Treatment of Tourette syndrome

α2-adrenergic receptor agonists

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.

Typical

There are no medications specifically designed to target tics. Typical neuroleptics, or antipsychotics, are primarily used to treat schizophrenia, but one–pimozide (Orap)–has been FDA-approved for treating Tourette's. Pimozide, along with haloperidol and fluphenazine are the medications with the most proven efficacy in controlling tics. These medications work by blocking dopamine receptors, but are associated with a large side effect profile, including tardive dyskinesia, parkinsonism, dystonia, dyskinesia, and akathisia when used long-term.

Atypical

Atypical antipsychotics are the second generation, and serve as an alternative method of 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, olanzapine, ziprasidone, quetiapine, clozapine, aripiprazole, tiapride, and sulpiride. Atypical antipsychotics appear 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 empirical support for the use of risperidone, and less support for the others.

Other medications

Other medications that can be used to treat tics include pergolide (brand name Permax), botulinum toxin, and with less empirical support for efficacy, tetrabenazine and baclofen.

Treatment of co-morbid conditions

Many patients with Tourette syndrome present with co-morbid (co-occurring) conditions, which can be a larger source of functional impairment than the tics themselves. The majority of people with Tourette's 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.

Attention Deficit Hyperactivity Disorder (ADHD)

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.

Obsessive-Compulsive Disorder (OCD)

Obsessive-Compulsive Disorder (OCD) co-morbid to Tourette's can be treated with clomipramine, a tricyclic antidepressant, and SSRIs, a class of antidepressants including fluoxetine, sertraline, paroxetine, fluvoxamine, and escitalopram.

Behavioral treatments

Habit reversal training (HRT), 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.

There is increasing evidence supporting the use of HRT in the treatment of tics; a 2013 systematic review (Dutta, Cavanna) found evidence that HRT reduced tic severity in children and adults, but also identified methodological limitations in all studies, and said that more specialists need to be better trained to administer HRT so that better large-scale studies can be conducted.

Cognitive Behavioral Therapy (CBT) is a useful treatment when OCD is present.

Dietary

Caffeine may trigger an exacerbation of tics in some children, so they are advised to limit its consumption.

Experimental treatments

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. 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. Two small, controlled studies have found that capsules of tetrahydrocannabinol (THC), the main psychoactive ingredient of cannabis, helped reduce tics. More research is needed to confirm this low-quality evidence for the effects of THC.

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".