Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

without ADHD or OCD

1st line – cognitive behavioural approaches

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without ADHD or OCD
1st line – 

cognitive 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] 

Medication should be recommended only when behavioural intervention has not been effective or is not available.[66]

2nd line – alpha-2 agonist

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without ADHD or OCD
2nd line – 

alpha-2 agonist

Used for mild to moderate tics, with or without anxiety, that interfere with the patient's functioning, but are not severe enough to require antipsychotics.

First-line pharmacotherapy 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]

Monotherapy at the minimal dosage required is preferable, although the treatment must be tailored to each patient's condition.

Primary options

guanfacine: children >6 years of age: 0.25 mg orally once daily initially, increase gradually according to response, maximum 4 mg/day given in 2-3 divided doses; adults: 0.5 mg orally once daily initially, increase gradually according to response, maximum 4 mg/day given in 2 divided doses

OR

clonidine: children: consult specialist for guidance on dose; adults: 0.1 to 0.4 mg/day orally

OR

clonidine transdermal: adults: 0.1 mg/24 hour patch once weekly initially, increase at weekly intervals according to response, maximum 0.5 mg/24 hour patch per week

3rd line – antipsychotic or tetrabenazine or topiramate

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without ADHD or OCD
3rd line – 

antipsychotic or tetrabenazine or topiramate

Patients with moderate to severe tics 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]

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]

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

Doses should be started low and increased gradually, according to response.

Primary options

aripiprazole: children >6 years of age: 1 mg orally once daily initially, increase gradually according to response, maximum 10 mg/day; adults: 10-15 mg orally once daily initially, increase according to response, maximum 30 mg/day

OR

risperidone: children >6 years of age: 0.01 to 0.05 mg/kg/day orally; adults: 0.25 to 3 mg/day orally

OR

ziprasidone: children >6 years of age and adults: 5 mg/day orally initially, increase by 5-10 mg/day increments at weekly intervals according to response, maximum 40 mg/day

Secondary options

haloperidol: children >2 years of age: 0.05 to 0.15 mg/kg/day orally given in 1-2 divided doses; adults: 1-15 mg/day orally given in 1-2 divided doses

OR

pimozide: children >6 years of age: 1-6 mg/day orally given in 1-2 divided doses; adults: 2-10 mg/day orally given in 1-2 divided doses

Tertiary options

tetrabenazine: children and adults: consult specialist for guidance on dose

OR

topiramate: children and adults: consult specialist for guidance on dose

4th line – botulinum toxin

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without ADHD or OCD
4th line – 

botulinum toxin

May be considered when other pharmacological options fail to reduce tics that are causing significant distress or functional impairment.

Botulinum toxin type A injections have been reported to reduce both the motor component of tics and also the premonitory sensations.[93] However, evidence is limited, and studies have focused on the treatment of specific or mild tics.[94][95][96]

Primary options

botulinum toxin type A: children and adults: consult specialist for guidance on dose

with ADHD

1st line – stimulant

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with ADHD
1st line – 

stimulant

Comorbid ADHD can be a more prominent part of the overall clinical picture and should be treated in the context of tic management.

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]

Doses should be started low and increased gradually according to response.

Primary options

methylphenidate: children >5 years of age and adults: 2.5 to 5 mg orally (immediate-release) twice daily initially, increase gradually according to response, maximum 60 mg/day

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OR

dexamfetamine: children 4-6 years of age: 2.5 mg orally once daily initially, increase gradually according to response, maximum 20 mg/day; children >6 years of age and adults: 5 mg orally once or twice daily initially, increase gradually according to response, maximum 40 mg/day

OR

amfetamine/dexamfetamine: children 3-5 years of age: 2.5 mg orally (immediate-release) once daily initially, increase gradually according to response, maximum 40 mg/day given in 1-3 divided doses; children >5 years of age: 5 mg orally (immediate-release) once or twice daily initially, increase gradually according to response, maximum 40 mg/day given in 1-2 divided doses; adults: 5-60 mg orally (extended-release) once daily in the morning

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Consider – alpha-2 agonist

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with ADHD
Consider – 

alpha-2 agonist

Additional treatment recommended for SOME patients in selected patient group

Clonidine and guanfacine have been found to be effective for ADHD in children with comorbid tics in combination with CNS 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]

Doses should be started low and increased gradually according to response.

Primary options

guanfacine: children >6 years of age: 0.25 mg orally once daily initially, increase gradually according to response, maximum 4 mg/day given in 2-3 divided doses; adults: 0.5 mg orally once daily initially, increase gradually according to response, maximum 4 mg/day given in 2 divided doses

OR

clonidine: children: consult specialist for guidance on dose; adults: 0.1 to 0.4 mg/day orally

OR

clonidine transdermal: adults: 0.1 mg/24 hour patch once weekly initially, increase at weekly intervals according to response, maximum 0.5 mg/24 hour patch per week

2nd line – atomoxetine

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with ADHD
2nd line – 

atomoxetine

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

Doses should be started low and increased gradually according to response.

Primary options

atomoxetine: 40 mg orally once daily in the morning for at least 3 days, increase gradually according to response, maximum 100 mg/day given in 1-2 divided doses

with OCD

1st line – primary treatment for OCD

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with OCD
1st line – 

primary treatment for OCD

Cognitive behavioural therapy (CBT) is an established treatment for OCD, and is the treatment of choice, with or without pharmacotherapy.

It involves a method known as exposure and response prevention, which aims to habituate the patient to the anxiety-producing situation.

Consider – selective serotonin-reuptake inhibitor (SSRI) or clomipramine

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with OCD
Consider – 

selective serotonin-reuptake inhibitor (SSRI) or clomipramine

Additional treatment recommended for SOME patients in selected patient group

If symptoms are refractory or incompletely treated with CBT, pharmacological therapy can be of additional benefit.

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 reuptake and has been shown to be as effective as the SSRI fluvoxamine for treating OCD.[105]

Doses should be started low and increased gradually according to response.

Primary options

fluoxetine: children >6 years of age: 10-60 mg/day orally; adults: 40-80 mg/day orally

OR

sertraline: children >5 years of age: 25-200 mg/day orally; adults: 50-200 mg/day orally

OR

fluvoxamine: children ≥8 years of age: 25-200 mg/day orally; adults: 50-300 mg/day

Secondary options

clomipramine: children >9 years of age: 25-200 mg/day orally; adults: 25-250 mg/day orally

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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