Digitally enabled therapy for chronic tic disorders and Tourette Syndrome: a systematic review and economic evaluation.

Background: Chronic 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. Objectives: We 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. Methods: We 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. Results: We 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. Limitations: Evidence 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. Conclusions: Both 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 studies: Replication 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 registration: This study is registered as PROSPERO CRD42024508045. Funding: This 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