The primary overall goal of treatment is to optimise the patient’s quality of life and to support a positive developmental trajectory. Approach to treatment is multidisciplinary and often multimodal.[64]Whittington C, Pennant M, Kendall T, et al. Practitioner review: treatments for Tourette syndrome in children and young people - a systematic review. J Child Psychol Psychiatry. 2016 May 2 [Epub ahead of print].
http://www.ncbi.nlm.nih.gov/pubmed/27132945?tool=bestpractice.com
An initial and imperative step is to educate family, clinicians, teachers, and peers regarding the symptoms and course of the disorder in order to reduce any associated stigma and distress.[65]Pringsheim T, Okun MS, Müller-Vahl K, et al. Practice guideline recommendations summary: treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology. 2019 May 7;92(19):896-906.
https://www.doi.org/10.1212/WNL.0000000000007466
http://www.ncbi.nlm.nih.gov/pubmed/31061208?tool=bestpractice.com
The next step is to establish whether psychiatric comorbid disorders are present, and to what degree they may be impacting the child’s functional capacity at home, at school, and with peers. It is important to remember that psychiatric comorbid conditions usually require more attention and treatment than the tics. If ADHD, OCD, mood disorders, or non-OCD anxiety disorders are present, referral to a child and adolescent psychiatrist is appropriate for further evaluation and treatment. Treatment of the comorbid condition may often reduce tics secondarily.
Treatment of the tics themselves is indicated only when they are causing significant distress or functional impairment. Many children’s tics will attenuate or remit on their own following puberty.[3]Bloch MH, Peterson BS, Scahill L, et al. Adulthood outcome of tic and obsessive-compulsive symptom severity in children with Tourette syndrome. Arch Pediatr Adolesc Med. 2006;160:65-69.
http://archpedi.ama-assn.org/cgi/content/full/160/1/65
http://www.ncbi.nlm.nih.gov/pubmed/16389213?tool=bestpractice.com
[65]Pringsheim T, Okun MS, Müller-Vahl K, et al. Practice guideline recommendations summary: treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology. 2019 May 7;92(19):896-906.
https://www.doi.org/10.1212/WNL.0000000000007466
http://www.ncbi.nlm.nih.gov/pubmed/31061208?tool=bestpractice.com
All patients should be actively monitored on a regular basis, particularly through the developmental period from ages 6 to 15, in which tics are most likely to be prominent.
If treatment is indicated, evidence-based cognitive behavioural approaches are first-line for children with mild to moderate tics.
Medication should be recommended only when behavioural intervention has not been effective or is not available.[66]Verdellen C, van de Griendt J, Hartmann A, et al; European Society for the Study of Tourette Syndrome (ESSTS) Guidelines Group. European clinical guidelines for Tourette syndrome and other tic disorders. Part III: behavioural and psychosocial interventions. Eur Child Adolesc Psychiatry. 2011;20:197-207.
https://link.springer.com/article/10.1007%2Fs00787-011-0167-3
http://www.ncbi.nlm.nih.gov/pubmed/21445725?tool=bestpractice.com
The same goals and evaluation and treatment approaches are used in adults with TS. Adults are likely to have a more complex clinical picture, including comorbid psychiatric disorders and complications.
Pharmacological options
There are a number of pharmacological options for the treatment of tics, once the decision is made to use pharmacotherapy.[65]Pringsheim T, Okun MS, Müller-Vahl K, et al. Practice guideline recommendations summary: treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology. 2019 May 7;92(19):896-906.
https://www.doi.org/10.1212/WNL.0000000000007466
http://www.ncbi.nlm.nih.gov/pubmed/31061208?tool=bestpractice.com
Monotherapy at the lowest effective dose is generally recommended, although treatment must be tailored to each patient's individual needs.[72]Roessner V, Plessen KJ, Rothenberger A, et al; European Society for the Study of Tourette Syndrome (ESSTS) Guidelines Group. European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment. Eur Child Adolesc Psychiatry. 2011;20:173-196.
https://link.springer.com/article/10.1007%2Fs00787-011-0167-3
http://www.ncbi.nlm.nih.gov/pubmed/21445724?tool=bestpractice.com
[73]Waldon K, Hill J, Termine C, et al. Trials of pharmacological interventions for Tourette syndrome: a systematic review. Behav Neurol. 2013;26:265-273.
