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Safety and efficacy of aripiprazole for the treatment of pediatric Tourette syndrome and other chronic tic disorders.

ABSTRACT: Tourette syndrome is a childhood-onset chronic tic disorder characterized by multiple motor and vocal tics and often accompanied by specific behavioral symptoms ranging from obsessionality to impulsivity. A considerable proportion of patients report significant impairment in health-related quality of life caused by the severity of their tics and behavioral symptoms and require medical intervention. The most commonly used medications are antidopaminergic agents, which have been consistently shown to be effective for tic control, but are also associated with poor tolerability because of their adverse effects. The newer antipsychotic medication aripiprazole is characterized by a unique mechanism of action (D2 partial agonism), and over the last decade has increasingly been used for the treatment of tics. We conducted a systematic literature review to assess the available evidence on the efficacy and safety of aripiprazole in pediatric patients with Tourette syndrome and other chronic tic disorders (age range: 4-18 years). Our search identified two randomized controlled trials (involving 60 and 61 participants) and ten open-label studies (involving between six and 81 participants). The majority of these studies used two validated clinician-rated instruments (Yale Global Tic Severity Scale and Clinical Global Impression scale) as primary outcome measures. The combined results from randomized controlled trials and open-label studies showed that aripiprazole is an effective, safe, and well-tolerated medication for the treatment of tics. Aripiprazole-related adverse effects (nausea, sedation, and weight gain) were less frequent compared to other antidopaminergic medications used for tic management and, when present, were mostly transient and mild. The reviewed studies were conducted on small samples and had relatively short follow-up periods, thus highlighting a need for further trials to assess the long-term use of aripiprazole in pediatric patients with Tourette syndrome and other chronic tic disorders with measurement of its efficacy using both clinician-rated and self-report scales.

SUBMITTER: Cox JH

PROVIDER: S-EPMC5683285 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Safety and efficacy of aripiprazole for the treatment of pediatric Tourette syndrome and other chronic tic disorders.

Cox Joanna H JH Seri Stefano S Cavanna Andrea E AE

Pediatric health, medicine and therapeutics 20160627

Tourette syndrome is a childhood-onset chronic tic disorder characterized by multiple motor and vocal tics and often accompanied by specific behavioral symptoms ranging from obsessionality to impulsivity. A considerable proportion of patients report significant impairment in health-related quality of life caused by the severity of their tics and behavioral symptoms and require medical intervention. The most commonly used medications are antidopaminergic agents, which have been consistently shown ...[more]

PMID: 29388585

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Project description:ImportanceThere are limited data concerning the risk of metabolic and cardiovascular disorders among individuals with Tourette syndrome (TS) or chronic tic disorder (CTD).ObjectiveTo investigate the risk of metabolic and cardiovascular disorders among individuals with TS or CTD over a period of 40 years.Design, settings, and participantsThis longitudinal population-based cohort study included all individuals living in Sweden between January 1, 1973, and December 31, 2013. Families with clusters of full siblings discordant for TS or CTD were further identified. Data analyses were conducted from August 1, 2017, to October 11, 2018.ExposuresPreviously validated International Classification of Diseases diagnoses of TS or CTD in the Swedish National Patient Register.Main outcomes and measuresRegistered diagnoses of obesity, dyslipidemia, hypertension, type 2 diabetes, and cardiovascular diseases (including ischemic heart diseases, arrhythmia, cerebrovascular diseases and transient ischemic attack, and arteriosclerosis).ResultsOf the 14 045 026 individuals in the cohort, 7804 individuals (5964 males [76.4%]; median age at first diagnosis, 13.3 years [interquartile range, 9.9-21.3 years]) had a registered diagnosis of TS or CTD in specialist care. Of 2 675 482 families with at least 2 singleton full siblings, 5141 families included siblings who were discordant for these disorders. Individuals with TS or CTD had a higher risk of any metabolic or cardiovascular disorders compared with the general population (hazard ratio adjusted by sex and birth year [aHR], 1.99; 95% CI, 1.90-2.09) and sibling controls (aHR for any disorder, 1.37; 95% CI, 1.24-1.51). Specifically, individuals with TS or CTD had higher risks for obesity (aHR, 2.76; 95% CI, 2.47-3.09), type 2 diabetes (aHR, 1.67; 95% CI, 1.42-1.96), and circulatory system diseases (aHR, 1.76; 95% CI, 1.67-1.86). The risk of any cardiometabolic disorder was significantly greater in males than in females (aHR, 2.13; 95% CI, 2.01-2.26 vs aHR, 1.79; 95% CI, 1.64-1.96), as was the risk of obesity (aHR, 3.24; 95% CI, 2.83-3.70 vs aHR, 1.97; 95% CI, 1.59-2.44). The risks were already evident from childhood (the groups were significantly different by age 8 years) and were significantly reduced with the exclusion of individuals with comorbid attention-deficit/hyperactivity disorder (aHR, 1.52; 95% CI, 1.42-1.62), while excluding other comorbidities did not significantly affect the results. Compared with patients with TS or CTD who were not taking antipsychotics, patients with a longer duration of antipsychotic treatment (>1 year) had significantly lower risks of metabolic and cardiovascular disorders.Conclusions and relevanceThe findings of this study suggest that TS and CTD are associated with a substantial risk of metabolic and cardiovascular disorders. The results highlight the importance of carefully monitoring cardiometabolic health in patients with TS or CTD across the lifespan, particularly in those with comorbid attention-deficit/hyperactivity disorder.

