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Tourette syndrome: Management

Tourette syndrome: Management
Literature review current through: Jan 2024.
This topic last updated: Nov 27, 2023.

INTRODUCTION — Tourette syndrome (TS) is a neurologic disorder manifested by motor and phonic tics with onset during childhood. This topic will review the management of TS. Other aspects of TS are reviewed separately. (See "Tourette syndrome: Pathogenesis, clinical features, and diagnosis".)

Other hyperkinetic movement disorders are discussed elsewhere. (See "Hyperkinetic movement disorders in children".)

APPROACH TO MANAGEMENT — The management of TS requires a careful assessment of the degree of functional impairment and effect on quality of life caused by tics and comorbid conditions [1]. Education is indicated for all.

Specific treatment of TS is guided by the need to treat the most troublesome symptoms, including both tics and comorbid conditions such as attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), behavioral problems, and mood disorders [2]. Therefore, it is important to determine which of these conditions is causing the greatest impairment [3]. Many patients require a combination of therapy to treat tics, ADHD, and OCD [4].

EDUCATION — Education about TS, its comorbid conditions, and its natural history is important for the patient, family, peers, teachers, employers, and all who interact with the patient [3,5,6]. There is no substitute for candid discussion with the patient and family about the fluctuating nature of tics and the need to individualize therapy and tailor it to the specific needs of the patient.

Information and resources are available online from the Tourette Association of America, Tourette Canada, and the Tourette Syndrome Association of Australia.

MANAGEMENT OF TICS — Intervention is indicated when symptoms of TS are interfering with social interactions, school or job performance, activities of daily living, or causing subjective discomfort, pain, or injury [2,3,5,7].

The main goal of treatment is to reduce the frequency of tics in order to improve function and quality of life [3,5]. However, there is no cure for TS, and treatment for tics seldom leads to complete cessation of tics [5].

Mild tics — Patients with TS who have tics that are mild and nondisabling should receive education, counseling, and supportive care; behavioral or pharmacologic tic suppression therapy is not clearly indicated [4]. This approach has been termed "watchful waiting" and is acceptable for those without functional impairment from their tics [5]. Patients are typically followed clinically with monitoring visits every 6 to 12 months (algorithm 1). (See 'Education' above.)

Debilitating tics

For patients with TS and tics that are causing psychosocial, physical, functional, or other problems, we suggest habit reversal training with Comprehensive Behavioral Intervention for Tics (CBIT) where access to this therapy is available, rather than treatment with medication (algorithm 1). (See 'Habit reversal training' below.)

When CBIT is not an option, we suggest pharmacologic treatment; options include guanfacine or clonidine (for children with comorbid attention deficit hyperactivity disorder [ADHD]), tetrabenazine, deutetrabenazine, topiramate, aripiprazole, fluphenazine, and tiapride (not available in the United States). (See 'Alpha adrenergic agonists' below and 'Antidopaminergic drugs' below and 'Topiramate' below.)

For patients with TS who have only focal motor or phonic tics, and patients who have repetitive, violent neck extension tics, we suggest treatment with botulinum toxin injections into the affected muscles. (See 'Botulinum toxin injection' below.)

Habit reversal training — A behavioral therapy called habit reversal training (HRT) may be effective for improving tics and controlling symptoms in TS [8-10].

Components – HRT consists of two main components. These are [11]:

Tic-awareness training, which teaches patients to recognize early signs that precede the onset of a tic

Competing-response training, which teaches patients to perform a voluntary movement that is incompatible with the particular type of tic

CBIT is based primarily on HRT and adds a third component of relaxation training and functional intervention to identify and mitigate situations that may exacerbate tic severity [9]. Where access is available, we suggest HRT with CBIT as initial therapy for patients with TS and debilitating tics.

Efficacy – A systematic review and meta-analysis of eight trials involving 438 subjects with TS who were treated with behavioral therapy (either HRT or CBIT) concluded that behavioral therapy produced moderate treatment effects and that participants receiving behavioral therapy were more likely to exhibit a treatment response compared with control interventions [8].

