Approach Considerations
Some general principles must be kept in mind. First, present treatments of Tourette syndrome (TS) are purely symptomatic. No curative or preventive treatments are known. Second, tics often are not the worst problem. Third, this is a chronic disorder, and usually the goal is long-term benefit rather than quick improvement at any cost. Fourth, symptoms frequently improve or worsen over any period of time, even in untreated TS.
Corollaries of these principles include the following:
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Treatment is not always needed
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Treatment should be directed first at the most troublesome symptom
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Apparent success or failure of any treatment may be coincidental
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Beginning with reasonable trials of single agents is usually better than rushing to high doses or polypharmacy
TS has been described as either a neurological or a psychiatric disorder. These labels have nothing to do with the cause or treatment of TS but simply relate to the fact that neurologists and psychiatrists have been the main medical experts who have researched and treated TS.
These specialists have been well represented on the medical and scientific advisory boards to the Tourette Syndrome Association (TSA). A parent of a child with TS gave the author the following advice on choosing a physician: "We don't care if it's a psychiatrist or a neurologist, but we do care that it is someone who has experience treating Tourette's syndrome and who will treat all the symptoms."
Chronic motor (or vocal) tic disorder is managed similarly to TS and not discussed separately.
Discussed below are proven treatments for tics from replicated controlled studies, other treatments for tics, treatment for obsessive-compulsive symptoms in patients with tics, treatment for attention deficit–hyperactivity disorder (ADHD) in patients with tics, and treatment for other symptoms in patients with tics.
Treatments for Tics
Treatments for tics that have demonstrated efficacy in replicated controlled trials (RCTs) include the following:
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Dopamine D2 receptor antagonist therapy
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Dopamine agonist therapy
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Habit reversal therapy
Dopamine D2 receptor antagonist therapy
In 1959, soon after its introduction, chlorpromazine was reported to dramatically improve tic severity. [156] Since then, several allocation randomized controlled trials with various neuroleptics (eg, haloperidol, fluphenazine, pimozide) have confirmed these initial results. [157] On average, tic severity declines by approximately 50-80% with neuroleptic treatment.
Neuroleptic drugs are the current standard in terms of efficacy in the treatment of tics. They can be effective at doses far below the usual treatment dose for psychosis, and most adverse effects are manageable with pharmacologic manipulations. Unfortunately, many patients do not tolerate acute adverse effects (most commonly sedation, weight gain, depression, lethargy, and akathisia), and prolonged treatment poses a small risk of tardive dyskinesia. Therefore, other treatments have been investigated.
Risperidone, olanzapine, [158] and ziprasidone have been shown to produce at least as much clinical effect as a classic neuroleptic comparator, with fewer adverse effects. [159, 160, 161] A small study of clozapine suggested little effect. [162] Small studies of the dopamine D2R partial agonist aripiprazole show that it is effective for tic suppression. [163, 164] RCT data are not yet available, however.
Metoclopramide is a D2 receptor antagonist that is usually used for nausea. A case series [165] and an RCT [166] suggest it treats tics with good short-term tolerability. However, long-term use of metoclopramide has been associated with tardive dyskinesia.
Dopamine agonist therapy
Paradoxically, several mixed dopamine agonists have also been proven effective in reducing tic frequency. [23, 167, 25] To date, they have been tested exclusively in relatively low doses, partly because of a theory that, at these doses, they must antagonize dopamine function by selective action at presynaptic receptors.
Accumulating evidence suggests that this rationale is faulty, however, and trials with higher doses may be expected.
Habit reversal therapy
Five RCTs have demonstrated the efficacy of a specific form of behavior therapy for tics. [168, 169, 83, 170, 171, 172] The originally tested treatment consisted of a package of interventions called habit reversal therapy, [173] which comprises monitoring, relaxation, and other nonspecific elements of behavior therapy. The most important element is application of a competing response whenever the patient notices either a tic or the urge to tic.
