Comorbid Tic Disorder Research Articles

Complex phenotype of Tourette syndrome in a ten-year-old boy (a clinical case)

Aim. The aim of the work is to draw attention to the symptoms associated with Tourette syndrome and to examine the association with comorbid diseases. Materials and methods. A review of the scientific literature on Tourette syndrome (TS) was conducted using the following Keywords “tics”, “Tourette syndrome”, “Tourette obsessive-compulsive disorder, TOCD”, “obsessive-compulsive disorder, OCD”, “attention deficit hyperactivity disorder, ADHD” using PubMed, MEDLINE, EMBASE as search engines. Taking into account studies conducted in the last 10 years, the abstracts of 275 articles were analyzed. Articles were selected for the study based on the criterion of their close relevance to the topic. The study results covered in 49 articles were examined in more detail. A description of a TOCD clinical case was prepared from primary medical documentation with parental informed consent. Results. The prevalence of TS is quite variable, depends on epidemiological research methods and ranges from 0.3 % to 1.0 % worldwide. Given the methodological limitations of most studies, the actual prevalence may be 10 times higher. TS is a progressive disease and is characterized by regular stages. Tourette syndrome-plus is distinguished, including autoaggressive actions besides the basic symptoms of OCD and ADHD. The etiology of TS is still being studied. In particular, the impact of environmental factors is considered: infection or inflammation, perinatal complications and chronic psychosocial stress in childhood. In 70–80 % of cases, TS is a hereditary disorder, making it one of the most heritable childhood-onset neuropsychiatric diseases. Various approaches have been applied to assess the genetic architecture of TS, including candidate gene studies, segregation analysis, linkage analysis, cytogenetics, copy number variants (CNV), rare variation studies, genome-wide association studies (GWAS), and whole exome sequencing (WES). Currently, there is no specific laboratory or genetic test for TS diagnosis. Pharmacological treatments are available but often ineffective; behavioral and surgical treatments are under development. The clinical case of TS in a 10-year-old boy is described with an onset at the age of 7 years following frequent infections, manifested as cephalocaudal motor tics and several vocal tics (coprolalia, echolalia) with a progression to obsessive-compulsive behavior (mysophobia, compulsive skin picking, self-hitting, self-biting, repetitive compulsions). The presented clinical case is of great interest from the viewpoint of somewhat belated diagnosis of TOCD syndrome, as well as indicates the need to continue the search for effective methods of diagnosis and treatment. Conclusions. The case of comorbid OCD and tic disorder is a unique endophenotype combining externalized disinhibited TS movements in parallel with internalized distress reminiscent of OCD. Clinicians should consider these features when choosing treatment methods.

Stress Level of Parents of Children Diagnosed with Attention-deficit/ Hyperactivity Disorder (ADHD) in Dubai, United Arab Emirates

Background: Attention-deficit/ hyperactivity disorder (ADHD) is a neurodevelopmental disorder that starts during childhood. It is commonly associated with elevated levels of parenting stress. This study aimed to examine parents’ stress levels, potential contributing factors, as well as changes associated with the COVID-19 pandemic. Methods: This study was based on a cross-sectional design. The target population was parents of children with ADHD aged 6-18 years who were evaluated in a tertiary care hospital in Dubai, United Arab Emirates (UAE) from January 2018 to August 2021. Participants completed a survey, which gathered information on the child’s personal characteristics and medical history as well as the parents’ and family characteristics. Additionally, the parents stress level was evaluated using the English and Arabic-translated versions of the Perceived Stress Scale (PSS). Results: Parents of 103 children diagnosed with ADHD participated in this study. Most children were males (74.8%), and their mean age was 10.0 ± 3.4 years. Most children had ADHD as a primary diagnosis (87.4%), with ADHD subtypes being mainly combined presentation (60.2%), followed by a predominately inattentive presentation (35.9%). Psychiatric morbidity was present in 87.4% of the children, mainly learning disorders (41.7%), conduct disorder (34%), or autism spectrum disorder (24.3%). On the other hand, physical disorders were present in 68.9% of the children. Parents’ perceived stress levels differed significantly according to their children’s ADHD subtypes (p=0.002), with the highest stress levels among parents of children with predominately hyperactive/impulsive ADHD. PSS scores were moderate in 62.1% of the sample and high in 32% of the sample. Significant associations with elevated PSS scores was found in the presence of comorbid tic disorders (p<0.001) as well as in comorbid autism spectrum disorder (p=0.029). The most frequently reported items on the PSS were: being upset because of something that happened unexpectedly; feeling nervous and stressed; being angered because of things that were outside of your control; feeling unable to control important things in life; and feeling that difficulties were piling up so high that could not be overcome. Various changes were reported during the COVID-19 pandemic, which included a significant decrease in social activities (31.1%), time spent with friends (26.2%), conflicts between the child and siblings (18.5%), and conflicts between parents (25.3%). Furthermore, a significant increase was reported in children’s average screen time (28.2%), the quality of the child’s relationship with parents (19.4%), and the overall stresses faced by the family (16.5%). Conclusion: ADHD is commonly associated with high levels of parental stress. Factors associated with an increased level of stress include ADHD predominantly hyperactive/ impulsive subtype as well as comorbidity with tic disorders or autism spectrum disorder. Furthermore, the COVID-19 pandemic had a marked impact on children with ADHD and their families’ social functioning.