One of the largest trials in the meta-analysis randomly assigned 126 children (ages 9 to 17 years) with TS to either behavioral therapy, consisting mainly of HRT, or to control treatment, consisting of supportive therapy and education [9,12]. Outcome evaluators were blind to treatment allocation. After 10 weeks of treatment, the group assigned to behavioral therapy had a significantly greater reduction on the total tic score of the Yale Global Tic Severity Scale compared with the control group (-7.6 versus -3.5, group difference 4.1, 95% CI 2.0-6.2). The group difference of 4.1 was considered clinically meaningful. In addition, the behavioral therapy group had a significantly greater improvement on a global measure of overall treatment response.

Limitations – Because of some barriers, only a limited number of patients are able to access CBIT as compared with pharmacologic treatment, which actually may be more effective. CBIT is generally not covered by insurance and there is an insufficient number of well-trained therapists. Furthermore, the success of this behavioral management is critically dependent on active involvement of the parents and the therapist, both of whom must be skilled in the various HRT and CBIT techniques. Given the demands on time and effort on the part of the patient, the therapist, and parents, it is unlikely that all parties will be able to maintain the needed compliance with the training program to provide sustained benefit. There is also some concern as to whether the mental effort required to fully comply with the various components of CBIT could actually interfere with patient's attention and learning.

While there has been a great deal of effort exerted over the last several decades making the scientific, clinical, and lay community understand the biologic basis of TS, the reported response to behavioral therapy may be misinterpreted by some as evidence that tics and TS are of psychologic etiology. This is one reason, albeit wrong, why behavioral therapies are often not covered by insurance or other third-party payers.

To overcome some of the limitations of access, alternative modes of delivery are being explored for various forms of psychotherapy [13,14]. One example in TS is internet-delivered, therapist-supported exposure and response prevention (ERP), which in a randomized trial in 224 patients with TS was more effective for tic reduction than a psychoeducation control [13].

Alpha adrenergic agonists — The alpha adrenergic agonists guanfacine and clonidine are effective for treating the symptoms of ADHD and may be helpful in patients with TS who have ADHD or predominant behavioral symptoms, particularly impulse control problems and rage attacks. (See "Pharmacology of drugs used to treat attention deficit hyperactivity disorder in children and adolescents", section on 'Alpha-2-adrenergic agonists'.)

Data from randomized trials suggest that clonidine [15-19] and guanfacine [20-22] are useful for suppressing tics [23], but the evidence for tic reduction with these agents is not consistent. In some trials, alpha adrenergic agonists were no better than placebo for reducing tics [16,21,22], and indirect evidence suggests that the magnitude of effect is less than that of the dopamine antagonists [4,24]. Nevertheless, meta-analyses have concluded that there is moderate confidence that clonidine is more effective for tic reduction compared with placebo, whereas there is low confidence that guanfacine is more effective than placebo [10,24].

Although alpha adrenergic agonists are only modestly effective against tics, they are used by some, particularly pediatricians and pediatric psychiatrists, as first-line therapy in patients with early or mild tics. When choosing an alpha adrenergic agonist, guanfacine may be preferred over clonidine because it is less sedating and can be given in fewer daily doses [25].

Suggested dosing regimens of guanfacine and clonidine for children with ADHD, and potential adverse effects, are discussed in detail separately. (See "Pharmacology of drugs used to treat attention deficit hyperactivity disorder in children and adolescents".)

Antidopaminergic drugs — In the United States, the only approved drugs for the treatment of TS are haloperidol, pimozide, and aripiprazole. All of these drugs act by blocking dopamine receptors and, as such, may cause tardive dyskinesia. While in the past we have used drugs that block dopamine receptors, such as fluphenazine or risperidone, we have gradually shifted to dopamine depleters, such as tetrabenazine, deutetrabenazine, and valbenazine, as the initial drugs of choice for patients with troublesome tics [26-29]. These drugs deplete dopamine by inhibiting vesicular monoamine transporter type 2 (VMAT2), and are particularly useful because observational data suggest that they are at least as effective as the typical neuroleptics, but do not cause tardive dyskinesia [1,27,30].

