Tourette Syndrome and Other Tic Disorders Treatment & Management
- Author: William C Robertson, Jr, MD; Chief Editor: Amy Kao, MD more...
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:
Treatment is not always needed
Treatment should be directed first at the most troublesome symptom
Apparent success or failure of any treatment may be coincidental
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:
Dopamine D2 receptor antagonist therapy
Dopamine agonist therapy
Habit reversal therapy
Dopamine D2 receptor antagonist therapy
In 1959, soon after its introduction, chlorpromazine was reported to dramatically improve tic severity. Since then, several allocation randomized controlled trials with various neuroleptics (eg, haloperidol, fluphenazine, pimozide) have confirmed these initial results. 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, 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. 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 and an RCT 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. Similarly, the present author and colleagues currently are conducting a placebo-controlled double-blind study of levodopa as a treatment for tics.
Habit reversal therapy
Five RCTs have demonstrated the efficacy of a specific form of behavior therapy for tics.[169, 170, 83, 171, 172, 173] The originally tested treatment consisted of a package of interventions called habit reversal therapy, 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).
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). 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. 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.[176, 177]
Other treatments for tics
Treatments for tics that have not been proven in replicated RCTs include the following:
Norepinephrine reuptake inhibitors
Botulinum toxin injections and oral baclofen
Selective serotonin reuptake inhibitors (SSRIs)
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. 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. Clonidine or guanfacine may be appropriate as a first agent in many patients.
The norepinephrine reuptake inhibitors desipramine and atomoxetine have shown definite though modest benefit for tics in tic patients being treated for ADHD.[180, 181]
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. 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. 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.
Baclofen has little effect on average. However, it also has relatively few adverse effects and may be appropriate in select patients.
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.
SSRIs (eg, clomipramine, fluoxetine) improve tics in some patients, worsen them in others, and have no effect on tics in yet others.[189, 190, 191, 192] 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.
Naltrexone/naloxone have been reported helpful in a few patients, but other studies have shown transient worsening of tics with opioid antagonists.[193, 194] An RCT of naloxone showed some benefit at low doses, but worsening of tics at higher doses. Case reports also have described benefit with opioid agonists.[196, 197]
Cannabinoids may reduce tic severity in some patients. Two RCTs support the efficacy of cannabinoids in this setting.
Nicotine, 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. A small blinded study did show some benefit. 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. 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. 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. 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.
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.
Stimulant use in people with ADHD does not cause future drug abuse and may even prevent it. A comorbid tic disorder should not be considered a serious contraindication to the use of stimulants for treatment of ADHD. Several studies have shown that stimulants do not cause lasting worsening of tics. Their labeling includes warnings that they may cause tics, but several recent prospective studies show that their effect on tics is at worst temporary, even with continued use.[207, 208, 209, 179]
Clonidine has also been proven useful for ADHD in people with TS. The benefits of clonidine and methylphenidate are additive. Guanfacine most likely has similar effects.
RCTs have also shown that desipramine and atomoxetine help with ADHD symptoms in people with TS[180, 181] ; tics also improve slightly.
A double-blind RCT showed possible benefit for selegiline on ADHD symptoms and tics.
Bupropion may benefit ADHD but may temporarily worsen tics.
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. 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. SSRIs may also be useful.
Research on the management of (other) conduct disorder symptoms in TS is sorely needed.
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. 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.
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.
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.
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:
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
Neuropsychological testing and educational interventions to address learning disabilities or to help formulate an individualized education program
Education of teachers, classmates, or work colleagues may be helpful 
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)
American Psychiatric Association. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed, Text Revision. Washington, DC: American Psychiatric Association; 2000.
The Tourette Syndrome Classification Study Group. Definitions and classification of tic disorders. Arch Neurol. 1993 Oct. 50(10):1013-6. [Medline].
Tamara P. Tourette syndrome and other tic disorders of childhood. Handb Clin Neurol. 2013. 112:853-6. [Medline].
Ludolph AG, Roessner V, Münchau A, Müller-Vahl K. Tourette syndrome and other tic disorders in childhood, adolescence and adulthood. Dtsch Arztebl Int. 2012 Nov. 109(48):821-288. [Medline]. [Full Text].
American Psychiatric Association. Obsessive-Compulsive and Related Disorders. In: Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. 5th ed. Arlington, Va: American Psychiatric Association; 2013.
McHenry LC Jr. Samuel Johnson's tics and gesticulations. J Hist Med Allied Sci. 1967 Apr. 22(2):152-68. [Medline].
Kushner HI. A Cursing Brain--The Histories of Tourette Syndrome. Cambridge, MA: Harvard University Press;. 1999.