Clinical characteristics of comorbid tic disorders in autism spectrum disorder: exploratory analysis

BackgroundThe frequency, clinical characteristics, and associated symptoms of comorbid tic disorders in individuals with autism spectrum disorder (ASD) remain unclear.MethodsWe included subsets of individuals from a larger genetic study who were diagnosed with ASD (n = 679; age: 4–18 years) and completed the Yale Global Tic Severity Scale (YGTSS) questionnaire. Based on the YGTSS score, the individuals were divided into two groups: ASD only (n = 554) and ASD with tics (n = 125). Individuals were assessed using the verbal and non-verbal intelligence quotient (IQ), Vineland Adaptive Behavior Scale (VABS-2), Social Responsiveness Scale-2 (SRS-2), Child Behavior Checklists (CBCL), and Yale-Brown Obsessive–Compulsive Scale (YBOCS), followed by between-group comparisons. All statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) version 26.ResultsTic symptoms were observed in 125 (18.4%) participants; among them, most participants presented both motor and vocal tics (n = 40, 40.0%). The ASD with tics group had a significantly higher average age and full-scale IQ score than the ASD only group. After adjusting for age, the ASD with tics group had significantly higher scores in the SRS-2, CBCL, and YBOCS subdomains than the ASD only group. Furthermore, all variables except the non-verbal IQ and VABS-2 scores were positively correlated with the YGTSS total score. Finally, the proportion of tic symptoms was significantly higher among individuals with a higher IQ score (≥ 70).ConclusionsThe IQ score was positively correlated with the proportion of tic symptoms among individuals with ASD. Moreover, the severity of the core and comorbid symptoms of ASD was associated with the occurrence and severity of tic disorders. Our findings suggest the need for appropriate clinical interventions for individuals with ASD.Trial registration This study retrospectively registered participants

Cerebellar Transcranial Direct Current Stimulation in Children with Autism Spectrum Disorder: A Pilot Study on Efficacy, Feasibility, Safety, and Unexpected Outcomes in Tic Disorder and Epilepsy.

Patients with autism spectrum disorder (ASD) display distinctive neurophysiological characteristics associated with significant cognitive, emotional, and behavioral symptoms. Transcranial direct current stimulation (tDCS) applied to the frontal or temporoparietal lobes has demonstrated potential to reduce the severity of ASD-related symptoms. Recently, the cerebellum has been identified as a brain area involved in ASD pathophysiology. In this open-label pilot study, seven ASD patients aged between 9 and 13 years underwent 20 daily sessions of 20 min cathodal stimulation of the right cerebellar lobe. At the end of the treatment, the Aberrant Behavior Checklist (ABC) scores showed a 25% mean reduction in global severity of symptoms, with a more pronounced reduction in the “social withdrawal and lethargy” (−35%), “hyperactivity and noncompliance” (−26%), and “irritability, agitation, and crying” (−25%) subscales. Minor and no improvement were observed in the “stereotypic behavior” (−18%) and “inappropriate speech” (−0%) subscales, respectively. Improvements were not detected in the two patients who were taking psychotropic drugs during the study. Clinical response showed a symptom-specific time course. Quality of sleep and mood improved earlier than hyperactivity and social withdrawal. The treatment was generally accepted by patients and well tolerated. No serious adverse events were reported. Stimulation also appeared to markedly reduce the severity of tics in a patient with comorbid tic disorder and led to the disappearance of a frontal epileptogenic focus in another patient with a history of seizures. In conclusion, cerebellar tDCS is safe, feasible, and potentially effective in the treatment of ASD symptoms among children. Strategies to improve recruitment and retention are discussed.

A question of information mismatch in the SPC and PIL on the effect of ADHD stimulant medications on tourette's syndrome

