Treatment of Tourette’s Syndrome
by Leslie E. Packer, PhD, 1998
Last Updated March 2011
Article Table of Contents:
* Treatment Overview
* Adverse Effects of Medications
* Nicotine Patch
* Botulinum Toxin (“Botox”) Injections
* Behavioral Therapy
* Supplements and Vitamins
* Deep Brain Stimulation
When a child or adult is diagnosed with TS, often the first question asked is “Is there a cure?” After finding out that there is no cure, the next question is often, “Is there anything we can do to reduce the tics or give our child some relief?”
The diagnosis of TS does not mean that the child or adult necessarily needs medication. Sometimes just educating the patient and those around him/her can make a significant difference, as can accommodations or modifications in school or on the job. Keep in mind that although stress does not cause TS, it can make the symptoms worse, so making lifestyle, school, or job changes that reduce stress may be of some benefit. Rushing to treatment — whether it is medication or therapy — before making other changes is generally not a recommended course. If the child or adult is not suffering pain or significant interference from the tics, and is functioning well in the significant areas of his/her life (home, school, job, peers), then stop, take a deep breath, and consider giving everyone time to learn about TS, finding out what can be accomplished by environmental modifications, and helping the individual, family, and significant others simply accept that the individual has TS, and that the symptoms will wax and wane at different times.
If you or your child has Tourette’s plus comorbid or associated conditions (“TS+”), then you will also need to prioritize to determine what to treat for: is it the tics that are really the most significant problem, or is it any ADHD or OCD or mood disorder? The medications you would use for tics are not necessarily what you would use for another condition and treating one condition might make symptoms of another condition worse.
Perhaps one of the best common-sense statements I have read about treatment appeared in a review article by Srour et al. (2008). They write:
The first therapeutic approach in tic disorders is education and demystification of symptoms. Persons in frequent contact with the child should be informed about tics, fluctuations and possible co-morbidities. It is important to emphasize the uselessness of constantly asking the child to control his/her tics. Such requests create tension which often exacerbates symptoms. The goal is to improve the tolerance of symptoms, and avoid situations that will augment stress or embarrassment. Following a complete evaluation, the treatment of tics and comorbidities should be prioritized according to the impairment caused by each problem. Physicians considering pharmacological treatments should be aware of the fluctuating nature of tics and the effect of comorbidities on outcome.
Medications for Tics
Bloch (2008), Srour et al. (2008), and Shprecher and Kurlan (2009) provide discussions and reviews of treatment approaches; the latter two articles are available online in free, full-text version. For a review of the literature on the use of atypical neuroleptics in children and teens with a description of the types of adverse metabolic effects, see the article by Dr. Constadina Panagiotopoulos and her colleagues, available in free full-text online. More recently, Eddy and Rickards (2011) provide a review of current pharmacological treatment options; their article is available in full text online.
In terms of effectiveness, neuroleptic medications that block dopamine have generally been the most effective tic medications.
Neuroleptics include older neuroleptics such as pimozide (Orap®), haloperidol (Haldol®), fluphenazine (Prolixin®), and sulpiride (not approved for use in the U.S. or Canada), and the newer “atypical” neuroleptics such as risperidone (Risperdal®), olanzapine (Zyprexa®), (Seroquel®), ziprasidone (Geodon®), and aripiprazole (Abilify®).
The preceding listing is not complete as there are many other atypical neuroleptics on the market, most of which have never been rigorously tested for their use in Tourette’s Syndrome. An open label study by McCracken et al. (2008), for example, investigated the use of olanzapine (Zyprexa®) in treating children and adolescents with tics. They reported significant benefit in tics as well as in associated symptoms, but the absence of adequate control groups precludes any firm conclusions.
Aripiprazole (Abilify®) is an atypical neuroleptic that has also been explored for its possible efficacy in treating tics. A number of preliminary reports suggest that it may be effective, including in patients who did not obtain satisfactory benefit from other neuroleptic medications [cf, Davies et al. (2006); Kawohl et al. (2008)]. Seo, Sung, et al. (2008) conduced an open label study in a small sample of children and teens and reported significant decreases in the scores of motor and phonic tics, global impairment, and global severity that appeared by the third week of treatment. An open label study, however, does not meet the “gold standard” for pharmaceutical research. Similarly, Budman et al. (2008) conducted a retrospective review of 37 children and teens with (8 had TS-only; the remaining 29 had TS+). Their review indicated that tics improved and explosive outbursts improved in those who did not discontinue treatment. They, too, concluded that aripiprazole warrants further investigation as a treatment for TS. Subsequent studies, noted by Eddy and Rickards, also show promise.
Tetrabenazine (Xenazine® Nitoman® in Canada) is another medication that affects the dopamine system, but unlike medications that block dopamine, Tetrabenazine depletes presynaptic dopamine and serotonin stores and blocks postsynaptic dopamine receptors. Although several studies and reviews have suggested that tetrabenazine may be of benefit in treating TS [cf, Ondo et al. (2008); Porta, Sassi et al. (2008)], it has not produced the kind of controlled research necessary to obtain FDA approval, and I have not seen any additional studies since 2008.
