Approach

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]

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]

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][65] 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]

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.

Behavioural approaches

Comprehensive behavioural intervention for tics (CBIT), with habit reversal therapy as its primary component, is recommended as the first-line treatment for TS.[65]

A number of reports have shown empirical benefit of habit reversal therapy, and it is supported by the largest body of evidence of behavioural therapies used in the management of TS. Studies have revealed a reduction in tic severity with habit reversal therapy when compared with supportive psychotherapy, in both adults and children.[67] Improvement in quality of life and psychosocial functioning, which remained stable at 6 months follow-up, was observed with both habit reversal and supportive psychotherapy.[68][69]

Exposure and response prevention may also be beneficial for TS.[66][70] Other behavioural therapies are generally considered to be adjunctive treatments.[71]

Pharmacological options

There are a number of pharmacological options for the treatment of tics, once the decision is made to use pharmacotherapy.[65] Monotherapy at the lowest effective dose is generally recommended, although treatment must be tailored to each patient's individual needs.[72][73]

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] 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][74]

Patients with moderate to severe tics that cause functional impairment can be treated with an antipsychotic.[65] 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][76][77] Aripiprazole can also be associated with metabolic adverse effects, including weight gain, increase in blood sugar and insulin resistance, and increase in lipids.[78]

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][80] 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][82] 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] 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] This finding has been replicated in meta-analyses on the effectiveness of aripiprazole in children and adolescents with tic disorders.[84][85]

Other atypical drugs such as quetiapine have not been studied as thoroughly, although there are some studies showing favourable findings.[86]

Topiramate has demonstrated efficacy compared with placebo in a randomised controlled trial in TS, and is an alternative treatment option.[87][88]

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] 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]

Benzodiazepines such as clonazepam have been reported to be effective in the treatment of Tourette’s syndrome.[91] 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]

Botulinum toxin type A injections have been reported to reduce both the motor component of tics and the premonitory sensations.[93] However, evidence is limited, and studies have focused on the treatment of specific or mild tics.[94][95][96] 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][98] Methylphenidate may be better tolerated than the amfetamines and is the recommended medication if a stimulant is indicated.[99]

Atomoxetine has also proven beneficial; one study demonstrated that in children with ADHD and tics, tics improved relative to placebo.[100]

Clonidine and guanfacine have been found to be effective for ADHD in children with comorbid tics in combination with stimulants.[101] 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][102]

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][103] 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]

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] 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] 

Complementary treatments

Complementary treatments, including herbs and supplements, are often used by families in the treatment of tics and TS. However, there is little evidence regarding efficacy.[106]

One randomised controlled study of omega-3 fatty acids derived from fish oil in 33 children and adolescents with TS reported that although this treatment did not reduce tic scores, it was beneficial in the reduction of tic-related impairment for some children and adolescents.[107]

A randomised, double-blind, placebo-controlled add-on trial with acetylcysteine found no evidence for efficacy of this supplement in treating tic symptoms.[108]

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