Initially, heavy effort on the part of the patient may be needed. However, in all 4 reported studies, at long-term follow-up at least one half of treated patients had greater than 75% reduction in overall tic severity, whether based on self-report of home tic counts or on blind review of a videotape filmed in the clinic.
The effort expended by patients decreased dramatically as tic frequency declined, usually within the first few weeks of treatment. No substitution of other tics was noted, which commonly occurs when patients substitute a volitional action on a haphazard basis (see image below).
Tourette syndrome and other tic disorders. In a randomized controlled trial of habit reversal therapy (HRT), results differed significantly from those of a control therapy (massed practice; P < .001, analysis of variance). The HRT group had a 97% reduction in tics at 18-month follow-up, with 80% of patients tic-free.
Anecdotally, others have not found such impressive results, which may relate to patient selection or therapeutic technique. Further replication studies are being supported by the TSA.
Interestingly, several elements of this treatment are reminiscent of treatments used by Brissaud in 1902 (though with a radically different theoretical background). [8] Some data now explain why his treatments may not have been as effective. If the competing response is not paired with tic urges or tics, no benefit is observed. [174] Similarly, other behavior therapies used in the last several decades (eg, massed practice) are relatively ineffective.
Since the realization of the failures of psychoanalysis in treating tic disorders in the 1970s, patients and physicians have looked askance at psychological treatment, including behavior therapy. The available data no longer justify this view.
In fact, the plausibility of behavior therapy makes some sense on an intuitive level. Since tics respond briefly even to random environmental influences, it is not surprising that a well-designed behavioral intervention may produce more satisfactory results. Note that this is very different from simply telling the patient not to tic, or from "trying harder," neither of which tends to be effective over the long run.
A parallel is present with obsessions and compulsions, which share many phenomenologic characteristics with tics. Obsessive-compulsive disorder (OCD) symptoms do not respond well to psychodynamic treatment but are effectively treated with behavior therapy. Such treatment has biologic effects, such as normalization of abnormally high baseline metabolism in the orbitofrontal cortex. Case series have shown a reduction in tics by using the same behavior therapy method proven to benefit patients with OCD. [175, 176]
Other treatments for tics
Treatments for tics that have not been proven in replicated RCTs include the following:
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Guanfacine
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Clonidine
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Topiramate
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Norepinephrine reuptake inhibitors
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Botulinum toxin injections and oral baclofen
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Tetrabenazine
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Benzodiazepines
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Levetiracetam
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Selective serotonin reuptake inhibitors (SSRIs)
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Ondansetron
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Naltrexone/naloxone
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Cannabinoids
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Nicotine
Guanfacine was tested in an RCT in children with both ADHD and chronic tic disorders and was found to be clearly superior to placebo in the reduction of both ADHD and tic symptoms (31% on average), with few adverse effects. [177] This drug also has been shown to be efficacious in adults with nontic ADHD.
Clonidine has frequently been used to treat tics. A large RCT confirmed its efficacy for both ADHD symptoms and tics in patients with TS. [178] Clonidine or guanfacine may be appropriate as a first agent in many patients.
A double-blind, placebo-controlled study examined topiramate at a dosage of about 100 mg/day, and concluded that it may be safe and effective in decreasing Total Tic Score, but noted that a larger study with longer followup than their 10 weeks was needed. [179] However, a Chinese meta-analysis of 9 randomized controlled trials did not show significant difference in reducing tic occurrence between topiramate and haloperidol or tiapride. [180]
The norepinephrine reuptake inhibitors desipramine and atomoxetine have shown definite though modest benefit for tics in tic patients being treated for ADHD. [181, 182]
Botulinum toxin injections and oral baclofen were initially the subject of enthusiastic retrospective reports, but blinded trials of these 2 agents have revealed statistically significant but clinically modest benefit compared with placebo. [183] Botulinum toxin injections may improve urges or sensory tics, as well as observable tics, and it may be the treatment of choice for patients with a single, especially problematic, dystonic tic.
