulsive symptoms and change in depressive symptoms during the course of an Exposure and Response Prevention (ERP) for pediatric OCD. Participants included 142 children and adolescents (7-17 years; mean age = 12.39, SD = 2.92; 51.40% female; 60.40% Non-Hispanic White) with a primary or co-primary diagnosis of OCD who received ERP in a two-site randomized controlled trial on d-cycloserine augmentation of CBT for pediatric OCD. Participants completed clinician-administered assessments of OC symptoms (Children's Yale-Brown Obsessive Compulsive Scale) and depressive symptoms (Children's Depression Rating Scale-Revised) from baseline to post-treatment follow-up. Lagged mediational analyses did not yield evidence in support of a mediating role for the change in OC symptoms in the effect of ERP on the change in depressive symptoms. In contrast, change in depressive symptoms mediated the effect of ERP treatment on the subsequent change in OC symptoms (95% confidence interval for indirect effect = -0.04 to -0.001), though the effect size was small. Controlling for the prior levels of the depressive symptoms this indirect effect became non-significant. Theoretical and clinical implications of the findings for the youth with OCD and comorbid depression are discussed.

Tic Disorders are Associated With Lower Child and Parent Quality of Life and Worse Family Functioning.

OBJECTIVE: Chronic tic disorders occur in approximately 3% of children. Neuropsychiatric symptoms of attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, anxiety, and depression are common. We evaluated the impact of tic disorders and comorbid symptoms on individual and parent quality of life and family functioning. METHOD: In two cross-sectional studies children with tic disorders were enrolled at the University of Rochester or the University of South Florida; data were pooled for analyses. Control subjects were enrolled at the University of Rochester. We compared quality of life and function in youth and families with and without tic disorders. We evaluated the associations between comorbid symptoms and individual quality of life and family impact in youth with tic disorders using multiple regression analyses. RESULTS: We enrolled 205 youths with tic disorders and 100 control subjects. Psychosocial (P < 0.0001) and physical (P < 0.0001) quality of life were lower in individuals with tic disorders compared with controls. Severity of attention-deficit/hyperactivity disorder (P < 0.0001) and depression (P = 0.046) symptoms were associated with lower psychosocial quality of life in youth with tic disorders. Families of youths with tic disorders had worse parent quality of life (P < 0.001) and family functioning (P < 0.001) than control families. Severity of attention-deficit/hyperactivity disorder (P < 0.0001), obsessive-compulsive disorder (P = 0.0004), and depression (P = 0.01) symptoms were associated with predicted worse family impact. CONCLUSION: Youths with tic disorders had lower individual and parent quality of life and worse family functioning than controls. The impact of tic disorders on the family may have significant implications for approaches to providing comprehensive care to these families.

Symptom Trajectories of Early Responders and Remitters among Youth with OCD.

Objectives: This study examined the phenomenology and predictors of early response and remission among youth with obsessive-compulsive disorder (OCD) receiving cognitive-behavioral therapy (CBT). Methods: One hundred and thirty-nine youth with a current primary diagnosis of OCD participated in this study. Participants received 10 sessions of CBT augmented by either placebo or d-cycloserine (DCS) as part of a randomized double-blind multi-site clinical trial. Early response and remission status were determined by clinician-rated global symptom improvement (CGI-I) and severity (CGI-S), respectively. Results: At the mid-treatment assessment, 45.3% of youth were early responders, and 28.1% were early remitters. At post-treatment assessment, 79.1% of youth were responders and 67.6% were remitters. Early response predicted a higher likelihood of post-treatment response and remission; early remission significantly predicted a higher likelihood of post-treatment remission. Bivariate logistic regressions showed that early response was predicted by lower baseline clinician-rated global severity (CGI-S) and lower depression severity; however, only depression severity remained a significant predictor in the multivariable logistic regression model. Furthermore, bivariate logistic regressions showed that early remission was predicted by lower baseline clinician-rated global severity (CGI-S), lower depression severity, and lower obsessive-compulsive symptom severity (CY-BOCS); however, only global severity remained a significant predictor in the multivariable logistic regression model. Conclusions: Lower OCD and depression symptom severity predicted a greater likelihood of early treatment response and remission to CBT. Findings suggest that low OCD and depression symptom severity could serve as baseline characteristics to identify potential candidates for lower-intensity initial interventions in a stepped care approach. The modest predictive value of the variables examined suggests that additional factors could add to prediction of treatment response and remission.