Practice may vary regionally, however, based on availability of VMAT2 inhibitors and other factors. As an example, European clinical guidelines for TS do not include VMAT2 inhibitors as an evidence-based treatment option; in a survey of experts, the top three recommended agents in decreasing order of preference were, for children, aripiprazole, clonidine, and tiapride (a benzamide antipsychotic with selective D2/D3 receptor antagonism, not available in the United States) and, for adults, aripiprazole, haloperidol, and clonidine [31].

VMAT2 inhibitors – The typical starting dose of tetrabenazine for a child with TS is 6.25 mg twice a day and the dose is gradually increased in weekly intervals up to a total of 75 mg per day in three divided doses, depending on the age of the patient, clinical response, and adverse effects. Analysis for CYP2D6 genotype to determine metabolizer status for patients prescribed doses >50 mg/day is recommended by some but is usually not necessary [32].

Adverse effects of tetrabenazine include sedation, akathisia, parkinsonism, and depressed mood. There is also a risk of suicidality.

Other VMAT2 inhibitors currently available in the United States include deutetrabenazine and valbenazine [33]. However, the improvement observed in the open-label studies of deutetrabenazine could not be replicated in two randomized double-blind placebo-controlled trials (ARTISTS1 [34] and ARTISTS2 [35]) involving 119 and 158 patients with TS, respectively [36]. There are many possible explanations for the unexpected negative results, including difficulties in assessing a highly variable disorder and subtherapeutic dosing. Indeed, long-term, open-label extension of these short-term controlled trials clearly shows the benefit of deutetrabenazine in suppressing tics. Given the benefits observed in real-world experience and open-label trials, as well as good tolerability without significant depression or risk of tardive dyskinesia, VMAT2 inhibitors should be considered as potential therapies before the introduction of antipsychotic medications.

Antipsychotics – Although haloperidol, pimozide, and aripiprazole are the only drugs approved by the US Food and Drug Administration (FDA) for the treatment of TS, they are not frequently used because of potentially serious adverse effects. If patients do not adequately respond to alpha adrenergic agonists, they may respond to one of the following antipsychotic agents to control their tics: fluphenazine (starting at 1 mg daily, and increasing in 0.5 mg to 1 mg increments every week based upon response and tolerability, with a usual dose range of 0.25 to 10 mg/day), aripiprazole (2.5 to 20 mg/day), or risperidone (0.5 to 5 mg per day).

Common adverse effects of first-generation antipsychotics (eg, fluphenazine) include parkinsonism, akathisia, acute dystonic reactions, tardive dyskinesia, and hyperprolactinemia.

Adverse effects associated with second-generation antipsychotics (eg, aripiprazole, risperidone) include metabolic side effect, QT interval prolongation, akathisia, and tardive dyskinesia. Risperidone also causes parkinsonism. Children, especially pre-adolescents, are more susceptible to the metabolic adverse effects (weight gain, diabetes, hyperlipidemia) than older patients. A table provides a recommended schedule for monitoring metabolic effects of first and second-generation antipsychotics (table 1).

Other antidopaminergic strategies are under investigation. As an example, ecopipam is an oral selective D1 receptor antagonist that is being studied in TS as well as other disorders. In two short-term trials in children and adolescents with TS, ecopipam reduced tic severity compared with placebo and was well tolerated [37,38]. The most common side effects were headache, insomnia, fatigue, and somnolence. Neither weight gain nor tardive dyskinesia was observed with up to 12 weeks of treatment. Longer studies in a more diverse patient population are needed.

Topiramate — Evidence from small randomized controlled trials suggests that topiramate provides short-term benefit for tic suppression in patients with TS [39,40]. Although larger and longer-term trials are needed to confirm the efficacy and tolerability of topiramate in the treatment of TS, a trial may be preferred before committing a patient to an antipsychotic agent since its side effect profile is more favorable.