Tetrabenazine is a presynaptic dopamine-depleting agent with the advantage that it has not been reported to cause tardive movement disorders. A retrospective report noted marked clinical improvement in 57% of 47 patients with TS. [184] Its acute adverse effects are similar to those of neuroleptics. Tetrabenazine is approved by the US Food and Drug Administration (FDA) only for the treatment of chorea in Huntington's disease. [185]
Baclofen has little effect on average. However, it also has relatively few adverse effects and may be appropriate in select patients. [186]
Benzodiazepines, such as clonazepam, have reduced tic severity in some patients in retrospective reports. The effect is less than that of neuroleptics and probably nonspecific. Adverse effects are fairly common. However, clonazepam is tolerated better than haloperidol on average, and when no clinical pressure exists for urgent treatment, it is a reasonable option.
Levetiracetam was found to be well tolerated and possibly effective in an initial study. [187] However, two subsequent double-blind studies found no benefit. [188, 189]
SSRIs (eg, clomipramine, fluoxetine) improve tics in some patients, worsen them in others, and have no effect on tics in yet others. [190, 191, 192, 193] SSRIs may be reasonable first agents in patients with significant depression or OCD symptoms.
Ondansetron (8-24 mg/d) showed efficacy for a self-report but not an observer-rated measure of clinical improvement in a double-blind RCT in patients aged 12-46 years with TS. [16]
Naltrexone/naloxone have been reported helpful in a few patients, but other studies have shown transient worsening of tics with opioid antagonists. [194, 195] An RCT of naloxone showed some benefit at low doses, but worsening of tics at higher doses. [196] Case reports also have described benefit with opioid agonists. [197, 198]
Cannabinoids may reduce tic severity in some patients. Two RCTs support the efficacy of cannabinoids in this setting. [17]
Nicotine, [199] as well as a nicotine antagonist, mecamylamine, have been touted as treatments for tics. The antagonist has few adverse effects at the doses recommended, but 1 RCT found no statistically significant effect versus placebo. [200] A small blinded study did show some benefit. [88] However, given that nicotine is not a safe drug, its therapeutic use should await more compelling proof of efficacy.
Repetitive transcranial magnetic stimulation (rTMS) has not been effective in TS. [201] Surgical treatments are described in Surgical Care.
Treatment for Obsessive-Compulsive Symptoms in Patients With Tics
Initial treatment of OCD in patients with tics usually consists of an SSRI, generally at 3-4 times the antidepressant dose. More recently, risperidone monotherapy has been advocated as a first treatment, especially in patients with significant impairment from tics and from OCD symptoms.
Behavior therapy for OCD (eg, exposure and response prevention) is clearly proven to be effective. [202] A trial of behavior therapy is indicated for every patient with clinically significant OCD symptoms unless the symptoms are substantially remitted by another intervention.
In patients with tics (and perhaps in their relatives), obsessions respond better to fluoxetine plus haloperidol than to fluoxetine plus placebo. [203] Therefore, even if tics are well-controlled, addition of a D2 antagonist is indicated if bothersome OCD symptoms do not respond adequately to conventional initial treatment.
In a highly select group of patients who fit research criteria for sudden onset of tics or OCD associated with a proven recent streptococcal infection, OCD responded dramatically to intravenous immunoglobulin G (IVIG) or plasmapheresis. [126]
See the article Obsessive-Compulsive Disorder or the 2003 review by Miguel and colleagues [204] for further details of OCD treatment.
Treatment for ADHD in Patients With Tics
ADHD can be significant in patients referred for treatment of TS. Stimulants such as methylphenidate or dextroamphetamine represent the oldest class of psychotropic drugs still in common use, and have known safety profiles. They are the most effective treatments of ADHD. Methylphenidate may be better tolerated than dextroamphetamine in people with TS. [205]
Stimulant use in people with ADHD does not cause future drug abuse and may even prevent it. [206] A comorbid tic disorder should not be considered a serious contraindication to the use of stimulants for treatment of ADHD. [207] Several studies have shown that stimulants do not cause lasting worsening of tics. Their labeling includes warnings that they may cause tics, [205] but several recent prospective studies show that their effect on tics is at worst temporary, even with continued use. [208, 209, 210, 178]
Clonidine has also been proven useful for ADHD in people with TS. The benefits of clonidine and methylphenidate are additive. [178] Guanfacine most likely has similar effects.