The Centrality of Doubting and Checking in the Network Structure of Obsessive-Compulsive Symptom Dimensions in Youth.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a heterogeneous condition with well-established symptom dimensions across the lifespan. The objective of the present study was to use network analysis to investigate the internal structure of these dimensions in unselected schoolchildren and in children with OCD. METHOD: We estimated the network structure of OCD symptom dimensions in 6,991 schoolchildren and 704 children diagnosed with OCD from 18 sites across 6 countries. All participants completed the Obsessive-Compulsive Inventory-Child Version. RESULTS: In both the school-based and clinic-based samples, the OCD dimensions formed an interconnected network with doubting/checking emerging as a highly central node, that is, having strong connections to other symptom dimensions in the network. The centrality of the doubting/checking dimension was consistent across countries, sexes, age groups, clinical status, and tic disorder comorbidity. Network differences were observed for age and sex in the school-based but not the clinic-based samples. CONCLUSION: The centrality of doubting/checking in the network structure of childhood OCD adds to classic and recent conceptualizations of the disorder in which the important role of doubt in disorder severity and maintenance is highlighted. The present results suggest that doubting/checking is a potentially important target for further research into the etiology and treatment of childhood OCD.

Fear extinction learning as a predictor of response to cognitive behavioral therapy for pediatric obsessive compulsive disorder.

BACKGROUND: While cognitive behavior therapy (CBT) is an effective treatment for many children and adolescents with Obsessive Compulsive Disorder (OCD), therapeutic response is variable. Fear conditioning and extinction are central constructs underlying exposure-based CBT. Fear extinction learning assessed prior to CBT may be a useful predictor of CBT response for guiding treatment decisions. METHODS: Sixty-four youth who participated in a randomized placebo-controlled trial of CBT with and without d-cycloserine (DCS) completed a fear conditioning task. Skin conductance response (SCR) scores were used to measure fear acquisition and extinction to determine whether extinction learning could predict CBT response. RESULTS: CBT responders and non-responders appeared to acquire conditioned fear SCRs in a similar manner. However, differences between treatment responders and non-responders emerged during the extinction phase. A responder (responder, non-responder) by conditioned stimulus type (CS+, CS-) interaction showed that CBT responders differentiated the stimulus paired with (CS+) and without (CS-) the unconditioned stimulus correctly during early and late extinction, whereas the CBT non-responders did not (p = .004). CONCLUSIONS: While the small sample size makes conclusions tentative, this study supports an emerging literature that differential fear extinction may be an important factor underlying clinical correlates of pediatric OCD, including CBT response.

Sudden gains in cognitive behavioral therapy among children and adolescents with obsessive compulsive disorder.

BACKGROUND AND OBJECTIVES: This study examined the occurrence of sudden gains (or reversal of gains) among children with obsessive-compulsive disorder (OCD) during the course of cognitive-behavioral therapy (CBT), as well as the association of sudden gains with treatment response, treatment group, and pre-treatment clinical characteristics. METHODS: The sample consisted of 136 youth (ages 7-17) with a primary diagnosis of OCD who were randomized in a double-blinded fashion to 10 sessions of CBT with augmentation of either d-cycloserine or placebo. Sudden gain status was determined based on clinician-rated obsessive-compulsive symptom severity, which was collected on 9 occasions across the study period. RESULTS: 42.6% of youth experienced at least one sudden gain, which tended to occur either after starting exposure and response prevention or towards the end of treatment. After applying the Benjamini-Hochberg procedure for multiple comparisons, there were no significant pre-treatment predictors of sudden gains and only reduced insight predicted the reversal of gains. Individuals with at least one sudden gain had improved overall treatment outcomes, measured both by reduction in OCD symptom severity, and by global illness severity. LIMITATIONS: Several clinical constructs were not examined. Symptomatology was not assessed at every treatment session. Differences in those who achieved sudden gains and those who did not may be obscured. There is the possibility that a sudden gain reflected a scoring error generated by an optimistic or inaccurate report. Finally, a relatively homogenous sample may limit the generalizability of results. CONCLUSIONS: The course of CBT for pediatric OCD is variable with many children experiencing sudden gains, but a sizable percentage experience a reversal of gains which was related to reduced insight. Sudden gains tended to occur after starting exposure and response prevention and towards the end of treatment. TRIALSREGISTRATION: ClinicaltrialsgovRegistry:NCT00864123. https://www.clinicaltrials.gov/ct2/show/NCT00864123.