http://www.ncbi.nlm.nih.gov/pubmed/22713420?tool=bestpractice.com
Patients without ADHD or OCD
First-line pharmacotherapy for mild to moderate tics is generally an alpha-2 agonist (e.g., clonidine and guanfacine).[65]Pringsheim T, Okun MS, Müller-Vahl K, et al. Practice guideline recommendations summary: treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology. 2019 May 7;92(19):896-906.
https://www.doi.org/10.1212/WNL.0000000000007466
http://www.ncbi.nlm.nih.gov/pubmed/31061208?tool=bestpractice.com
Both clonidine and guanfacine have been shown to be efficacious for tics; generally guanfacine has a slightly more favourable side-effect profile, in that it may be less likely to cause drowsiness or sedation, but head-to-head comparisons with clonidine are not available.[50]Leckman JF, Pauls DL, Peterson BS, et al. Pathogenesis of Tourette syndrome. Clues from the clinical phenotype and natural history. Adv Neurol. 1992;58:15-24.
http://www.ncbi.nlm.nih.gov/pubmed/1414618?tool=bestpractice.com
[74]Jimenez-Jimenez FJ, Garcia-Ruiz PJ. Pharmacological options for the treatment of Tourette's disorder. Drugs. 2001;61:2207-2220.
http://www.ncbi.nlm.nih.gov/pubmed/11772131?tool=bestpractice.com
Patients with moderate to severe tics that cause functional impairment can be treated with an antipsychotic.[65]Pringsheim T, Okun MS, Müller-Vahl K, et al. Practice guideline recommendations summary: treatment of tics in people with Tourette syndrome and chronic tic disorders. Neurology. 2019 May 7;92(19):896-906.
https://www.doi.org/10.1212/WNL.0000000000007466
http://www.ncbi.nlm.nih.gov/pubmed/31061208?tool=bestpractice.com
Haloperidol, pimozide, and aripiprazole are the only US Food and Drug Administration-approved medications. However, adverse effects associated with their use are significant, including: sedation; depression; weight gain; hepatotoxicity; drug-induced movement disorders; acute extrapyramidal symptoms (akathisia and acute dystonic reactions); parkinsonism; and, with chronic use, tardive syndromes (such as tardive dyskinesias and tardive dystonia).[75]Robertson MM. Tourette syndrome, associated conditions and the complexities of treatment. Brain. 2000;123:425-462.
http://www.ncbi.nlm.nih.gov/pubmed/10686169?tool=bestpractice.com
[76]Panagiotopoulos C, Ronsley R, Elbe D, et al. First do no harm: promoting an evidence-based approach to atypical antipsychotic use in children and adolescents. J Can Acad Child Adolesc Psychiatry. 2010;19:124-137.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2868560/?tool=pubmed
http://www.ncbi.nlm.nih.gov/pubmed/20467549?tool=bestpractice.com
[77]Yoo HK, Joung YS, Lee JS, et al. A multicenter, randomized, double-blind, placebo-controlled study of aripiprazole in children and adolescents with Tourette's disorder. J Clin Psychiatry. 2013;74:e772-e780.
http://www.ncbi.nlm.nih.gov/pubmed/24021518?tool=bestpractice.com
Aripiprazole can also be associated with metabolic adverse effects, including weight gain, increase in blood sugar and insulin resistance, and increase in lipids.[78]De Hert M, Dobbelaere M, Sheridan EM, et al. Metabolic and endocrine adverse effects of second-generation antipsychotics in children and adolescents: a systematic review of randomized, placebo controlled trials and guidelines for clinical practice. Eur Psychiatry. 2011;26:144-158.
http://www.ncbi.nlm.nih.gov/pubmed/21295450?tool=bestpractice.com
Use of atypical antipsychotics (e.g., aripiprazole, risperidone, ziprasidone) has overtaken that of haloperidol and pimozide, because of the reduced occurrence of extrapyramidal symptoms. The risk of developing tardive syndromes may be less with second-generation agents.[79]Correll CU, Kane JM. One-year incidence rates of tardive dyskinesia in children and adolescents treated with second-generation antipsychotics: a systematic review. J Child Adolesc Psychopharmacol. 2007;17:647-656.
