Tics and tourette’s disorder: Which therapies, and when to use them
First-line medications have changed; a new 6-step approach considers clinical experience and insights into tic causes and comorbidities.
When managing pediatric tics and Tourette’s disorder, we do not seek to eliminate tic symptoms. Instead—based on evidence and our experience—we use a six-step approach to increase tic control, decrease our patients’ embarrassment and discomfort, and help them function more normally.
Drug therapy is not appropriate for all children and adolescents with tic disorders. Mild transient tics and Tourette’s disorder usually do not require treatment, and medications should not be given to patients whose tics do not impair their quality of life. Treatment is warranted, however, when tics interfere with peer relations, social interactions, academic performance, or activities of daily living.
Standard treatment of pediatric tic disorders is changing. Instead of using typical antipsychotics, many experienced clinicians are using other medications that are safer and more effective, particularly for children and adolescents with psychiatric comorbidities such as attention-deficit/hyperactivity disorder (ADHD). In these patients, it is difficult to avoid drug interactions and exacerbation of non-targeted conditions when you attempt to control the tics.
Diagnostic criteria for tic disorders
Transient tic disorder
Chronic motor or vocal tic disorder
Source: Adapted from DSM-IV-TR
TICS’ FLUCTUATING COURSE
Tics and Tourette’s disorder are characterized by a fluctuating course. Tic activity tends to occur in bursts over hours to weeks, followed by relative quiescence—spontaneously varying from one extreme to the other. Tics:
- are often preceded by mounting tension
- occur most frequently without volition, although they can be consciously suppressed
- are influenced by emotional state and tend to worsen during increased stress, excitement, or fatigue.
This variable natural history limits the value of uncontrolled studies, as symptom changes are not necessarily treatment-related.
DSM-IV-TR lists three types of childhood tic disorders (Table 1). Transient tics are seen in up to 10% of children, chronic tics are less common, and Tourette’s disorder has a community prevalence of 0.1 to 0.8%.1 Tic disorders usually present by age 11 2 and are three times more common in boys than in girls. One-half of cases remit spontaneously by late adolescence or adulthood, with important treatment implications.2
Causes. Neurophysiologic studies suggest disinhibition and dysfunction of dopamine and related serotonergic pathways in the cortico-striatal-thalamic-cortical circuit.3 Corollary neuroimaging studies have found decreased metabolism and blood flow in the basal ganglia—specifically the caudate nucleus, thalamus, globus pallidus, and putamen—and increased activity in the frontotemporal cortex—specifically the prefrontal and supplementary motor areas.4,5
Comorbidities. Tics and Tourette’s disorder rarely occur in isolation. The most common comorbidities and the frequencies with which they occur with tic disorders and Tourette’s disorder are:
- ADHD (50% and 90%)6
- obsessive-compulsive disorder (OCD)(11% and 80%)6
- major depressive disorder (40% and 44%).1,6
Additional comorbid problems include rage attacks, poor impulse control, and learning disorders. Many children with Tourette’s disorder display explosive rage.7
GUIDE TO WORKUP
During initial assessment, clearly delineate the onset, severity, complexity, and course of tics. Use empirically validated instruments—such as the Yale Global Tic Severity Scale8—at baseline and follow-up visits to monitor the natural history and clinical course, including treatment response. Determine predominant sources of distress and domains of impaired function.
Identify comorbid psychiatric illnesses (Box). Often, tics are not impairing9 and take on less clinical importance than the associated disorders. Prioritize target symptoms after considering the youth’s and family’s wishes. Follow a multidisciplinary approach, including behavioral, psychotherapeutic, and drug treatment as needed. Involve patients’ parents, schools, and teachers to help monitor functional impairment and treatment impact.
Use follow-up visits as needed to monitor treatment effectiveness. Follow-up frequency may decrease after tics are controlled to an acceptable level, although comorbid disorders may require continued attention.
PANDAS. Consider a diagnosis of pediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS) when tics present abruptly with upper respiratory tract illness.10 In this context, throat culture and antibody titers for group A beta hemolytic streptococcal infection may be warranted. Treat aggressively with antibiotics such as penicillin V when tests are positive.
Keys to managing childhood tic disorders
- Assess for comorbid illnesses, then prioritize and treat the most troublesome symptoms
- Aim to decrease rather than eliminate tic-related discomfort
- Medicate only if tics cause distress and dysfunction
- Use one agent when needed at the lowest effective dosage to minimize side effects and drug interactions
- Involve the family and school to monitor progress
- Reassess treatment efficacy often
6-STEP TREATMENT APPROACH
A six-step approach—based on our experience and available evidence—can guide treatment. Tics coexisting with ADHD/disruptive disorders, OCD/anxiety disorders, or major depressive disorder call for specialized strategies (Algorithm).
Step 1: Nondrug therapies. Psychoeducation, supportive therapy, and behavioral therapy are appropriate for all patients with burdensome tics. The unusual behaviors associated with tic disorders may have a far-reaching impact on a child’s functioning, self-esteem, and confidence. These effects can be moderated when children and their families understand tics’ fluctuating nature, including their:
- increase with stress and fatigue
- capacity for brief inhibition
- and high rate of spontaneous remission.
Because of this fluctuating pattern, observe the patient for a few weeks before starting medical treatment, unless dysfunction is severe. Observation is especially useful for initial presentations, in which symptom peaks tend to precede quiescence. Carefully weigh the benefits and potential risks of medical treatment for each patient.
