Treatment of Tourette syndrome
Tourette syndrome (also Tourette's syndrome or TS) is an inherited neuropsychiatric disorder with onset in childhood, characterized by the presence of motor and phonic tics. Treatment of Tourette syndrome has the goal of managing symptoms to achieve optimum functioning, rather than eliminating symptoms; not all persons with Tourette's require treatment, and there is no cure or universally effective medication. Explanation and reassurance alone are often sufficient treatment; education is an important part of any treatment plan.
Tourette syndrome patients may exhibit symptoms of other comorbid conditions along with their motor and phonic tics. Associated conditions include attention-deficit hyperactivity disorder (ADD or ADHD), obsessive-compulsive disorder (OCD), learning disabilities and sleep disorders. Patients who have ADHD along with Tourette's may also have problems with disruptive behaviors, overall functioning, and cognitive function. Co-occurring OCD can also be a source of impairment, necessitating treatment. Not all persons with tics will also have other conditions and not all persons with tics require treatment, but when comorbid disorders are present, they often require treatment.
Stimulants (such as Adderall and Ritalin) are underused in the treatment of ADHD when tics are also present because of fears that they increase tics. Experimental treatments such as deep brain stimulation, nicotine, cannabis and complementary and alternative medicine approaches have widespread appeal but unproven safety and efficacy.
Treatment of Tourette syndrome can be divided into treatment of tics, and treatment of co-occurring conditions, which, when present, are often a larger source of functional impairment than the tics themselves.
There is no cure for Tourette's and no medication which works universally for all individuals without significant adverse effects; knowledge and understanding are the best treatments available for tics. Management of the symptoms of Tourette's may include pharmacological, behavioral and psychological therapies. While pharmacological treatment is reserved for more severe symptoms, other types of treatments may help avoid or improve symptoms of depression or social isolation, and improve supportive family functioning. Educating the patient, family, and surrounding community (school, church, friends, etc.) is a key part of treatment.
The majority of people with TS require no medication, but medication is available to help when symptoms interfere with functioning. Because children with tics often present to physicians when their tics are at their highest severity, and because of the waxing and waning nature of tics, medication is not usually started immediately or changed often. Frequently, the tics subside with understanding of the condition and a supportive environment. When medication is necessary, pharmaceutical intervention should be targeted at the most impairing symptoms, taking into account co-occurring conditions such as ADHD or OCD, which when present, may warrant treatment even when tics are mild.
The classes of medication with the most proven efficacy in treating tics—typical and atypical neuroleptics including risperidone (trade name Risperdal), ziprasidone (Geodon), haloperidol (Haldol), pimozide (Orap) and fluphenazine (Prolixin)—can have long-term and short-term adverse effects. The antihypertensive agents, clonidine (Catapres) and guanfacine (Tenex), are also used to treat tics; studies show variable efficacy, but a lower side effect profile than the neuroleptics. Stimulants and other medications may be useful in treating ADHD when it co-occurs with tic disorders. Drugs from several other classes of medications can be used when stimulant trials fail, including guanfacine (Tenex), atomoxetine (Strattera) and tricyclics. Clomipramine (Anafranil), a tricyclic antidepressant, and SSRIs—a class of antidepressants including fluoxetine (Prozac), sertraline (Zoloft), and fluvoxamine (Luvox)—may be prescribed when a Tourette's patient also has symptoms of obsessive–compulsive disorder.
Treatment of tics
There are no medications specifically designed to target tics, although some antipsychotics (for example, pimozide) have been FDA-approved for treating Tourette's. Medications which are used as primary treatment in other conditions are used with some success in treating tics. Neuroleptic medications (antipsychotics), such as haloperidol (brand name Haldol) or pimozide (brand name Orap), have historically been and continue to be the medications with the most proven efficacy in controlling tics. These medications work by blocking dopamine receptors, and are associated with a high side effect profile. The traditional antipsychotic drugs are associated with tardive dyskinesia when used long-term; and parkinsonism, dystonia, dyskinesia, and akathisia when used short-term. Additional side effects can be school phobia (a form of separation anxiety), depression, weight gain, and cognitive blunting (dulling of cognitive ability). Another traditional antipsychotic used in treating Tourette's is fluphenazine (brand name Prolixin), although the evidence supporting its use is less than that of haloperidol and pimozide.