http://www.ncbi.nlm.nih.gov/pubmed/17979584?tool=bestpractice.com
[80]Pringsheim T, Marras C. Pimozide for tics in Tourette's syndrome. Cochrane Database Syst Rev. 2009;(2):CD006996.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD006996.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/19370666?tool=bestpractice.com
In a comparative double-blind parallel-group study of risperidone versus pimozide, both were found to be efficacious for tics; however, the risperidone-treated group had fewer extrapyramidal adverse effects.[81]Bruggeman R, van der Linden C, Buitelaar JK, et al. Risperidone versus pimozide in Tourette's disorder: a comparative double-blind parallel-group study. J Clin Psychiatry. 2001;62:50-56.
http://www.ncbi.nlm.nih.gov/pubmed/11235929?tool=bestpractice.com
[82]Cheng W, Lin L, Guo S. A meta-analysis of the effectiveness of risperidone versus traditional agents for Tourette's syndrome [in Chinese]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2012;37:359-365.
http://www.ncbi.nlm.nih.gov/pubmed/22561566?tool=bestpractice.com
A double-blind, placebo-controlled study of 28 patients with TS showed that ziprasidone was effective in reducing tics; somnolence was the most common adverse effect.[83]Sallee FR, Kurlan R, Goetz CG, et al. Ziprasidone treatment of children and adolescents with Tourette's syndrome: a pilot study. J Am Acad Child Adolesc Psychiatry. 2000;39:292-299.
http://www.ncbi.nlm.nih.gov/pubmed/10714048?tool=bestpractice.com
A double-blind, placebo controlled study of aripiprazole in children and adolescents with TS indicated that aripiprazole was more effective than placebo in tic reduction.[77]Yoo HK, Joung YS, Lee JS, et al. A multicenter, randomized, double-blind, placebo-controlled study of aripiprazole in children and adolescents with Tourette's disorder. J Clin Psychiatry. 2013;74:e772-e780.
http://www.ncbi.nlm.nih.gov/pubmed/24021518?tool=bestpractice.com
This finding has been replicated in meta-analyses on the effectiveness of aripiprazole in children and adolescents with tic disorders.[84]Liu Y, Ni H, Wang C, et al. Effectiveness and tolerability of aripiprazole in children and adolescents with Tourette's disorder: a meta-analysis. J Child Adolesc Psychopharmacol. 2016;26:436-441.
http://online.liebertpub.com/doi/full/10.1089/cap.2015.0125
http://www.ncbi.nlm.nih.gov/pubmed/26914764?tool=bestpractice.com
[85]Yang CS, Huang H, Zhang LL, et al. Aripiprazole for the treatment of tic disorders in children: a systematic review and meta-analysis. BMC Psychiatry. 2015;15:179.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518630
http://www.ncbi.nlm.nih.gov/pubmed/26220447?tool=bestpractice.com
Other atypical drugs such as quetiapine have not been studied as thoroughly, although there are some studies showing favourable findings.[86]de Jonge JL, Cath DC, van Balkom AJ. Quetiapine in patients with Tourette's disorder: an open-label, flexible-dose study. J Clin Psychiatry. 2007;68:1148-1150.
http://www.ncbi.nlm.nih.gov/pubmed/17685760?tool=bestpractice.com
Topiramate has demonstrated efficacy compared with placebo in a randomised controlled trial in TS, and is an alternative treatment option.[87]Yang CS, Zhang LL, Zeng LN, et al. Topiramate for Tourette's syndrome in children: a meta-analysis. Pediatr Neurol. 2013;49:344-350.
http://www.ncbi.nlm.nih.gov/pubmed/24139534?tool=bestpractice.com
[88]Jankovic J, Jimenez-Shahed J, Brown LW. A randomised, double-blind, placebo-controlled study of topiramate in the treatment of Tourette syndrome. J Neurol Neurosurg Psychiatry. 2010;81:70-73.
http://www.ncbi.nlm.nih.gov/pubmed/19726418?tool=bestpractice.com
Tetrabenazine, which depletes pre-synaptic monoamine stores and blocks post-synaptic dopamine receptors, has been used off-label to treat TS and seems to be well tolerated.[89]Jankovic J, Beach J. Long-term effects of tetrabenazine in hyperkinetic movement disorders. Neurology. 1997;48:358-362.
http://www.ncbi.nlm.nih.gov/pubmed/9040721?tool=bestpractice.com
The most common adverse effects are similar to those of antipsychotics, including extrapyramidal symptoms, but not tardive syndromes. It can also cause or worsen depression, but depression was reported as an adverse effect in only 7.6% of patients in a review of long-term treatment of hyperkinetic movement disorders.[90]Kenney C, Hunter C, Jankovic J. Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders. Mov Disord. 2007;22:193-197.