Project description:ImportanceSevere forms of Tourette syndrome or chronic tic disorder (TS/CTD) may involve repeated head jerking. Isolated case reports have described a spectrum of severe neck disorders in individuals with TS/CTD. However, the nature and prevalence of cervical spine disorders in TS/CTD are unknown.ObjectiveTo establish if TS/CTD are associated with an increased risk of cervical spine disorders and related neurological complications compared with individuals from the general population.Design, setting, and participantsAll individuals born from 1973 to 2013 and living in Sweden between 1997 and 2013 were identified. Individuals with a record of TS/CTD diagnosed in specialist settings were matched on age, sex, and county of birth with 10 unexposed individuals randomly selected from the general population. Cox proportional hazards regression models were used to estimate the risk of vascular and nonvascular cervical spine disorders among exposed individuals, compared with unexposed individuals. Models were adjusted for other known causes of cervical spine injury. Data were analyzed from March 19 to May 16, 2021.ExposuresInternational Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses of TS/CTD in the Swedish National Patient Register.Main outcomes and measuresRecords of cervical vascular disorders (ie, aneurysm, cerebral infarction, transitory cerebral ischemia) and cervical nonvascular disorders (ie, spondylosis, cervical disc disorders, fractures of the cervical spine, cervicalgia) and cervical surgeries. Covariates included rheumatic disorders, traffic injuries, fall- or sport-related injuries, and attention-deficit/hyperactivity disorder comorbidity.ResultsA total of 6791 individuals with TS/CTD were identified (5238 [77.1%] were male; median [interquartile] age at first diagnosis, 15.6 [11.4-23.7] years) and matched to 67 910 unexposed individuals. Exposed individuals had a 39% increased risk of any cervical spine disorder (adjusted hazard ratio, 1.39; 95% CI, 1.22-1.59). Adjusted hazard ratios for cervical vascular and nonvascular disorders were 1.57 (95% CI, 1.16-2.13) and 1.38 (95% CI, 1.19-1.60), respectively. Risks were similar among men and women.Conclusions and relevanceIndividuals with severe TS/CTD are at increased risk of cervical spine disorders. These outcomes are relatively rare but may lead to persistent disability in some individuals and thus require close monitoring to facilitate early interventions.

