{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:18:59Z","timestamp":1790619539090,"version":"4.1.0"},"reference-count":109,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder characterized by motor and phonic tics, often including attention deficit, hyperactivity, and obsessive\u2013compulsive behaviours. The pathophysiology involves the dysfunction of cortico-striato-thalamo-cortical circuits, primarily implicating dopaminergic hyperactivity, but also involving multiple different neurotransmitter systems. Treatment of GTS is complex, highly individualized, and influenced by considerable variability in symptom presentation. Behavioural approaches, such as Habit Reversal Therapy (HRT), play a key role, especially in milder cases. Pharmacological therapy is largely empirical and varies across countries, influenced by drug availability and the perceived risks of certain classes of drugs, particularly dopamine receptor blocking agents. Drug options for managing tics include dopamine receptor antagonists, monoamine depleting agents, and alpha-2 agonists, all of which require close monitoring for metabolic, cardiovascular, and neurological side effects. Botulinum toxin injections represent an effective solution for focal tics that are resistant to systemic treatments. Cannabinoids and antiepileptics have limited efficacy, yet they may still offer relevant therapeutic potential in selected cases. Serotonergic drugs are useful for treating obsessive\u2013compulsive symptoms. For patients with refractory tics, deep brain stimulation (DBS) represents an intervention of last-resort; however, DBS remains off-label and consensus on optimal targets is lacking. This narrative review draws on both the relevant literature and extensive personal clinical experience to explore the complexities of managing GTS, with a focus on evidence-based treatments for tics and associated neuropsychiatric symptoms. A therapeutic algorithm is proposed, emphasizing a \u201cstart low, go slow\u201d approach, combining pharmacological interventions with cognitive behavioural and surgical therapies, when needed. We underscore the importance of tailoring treatments to individual patient profiles and symptom variability over time, highlighting the need for further research in GTS management.<\/jats:p>","DOI":"10.3390\/ijms26188831","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T15:39:23Z","timestamp":1757518763000},"page":"8831","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["From Pharmacological Treatment to Neuromodulation: A Comprehensive Approach to Managing Gilles de la Tourette Syndrome"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4720-9234","authenticated-orcid":false,"given":"Edoardo","family":"Monfrini","sequence":"first","affiliation":[{"name":"Neurology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5225-5414","authenticated-orcid":false,"given":"Christian","family":"Saleh","sequence":"additional","affiliation":[{"name":"University of Basel, 4001 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Servello","sequence":"additional","affiliation":[{"name":"Centro Malattie Extrapiramidali e Sindrome di Tourette, IRCCS Ospedale Galeazzi-Sant\u2019Ambrogio, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Jaszczuk","sequence":"additional","affiliation":[{"name":"Interdisciplinary Spine Center, Luzern Cantonal Hospital, University of Luzern, 6000 Luzern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Porta","sequence":"additional","affiliation":[{"name":"Centro Malattie Extrapiramidali e Sindrome di Tourette, IRCCS Ospedale Galeazzi-Sant\u2019Ambrogio, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/B978-0-323-98817-9.00002-8","article-title":"Tourette Syndrome and Other Tic Disorders of Childhood","volume":"196","author":"Nilles","year":"2023","journal-title":"Handb. 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