http://www.ncbi.nlm.nih.gov/pubmed/17133512?tool=bestpractice.com
Benzodiazepines such as clonazepam have been reported to be effective in the treatment of Tourette’s syndrome.[91]Gonce M, Barbeau A. Seven cases of Gilles de la tourette's syndrome: partial relief with clonazepam: a pilot study. Can J Neurol Sci. 1977 Nov;4(4):279-83.
https://www.doi.org/10.1017/s0317167100025129
http://www.ncbi.nlm.nih.gov/pubmed/271517?tool=bestpractice.com
However, there have been no systematic studies to support the use of this medication and the potential for tolerance and/or abuse should be considered. They are therefore considered as a last resort, and only for short-term treatment of acute tic exacerbations.
Use of valproate for treatment of TS in children is not recommended.[92]Yang CS, Zhang LL, Lin YZ, et al. Sodium valproate for the treatment of Tourette׳s syndrome in children: a systematic review and meta-analysis. Psychiatry Res. 2015;226:411-417.
http://www.ncbi.nlm.nih.gov/pubmed/25724485?tool=bestpractice.com
Botulinum toxin type A injections have been reported to reduce both the motor component of tics and the premonitory sensations.[93]Kwak CH, Hanna PA, Jankovic J. Botulinum toxin in the treatment of tics. Arch Neurol. 2000;57:1190-1193.
http://archneur.ama-assn.org/cgi/content/full/57/8/1190
http://www.ncbi.nlm.nih.gov/pubmed/10927800?tool=bestpractice.com
However, evidence is limited, and studies have focused on the treatment of specific or mild tics.[94]Pandey S, Srivanitchapoom P, Kirubakaran R, et al. Botulinum toxin for motor and phonic tics in Tourette's syndrome. Cochrane Database Syst Rev. 2018 Jan 5;1:CD012285.
https://www.doi.org/10.1002/14651858.CD012285.pub2
http://www.ncbi.nlm.nih.gov/pubmed/29304272?tool=bestpractice.com
[95]Porta M, Maggioni G, Ottaviani F, et al. Treatment of phonic tics in patients with Tourette's syndrome using botulinum toxin type A. Neurol Sci. 2004 Feb;24(6):420-3.
http://www.ncbi.nlm.nih.gov/pubmed/14767691?tool=bestpractice.com
[96]Rath JJ, Tavy DL, Wertenbroek AA, et al. Botulinum toxin type A in simple motor tics: short-term and long-term treatment-effects. Parkinsonism Relat Disord. 2010 Aug;16(7):478-81.
http://www.ncbi.nlm.nih.gov/pubmed/20034838?tool=bestpractice.com
Botulinum toxin type A injections may be considered when other recommended pharmacological options fail to reduce tics that are causing significant distress or functional impairment.
Patients with comorbid ADHD
Central nervous system stimulants, including methylphenidate and dexamfetamine, are the most effective treatment for ADHD. Meta-analyses of controlled trials do not support an association between new onset or worsening of tics and psychostimulant use.[97]Bloch MH, Panza KE, Landeros-Weisenberger A, et al. Meta-analysis: treatment of attention-deficit/hyperactivity disorder in children with comorbid tic disorders. J Am Acad Child Adolesc Psychiatry. 2009;48:884-893.
http://www.ncbi.nlm.nih.gov/pubmed/19625978?tool=bestpractice.com
[98]Cohen SC, Mulqueen JM, Ferracioli-Oda E, et al. Meta-analysis: risk of tics associated with psychostimulant use in randomized, placebo-controlled trials. J Am Acad Child Adolesc Psychiatry. 2015;54:728-736.
http://www.ncbi.nlm.nih.gov/pubmed/26299294?tool=bestpractice.com
Methylphenidate may be better tolerated than the amfetamines and is the recommended medication if a stimulant is indicated.[99]Robertson MM, Eapen V. Pharmacologic controversy of CNS stimulants in Gilles de la Tourette's syndrome. Clin Neuropharmacol. 1992;15:408-425.
