CANNA-TICS: Efficacy and safety of oral treatment with nabiximols in adults with chronic tic disorders – Results of a prospective, multicenter, randomized, double-blind, placebo controlled, phase IIIb superiority study

Müller-Vahl et al. ·Psychiatry Research Impact 4.1

Mixed GRADE Moderate 36 citations

Samplen = 97 Pat.

Duration13 weeks

ControlPlacebo

EndpointYGTSS-TTS

Blindingdoppelblind

DesignRCT

Cannabinoidkombination

THC:CBD1:1

Routeoral

Key finding

Nabiximols showed numerically higher responder rates than placebo (21,9% vs. 9,1%), but did not formally achieve superiority in the primary endpoint; secondary analyses indicated substantial improvements in tics, depression and quality of life.

Summary

Multicentre phase IIIb RCT of nabiximols vs. placebo in adults with Tourette/chronic tic disorders (n=97, 2:1 randomisation). Primary endpoint (≥25% tic reduction after 13 weeks) formally not met, but responder rate nabiximols 21,9% vs. placebo 9,1%. Secondary analyses showed substantial trends for improvement in tics, depression and quality of life; exploratory subgroup analyses suggest benefit for men, more severe tics and comorbid ADHD. No relevant safety concerns.

PopulationAdults with Tourette syndrome/chronic tic disorders, n=97

InterventionNabiximols (oral cannabis extract), titration over 13 weeks, 2:1 randomisation

ControlPlacebo

OutcomePrimary endpoint (≥25% tic reduction in YGTSS-TTS after 13 weeks): 21,9% (nabiximols) vs. 9,1% (placebo); formal superiority not demonstrated

Confidence in the evidence

Moderate

The third of four GRADE levels, the effect estimate is probably reliable.

Downgraded for

Imprecision

Quality profile

Sample size ★★★★★

Blinding Double-blind

Effect size Mixed

Citations / year ★★★★★

Authors

Müller-Vahl K R, Pisarenko A, Szejko N et al.

DOI 10.1016/j.psychres.2023.115135↗

Design: RCT

Abstract

Preliminary data suggest that cannabis-based medicines might be a promising new treatment for patients with Tourette syndrome (TS)/chronic tic disorders (CTD) resulting in an improvement of tics, comorbidities, and quality of life. This randomized, multicenter, placebo-controlled, phase IIIb study aimed to examine efficacy and safety of the cannabis extract nabiximols in adults with TS/CTD (n = 97, randomized 2:1 to nabiximols:placebo). The primary efficacy endpoint was defined as a tic reduction of >/= 25% according to the Total Tic Score of the Yale Global Tic Severity Scale after 13 weeks of treatment. Although a much larger number of patients in the nabiximols compared to the placebo group (14/64 (21.9%) vs. 3/33 (9.1%)) met the responder criterion, superiority of nabiximols could formally not be demonstrated. In secondary analyses, substantial trends for improvements of tics, depression, and quality of life were observed. Additionally exploratory subgroup analyses revealed an improvement of tics in particular in males, patients with more severe tics, and patients with comorbid attention deficit/hyperactivity disorder suggesting that these subgroups may benefit better from treatment with cannabis-based medication. There were no relevant safety issues. Our data further support the role of cannabinoids in the treatment of patients with chronic tic disorders.

The impediment to action advances action. — Marcus Aurelius