Newer neuroleptics, the atypical neuroleptics, are an alternative to the traditional medications used for treating tics. These medications have more selective dopamine blocking effects, or block serotonin with some blocking of dopamine. The medications in this class used to treat tics include risperidone (brand name Risperdal), olanzapine (brand name Zyprexa), ziprasidone (brand name Geodon), quetiapine (brand name Seroquel), clozapine (brand name Clozaril), tiapride, and sulpiride. They seem to have lower risks of neurological side effects (such as tardive dyskinesia) when used short-term, but longer trials are needed to confirm this. Some of the side effects associated with these medications are insomnia, weight gain, and school phobia. Abnormalities in metabolism, cardiac conduction times, and increased risk of diabetes are concerns with these medications. There is good empirical support for the use of risperidone, and less support for the others.
The α2-adrenergic receptor agonists (antihypertensive agents) show some efficacy in reducing tics, as well as other comorbid features of some people with Tourette's. Originally developed to treat high blood pressure, these medications are a safer alternative to neuroleptic medications for the people with TS that respond to them. This class of medication is often the first tried for tics, as the antihypertensives have a lower side effect profile than some of the medications which more proven efficacy. The evidence for their safety and efficacy is not as strong as the evidence for some of the standard and atypical neuroleptics, but there is fair supportive evidence for their use, nonetheless. This class of medication takes about six weeks to begin to work on tics, so sustained trials are warranted. Because of the blood pressure effects, antihypertensive agents should not be discontinued suddenly. Clonidine (brand name Catapres) works on tics for about half of people with TS. Maximal benefit may not be achieved for 4–6 months. A small number of patients may worsen on clonidine. Guanfacine (brand name Tenex) is another antihypertensive that is used in treating TS. Side effects can include sedation, dry mouth, fatigue, headaches and dizziness. Sedation can be problematic when treatment is first initiated, but may wear off as the patient adjusts to the medication.
Treatment of ADHD in the presence of tic disorders
Patients with Tourette's who are referred to specialty clinics have a high rate of comorbid attention-deficit hyperactivity disorder (ADHD), so the treatment of ADHD co-occurring with tics is often part of the clinical treatment of Tourette's. Patients who have ADHD along with Tourette's may also have problems with disruptive behaviors, overall functioning, and cognitive function, accounted for by the comorbid ADHD, highlighting the importance of identifying and treating other conditions when present.
The treatment of ADHD in the presence of tic disorders has long been a controversial topic. Past medical practice held that stimulants (such as Ritalin) could not be used in the presence of tics, due to concern that their use might worsen tics; however, multiple lines of research have shown that stimulants can be cautiously used in the presence of tic disorders. Several studies have shown that stimulants do not exacerbate tics any more than placebo does, and suggest that stimulants may even reduce tic severity. Controversy remains, and the PDR continues to carry a warning that stimulants should not be used in the presence of tic disorders, so physicians may be reluctant to use them. Others are comfortable using them and even advocate for a stimulant trial when ADHD co-occurs with tics, because the symptoms of ADHD can be more impairing than tics.
The stimulants are the first line of treatment for ADHD, with proven efficacy, but they do fail in up to 20% of cases, even in patients without tic disorders. Current prescribed stimulant medications include: methylphenidate (brand names Ritalin, Metadate, Concerta), dextroamphetamine (Dexedrine), and mixed amphetamine salts (Adderall). Other medications can be used when stimulants are not an option. These include the alpha-2 agonists (clonidine and guanfacine), tricyclic antidepressants (desipramine and nortriptyline), and newer antidepressants (bupropion, venlafaxine and atomoxetine). A retrospective case series published in 1993 suggested that treatment with bupropion (trade name Wellbutrin) can worsen tics, but there is no data from placebo-controlled trials to support this. There is good empirical support for the use of desipramine, bupropion and atomoxetine (brand name Strattera). Atomoxetine is the only non-controlled Food and Drug Administration (FDA) approved drug for the treatment of ADHD, but is less effective than stimulants for ADHD, is associated with individual cases of liver damage, carries an FDA black box warning regarding suicidal ideation, and controlled studies show increases in heart rate, decreases of body weight, decreased appetite and treatment-emergent nausea.
