Tourette syndrome - Emerging treatments

Cannabinoids

Cannabinoids are being studied with promising results. Tetrahydrocannabinol has been associated with a significant improvement in tic severity in patients with TS in two small placebo-controlled studies.[110] The American Academy of Neurology guideline recommends that cannabis-based medications may be considered for adults with treatment-resistant TS where legislation allows, but they should not be used in children, adolescents, women who are pregnant or breastfeeding, or patients with psychosis.[66] Further large, robust, randomized controlled trials are needed to confirm the effects of cannabinoids on TS.[111]

Deutetrabenazine

A selective VMAT2 inhibitor that may become an alternative to tetrabenazine given its reduced side-effect profile.[66][112] An open-label study of 33 adolescents with TS-related tics reported a 37.6% reduction in tic severity after 8 weeks of treatment with deutetrabenazine.[112]

Transcranial magnetic stimulation (TMS)

In the last decade, there has been growing interest in the use of TMS in tic disorders. Open-label studies targeting the supplementary motor area had shown this technique to be effective in reducing tics in TS.[113][114][115][116] However, this finding was not replicated in the first randomized, double-blind, sham-controlled trial conducted in 20 adults with TS.[117] One meta-analysis found that repetitive TMS significantly improved tic and obsessive-compulsive symptoms in patients with TS, but was not effective when controlled for placebo. Younger age was associated with greater treatment efficacy.[118] More research is needed in this area.

Deep-brain stimulation (DBS)

Most published cases of DBS for TS target the centro-median-parafascicular complex (CM-PF) of the medial thalamus, and a few cases target the globus pallidus interna (GPi), both the CM-PF and GPi, the anterior limb of the internal capsule, or the nucleus accumbens.[119] There has yet to be a consensus on which target is the most appropriate for treatment of tics in TS.[66] One randomized double-blind crossover trial of 15 adults with severe refractory TS found significant improvement in Yale Global Tic Severity Scale score after bilateral globus pallidus DBS; there were three serious adverse events (two infections of DBS hardware and one episode of DBS-induced hypomania).[120] The use of DBS in neuropsychiatric conditions, such as OCD, is beyond the scope of this review, but may be important to consider in adults with refractory or severe TS cases. As reports of DBS in TS increase in the literature, and well-designed studies are carried out using uniform rating scales and diagnostic criteria, DBS may become a viable option for those patients with severe and intractable TS.[66][121][122][123] However, caution must be shown regarding the neuropsychiatric aspects of DBS, which are still being explored.[124][125]