AimsTo assess the quality of information provided by pharmaceutical companies to patients and doctors regarding the impact of stimulant medications indicated for the treatment of Attention Deficit Hyperactive Disorder (ADHD) on Tourette's syndrome(TS) and tics in children and its implication on treatment.BackgroundIt is estimated that between 35% to 90% of TS patients also have ADHD. However, there remains a pervasive belief that the use of stimulants to treat ADHD symptoms in children with comorbid tic disorders is contraindicated because of concerns about possible tic exacerbation. Recent studies has disproved this, which is reflected in United Kingdom(UK) and European ADHD and TS guidelines. Pharmaceutical companies are legally required to provide a Summary of Product Characteristic (SPC) and Patient Information Leaflet (PIL) for each medicine as it is an integral part of the marketing authorisation approval. The SPC contains vital information for the usage and prescription of a drug for use by healthcare professionals. The PIL included in the medication packaging is a patient-friendly version of the SPC.MethodThe available stimulant medications licenced for use in paediatric patients with ADHD in the UK were identified through the Medicines & Healthcare products regulatory Agency (MHRA) website. The SPC and PIL were then accessed from the Electronic Medicines Compendium (EMC) website. Those not on the site were obtained directly from the marketing authorisation holder. Any direct mention of tics or Tourette's in the contraindication, warning and caution, or side effect section were documented. The information was then tabulated and compared.ResultOf the three stimulant drug types, 17 variations are currently available for use in the UK. There were inconsistencies found between the SPC and PIC in reference to the impact of these drugs on tics and TS in all 17 licensed medication. Most discrepancy was found in regard to TS as a side effect (16/17) and also tics (15/17). TS is also listed as a contraindication in the SPC and PIL for all available variety of Dexamphetamine class drugs. This is inconsistent with current clinical evidence and guidelines.ConclusionThe disparities in information regarding the impact of stimulant medications on tics and TS can have wide ranging effects. Outcomes could include poor patient adherence, or prevention of initiation of potentially beneficial treatment. It would benefit to standardize the information between these two documents to minimize inconsistencies in understanding between doctor and patient.

What is the effect of pharmacological treatment for attention-deficit/hyperactivity disorder in children with comorbid tic disorders? A Cochrane Review summary with commentary.

Objective: The Covid-19 related pandemic has negatively impacted NHS service provision We investigated its effect on specialist paediatric neuro-rehabilitation services in England and Wales Methods: A questionnaire was sent to UK National Neuro-rehabilitation network members by survey monkey app Questions explored: (1) centre details;(2) Covid-19 impact;(3) mitigation strategies;(4) recovery planning Results: 19 centres responded, including 17 Regional Neuroscience Centres;one stand-alone neurorehabilitation unit;one community-based specialist unit 18 reported Covid-19 had had a significant impact on service provision Six reported the impact was wholly negative;9 mainly negative, with some positive aspects;3 mainly positive, with some negative aspects;one was unsure 16 reported having fewer neurorehabilitation beds than pre-Covid-19;in 2, >80% were closed;2, 61-80%;3, 41-60%;7, 21-40% and 2, <20% Six indicated they were unable to accept internal or external referrals;3 only in exceptional circumstances 7 centres offer full rehabilitation to existing inpatients;11 only restricted rehabilitation 14 had discharged inpatients early;8 provided outpatient therapy post-discharge, 6 could not Two-thirds of centres transferred patients out at the start of the crisis, 9 to another neurorehabilitation unit and 3 to district hospitals Outpatient services were closed in 5 centres;operating fully (2);on a limited basis (8);on an increased basis due to reduced inpatient work (2) No community teams were offering normal services 9 centres were concerned about service restoration in the short term;12 in the medium term;10 in the long term Only 5 reported having a neurorehabilitation recovery plan Conclusion: Results highlight importance of developing robust neurorehabilitation service recovery plans to prevent children with acquired disability being further disadvantaged

What are the benefits and harms of pharmacological treatments for children with comorbid tic disorders?

What are the benefits and harms of pharmacological treatments for children with comorbid tic disorders?

A population-based family clustering study of tic-related obsessive-compulsive disorder

In the latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), obsessive-compulsive disorder (OCD) included a new “tic-related” specifier. However, strong evidence supporting tic-related OCD as a distinct subtype of OCD is lacking. This study investigated whether, at the population level, tic-related OCD has a stronger familial load than non-tic-related OCD. From a cohort of individuals born in Sweden between 1967 and 2007 (n = 4,085,367; 1257 with tic-related OCD and 20,975 with non-tic-related OCD), we identified all twins, full siblings, maternal and paternal half siblings, and cousins. Sex- and birth year-adjusted hazard ratios (aHR) were calculated to estimate the risk of OCD in relatives of individuals with OCD with and without comorbid tics, compared with relatives of unaffected individuals. We found that OCD is a familial disorder, regardless of comorbid tic disorder status. However, the risk of OCD in relatives of individuals with tic-related OCD was considerably greater than the risk of OCD in relatives of individuals with non-tic-related OCD (e.g., risk for full siblings: aHR = 10.63 [95% CI, 7.92–14.27] and aHR = 4.52 [95% CI, 4.06–5.02], respectively; p value for the difference < 0.0001). These differences remained when the groups were matched by age at first OCD diagnosis and after various sensitivity analyses. The observed familial patterns of OCD in relation to tics were not seen in relation to other neuropsychiatric comorbidities. Tic-related OCD is a particularly familial subtype of OCD. The results have important implications for ongoing gene-searching efforts.

Hoarding in children and adolescents with obsessive-compulsive disorder: prevalence, clinical correlates, and cognitive behavioral therapy outcome.