Other behavioral therapies including habit reversal training (HRT)/comprehensive behavioral intervention (CBIT) and exposure and response prevention (ERP) are first-line interventions, subject to some limitations: children younger than ten may not understand the treatment, people with severe tics or ADHD may not be able to suppress their tics or sustain the required focus to benefit from behavioral treatments, and there is a lack of therapists trained in behavioral interventions.
Massed negative practice, biofeedback, relaxation, hypnosis and other behavioral approaches are proposed as alternative treatments of tics, but few have been well assessed. Relaxation techniques, such as exercise, yoga or meditation, may be useful in relieving stress that may aggravate tics, but the majority of behavioral interventions (such as relaxation training and biofeedback, with the exception of habit reversal) have not been systematically evaluated and are not proven therapies for Tourette's.
Complementary and alternative medicine approaches, such as dietary modification, allergy testing and allergen control, and neurofeedback, have popular appeal, but no role has been proven for any of these in the treatment of Tourette syndrome. While a balanced diet may aid in overall health, and avoidance of caffeine may help minimize tics for some children, no particular diet or alternative therapy (vitamin or diet) is supported by scientific evidence. As of 2018, in spite of no evidence base supporting dietary approaches to management of TS symptoms, anecdotal reports indicate that parents, caregivers, and individuals with TS are using dietary approaches and nutritional supplements nonetheless.
Regular exercise can help reduce stress and improve a child's sense of accomplishment and self-esteem, but the effect of exercise on symptoms remains unstudied.
Administration of nicotine via transdermal patches was found beneficial, in preliminary case studies, but these effects were not reproduced in well-controlled trials several years later. Studies of nicotine derivatives (mecamylamine, inversine) also showed that they were not effective as a single therapy for the symptoms of Tourette's.
Limited evidence suggests that tetrahydrocannabinol (THC), the main psychoactive ingredient of cannabis, may help reduce tics in adults. More research is needed to confirm this low-quality evidence for the effects of THC. There is insufficient evidence for other cannabis-based medications in the treatment of Tourette's.
Deep brain stimulation has been used to treat adults with severe Tourette's that does not respond to conventional treatment, but is regarded as an experimental and dangerous procedure that is unlikely to become widespread.  The procedure is well tolerated, but complications include "short battery life, abrupt symptom worsening upon cessation of stimulation, hypomanic or manic conversion, and the significant time and effort involved in optimizing stimulation parameters". As of 2006, there were five reports in patients with TS; all experienced reduction in tics and the disappearance of obsessive-compulsive behaviors. Robertson reports that DBS had been used on 55 adults as of 2011, remains an experimental treatment, and "should only be conducted by experienced functional neurosurgeons operating in centres which also have a dedicated Tourette syndrome clinic". According to Malone et al (2006), "Only patients with severe, debilitating, and treatment-refractory illness should be considered; while those with severe personality disorders and substance abuse problems should be excluded." Du et al (2010) say that "As an invasive therapy, DBS is currently only advisable for severely affected, treatment-refractory TS adults". Singer (2011) says that "pending determination of patient selection criteria and the outcome of carefully controlled clinical trials, a cautious approach is recommended". Viswanathan A et al (2012) say that DBS should be used in patients with "severe functional impairment that can not be managed medically".
In 2019, the American Academy of Neurology (AAN) published practice guidelines, "Treatment of tics in people with Tourette syndrome and chronic tic disorders", including 46 recommendations based on a systematic review by nine physicians, two psychologists, and two patient representatives. The panel assigned three levels of recommendations corresponding to the strength of the evidence supporting the recommendation:
- A: "rare because they are based on high confidence in the evidence and require both a high magnitude of benefit and low risk".
- B: "common because the requirements are less stringent but still based on the evidence and benefit–risk profile".
- C: "lowest allowable recommendation level that the AAN considers useful within the scope of clinical practice and accommodates the highest degree of practice variation".