http://www.ncbi.nlm.nih.gov/pubmed/1358442?tool=bestpractice.com
Atomoxetine has also proven beneficial; one study demonstrated that in children with ADHD and tics, tics improved relative to placebo.[100]Allen AJ, Kurlan RM, Gilbert DL, et al. Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders. Neurology. 2005;65:1941-1949.
http://www.ncbi.nlm.nih.gov/pubmed/16380617?tool=bestpractice.com
Clonidine and guanfacine have been found to be effective for ADHD in children with comorbid tics in combination with stimulants.[101]Tourette's Syndrome Study Group. Treatment of ADHD in children with tics: a randomized controlled trial. Neurology. 2002;58:527-536.
http://www.ncbi.nlm.nih.gov/pubmed/11865128?tool=bestpractice.com
A meta-analysis of medication efficacy in children with both persistent tics and ADHD symptoms revealed that methylphenidate was best for ADHD, and that alpha 2-agonists were best for both ADHD and tic symptoms.[97]Bloch MH, Panza KE, Landeros-Weisenberger A, et al. Meta-analysis: treatment of attention-deficit/hyperactivity disorder in children with comorbid tic disorders. J Am Acad Child Adolesc Psychiatry. 2009;48:884-893.
http://www.ncbi.nlm.nih.gov/pubmed/19625978?tool=bestpractice.com
[102]Rizzo R, Gulisano M, Calì PV, et al. Tourette syndrome and comorbid ADHD: current pharmacological treatment options. Eur J Paediatr Neurol. 2013;17:421-428.
http://www.ncbi.nlm.nih.gov/pubmed/23473832?tool=bestpractice.com
One meta-analysis and one Cochrane review reported that methylphenidate, alpha-2 agonists, and atomoxetine were effective in improving ADHD symptoms in children with comorbid tics.[97]Bloch MH, Panza KE, Landeros-Weisenberger A, et al. Meta-analysis: treatment of attention-deficit/hyperactivity disorder in children with comorbid tic disorders. J Am Acad Child Adolesc Psychiatry. 2009;48:884-893.
http://www.ncbi.nlm.nih.gov/pubmed/19625978?tool=bestpractice.com
[103]Osland ST, Steeves TD, Pringsheim T. Pharmacological treatment for attention deficit hyperactivity disorder (ADHD) in children with comorbid tic disorders. Cochrane Database Syst Rev. 2018 Jun 26;6:CD007990.
https://www.doi.org/10.1002/14651858.CD007990.pub3
http://www.ncbi.nlm.nih.gov/pubmed/29944175?tool=bestpractice.com
Alpha-2 agonists and atomoxetine significantly improved comorbid tic symptoms, and although supra-therapeutic doses of dexamfetamine reportedly worsened tics, therapeutic doses of dexamfetamine and methylphenidate did not.[97]Bloch MH, Panza KE, Landeros-Weisenberger A, et al. Meta-analysis: treatment of attention-deficit/hyperactivity disorder in children with comorbid tic disorders. J Am Acad Child Adolesc Psychiatry. 2009;48:884-893.
http://www.ncbi.nlm.nih.gov/pubmed/19625978?tool=bestpractice.com
Patients with comorbid OCD
Cognitive behavioural therapy (CBT) is an established treatment for OCD. It is the treatment of choice, with or without pharmacotherapy, for OCD in patients with TS. It involves a method known as exposure and response prevention, which aims to habituate the patient to the anxiety-producing situation.
If symptoms are refractory or incompletely treated with CBT, pharmacological therapy can be of additional benefit. Selective serotonin-reuptake inhibitors (SSRIs), such as fluoxetine, have been reported to be effective in the treatment of OCD and tics.[104]Scahill L, Riddle MA, King RA, et al. Fluoxetine has no marked effect on tic symptoms in patients with Tourette's syndrome: a double-blind placebo-controlled study. J Child Adolesc Psychopharmacol. 1997;7:75-85.
http://www.ncbi.nlm.nih.gov/pubmed/9334893?tool=bestpractice.com
Clomipramine, a tricyclic antidepressant, also inhibits noradrenaline and serotonin re-uptake and has been shown to be as effective as the SSRI fluvoxamine for treating OCD.[105]Milanfranchi A, Ravagli S, Lensi P, et al. A double-blind study of fluvoxamine and clomipramine in the treatment of obsessive-compulsive disorder. Int Clin Psychopharmacol. 1997;12:131-136.
http://www.ncbi.nlm.nih.gov/pubmed/9248868?tool=bestpractice.com