Hoarding, common in pediatric obsessive-compulsive disorder (OCD), has specific clinical correlates and is associated with poor prognosis. However, there are few studies of hoarding in pediatric OCD. This study estimates the occurrence of hoarding symptoms in a sample of children and adolescents with OCD, investigating possible differences in demographic and clinical variables between pediatric OCD with and without hoarding symptoms. Furthermore, the study investigates whether hoarding symptoms predict poorer treatment outcomes after cognitive behavioral therapy (CBT). The study sample comprised 269 children and adolescents with OCD, aged 7-17years, from Denmark, Sweden, and Norway, who were all included in the Nordic long-term obsessive-compulsive disorder Treatment Study. All had an OCD diagnosis according to the DSM-IV and were treated with 14 weekly sessions of manualized, exposure-based CBT. Hoarding symptoms and OCD severity were assessed with the Children's Yale-Brown Obsessive-Compulsive Scale and group differences in treatment outcome were analyzed using linear mixed-effect modelling. Seventy-two patients (26.8%) had one or more symptoms of hoarding. Comorbid tic disorders (p = 0.005) and indecision (p = 0.024) were more prevalent among those with hoarding symptoms than those without hoarding symptoms. In addition, youth with hoarding symptoms had a different OCD symptom profile. Having symptoms of hoarding did not affect CBT outcome (p = 0.933). Results from the study suggest that CBT is equally effective for those with and without hoarding-related OCD.

주의력결핍과잉행동장애에 동반된 틱장애의 신경생물학과 약물치료

주의력결핍과잉행동장애에 동반된 틱장애의 신경생물학과 약물치료

Pharmacological treatment for attention deficit hyperactivity disorder (ADHD) in children with comorbid tic disorders.

This is an update of the original Cochrane Review published in Issue 4, 2011.Attention deficit hyperactivity disorder (ADHD) is the most prevalent of the comorbid psychiatric disorders that complicate tic disorders. Medications commonly used to treat ADHD symptoms include stimulants such as methylphenidate and amphetamine; non-stimulants, such as atomoxetine; tricyclic antidepressants; and alpha agonists. Alpha agonists are also used as a treatment for tics. Due to the impact of ADHD symptoms on the child with tic disorder, treatment of ADHD is often of greater priority than the medical management of tics.However, for many decades, clinicians have been reluctant to use stimulants to treat children with ADHD and tics for fear of worsening their tics. OBJECTIVES: To assess the effects of pharmacological treatments for ADHD in children with comorbid tic disorders on symptoms of ADHD and tics. In September 2017, we searched CENTRAL, MEDLINE, Embase, and 12 other databases. We also searched two trial registers and contacted experts in the field for any ongoing or unpublished studies. We included randomized, double-blind, controlled trials of any pharmacological treatment for ADHD used specifically in children with comorbid tic disorders. We included both parallel-group and cross-over study designs. We used standard methodological procedures of Cochrane, in that two review authors independently selected studies, extracted data using standardized forms, assessed risk of bias, and graded the overall quality of the evidence by using the GRADE approach. We included eight randomized controlled trials (four of which were cross-over trials) with 510 participants (443 boys, 67 girls) in this review. Participants in these studies were children with both ADHD and a chronic tic disorder. All studies took place in the USA and ranged from three to 22 weeks in duration. Five of the eight studies were funded by charitable organizations or government agencies, or both. One study was funded by the drug manufacturer. The other two studies did not specify the source of funding. Risk of bias of included studies was low for blinding; low or unclear for random sequence generation, allocation concealment, and attrition bias; and low or high for selective outcome reporting. We were unable to combine any of the studies in a meta-analysis due to important clinical heterogeneity and unit-of-analysis issues.Several of the trials assessed multiple agents. Medications assessed included methylphenidate, clonidine, desipramine, dextroamphetamine, guanfacine, atomoxetine, and deprenyl. There was low-quality evidence for methylphenidate, atomoxetine, and clonidine, and very low-quality evidence for desipramine, dextroamphetamine, guanfacine and deprenyl in the treatment of ADHD in children with tics. All studies, with the exception of a study using deprenyl, reported improvement in symptoms of ADHD. Tic symptoms also improved in children treated with guanfacine, desipramine, methylphenidate, clonidine, and a combination of methylphenidate and clonidine. In one study, tics limited further dosage increases of methylphenidate. High-dose dextroamphetamine appeared to worsen tics in one study, although the length of this study was limited to three weeks. There was appetite suppression or weight loss in association with methylphenidate, dextroamphetamine, atomoxetine, and desipramine. There was insomnia associated with methylphenidate and dextroamphetamine, and sedation associated with clonidine. Following an updated search of potentially relevant studies, we found no new studies that matched our inclusion criteria and thus our conclusions have not changed.Methylphenidate, clonidine, guanfacine, desipramine, and atomoxetine appear to reduce ADHD symptoms in children with tics though the quality of the available evidence was low to very low.Although stimulants have not been shown to worsen tics in most people with tic disorders, they may, nonetheless, exacerbate tics in individual cases.In these instances, treatment with alpha agonists or atomoxetine may be an alternative. Although there is evidence that desipramine may improve tics and ADHD in children, safety concerns will likely continue to limit its use in this population.

