Tourette Syndrome

In 2011, the European Society for the Study of Tourette Syndrome (ESSTS) published the first European guidelines for Tourette Syndrome (TS). We now present an update of the part on pharmacological treatment, based on a review of new literature with special attention to other evidence-based guidelines, meta-analyses, and randomized double-blinded studies. Moreover, our revision took into consideration results of a recent survey on treatment preferences conducted among ESSTS experts. The first preference should be given to psychoeducation and to behavioral approaches, as it strengthens the patients' self-regulatory control and thus his/her autonomy. Because behavioral approaches are not effective, available, or feasible in all patients, in a substantial number of patients pharmacological treatment is indicated, alone or in combination with behavioral therapy. The largest amount of evidence supports the use of dopamine blocking agents, preferably aripiprazole because of a more favorable profile of adverse events than first- and second-generation antipsychotics. Other agents that can be considered include tiapride, risperidone, and especially in case of co-existing attention deficit hyperactivity disorder (ADHD), clonidine and guanfacine. This view is supported by the results of our survey on medication preference among members of ESSTS, in which aripiprazole was indicated as the drug of first choice both in children and adults. In treatment resistant cases, treatment with agents with either a limited evidence base or risk of extrapyramidal adverse effects might be considered, including pimozide, haloperidol, topiramate, cannabis-based agents, and botulinum toxin injections. Overall, treatment of TS should be individualized, and decisions based on the patient's needs and preferences, presence of co-existing conditions, latest scientific findings as well as on the physician's preferences, experience, and local regulatory requirements.

Part II of the European clinical guidelines for Tourette syndrome and other tic disorders (ECAP journal, 2011) provides updated information and recommendations for psychological interventions for individuals with tic disorders, created by a working group of the European Society for the Study of Tourette Syndrome (ESSTS). A systematic literature search was conducted to obtain original studies of psychological interventions for tic disorders, published since the initial European clinical guidelines were issued. Relevant studies were identified using computerized searches of the MEDLINE and PsycINFO databases for the years 2011-2019 and a manual search for the years 2019-2021. Based on clinical consensus, psychoeducation is recommended as an initial intervention regardless of symptom severity. According to a systematic literature search, most evidence was found for Habit Reversal Training (HRT), primarily the expanded package Comprehensive Behavioral Intervention for Tics (CBIT). Evidence was also found for Exposure and Response Prevention (ERP), but to a lesser degree of certainty than HRT/CBIT due to fewer studies. Currently, cognitive interventions and third-wave interventions are not recommended as stand-alone treatments for tic disorders. Several novel treatment delivery formats are currently being evaluated, of which videoconference delivery of HRT/CBIT has the most evidence to date. To summarize, when psychoeducation alone is insufficient, both HRT/CBIT and ERP are recommended as first-line interventions for tic disorders. As part of the development of the clinical guidelines, a survey is reported from ESSTS members and other tic disorder experts on preference, use and availability of psychological interventions for tic disorders.

ObjectivesAripiprazole modulates dopaminergic and serotonergic pathways that may play a role in the pathogenesis of Tourette's disorder (TD). This trial evaluated the efficacy and safety of oral aripiprazole in the suppression of tics in children and adolescents with TD.MethodsThis phase 3, randomized, double-blind, placebo-controlled trial ( ClinicalTrials.gov , NCT01727700) recruited patients who were 7-17 years old with a diagnosis of TD from hospitals, private practices, and research clinics at 76 sites in the United States, Canada, Hungary, and Italy. Patients were randomized in a 1:1:1 ratio by using an interactive voice/web-response system to low-dose aripiprazole (5 mg/day if ResultsBetween November 2012 and May 2013, 133 patients were recruited and randomized to low-dose aripiprazole (n = 44), high-dose aripiprazole (n = 45), or placebo (n = 44). Least-squares mean treatment differences versus placebo in change from baseline to week 8 in the YGTSS-TTS were statistically significant (high dose, -9.9 [95% confidence interval, CI, -13.8 to -5.9], low dose, -6.3 [95% CI, -10.2 to -2.3]). At week 8, 69% (29/42) of patients in the low-dose and 74% (26/35) of patients in the high-dose aripiprazole groups demonstrated a Clinical Global Impression-Tourette's Syndrome improvement score of 1 (very much improved) or 2 (much improved) compared with 38% (16/42) in the placebo group. The most common adverse events (AEs) were sedation (low dose, 8/44 [18.2%], high dose, 4/45 [8.9%], placebo, 1/44 [2.3%]), somnolence (low dose, 5/44 [11.4%], high dose, 7/45 [15.6%], placebo, 1/44 [2.3%]), and fatigue (low dose, 3/44 [6.8%], high dose, 7/45 [15.6%], placebo, 0). No serious AEs or deaths occurred.ConclusionsThis study indicates that oral aripiprazole is a safe and effective treatment for tics in children and adolescents with TD.