The panel attached a helping verb to each level of recommendation: A = must; B = should, and C = may.
|Description||Recommendation per American Academy of Neurology 2019 practice guidelines||Clinicians|
|A: Must||B: Should||C: May|
|Counseling||Inform individuals and caregivers about the natural course of tic disorders|
|Counseling||Evaluate tic-related impairment in functioning|
|Counseling||Inform about watchful waiting for those who do not experience impairment|
|Counseling||Initially prescribe Comprehensive Behavioral Intervention for Tics (CBIT) for those who are motivated and without functional impairment|
|Counseling||Periodically re-evaluate need for any prescribed medications for tics|
|Psychoeducation||Refer teachers and peers to resources for education about TS|
|ADHD assessment and management||Assess for comorbid ADHD|
|ADHD assessment and management||Evaluate impairment from symptoms of ADHD|
|ADHD assessment and management||Ensure ADHD is treated when it is causing impairment|
|OCD assessment and management||Assess for comorbid OCD|
|OCD assessment and management||Ensure OCD is treated when it is present|
|Other comorbid disorders||Screen for comorbid anxiety, mood, and disruptive behavior disorders|
|Other comorbid disorders||Inquire about suicidal ideation and recommend resources if present|
|Tic severity assessment||Measure severity of tics using a validated assessment scale|
|Treatment expectations||Inform that treating tics rarely leads to complete cessation of tics|
|Behavioral treatments||For those who have access to it, prescribe CBIT initially relative to other behavioral interventions|
|Behavioral treatments||Offer CBIT initially relative to medication|
|Behavioral treatments||If face-to-face CBIT is not available, prescribe CBIT via Internet, or prescribe other behavioral interventions|
|α agonist treatment||Inform individuals with comorbid ADHD that α2 agonists may treat both tics and ADHD|
|α agonist treatment||Prescribe α2 agonists when benefits outweigh risks|
|α agonist treatment||Inform individuals treated about side effects of α2 agonists|
|α agonist treatment||In those treated with α2 agonists, monitor heart rate and blood pressure|
|α agonist treatment||For those taking extended release guanfacine, monitor QTc interval as indicated|
|α agonist treatment||Gradually taper α2 agonists when discontinuing them|
|Antipsychotic treatment||Prescribe antipsychotics when benefit outweighs risks|
|Antipsychotic treatment||Inform patients about adverse effects (extrapyramidal, hormonal, and metabolic) of antipsychotics|
|Antipsychotic treatment||Prescribe lowest effective dosage of antipsychotics when using them|
|Antipsychotic treatment||When using antipsychotics, use evidence-based monitoring for drug-induced movement disorders and adverse effects|
|Antipsychotic treatment||When prescribing certain antipsychotics, monitor QTc interval and perform elecrocardiography|
|Antipsychotic treatment||Gradually taper (over weeks to months) antipsychotics when discontinuing|
|Botulinum toxin injections||Prescribe botulinum toxin injections for localized simple motor tics to adolescents and adults when benefits outweigh risks|
|Botulinum toxin injections||Prescribe botulinum toxin injections for aggressive or disabling vocal tics to adolescents and adults when benefits outweigh risks|
|Botulinum toxin injections||Inform individuals that temporary effects of botulinum toxin injections of hypophonia and weakness may occur|
|Topiramate treatment||Prescribe topiramate when benefits outweigh risks|
|Topiramate treatment||Inform individuals when prescribing topiramate of adverse effects|
|Cannabis-based treatment||When individuals are using cannabis as self-medication for tics, direct them to appropriate medical supervision|
|Cannabis-based treatment||For "treatment-resistant adults with clinically relevant tics", consider cannabis-based products where legislation permits it.|
|Cannabis-based treatment||For adults who already self-medicate tics with cannabis-based products, consider cannabis-based medication where legislation permits it.|
|Cannabis-based treatment||When prescribing cannabis-products where legislation permits it, use lowest effective dose|
|Cannabis-based treatment||When prescribing, inform individuals that cannabis-based products can affect driving|
|Cannabis-based treatment||When prescribing, provide ongoing re-evaluation of need|
|Deep brain stimulation treatment||Employ multidisciplinary evaluation of benefits versus risks|
|Deep brain stimulation treatment||Exclude secondary causes of tic-like movements and confirm TS diagnosis when considering deep brain stimulation|
|Deep brain stimulation treatment||Screen for psychiatric disorders and follow deep brain stimulation subjects post-operatively|
|Deep brain stimulation treatment||Before prescribing, assure that multiple classes of medications have been tried|
|Deep brain stimulation treatment||Consider deep brain stimulation for "severe, self-injurious tics"|
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