Project description:Importance:The influence of Tourette syndrome and chronic tic disorders on academic performance has not been objectively quantified. Objective:To investigate the association of Tourette syndrome and chronic tic disorders with objectively measured educational outcomes, adjusting for measured covariates and unmeasured factors shared between siblings and taking common psychiatric comorbidities into account. Design, Setting, and Participants:A population-based birth cohort consisting of all individuals born in Sweden from 1976 to 1998 was followed up until December 2013. Individuals with organic brain disorders, mental retardation, and 2 foreign-born parents were excluded. We further identified families with at least 2 singleton full siblings and families with siblings discordant for Tourette syndrome or chronic tic disorders. Exposures:Previously validated International Classification of Diseases diagnoses of Tourette syndrome or chronic tic disorders in the Swedish National Patient Register. Main Outcomes and Measures:Eligibility to access upper secondary school after compulsory education, finishing upper secondary school, starting a university degree, and finishing a university degree. Results:Of the 2?115?554 individuals in the cohort, 3590 had registered a diagnosis of Tourette syndrome or a chronic tic disorder in specialist care (of whom 2822 [78.6%] were male; median [interquartile] age at first diagnosis, 14.0 [11-18] years). Of 726?198 families with at least 2 singleton full siblings, 2697 included siblings discordant for these disorders. Compared with unexposed individuals, people with Tourette syndrome or chronic tic disorders were significantly less likely to pass all core and additional courses at the end of compulsory school (odds ratios ranging from 0.23 [95% CI, 0.20-0.26] for the handcraft textile/wood course to 0.36 [95% CI, 0.31-0.41] for the English language course) and to access a vocational program (adjusted OR [aOR], 0.31; 95% CI, 0.28-0.34) or academic program (aOR, 0.43; 95% CI, 0.39-0.47) in upper secondary education. Individuals with the disorders were also less likely to finish upper secondary education (aOR, 0.35; 95% CI, 0.32-0.37), start a university degree (aOR, 0.41; 95% CI, 0.37-0.46), and finish a university degree (aOR, 0.39; 95% CI, 0.32-0.48). The results were only marginally attenuated in the fully adjusted sibling comparison models. Exclusion of patients with neuropsychiatric comorbidities, particularly attention-deficit/hyperactivity disorder and pervasive developmental disorders, resulted in attenuated estimates, but patients with Tourette syndrome or chronic tic disorders were still significantly impaired across all outcomes. Conclusions and Relevance:Help-seeking individuals with Tourette syndrome or chronic tic disorders seen in specialist settings experience substantial academic underachievement across all educational levels, spanning from compulsory school to university, even after accounting for multiple confounding factors and psychiatric comorbidities.

Project description:ImportanceTic disorders are associated with multiple social adversities, but little is known about the experience of violent assault (including sexual assault) and criminality in this group.ObjectiveTo establish if Tourette syndrome (TS) and chronic tic disorder (CTD) are associated with an increased risk of experiencing violent assault and criminal convictions.Design, setting, and participantsIn this cohort study, all individuals living in Sweden at any time between January 1, 1973, and December 31, 2013, were identified from Swedish nationwide health and administrative registers. Cox proportional hazards regression models were used to estimate the risk of violent assault and criminal convictions among people with TS or CTD, compared with the general population and unaffected full siblings. Data analyses were conducted between September 1 and October 22, 2021.ExposuresThe Swedish version of the International Classification of Diseases, Eighth Revision (ICD-8), ICD-9, and ICD-10 diagnoses of TS or CTD in the Swedish National Patient Register.Main outcomes and measuresRecords of sexual and nonsexual violent assault and death due to violent assaults were obtained from the National Patient Register and the Cause of Death Register, respectively. Convictions for violent and nonviolent criminal offenses were obtained from the Crime Register. Covariates included sex and birth year.ResultsThe study cohort included 13 819 284 individuals living in Sweden between 1973 and 2013. A total of 7791 individuals with TS or CTD were identified (median [IQR] age at first diagnosis, 13.4 [10.0-21.8] years; 5944 [76%] male). Compared with unaffected individuals from the general population, people with TS or CTD had a 2-fold increased risk of experiencing any violent assault (sexual and nonsexual) (adjusted hazard ratio [aHR], 2.21; 95% CI, 2.00-2.43), a 3-fold increased risk of violent convictions (aHR, 3.13; 95% CI, 2.92-3.36), and a 1.6-fold increased risk of nonviolent crime convictions (aHR, 1.62; 95% CI, 1.54-1.71). Among people with TS or CTD, 37.0% (114 of 308; 95% CI, 31.6%-42.4%) of individuals who had experienced violent assault also had a violent crime conviction, compared with 17.9% (16 067 of 89 920; 95% CI, 17.6%-18.1%) in the general population. Exclusion of individuals with attention-deficit/hyperactivity disorder and substance use disorders partially attenuated the associations. Similarly, within-sibling models attenuated but did not eliminate the associations (any violent assault: aHR, 1.32; 95% CI, 1.08-1.61; violent crime: aHR, 2.23; 95% CI, 1.86-2.67; nonviolent crime: aHR, 1.34; 95% CI, 1.20-1.50).Conclusions and relevanceResults of this cohort study suggest that most individuals with TS or CTD are not assaulted nor are perpetrators of crime. However, individuals with TS or CTD diagnosed in specialist settings were more likely to both experience violent assault and be perpetrators of violence compared with the general population. The risk was highest in individuals with comorbid attention-deficit/hyperactivity disorder and substance use disorders. The increased risk found in specialty clinics will need to be better understood in the general population.

Dataset Information

Safety and efficacy of aripiprazole for the treatment of pediatric Tourette syndrome and other chronic tic disorders.

Publications

Safety and efficacy of aripiprazole for the treatment of pediatric Tourette syndrome and other chronic tic disorders.

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