BackgroundChronic tic disorders and Tourette syndrome typically present around age 5, with peak severity between ages 10 and 12. Treatment approaches vary by country and service availability and include psychoeducation, behavioural therapy, pharmacological therapies and deep brain stimulation. Digitally enabled interventions may improve outcomes.ObjectivesWe evaluate the clinical and cost-effectiveness of two digital technologies, Online Remote Behavioural Treatment for Tics and Neupulse and identify evidence gaps for future research.MethodsWe searched major electronic databases (MEDLINE, EMBASE, Cochrane Library, Web of Science, and Cumulative Index to Nursing and Allied Health Literature) for published studies on clinical and cost-effectiveness. Data were extracted, assessed for bias using Cochrane risk-of-bias tool (version 2), and pooled using random-effects meta-analysis where appropriate. Cost-effectiveness was evaluated using a Markov cohort model with five tic severity states based on the Yale Global Tic Severity Scale - Total Tic Severity Score scale, from a United Kingdom National Health Service perspective. Model inputs were obtained from the Online Remote Behavioural Treatment for Tics study, company data, expert opinion and additional literature.ResultsWe identified three trials reported across 14 publications: 2 comparing Online Remote Behavioural Treatment for Tics with online psychoeducation, and 1 comparing Neupulse with sham stimulation and a waitlist control. All were assessed as low risk of bias. Meta-analysis of the 2 Online Remote Behavioural Treatment for Tics studies (445 participants) showed significantly lower Yale Global Tic Severity Scale - Total Tic Severity Score at 3 and 12 months compared to online psychoeducation. Results of secondary outcomes were mixed. Neupulse showed significantly lower Yale Global Tic Severity Scale - Total Tic Severity Score, and improvements in motor and phonic tic scores at 4 weeks compared to sham, but no differences in Yale Global Tic Severity Scale-Impairment or Premonitory Urge for Tics Scale - Revised scores. A definitive base-case incremental cost-effectiveness ratio could not be determined due to limited long-term data and uncertainty around long-term combinations of effectiveness and intervention costs in United Kingdom National Health Service practice. Probabilistic incremental cost-effectiveness ratios ranged from £642 per quality-adjusted life-year gained to Online Remote Behavioural Treatment for Tics being dominated. The probability of Online Remote Behavioural Treatment for Tics being cost-effective at a threshold value of £20,000 per quality-adjusted life-year ranged from 52% to 89% across a range of scenarios. Cost-effectiveness results for Neupulse were even more uncertain due to a lack of published data, only a 4-week follow-up and uncertainty surrounding the intervention cost.LimitationsEvidence for Online Remote Behavioural Treatment for Tics and Neupulse was limited, with inconsistencies in the outcomes assessed. Comparators did not include face-to-face behavioural therapy and it was not possible to differentiate the effects of online delivery from those of exposure and response prevention. Cost-effectiveness results are uncertain due to a lack of long-term data.ConclusionsBoth Online Remote Behavioural Treatment for Tics and Neupulse appear to significantly reduce Yale Global Tic Severity Scale - Total Tic Severity Score, but there were no improvements in the Yale Global Tic Severity Scale-Impairment scores and mixed results across other secondary outcomes, meaning it is unclear to what extent improvements in tic severity scores can translate to improvements in quality of life. Cost-effectiveness estimates were highly uncertain due to a lack of long-term evidence.Future studiesReplication studies are needed to confirm findings. Longer follow-up - particularly for Neupulse - is essential to understand sustained effects and long-term cost-effectiveness. More data on the natural course of tic severity and the sustainability of treatment effects would reduce uncertainty in economic modelling. Future research should also prioritise outcomes that reflect real-life impact on people's daily functioning.Study registrationThis study is registered as PROSPERO CRD42024508045.FundingThis award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR136022) and is published in full in Health Technology Assessment; Vol. 30, No. 8. See the NIHR Funding and Awards website for further award information.