Botulinum toxin injection — Focal motor and phonic tics may be treated effectively with injections of botulinum toxin into the affected muscles [41-44]. In a single randomized controlled clinical trial of 18 patients with simple motor tics, botulinum toxin treatment resulted in a significant decline in the number of tics per minute within two weeks of injection compared with placebo (39 percent reduction versus 6 percent increase) [42]. Botulinum toxin may be effective not only for the treatment of motor tics, such as blinking and cervical dystonic tics but also for the local premonitory urge [10], although high-quality evidence is lacking [45]. Patients with repetitive, violent neck extension ("whiplash") tics can be treated with botulinum toxin injections into the affected neck muscles early to prevent secondary compressive cervical myelopathy [46]. Patients with severe, loud screaming tics (even when associated with coprolalia) have been reported to benefit from botulinum toxin injections into vocal cords.

Failure of initial therapy — When initial therapy with CBIT is unsuccessful or patients are unable to access CBIT, reasonable options include pharmacotherapy with a dopamine depleting drug, a dopamine blocking drug, an alpha adrenergic agonist, or topiramate. Botulinum toxin is particularly helpful in focal tics, such as blinking and cervical tics.

Patients with TS who have disabling tics that are refractory to optimal medical management, including various dopamine depleters and dopamine receptor blockers, may be candidates for deep brain stimulation (DBS) of globus pallidus, thalamus, or other subcortical targets [47-50]. Preliminary evidence, while inconsistent, suggests that DBS can lead to symptomatic improvement in tics but is associated with a high rate of adverse events [51-56]. Larger clinical trials are needed to determine whether DBS is safe and beneficial for controlling tics in patients with TS.

Duration of therapy — Although there is no fixed time to stop treatment, it is reasonable to gradually taper off drug therapy for tics after age 18 years, at which time tics often spontaneously resolve [3].

MANAGEMENT OF COMORBIDITIES

Attention deficit hyperactivity disorder — Attention deficit hyperactivity disorder (ADHD) is often associated with TS. Behavioral interventions are preferred as the initial intervention for ADHD in preschool children (age 4 through 5 years) and as adjuncts to ADHD medication for school-aged children and adolescents. Medication options that treat both tics and ADHD include the alpha adrenergic agonists guanfacine and clonidine. (See 'Alpha adrenergic agonists' above.)

When central nervous system (CNS) stimulants are required to control ADHD symptoms in the setting of tics, we prefer to treat the tics first with an alpha-adrenergic agonist (eg, guanfacine, clonidine) before initiating CNS stimulants such as methylphenidate, dexmethylphenidate, methamphetamine, or dextroamphetamine, because clinical experience suggests that these drugs tend to trigger or exacerbate tics. We find atomoxetine, a non-stimulator, only modestly effective in the treatment of TS-related ADHD. Antidopaminergic drugs may be used as second-line therapies for worsening tics. (See "Attention deficit hyperactivity disorder in children and adolescents: Overview of treatment and prognosis".)

Other experts prefer to start treatment for ADHD and closely follow tic severity, despite concerns that CNS stimulants may precipitate or exacerbate tics [57]. A meta-analysis found that methylphenidate did not worsen tic severity among four placebo-controlled randomized trials involving 191 subjects with both TS and ADHD [58]. In addition, a later meta-analysis of 22 studies involving 2385 children with ADHD and no tic disorder at baseline found that psychostimulant treatment compared with placebo did not increase the risk of new-onset or worsening tics [59]. (See "Pharmacology of drugs used to treat attention deficit hyperactivity disorder in children and adolescents", section on 'Stimulant adverse effects'.)

Obsessive-compulsive disorder — For children who have TS and comorbid obsessive-compulsive disorder (OCD), the suggested initial treatment of OCD is cognitive-behavioral therapy (CBT) with or without pharmacotherapy with a selective serotonin reuptake inhibitor (SSRI). Antipsychotic therapy may be used selectively for severe tics that persist despite these therapies. Management of OCD, including tic-related OCD, is reviewed in detail separately. (See "Obsessive-compulsive disorder in children and adolescents: Treatment overview", section on 'Treatment of associated syndromes'.)

GENETIC COUNSELING — While there is evidence of a genetic component in the etiology of TS [60], the pathogenesis is complex, and the genetic basis of TS remains poorly understood. (See "Tourette syndrome: Pathogenesis, clinical features, and diagnosis", section on 'Pathogenesis'.)