Defining Treatment Outcomes in Pediatric Obsessive-Compulsive Disorder Using a Self-Report Scale.

This study examined benchmarks of treatment response and clinical remission on the Obsessive Compulsive Inventory-Child Version (OCI-CV) for youth with obsessive-compulsive disorder (OCD). Participants were 91 youth who enrolled in a randomized controlled trial that examined the benefit of augmenting cognitive behavior therapy (CBT) with either d-cycloserine or placebo. Youth completed the OCI-CV at baseline, Week 4 (prior to initiating exposure therapy), and posttreatment. Receiver operator curve (ROC) analyses examined optimal benchmarks for treatment response and clinical remission as identified by independent evaluators at the posttreatment assessment using the Clinical Global Impression (CGI) scales of Improvement (CGI-Improvement), Severity (CGI-Severity), and Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Optimal benchmarks for treatment response were a 20%-25% reduction in the OCI-CV total score. Meanwhile, optimal benchmarks for remission were a 55%-65% reduction in the OCI-CV total score and a posttreatment total score ≤6-8. OCI-CV benchmarks exhibited moderate agreement with the CY-BOCS for treatment response and clinical remission. Meanwhile, fair agreement was observed for response and remission with CGI scales. A lower pretreatment OCI-CV total score was associated with less agreement between classification approaches. Findings provide benchmarks for classifying treatment response and clinical remission in an efficient manner. Given the moderate agreement between the CY-BOCS and OCI-CV benchmarks, the OCI-CV may serve as a useful alternative when clinician-rated scales cannot be administered due to limited resources (e.g., time, training). Thus, evidence-based measurement can be incorporated to monitor therapeutic response and remission in clinical practice.

Comorbid Psychopathology and the Clinical Profile of Family Accommodation in Pediatric OCD.

Family accommodation (FA) has been linked with myriad negative outcomes in pediatric obsessive-compulsive disorder (OCD), but extant literature has yielded differential relationships between FA and clinical variables of interest. Consequently, this study examined the phenomenology, clinical profile, and effects of comorbid psychopathology on FA to better understand these behaviors. A total of 150 youths and their caregivers completed clinician- and self-reported measures at a baseline visit for a larger randomized controlled trial. Sociodemographic variables were not associated with FA, but specific types of OCD symptom clusters were. Higher OC-symptom severity and functional impairment were associated with increased FA. Comorbid anxiety disorders moderated the relationship between OC-symptom severity and FA, but comorbid attention deficit hyperactivity, oppositional defiant, and mood disorders did not. Internalizing and externalizing problems both mediated the relationship between FA and functional impairment. These findings provide clinical implications for important treatment targets and factors that may impact FA.

Parents' Perceptions of Internalizing and Externalizing Features in Childhood OCD.

Although obsessive-compulsive disorder (OCD) has often been characterized as an internalizing disorder, some children with OCD exhibit externalizing behaviors that are specific to their OCD. This study sought to demonstrate that parents perceive both internalizing and externalizing behaviors in childhood OCD by examining the factor structure of the Child Obsessive-Compulsive Externalizing/Internalizing Scale (COCEIS), a parent-report questionnaire intended to measure these constructs. This study also investigated clinical correlates of internalizing and externalizing factors in the COCEIS. A factor analysis of questionnaire responses from 122 parents of youth with OCD revealed both externalizing and internalizing factors in the COCEIS. Externalizing behaviors in childhood OCD were associated with other, co-occurring externalizing behavior problems, while both factors were positively correlated with OCD severity and co-occurring internalizing symptoms. They were positively associated with each other at a trend level, and neither showed a significant relationship with insight. Sixty-two percent of parents endorsed "often" or "always" to at least one externalizing item, though modal responses to items suggested that each individual feature captured by the COCEIS may be relatively uncommon. Mean responses were significantly greater for internalizing items. This study provides evidence for distinct but related externalizing and internalizing behaviors specific to childhood OCD. Treatment for children with OCD presenting with more externalizing behaviors may require a greater emphasis on behavioral parent training and motivational enhancement.