Review of the evidence for the management of co-morbid Tic disorders in children and adolescents with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children and adolescents, with prevalence ranging between 5% and 12% in the developed countries. Tic disorders (TD) are common co-morbidities in paediatric ADHD patients with or without pharmacotherapy treatment. There has been conflicting evidence of the role of psychostimulants in either precipitating or exacerbating TDs in ADHD patients. We carried out a literature review relating to the management of TDs in children and adolescents with ADHD through a comprehensive search of MEDLINE, EMBASE, CINAHL and Cochrane databases. No quantitative synthesis (meta-analysis) was deemed appropriate. Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and normal doses of psychostimulant use. Supratherapeutic doses of dextroamphetamine have been shown to exacerbate TD. Most tics are mild or moderate and respond to psychoeducation and behavioural management. Level A evidence support the use of alpha adrenergic agonists, including Clonidine and Guanfacine, reuptake noradrenenaline inhibitors (Atomoxetine) and stimulants (Methylphenidate and Dexamphetamines) for the treatment of Tics and comorbid ADHD. Priority should be given to the management of co-morbid Tourette’s syndrome (TS) or severely disabling tics in children and adolescents with ADHD. Severe TDs may require antipsychotic treatment. Antipsychotics, especially Aripiprazole, are safe and effective treatment for TS or severe Tics, but they only moderately control the co-occurring ADHD symptomatology. Short vignettes of different common clinical scenarios are presented to help clinicians determine the most appropriate treatment to consider in each patient presenting with ADHD and co-morbid TDs.

Approaches to the Diagnosis and Treatment of OCD with Comorbid Tic Disorders

Bidirectional overlap has long been described between obsessive–compulsive disorder (OCD) and tic disorders. Similar features, including underlying neurobiological genesis in frontal-striatal circuitry, familiality, relatively early onset, waxing and waning course, and overlapping phenomenology in repetitive behaviors, suggest different variations of the same disorder. Nevertheless, some differences have been described between OCD and tic disorders: tics begin early in childhood and typically attenuate or remit by late adolescence, whereas OCD tends to onset later and persist, and tic disorders are far more common in males than is the case in OCD. Individuals with OCD plus comorbid tics may represent a specific sub-type of OCD or tic disorders, and possess some important phenomenological differences from those with OCD without tics; for example, tic-related OCD tends to have earlier onset, higher prevalence in males, prominent symmetry, evening-up, counting, and “just-right” phenomenology, when compared with non-tic-related OCD. Recent DSM-5 classification changes now recognize presence of tics as a specifier in diagnosis of OCD; despite a 40 % prevalence rate of comorbid tics in childhood-onset OCD, there is still little data regarding risk factors, validated distinguishing features, course and treatment of this diagnostic group. Prominence of premonitory sensory phenomena, urges or sensations experienced prior to the repetitive behaviors, is no longer thought to distinguish complex motor tics from compulsions. Well established treatments of OCD include cognitive behavioral interventions and pharmacotherapy, specifically the serotonin re-uptake inhibitors (SRIs); although these treatments are also beneficial in tic-related OCD, some studies suggest that at least for pharmacotherapy, SRIs may not be as effective in OCD patients with comorbid tics. Given the frequent overlap of OCD and tics, and the recent designation of tic-related OCD as an OCD specifier, more investigation of the comorbid subtype is clearly needed.

Tricyclic antidepressants for attention deficit hyperactivity disorder (ADHD) in children and adolescents.