At the present time, the only medications that are approved by the Food and Drug Administration (FDA) for treating tics are haloperidol (Haldol®) and pimozide (Orap®).
In the U. S., clonidine hydrochloride (Catapres®), an alpha 2-adrenergic agonist, is often prescribed for tics, even though it is not as effective as the neuroleptics and is not FDA-approved for this type of use. Clonidine is actually a blood pressure medication, and does not pose the same risks as the neuroleptic medications. It also may have some beneficial effects on the symptoms of Attention Deficit Hyperactivity Disorder, which is frequently comorbid with TS. Du, Li et al. (2008) recently compared the clonidine patch to placebo in children and teens. After 4 weeks of treatment, there was a signficant improvement in the children’s Tourette’s symptoms compared to the control group. Clonidine may also be of benefit in those children who have comorbid rage or “melt-down” problems.
Like all medications, clonidine does have some side effects that can be problematic. The most problematic side effects reported have been dry mouth and drowsiness or somnolence. Another disadvantage of clonidine is that it may take two to three months before an effect is detected, whereas neuroleptics often provide symptom relief within days of starting treatment.
Clonazepam (Klonopin®) has also been used with some success in augmenting other medications, although its may benefit be in reducing anxiety and thereby reducing tics by reducing anxiety. Its most common side effects are sedation and unsteadiness.
Adverse Effects of Medications
Although the neuroleptics may be more potent in treating tics than clonidine, they have a more severe side effect profile. Apart from metabolic concerns, described below, one particular concern is what are called “extrapyramidal syndromes” which include the risk of tardive dyskinesia (TD) and neuroleptic malignant syndrome (NMS). TD is a generally (but not always) irreversible movement disorder that may develop in some small percentage of patients who are on neuroleptics, while NMS is a rare but life-threatening reaction characterized by high fever, rigidity, mental changes, and instability of the autonomic system. NMS is usually treatable and reversible.
The actual number of cases in which TD has developed in patients with TS is extremely small (perhaps because of the low doses used when treating tics), but fear of developing TD has led many parents and patients to avoid those medications. Tarsy et al. (2002) provide a review of the research on the extrapyramidal side effects of the newer neuroleptic medications.
Concerns have also been raised about cardiac changes (in the QT interval) with pimozide and ziprasidone, and many physicians will recommend pre-medication monitoring and periodic monitoring throughout treatment.
The newer generation of neuroleptic medications have been linked to both weight gain and metabolic syndrome. The latter can lead to insulin resistance, high blood pressure (hypertension), and high levels of triglycerides. Individuals with metabolic syndrome are at a two to three-fold increased risk of cardiovascular mortality and a two-fold increased risk of all-cause mortality (Lakka et al, 2002). In 2003, the US FDA asked the manufacturers of all atypical neuroleptics to revise their warning labels. Warnings now include the increased risk of diabetes mellitus and hyperglycemia.
In terms of day-to-day adverse effects, sleepiness, depressed mood, and weight gain are the most frequent concerns with the neuroleptics.
As with most medications, potential interaction between neuroleptics and other medications requires careful patient education.
Some clinicians and investigators explored the value of nicotine patches or mecamylamine (Inversine®), a medication that blocks nicotine receptors in the brain. Over all, however, it seems that the nicotine patch’s use is as a supplement to tic medication, and not as a sole treatment. A study by Howson et al. (2004) found that a single nicotine patch was effective in reducing complex tics and improving attention in children and teens receiving neuroleptic medication when compared to children on neuroleptics given a placebo.
Botulinum Toxin (“Botox”) Injections
Some investigators have explored the possible efficacy of botulinum toxin (“Botox”) in decreasing tics. Unlike central nervous system medications that affect the entire system, botulinum toxin acts locally (think of getting an injection of local anesthetic for dental work as an analogy for a locally acting medication). Awaad (1999) reported that in a series of 450 patients with TS, baclofen/botulinum toxin Type A was effective and safe, and subsequent studies have also indicated effectiveness in reducing tics, although global improvement outcomes vary between studies. For example, Marras et al. (2001) reported that botulinum toxin produced significant decreases in both tic frequency and urge to tic, but no patient-reported overall benefit from the treatment, whereas a subsequent study by Porta et al. (2004) used botox injections for 30 patients with phonic tics associated with TS and reported not only rapid and significant tic reduction, but improved quality of life as reported by the participants. The one adverse effect noted was hypophonia (low speech volume or “quiet speech”), noted in 80% of the sample.
A more recent study by Drs. Rath, Tavy, and their colleagues (2009) investigated the efficacy of botulinum toxin injections for simple motor tics in a sample of 15 patients who underwent repeat injections every three months. They reported short-term and long-term benefit of the injections, with three of the patients experiencing complete remission of the treated tics over a 10-year follow-up period. In light of the efficacy data and reduced risk of adverse effects of the kinds associated with neuroleptic medications, this type of treatment might be considered sooner in the treatment protocols for individuals with chronic motor tics or powerful motor tics that are causing pain or injury to the individual.