RCTs have also shown that desipramine and atomoxetine help with ADHD symptoms in people with TS [181, 182] ; tics also improve slightly.
A double-blind RCT showed possible benefit for selegiline on ADHD symptoms and tics. [211]
Bupropion may benefit ADHD but may temporarily worsen tics. [212]
See the article Attention Deficit/Hyperactivity Disorder for further details on the conventional pharmacologic and behavioral treatment of ADHD.
Treatment for Other Symptoms in Patients With Tics
In carefully selected, tic-free adolescents with affect-laden episodes of aggression, replicated results from controlled trials show substantial efficacy of divalproex. [213] Whether these results can be confirmed for rage attacks in TS remains to be proven. A retrospective observational study found that explosive outbursts refractory to previous treatment improved with aripiprazole in 24 of 25 patients; however, 22% of subjects discontinued treatment due to inability to tolerate the drug. [214] SSRIs may also be useful. [190]
Research on the management of (other) conduct disorder symptoms in TS is sorely needed.
Stereotactic Neurosurgery
Stereotactic neurosurgery, either to place deep brain stimulators or to ablate tissue, is indicated only rarely for the treatment of obsessions, compulsions, and possibly tics. Case reports suggest deep brain stimulation (DBS) in various sites may be helpful.
A double-blind, randomized, cross-over trial by Ackermans et al determined that stimulation of the centromedian nucleus–substantia periventricularis–nucleus ventro-oralis internus crosspoint in the thalamus may reduce tic severity in refractory TS. [215] The study was limited by small size and unique indication.
This approach is limited to patients with exceptionally debilitating symptoms and those in whom prior, thorough trials of less dramatic interventions were ineffective. Such surgery should be carried out only in referral centers experienced with these procedures and after multispecialty evaluation of the patient.
Dietary Considerations
Ordinary diet is not known to have an effect on tics. Some concentrated dietary supplements used as drugs (also called nutraceuticals) may affect tic severity. For example, one of the author's patients had a marked increase in tic severity while taking an herbal product marketed for weight loss that contained ephedrine, ginkgo, caffeine, guaraná, and other ingredients.
Some nutraceuticals may possibly improve tic symptoms, but no adequate evidence exists at present. Furthermore, because these products do not undergo the meticulous scrutiny required of other drugs by the FDA, their safety in general is not well established. This is important since a large majority of patients with TS have used these drugs. However, both the National Institutes of Health and the TSA have expressed interest in supporting properly designed research on such treatments, and adequately tested products may be hoped for in the future.
Medical/Legal Issues
No reason exists to suspect that an individual has diminished capacity (eg, the ability to consent to treatment, participate in research, or make a will) because of a diagnosis of TS.
Parents of children with TS frequently ask whether TS causes diminished responsibility—for example, "When he hits his brother during a rage attack, is that him or is that the Tourette disease?" Occasionally the same question comes up in the legal arena, eg, "Should Mr A be exculpated for a crime he committed because he has TS?"
Group studies clearly show that TS can cause complex unwanted behavior. Sometimes, the answer is obvious, and sometimes, all that is needed is education about what is and is not typical of TS. The TSA and its local affiliates produce some excellent education materials addressed to family, friends, or teachers.
Convincingly answering what caused a specific complex act in an individual patient often is impossible. The author finds that discussions about whether the child is guilty tend to be fruitless. It is more helpful to focus on interventions and results: Are we likely to fix this problem by writing a prescription, by providing rewards and punishments, by instructing the patient to stop doing it, or by simply ignoring it?
The public does not necessarily credit the physician with indisputable authority regarding guilt, forgiveness, or legal culpability. However, physicians speak from a position of strength when they focus on available treatments and likely prognosis. Also, this approach focuses attention away from punishment and toward problem solving.