Attention deficit hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder of childhood onset, which may persist into adulthood. ADHD has a significant impact on a child's daily life, affecting relationships and academic performance. Its core symptoms include developmentally inappropriate levels of inattention, hyperactivity, and impulsive behaviour. Tricyclic antidepressants (TCAs) are sometimes used as second line of treatment in the reduction of ADHD symptoms in children and adolescents with ADHD. However, their efficacy is not yet known. To assess the efficacy of TCAs in the reduction of ADHD symptoms within the broad categories of hyperactivity, impulsivity, and inattentiveness in young people aged 6 to 18 years with established diagnoses of ADHD. On 26 September 2013, we searched CENTRAL, Ovid MEDLINE, Embase, PsycINFO, CINAHL, seven other databases, and two trials registers. We also searched the reference lists of relevant articles, and contacted manufacturers and known experts in the field to determine if there were any ongoing trials or unpublished studies available. Randomised controlled trials (RCTs), including both parallel group and cross-over study designs, of any dose of TCA compared with placebo or active medication in children or adolescents with ADHD, including those with comorbid conditions. Working in pairs, three review authors independently screened records, extracted data, and assessed trial quality. We calculated the standardised mean differences (SMD) for continuous data, the odds ratio (OR) for dichotomous data, and 95% confidence intervals (CIs) for both. We conducted the meta-analyses using a random-effects model throughout. We used the Cochrane 'Risk of bias' tool to assess the risk of bias of each included trial and the GRADE approach to assess the quality of the body evidence. We included six RCTs with a total of 216 participants. Five of the six trials compared desipramine with placebo; the remaining trial compared nortriptyline with placebo. One trial compared desipramine with clonidine and placebo, and another compared two TCAs (desipramine and clomipramine) with methylphenidate and placebo. Of the six trials, one RCT primarily assessed the efficacy of TCA in children with ADHD and comorbid tic or Tourette disorder, and another one trial was in children with comorbid tic disorder. RCTs that met our inclusion criteria varied both in design and quality, and none were free of bias. The quality of the evidence was low to very low according to our GRADE assessments.TCA outperformed placebo regarding the proportions of patients achieving a predefined improvement of core ADHD symptom severity (OR 18.50, 95% CI 6.29 to 54.39, 3 trials, 125 participants, low quality evidence). In particular, there was evidence that desipramine improved the core symptoms of ADHD in children and adolescents as assessed by parents (SMD -1.42, 95% CI -1.99 to -0.85, 2 trials, 99 participants, low quality evidence), teachers (SMD -0.97, 95% CI -1.66 to -0.28, 2 trials, 89 participants, low quality evidence), and clinicians (OR 26.41, 95% CI 7.41 to 94.18, 2 trials, 103 participants, low quality evidence). Nortriptryline was also efficacious in improving the core symptoms of ADHD in children and adolescents as assessed by clinicians (OR 7.88, 95% CI 1.10 to 56.12). Desipramine and placebo were similar on "all-cause treatment discontinuation" (RD -0.10, 95% CI -0.25 to 0.04, 3 trials, 134 participants, very low quality evidence). Desipramine appeared more efficacious than clonidine in reducing ADHD symptoms as rated by parents (SMD -0.90, 95% CI -1.40 to -0.40, 1 trial, 68 participants, very low quality evidence) in participants with ADHD and comorbid tics or Tourette syndrome.Although this Cochrane Review did not identify serious adverse effects in patients taking TCAs, it did identify mild increases in diastolic blood pressure and pulse rates. Also, patients treated with desipramine had significantly higher rates of appetite suppression compared to placebo whilst nortriptyline resulted in weight gain. Other reported adverse effects included headache, confusion, sedation, tiredness, blurred vision, diaphoresis, dry mouth, abdominal discomfort, constipation, and urinary retention. Most evidence on TCAs relates to desipramine. Findings suggest that, in the short term, desipramine improves the core symptoms of ADHD, but its effect on the cardiovascular system remains an important clinical concern. Thus, evidence supporting the clinical use of desipramine for the treatment of children with ADHD is low.

Atomoxetine-Induced Hypomania-Like Symptoms in a Preadolescent Patient

[Author Affiliation]Esra Guney. Ankara Pediatric & Pediatric Hematology Oncology Training and Research Hospital, Child and Adolescent Psychiatry Department, Ankara, Turkey.Ozden Sukran Uneri. Ankara Pediatric & Pediatric Hematology Oncology Training and Research Hospital, Child and Adolescent Psychiatry Department, Ankara, Turkey.Address correspondence to: Esra Guney, MD, Ankara cocuk sagligi ve hastaliklari egitim arastirma hastanesi, Ziraat Mah, Irfan Bastug Cad. Kurtdereli Sk. No: 10, Diskapi-Ankara, Turkey, E-mail, : dresraguney@gmail.comTo The Editor:Atomoxetine, a selective noradrenaline reuptake inhibitor, is the first nonstimulant drug approved by the Food and Drug Administration for the treatment of attention- deficit/hyperactivity disorder (ADHD) (Kaplan and Newcorn 2011). It has been reported that atomoxetine can be safely used in comorbid anxiety disorder and tic disorders (Christman et al. 2004). In this article, we aimed to report hypomania-like symptoms triggered by atomoxetine in a patient with ADHD and social anxiety disorder.Case ReportA 10-year-old male patient presenting with attention deficit, forgetfulness, difficulty in memorizing, and low school success underwent a Wechsler Intelligence Scale For Children-Revised (WISC-R) test to assess his mental capacity. The test revealed that his verbal subtest score was 64, performance subtest score was 68, and total subtest score was 63. According to observations of the psychologist applying the test, attention deficit and performance anxiety affected the test result unfavorably. In addition, it was determined that the patient could not express himself properly in social settings, avoided activities requiring performance, such as not attending classes out of fear of making mistakes, and was usually quiet and shy; therefore, his daily functions were unfavorably affected by his condition.Assessment with respect to ADHD revealed that his time spent studying was limited. In addition, he made careless mistakes in homework, was easily distracted, forgot daily activities easily, and, hence, was frequently warned by his family and teacher. The assessment indicated no activity or impulsivity that had an impact on functionality. He had been advised to take methylphenidate for similar symptoms at the age of 7, but the treatment had been stopped by the family because of side effects such as marked sedation, appetite loss, and irritability. The teacher notification form that was sent via the family also supported these findings.For diagnosis, semistructured interviews based on the American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) diagnostic criteria were conducted with the child and his parents (American Psychiatric Association 1994). Moreover, Conners' Parent and Teacher Rating Scales (Goyette et al. 1978; Conners 1997) were applied. According to the evaluation of the patient, it was determined that he fulfilled the diagnostic criteria for ADHD--attention-deficit subtype and social anxiety disorder--common type. The patient was also evaluated through a semistructured interview based on the DSM-IV diagnostic criteria for any symptoms of other anxiety disorders, mood disorder, and oppositional defiant disorder/conduct disorder, as well as tics and elimination disorders; no signs of these psychiatric disorders were observed. He was begun on atomoxetine 10 mg/day (body weight 36 kg) with gradual dose increases. Special educational support was postponed until a repeat WISC-R test could be administered at 6 months after the treatment.The patient was brought to our polyclinic with nervousness, defiance to parents, and overactivity on 7th day of atomoxetine treatment. A repeat evaluation revealed that his self-esteem increased; he also developed behavioral and emotional changes in the form of occasional anxiety and irritability, and sometimes excessive joy, restlessness, impatience, pugnaciousness, pressured speech, speech interruption behavior, tendency to commit violence against friends, one attempt to kiss one of his friends on her cheeks, and very frequent and irritating kissing behavior toward his mother. …

