Two New ‘Alternative’ Treatments for Tics
May 1, 2001
Two New Alternative’ Treatments for Tics
Abstracts & Commentary
Sources: Singer HS, et al. Baclofen treatment in Tourette syndrome. Neurology. 2001;56:599-604; Marras C, et al. Botulinum toxin for simple motor tics. Neurology. 2001;56:605-510.
Tourette syndrome (TS) and related tic disorders are relatively common chronic neuropsychiatric disorders that typically begin in childhood and may persist throughout adult life. Although epidemiological studies generally suggest an incidence of the order of 0.1-1%,1 a more recent community-based study suggests that about 3% of school-aged children may have TS.2 By either estimate, TS is by far the most common movement disorder of childhood.
The traditional treatment for the tics associated with TS include potent neuroleptics of the butyrophenone or phenothiazine class (so called "typical neuroleptics), which block D2 dopamine receptors. These agents, while highly effective at tic suppression, may have a problematic side effect profile in some patients. Atypical antipsychotic agents such as olanzapine (Zyprexa—Lilly) or risperidone (Risperdal—Janssen) may be preferred in some patients due to the potential of lesser risk of acute effects of D2 dopaminergic blockade, such as acute dystonia or parkinsonism. However, both typical and atypical agents may be associated with a risk of development of tardive movement disorders with long-term use. Alpha2- agonists, such as clonidine and guanfacine, may have some efficacy against tics but may be associated with significant sedation in many patients before adequate tic control is obtained. Thus, there is a need for new treatments for tics that do not have the problems that these agents may pose.
Singer and colleagues and Marras and colleagues have examined 2 such new treatments in the setting of small, but well-designed, clinical trials. Singer et al examined the use of baclofen, a GABA-B agonist, which a recent open-label trial3 had suggested might be effective in suppressing motor tics. Nine children with TS completed a double-blinded, placebo-controlled crossover trial, with multiple outcome measures, including the Yale Global Tic Severity Scale (YGTSS). The YGTSS is composed of 2 subscores, a "total tic score (TTS)," which takes into account the number, frequency, intensity, and complexity of tics, and "tic interference score" (TIS), which assesses the effect of tics on issues such as self-esteem, school performance, job performance, and social functioning. Singer et al found that while baclofen treatment seemed to improve the YGTSS rating, this was largely due to an improvement in the TIS rather than the TTS. Simply put, baclofen did not reduce tics significantly but made them less bothersome to the patient.
Marras et al examined an entirely different approach. They examined botulinum toxin, which has been widely used in the treatment of focal movement disorders such as cervical dystonia and spastic dysphonia. Previous uncontrolled studies have suggested that botulinum toxin might be effective in the treatment of tics, particularly dystonic tics.4,5 Marras et al examined 18 patients in a randomized, double-blinded clinical trial. In this study, there had to be a focus on a "target tic," which was the tic "sufficiently bothersome to the patient to require therapy." Using some of the same outcome measures as in the Singer et al study, Marras et al found that tic frequency and the "urge to tic" seemed to be reduced by botulinum toxin treatment, but the "interference" of these tics, using the TIS component or other measures, was not significantly affected. Simply put, botulinum toxin seems to reduce the tics significantly, but the residual tics are just as bothersome to the patient.
Commentary
These papers highlight some of the difficulties one encounters in treating TS and related tic disorders, and they do so in a complementary fashion. The finding by Singer et al that baclofen may make the disorder less bothersome to the patient, without actually substantially reducing tics themselves, suggests that baclofen may act to reduce anxiety, self-awareness of tics, or perhaps some other behavioral factor. On the other hand, Marras et al find that botulinum toxin may reduce selected "target tics," but the residual tics are just as bothersome to the patient. The nature of TS is that it involves multiple motor tics that vary over time (ie, a varying "repertoire" of tics), so that it is understandable that reduction of a few selected tics out of many may not make that much of a difference to the patient. When a particular target tic is especially bothersome, botulinum toxin treatment may be especially useful; for example, it may be useful in the treatment of "malignant coprolalia," in which botulinum toxin injections into the vocal cord have been reported to be effective.6
One must also keep in mind that there is a strong association of a number of comorbid conditions with TS, including obsessive-compulsive disorder, anxiety disorder, and attention deficit disorder. The sense of "interference" that a patient experiences from tics likely varies according to their overall neuropsychiatric profile. Thus, it is important to try to take a holistic approach in many patients, rather than just focus on the tics themselves.—Rosario Trifiletti
References
1. Apter A, et al. An epidemiologic study of Gilles de la Tourette’s syndrome in Israel. Arch Gen Psychiatry. 1993;50(9):734-738.
2. Mason A, et al. The prevalence of Tourette syndrome in a mainstream school population. Dev Med Child Neurol. 1998;40(5):292-296.
3. Awaad Y. Tics in Tourette syndrome: New treatment options. J Child Neurol. 1999;14(5):316-319.
4. Jankovic J. Botulinum toxin in the treatment of dystonic tics. Mov Disord. 1994;9(3):347-349.
5. Kwak CH, et al. Botulinum toxin in the treatment of tics. Arch Neurol. 2000;57(8):1190-1193.
6. Scott BL, et al. Botulinum toxin injection into vocal cord in the treatment of malignant coprolalia associated with Tourette’s syndrome. Mov Disord. 1996;11(4): 431-433.
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