The rate of TS in parents of an affected child has been reported to be up to 16 percent [61], although the rate is much higher if a parental history of childhood tics, attention deficit hyperactivity disorder (ADHD), or obsessive-compulsive disorder (OCD) is considered. Using rigorous diagnostic criteria, one study found that both parents had some features of TS or an associated disorder (tics, OCD, or ADHD), so-called bilineal transmission, in at least 25 percent of TS cases [62].

Most but not all studies suggest that the prevalence of TS is similar among different ethnic groups [61]. However, a population study from Japan found a comparatively low rate of TS in both parents (approximately 2 percent) [63].

In siblings of an affected child, the risk of TS is approximately 8 percent in most studies [61] but was 2 percent in the Japanese population study [63]. The risk of OCD in siblings is 10 to 22 percent, while the risk for chronic tics in siblings ranges from 0 to 11 percent [64,65].

For offspring of parents with TS, a prospective longitudinal study found that the overall empiric risk of TS was 22 percent, while the risk of any tic disorder was >50 percent [66]. The risk of TS was increased in bilineal families (43 percent, compared with 15 percent for unilineal families). Additionally, the rates of any tic diagnosis, OCD, and ADHD were increased in bilineal compared with unilineal families [66].

PROGNOSIS — Tics often decline during adolescence and young adulthood and even resolve in a substantial minority. The natural history of TS is reviewed in greater detail separately. (See "Tourette syndrome: Pathogenesis, clinical features, and diagnosis", section on 'Onset and natural history'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Tourette syndrome".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Tourette syndrome (The Basics)")

SUMMARY AND RECOMMENDATIONS

General approach – Specific treatment of Tourette syndrome (TS) is guided by the need to treat the most troublesome symptoms, including both tics and comorbid conditions such as attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). Education is indicated for all. (See 'Approach to management' above and 'Education' above.)

Mild, nondisabling tics – Patients with TS who have tics that are mild and nondisabling should receive education, counseling, and supportive care; behavioral or pharmacologic tic suppression therapy is not clearly indicated (algorithm 1). (See 'Mild tics' above.)

Patients with comorbid ADHD – For patients who have TS and ADHD, behavioral interventions are preferred to medication as the initial treatment for ADHD in preschool children and as adjuncts to medication for school-aged children and adolescents. Medication options that treat both tics and ADHD include the alpha adrenergic agonists guanfacine or clonidine. (See 'Attention deficit hyperactivity disorder' above and 'Alpha adrenergic agonists' above.)

Patients with comorbid OCD – For children who have TS and comorbid OCD, cognitive-behavioral therapy with or without pharmacotherapy with a selective serotonin reuptake inhibitor (SSRI) is the preferred initial treatment. (See "Obsessive-compulsive disorder in children and adolescents: Treatment overview", section on 'Treatment of associated syndromes'.)

Debilitating tics (algorithm 1)

For patients with TS and tics that are causing psychosocial, physical, functional, or other problems, we suggest habit reversal training with Comprehensive Behavioral Intervention for Tics (CBIT) where access to this therapy is available, rather than treatment with medication (Grade 2C). (See 'Habit reversal training' above.)

When CBIT is not an option for patients with TS and debilitating tics, we suggest medication treatment with tetrabenazine or deutetrabenazine (Grade 2C). Alternatives include topiramate, fluphenazine, aripiprazole, and risperidone. (See 'Antidopaminergic drugs' above and 'Topiramate' above.)

For patients with TS who have only focal motor or phonic tics, we suggest treatment with botulinum toxin injections into the affected muscles (Grade 2C). (See 'Botulinum toxin injection' above.)

Genetic counseling – In siblings of an affected child, the risk of TS is approximately 8 percent in most studies. For offspring of a parent with TS, the empiric risk of TS is approximately 15 percent. (See 'Genetic counseling' above.)

Prognosis – Tics often decline during adolescence and young adulthood and even resolve in a substantial minority. The natural history of TS is reviewed in greater detail separately. (See "Tourette syndrome: Pathogenesis, clinical features, and diagnosis", section on 'Onset and natural history'.)

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Topic 126069 Version 12.0

References

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