Some rights of people with TS are protected by US federal legislation. Examples include the right to public education in the least restrictive educational setting (Individuals with Disabilities Education Act) and the right to reasonable accommodations in public settings or the workplace (Americans with Disabilities Act). Legal advice and discussion with experienced support group members can be helpful in deciding when and how to pursue legal remedies under these laws.
Consultations
Patients should be evaluated at least once by someone with experience treating patients with TS, and they should be informed about how to contact a local support group or the national Tourette Syndrome Association office.
Additional referrals may be needed for the following measures, depending on the needs of the patient and the skills of the primary physician evaluating the patient's TS:
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Botulinum injections
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Habit reversal therapy for tics; behavior therapy for OCD, ADHD, or conduct disorder; or psychiatric care of OCD, ADHD, or comorbid anxiety or depressive illness
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Neuropsychological testing and educational interventions to address learning disabilities or to help formulate an individualized education program
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Education of teachers, classmates, or work colleagues may be helpful [216]
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Legal assistance (eg, to protect a child's educational rights under the federal Individuals with Disabilities Education Act or for protection under the Americans with Disabilities Act)
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Family counseling
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Tourette syndrome and other tic disorders. Schematic of the hypothetical reorganization of the basal ganglia output in tic disorders, with excitatory projections (open arrows) and inhibitory projections (solid arrows). Line thickness represents the relative magnitude of activity. When a discrete set of striatal neurons becomes active inappropriately (right), aberrant inhibition of a discrete set of internal segment of globus pallidus (GPi) neurons occurs. The abnormally inhibited GPi neurons disinhibit thalamocortical mechanisms involved in a specific unwanted competing motor pattern, resulting in a stereotyped involuntary movement.
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Tourette syndrome and other tic disorders. Segregated anatomy of the frontal-subcortical circuits: dorsolateral (blue), lateral orbitofrontal (green), and anterior cingulate (red) circuits in the striatum (top), pallidum (center), and mediodorsal thalamus (bottom).
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Tourette syndrome and other tic disorders. Graphic shows the relative likelihood of lifetime sensory tics in a given region, as based on self-report of patients with Tourette syndrome. Overt tics are distributed similarly.
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Tourette syndrome and other tic disorders. Immunologic response found in patients with Sydenham chorea is also found in patients with Tourette syndrome and obsessive-compulsive disorder. Points on the graph represent percent expression of D8/17 antigen on circulating B lymphocytes.
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Tourette syndrome and other tic disorders. In a randomized controlled trial of habit reversal therapy (HRT), results differed significantly from those of a control therapy (massed practice; P < .001, analysis of variance). The HRT group had a 97% reduction in tics at 18-month follow-up, with 80% of patients tic-free.
Tables
Symptom |
Description/Comment |
Sensory hypersensitivity |
Cannot stand to have wrinkly socks, cuts the tags off his or her shirts, refuses all but bland food, or becomes agitated in a visually complex environment |
Learning disability |
Approximately 20% in clinical samples, more closely associated with comorbid ADHD than with tics; also associated with male sex, earlier onset, severity, perinatal problems, and lower rates in family members [140] |
School phobia |
Can be an adverse effect of neuroleptic treatment |
Complex socially inappropriate behavior |
Insults, racial slurs, and paraphilias (or, more commonly, suppressed urges) are present in a large minority of patients with TS, associated with comorbid ADHD |
Rage attacks |
Sudden outbursts lasting approximately 5-30 min, usually in children or teenagers; inconsolable, unremitting violent frustration, commonly after being denied an unreasonable request; often followed by apparently sincere contrition and remorse |
Insistence on sameness |
Refusal to take a different route home or omit a step in a routine, even when hurried; often without a clear obsession or other obsessive-compulsive symptoms |
Anxiety and depression |
Common in patient samples but not clearly more common in the general TS population |
TS with both OCD and episodes of mania |
Surprisingly high rates of mania in patients with TS and OCD shown in at least 2 studies, management frequently difficult |
ADHD = attention deficit hyperactivity disorder; OCD = obsessive-compulsive disorder. |
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