Neuropsychological functioning in youth with obsessive compulsive disorder: An examination of executive function and memory impairment

Preliminary research suggests neuropsychological deficits in youth with obsessive-compulsive disorder (OCD) similar to those in adults; however, small samples and methodological confounds limit interpretation. We aimed to examine the rates and clinical correlates of cognitive sequelae in youth with OCD, focusing on executive functioning and memory abilities. Youth ages 7–17 years with OCD (N=96) completed a hypothesis-driven neuropsychological battery (including the Rey–Osterreith Complex Figure, California Verbal Learning Test, and subtests of the Delis–Kaplan Executive Function System and Wide Range Assessment of Memory and Learning) that primarily assessed executive functioning, memory and processing speed. Cognitive sequelae were identified in 65% of youth (37% using a more stringent definition of impairment). Magnitude of cognitive sequelae was not associated with OCD severity or age; however, greater neuropsychological impairments were found amongst youth prescribed atypical neuroleptics and those diagnosed with comorbid tic disorders. Comorbidity burden was associated with presence of neuropsychological impairment, but was not specific to any single test. Findings suggest that the presence of cognitive sequelae is prevalent amongst treatment-seeking youth with OCD. Deficits were found in executive functioning and non-verbal memory performance but these impairments were not associated with OCD severity.

Cochrane Review: Pharmacological treatment for Attention Deficit Hyperactivity Disorder (ADHD) in children with comorbid tic disorders

AbstractBackgroundAttention Deficit Hyperactivity Disorder (ADHD) is the most prevalent of the comorbid psychiatric disorders that complicate tic disorders. Medications commonly used to treat ADHD symptoms include the stimulants methylphenidate and amphetamine; nonstimulants, such as atomoxetine; tricyclic antidepressants; and alpha agonists. Due to the impact of ADHD symptoms on the child with tic disorder, treatment of ADHD is often of greater priority than the medical management of tics. However, for many decades clinicians have been reluctant to use stimulants to treat children with ADHD and tics for fear of worsening their tics.ObjectivesTo assess the effects of pharmacological treatments for ADHD on ADHD symptoms and tic severity in children with ADHD and comorbid tic disorders.Search methodsWe searched CENTRAL (The Cochrane Library 2009, Issue 4), MEDLINE (1950 to July 2009), EMBASE (1980 to July 2009), CINAHL (1982 to July 2009), PsycINFO (1806 to July Week 4 2009) and BIOSIS Previews (1985 to July 2009). Dissertation Abstracts (searched via Dissertaation Express), and the metaRegister of Controlled Trials were searched (30 July 2009).Selection criteriaWe included randomized, double‐blind, controlled trials of any pharmacological treatment for ADHD used specifically in children with comorbid tic disorders. We included both parallel group and cross‐over study designs.Data collection and analysisTwo authors independently extracted data using standardized forms.Main resultsWe included a total of eight randomized controlled studies in the review but were unable to combine any of these in meta‐analysis. Several of the trials assessed multiple agents. Medications assessed included methylphenidate, clonidine, desipramine, dextroamphetamine, guanfacine, atomoxetine, and deprenyl. All treatments, with the exception of deprenyl, were efficacious in treating symptoms of ADHD. Tic symptoms improved in children treated with guanfacine, desipramine, methylphenidate, clonidine, and the combination of methylphenidate and clonidine. Fear of worsening tics limited dose increases of methylphenidate in one study. High dose dextroamphetamine appeared to worsen tics in one study, although the length of this study was limited.Authors' conclusionsMethylphenidate, clonidine, guanfacine, desipramine and atomoxetine appear to reduce ADHD symptoms in children with tics. Although stimulants have not been shown to worsen tics in most people with tic disorders, they may nonetheless exacerbate tics in individual cases. In these instances, treatment with alpha agonists or atomoxetine may be an alternative. Although there is evidence that desipramine is effective for both tics and ADHD in children, safety concerns will likely continue to limit its use in this population. Plain Language SummaryMedications for Attention Deficit Hyperactivity Disorder in children with ticsAs many as half of all children with tic disorders also have Attention Deficit Hyperactivity Disorder (ADHD). Symptoms of ADHD are often more disabling for children than their tics. Historically, the reported ability of stimulant medications to worsen tics has limited their use in children who have both a chronic tic disorder and ADHD. To evaluate evidence for this reported phenomenon we searched for clinical trials of medications for ADHD used specifically in children with tic disorders. The trials indicate that a number of stimulant and non‐stimulant medications are safe and effective treatments for ADHD symptoms and do not worsen tics. High dose stimulants may transiently worsen tics in some children, and worsening tics may limit dose increases of stimulants in some children, but in the majority of children both tics and ADHD symptoms improve with use of stimulant medications.