Ecopipam, a D1 receptor antagonist, for treatment of tourette syndrome in children: A randomized, placebo-controlled crossover study.

BACKGROUND: Dopamine D2 receptor antagonists used to treat Tourette syndrome may have inadequate responses or intolerable side effects. We present results of a 4-week randomized, double-blind, placebo-controlled crossover study evaluating the safety, tolerability, and efficacy of the D1 receptor antagonist ecopipam in children and adolescents with Tourette syndrome. METHODS: Forty youth aged 7 to 17 years with Tourette syndrome and a Yale Global Tic Severity Scale - total tic score of ≥20 were enrolled and randomized to either ecopipam (50 mg/day for weight of <34 kg, 100 mg/day for weight of >34 kg) or placebo for 30 days, followed by a 2-week washout and then crossed to the alternative treatment for 30 days. Stimulants and tic-suppressing medications were excluded. The primary outcome measure was the total tic score. Secondary outcomes included obsessive compulsive and attention deficit/hyperactivity disorder scales. RESULTS: Relative to changes in placebo, reduction in total tic score was greater for ecopipam at 16 days (mean difference, -3.7; 95% CI, -6.5 to -0.9; P = 0.011) and 30 days (mean difference, -3.2; 95% CI, -6.1 to -0.3; P = 0.033). There were no weight gain, drug-induced dyskinesias, or changes in laboratory tests, electrocardiograms, vital signs, or comorbid symptoms. Dropout rate was 5% (2 of 40). Adverse events reported for both treatments were rated predominantly mild to moderate, with only 5 rated severe (2 for ecopipam and 3 for placebo). CONCLUSIONS: Ecopipam reduced tics and was well tolerated. This placebo-controlled study of ecopipam supports further clinical trials in children and adolescents with Tourette syndrome. © 2018 International Parkinson and Movement Disorder Society.

A multicenter examination and strategic revisions of the Yale Global Tic Severity Scale.

OBJECTIVE: To examine the internal consistency and distribution of the Yale Global Tic Severity Scale (YGTSS) scores to inform modification of the measure. METHODS: This cross-sectional study included 617 participants with a tic disorder (516 children and 101 adults), who completed an age-appropriate diagnostic interview and the YGTSS to evaluate tic symptom severity. The distributions of scores on YGTSS dimensions were evaluated for normality and skewness. For dimensions that were skewed across motor and phonic tics, a modified Delphi consensus process was used to revise selected anchor points. RESULTS: Children and adults had similar clinical characteristics, including tic symptom severity. All participants were examined together. Strong internal consistency was identified for the YGTSS Motor Tic score (α = 0.80), YGTSS Phonic Tic score (α = 0.87), and YGTSS Total Tic score (α = 0.82). The YGTSS Total Tic and Impairment scores exhibited relatively normal distributions. Several subscales and individual item scales departed from a normal distribution. Higher scores were more often used on the Motor Tic Number, Frequency, and Intensity dimensions and the Phonic Tic Frequency dimension. By contrast, lower scores were more often used on Motor Tic Complexity and Interference, and Phonic Tic Number, Intensity, Complexity, and Interference. CONCLUSIONS: The YGTSS exhibits good internal consistency across children and adults. The parallel findings across Motor and Phonic Frequency, Complexity, and Interference dimensions prompted minor revisions to the anchor point description to promote use of the full range of scores in each dimension. Specific minor revisions to the YGTSS Phonic Tic Symptom Checklist were also proposed.