Behavioral options include habit reversal, relaxation training, and self-monitoring. One of the few studies of behavioral therapy found tic symptoms decreased 55% with habit reversal, 44% with self-monitoring, and 32% with relaxation training. 11
Step 2: Adrenergic alpha-2 agonists. If medication seems appropriate for moderate to severe tics, we recommend clonidine or guanfacine (Table 2) as first-line therapy. These agents decrease the release of norepinephrine, dopamine, and gluta-mate, and norepinephrine turnover. 12 They are commonly used to treat Tourette’s disorder because they are better tolerated than antipsychotics, although controlled studies supporting their use are limited and the FDA has not approved this indication.
Approximately one-fourth of Tourette’s disorder patients respond well to clonidine.6 Pulse and blood pressure need to be monitored when using these medications, which in rare cases cause hypotension, bradycardia, and cardiac conduction delay. Because of its sedating properties, clonidine is frequently given at bedtime to promote sleep. Use caution when giving clonidine with medications that have potential cardiovascular effects—such as propranolol or tricyclic antidepressants.
Guanfacine is similar to clonidine except that it binds alpha-2a receptors more selectively and has a longer half-life. As such, it is associated with lower rates of sedation and hypotension than clonidine.
Step 3: Atypical antipsychotics. If symptoms do not respond adequately to an adrenergic alpha-2 agonist, try an atypical antipsychotic. Atypicals block dopamine (D2) receptors and—as a result of serotonergic-2 blockade—are less likely to cause extrapyramidal symptoms than are older antipsychotics.
Risperidone, the most studied atypical in Tourette’s disorder, has been shown to reduce symptoms by 21 to 61%—an effect significantly greater than placebo13 and similar to that of pimozide 14 and clonidine. Because it is also relatively well-tolerated, a risperidone trial is warranted before using typical antipsychotics. Tics may worsen during withdrawal while switching a patient from a typical to an atypical antipsychotic.
In one comparative, crossover study in adults with severe Tourette’s disorder, olanzapine was more effective at 5 and 10 mg/d than pimozide at 2 and 4 mg/d, respectively.15 Weight gain and abnormal glucose tolerance associated with olanzapine may be troublesome side effects. Ziprasidone has demonstrated a 35% decrease in tic symptoms in placebo-controlled studies.16 Its use has been associated with increased risk of QTc interval prolongation, requiring ECG monitoring.
Two case series have reported positive effects when quetiapine was used for tics and Tourette’s disorder.17 Like clozapine (which is ineffective for tics), quetiapine has relatively low D2 antagonist potency, suggesting its efficacy in treating tics may be limited. Unlike clozapine, however, quetiapine has few anticholinergic effects. Aripiprazole’s pharmacodynamic profile suggests similar efficacy, but its use in tic disorders has not been validated.
Algorithm 6-step treatment approach to tics and Tourette’s disorder
Further controlled trials of atypical antipsychotics in children and adolescents with tic disorders are needed. ECGs are recommended to monitor QTc intervals when using these medications.
Step 4: Typical antipsychotics. Haloperidol is the most commonly used medication for treating pediatric Tourette’s disorder13 and one of two drugs (pimozide is the other) approved by the FDA for this indication. These postsynaptic D2 antagonists are the most-studied and most-potent medications for treating tics and Tourette’s disorder. Many other typical antipsychotics such as fluphenazine, thioridazine, trifluoperazine, molindone, and thiothixene also have been used.
In controlled trials, haloperidol improved symptoms by 43 to 66%, 18 which was greater than placebo and equal to the effect of fluphenazine and trifluoperazine. Haloperidol, however, demonstrated a higher rate of EPS.
Pimozide’s indication for pediatric Tourette’s disorder applies only to treatmentrefractory cases. In controlled studies, pimozide was at least as effective as haloperidol,18 equal to risperidone 14 and less effective than olanzapine.15 Pimozide caused fewer side effects than haloperidol but more than atypical antipsychotics. Pimozide may cause QTc prolongation, and regular ECG monitoring is required.
Despite their efficacy, typical antipsychotics are associated with common and occasionally severe side effects that limit their long-term tolerability.6 Fear of tardive dyskinesia generally limits their use to only severe and treatmentresistant cases.
Step 5: Benzodiazepines. Although controlled trials of tic disorders have not evaluated benzodiazepines, these drugs were effective adjuncts in one case series using haloperidol.6 Anecdotal reports suggest they may reduce tics indirectly by lessening anxiety. Many experienced clinicians use clonazepam, 0.5 to 3 mg/d, or lorazepam, 0.5 to 4 mg/d, to treat Tourette’s disorder. Aside from its anxiolytic effects, clonazepam is also considered a minor mood stabilizer.
Step 6: Other options. Numerous novel medications have been studied in trials of tics and Tourette’s, although most—including the mixed D1/D2 agonist pergolide—have not been proven effective. In an uncontrolled study, the parenteral opioid antagonist naloxone decreased tics at low doses and increased them at higher doses. Botulinum toxin, nicotine, mecamylamine (a nicotine antagonist), baclofen, and flutamide have not proven efficacy in placebo-controlled trials.
Transcranial magnetic stimulation and neurosurgery have been used in patients with severe refractory tics and Tourette’s disorder but are not well-established treatments.
TICS AND COMORBIDITIES
ADHD. When it presents with tics, ADHD is frequently an independent target—or even the main target—of management. Because stimulants may exacerbate tics, nonstimulant medications such as clonidine, guanfacine, or desipramine could be tried first.19 Clonidine has been shown to ameliorate aggression, hyperactivity, and impulsivity but has sedating side effects. Atomoxetine—a nonstimulant ADHD medication—is another option for youth with comorbid tics and ADHD.
In our experience, carefully monitored stimulant trials may also be tried. A recent controlled trial showed that methylphenidate and clonidine, separately and combined, are effective for ADHD and comorbid Tourette’s disorder.20 Stimulants of potential benefit include methylphenidate and amphetamine (not just dextroamphetamine), including their long-acting formulations. Combining stimulants with antipsychotics or clonidine may also be useful.