Misplaced Fear? FDA Contraindication to Psychostimulant Use in Children with Tics.

AbstractThese are commentaries on a Cochrane review, published in this issue of EBCH, first published as: Pringsheim T, Steeves T. Cochrane Database of Systematic Reviews 2011, Issue 4. Art. No.: CD007990. DOI: 10.1002/ 14651858.CD007990.pub2Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2012 The Cochrane Collaboration. Published by John Wiley &amp; Sons, Ltd. The Cochrane Collaboration

Clinical features of tic-related obsessive-compulsive disorder: results from a large multicenter study

To evaluate the clinical features of obsessive-compulsive disorder (OCD) patients with comorbid tic disorders (TD) in a large, multicenter, clinical sample. A cross-sectional study was conducted that included 813 consecutive OCD outpatients from the Brazilian OCD Research Consortium and used several instruments of assessment, including the Yale-Brown Obsessive-Compulsive Scale, the Dimensional Yale-Brown Obsessive-Compulsive Scale, the Yale Global Tic Severity Scale (YGTSS), the USP Sensory Phenomena Scale, and the Structured Clinical Interview for DSM-IV Axis I Disorders. The sample mean current age was 34.9 years old (SE 0.54), and the mean age at obsessive-compulsive symptoms (OCS) onset was 12.8 years old (SE 0.27). Sensory phenomena were reported by 585 individuals (72% of the sample). The general lifetime prevalence of TD was 29.0% (n = 236), with 8.9% (n = 72) presenting Tourette syndrome, 17.3% (n = 141) chronic motor tic disorder, and 2.8% (n = 23) chronic vocal tic disorder. The mean tic severity score, according to the YGTSS, was 27.2 (SE 1.4) in the OCD + TD group. Compared to OCD patients without comorbid TD, those with TD (OCD + TD group, n = 236) were more likely to be males (49.2% vs. 38.5%, p < .005) and to present sensory phenomena and comorbidity with anxiety disorders in general: separation anxiety disorder, social phobia, specific phobia, generalized anxiety disorder, post-traumatic stress disorder, attention-deficit hyperactivity disorder, impulse control disorders in general, and skin picking. Also, the "aggressive," "sexual/religious," and "hoarding" symptom dimensions were more severe in the OCD + TD group. Tic-related OCD may constitute a particular subgroup of the disorder with specific phenotypical characteristics, but its neurobiological underpinnings remain to be fully disentangled.

Tourette syndrome in youth with and without obsessive compulsive disorder and attention deficit hyperactivity disorder

Chronic tic disorders (TD) are consistently found to have high rates of comorbidity with obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD). The purpose of this study is to compare the severity of TD only to TD with comorbid OCD or ADHD based on severity of tics, measures of psychopathology and additional comorbid diagnoses. Baseline data from 158 youth with a chronic TD who participated in two longitudinal studies were examined. Fifty-three percent (N = 85) of the youth also met criteria for a diagnosis of OCD, 38.6 % (n = 61) met criteria for ADHD and 24.1 % (N = 38) met criteria for both. Measures of interest addressed severity of tics, symptoms of anxiety, depression, ADHD, psychosocial stress, global functioning and the presence of comorbid diagnoses. Youth with comorbid TD and OCD were characterized by more severe tics, increased levels of depressive and anxious symptoms, heightened psychosocial stress and poorer global functioning. Youth with comorbid TD and ADHD did not differ from those with TD alone on measures of tic severity, but experienced greater psychosocial stress and poorer global functioning. Subjects with comorbid TD and OCD had more internalizing disorders than those without OCD, while those with comorbid ADHD were more likely to meet criteria for oppositional defiant disorder. TD with OCD is a more severe subtype of TD than TD without OCD. TD with ADHD is associated with higher psychosocial stress and more externalizing behaviors. Further research is needed into the underlying relationships between these closely associated conditions.