Although the use of marijuana may pose legal issues in many states and/or countries, it is worth noting that Mueller-Vahl (2003) provided pilot data demonstrating a significant reduction in tics in two studies: a single-dose crossover study with 12 adults and a randomized trial in 24 patients with TS. Unfortunately, there do not seem to have been any controlled studies on this issue since that time the data do not really support its use.
Comprehensive Behavior Intervention Tics (CBIT) and Exposure and Response Prevention Therapy (ERP)
In the past decade, there has been a resurgence of interest in adapting a behavioral technique formerly known as habit reversal. As applied to tics, habit reversal generally involves making the patient aware of the tic or the urge to tic building up and training the patient to engage in a response that would be muscularly competing or incompatible with the tic. Different investigators and clinicians may use slightly different variations in their protocols, but the competing response is a core feature of the technique. In recent years, the name “Habit Reversal Therapy” was changed to “Comprehensive Behavior Intervention for Tics” (CBIT), partly because it was feared that the word “Habit” was incorrectly suggesting that tics were voluntarily learned behaviors.
CBIT is one of the only behavioral techniques for tics that has been empirically validated. For example, Wilhelm et al. (2003) compared HRT (now CBIT) to supportive psychotherapy in a randomized groups design. The patients who received HRT showed significant decreases in tics compared to those who received supportive psychotherapy, and the improvement was maintained at the 10-month follow-up. The results of a number of subsequent studies suggest that CBIT reduces tics, although not necessarily in all subjects, and it does not eliminate all tics (cf, Himle & Woods, 2008) (pdf).
More recently, Drs. Piacentini, Woods, and their colleagues (2010) reported on a larger sample of children who underwent CBIT. They found that CBIT led to a significantly greater decrease in tic severity compared to the control group that had received only supportive therapy and education. Over half of the children in the CBIT condition were rated as very much improved or much improved. Gains made during treatment were maintained in 87% of the participants at 6-month follow-up.
Another behavioral approach that shows promise is Exposure- Response Prevention, although it has not accumulated as much research. In ERP, the patient feels the urge to tic building, but does not allow the tic to be expressed. Dr. Verdellen and her colleagues report that not only do tics decrease during and between sessions, but the urge to tic habituates and decreases. ERP is the same approach that has been very successful in treating Obsessive-Compulsive Disorder, and it will be interesting to see what future research suggests.
Supplements, Vitamins, and the Like
Many patients and their families have inquired about the role of vitamins, minerals, supplements, and other regimens. There has been very little controlled research on their efficacy in ameliorating the tics of Tourette’s. If you’re interested in anecdotal reports, you can find such discussions in online fora. Perhaps the most ardent proponents of alternative or complementary treatments is the organization known as Latitudes.
In Spain, Dr. López-Garcia and colleagues conducted an open label study of magnesium and vitamin B6. Children and teen’s TS symptoms were measured periodically over a period of three months. They reported significant reductions in symptoms as measured by the Yale Global Tics Severity Scale. Again, without any randomized controls, it is difficult to draw any firm conclusions because if my Spanish hasn’t totally failed me, it seems like they started administering the magnesium and B6 during a cycle of symptom worsening. If that’s the case, then symptoms would have likely declined anyway due to the nature of waxing and waning cycles. The biggest decreases seem to have occurred two weeks after initiation, with continuing smaller decreases noted thereafter.The study is reportedly ongoing, and Dr. Garcia-Lopez informed me that they have no definitive results regarding its efficacy yet (personal communication, 2009), and I do not find any subsequent reports in a search of PubMed.
Deep Brain Stimulation
When conservative treatment fails in patients with severe TS, deep brain stimulation (DBS) may be a therapeutic option. DBS involves placing the tip of a a very fine wire into the targeted area of the brain. The wire then runs up through a small hole in the skull and under the scalp down to a little device implanted under the collarbone. That device (a neurostimulator) sends tiny electrical impulses down the wire into the brain. The person can turn the DBS on when needed, and turn it off during sleep (when tremors are less). In some respects, DBS is like a pacemaker for the brain, but whereas a cardiac monitor adjusts the output automatically, with DBS, the individual can adjust the output from the stimulator.
Welter et al. (2008) conducted a controlled, double-blind, randomized crossover study. They found a dramatic improvement on the Yale Global Tic Severity Scale with bilateral stimulation in part of the basal ganglia. Ackermans et al. (2008) provide a review of some of the research on DBS.
Since that time, there have been other publications, with somewhat mixed results. One study of note, however, is that by Drs. Porta, Brambilla and their colleagues (2009), who followed 18 patients with intractable TS who underwent bilateral thalamic DBS. At 24-month follow-up. not only was tic improvement maintained, but ratings of obsessive-compulsive symptoms, anxiety symptoms, depressive symptoms, and subjective perception of social functioning/quality of life were improved in 15 of of the 18 patients.