Gilles de la Tourette G. Etude sur une Affection Nerveuse Caracterisee par de l'Incoordination Motrice Accompagnee d'Echolalie et de Coprolalie. Archives de Neurologie. 1885. 9:19-42, 158-200.
Miller AM, Bansal R, Hao X, Sanchez-Pena JP, Sobel LJ, Liu J. Enlargement of thalamic nuclei in Tourette syndrome. Arch Gen Psychiatry. 2010 Sep. 67(9):955-64. [Medline].
Kurlan R, Goetz CG, McDermott MP. Treatment of ADHD in children with tics: a randomized controlled trial. Neurology. 2002 Feb 26. 58(4):527-36. [Medline].
Comings DE. Blood serotonin and tryptophan in Tourette syndrome. Am J Med Genet. 1990 Aug. 36(4):418-30. [Medline].
Comings DE, Gade R, Muhleman D, et al. Exon and intron variants in the human tryptophan 2,3-dioxygenase gene: potential association with Tourette syndrome, substance abuse and other disorders. Pharmacogenetics. 1996 Aug. 6(4):307-18. [Medline].
Muller-Vahl KR, Meyer GJ, Knapp WH, et al. Serotonin transporter binding in Tourette Syndrome. Neurosci Lett. 2005 Sep 9. 385(2):120-5. [Medline].
Niesler B, Frank B, Hebebrand J, et al. Serotonin receptor genes HTR3A and HTR3B are not involved in Gilles de la Tourette syndrome. Psychiatr Genet. 2005 Dec. 15(4):303-4. [Medline].
Toren P, Weizman A, Ratner S, et al. Ondansetron treatment in Tourette's disorder: a 3-week, randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2005 Apr. 66(4):499-503. [Medline].
Muller-Vahl KR. Cannabinoids reduce symptoms of Tourette''s syndrome. Expert Opin Pharmacother. 2003 Oct. 4(10):1717-25. [Medline].
McGrath MJ, Campbell KM, Parks CR, Burton FH. Glutamatergic drugs exacerbate symptomatic behavior in a transgenic model of comorbid Tourette''s syndrome and obsessive-compulsive disorder. Brain Res. 2000 Sep 15. 877(1):23-30. [Medline].
van Wattum PJ, Anderson GM, Chappell PB, et al. Cerebrospinal fluid dynorphin A[1-8] and beta-endorphin levels in Tourette''s syndrome are unaltered. Biol Psychiatry. 1999 Jun 1. 45(11):1527-8. [Medline].
Weeks RA, Lees AJ, Brooks DJ. Tourette''s syndrome and the opioid system. Lancet. 1994 Apr 30. 343(8905):1107-8. [Medline].
Kumar R, Lang AE. Coexistence of tics and parkinsonism: evidence for non-dopaminergic mechanisms in tic pathogenesis. Neurology. 1997 Dec. 49(6):1699-701. [Medline].
Damier P, Hirsch EC, Agid Y, Graybiel AM. The substantia nigra of the human brain. II. Patterns of loss of dopamine-containing neurons in Parkinson''s disease. Brain. 1999 Aug. 122 (Pt 8):1437-48. [Medline].
Black KJ, Mink JW. Response to levodopa challenge in Tourette syndrome. Mov Disord. 2000 Nov. 15(6):1194-8. [Medline].
Gilbert DL, Sallee FR, Sine L. Behavioral and hormonal effects of low-dose pergolide in children and adolescents with Gilles de la Tourette's syndrome. Curr Ther Res Clin Exp. 2000. 61:378.
Gilbert DL, Dure L, Sethuraman G, et al. Tic reduction with pergolide in a randomized controlled trial in children. Neurology. 2003 Feb 25. 60(4):606-11. [Medline].
Diaz-Anzaldua A, Joober R, Riviere JB, et al. Tourette syndrome and dopaminergic genes: a family-based association study in the French Canadian founder population. Mol Psychiatry. 2004 Mar. 9(3):272-7. [Medline].
Lee CC, Chou IC, Tsai CH, et al. Dopamine receptor D2 gene polymorphisms are associated in Taiwanese children with Tourette syndrome. Pediatr Neurol. 2005 Oct. 33(4):272-6. [Medline].
Heinz A, Knable MB, Wolf SS, et al. Tourette''s syndrome: [I-123]beta-CIT SPECT correlates of vocal tic severity. Neurology. 1998 Oct. 51(4):1069-74. [Medline].
Singer HS, Wong DF, Brown JE, et al. Positron emission tomography evaluation of dopamine D-2 receptors in adults with Tourette syndrome. Adv Neurol. 1992. 58:233-9. [Medline].
Turjanski N, Sawle GV, Playford ED, et al. PET studies of the presynaptic and postsynaptic dopaminergic system in Tourette''s syndrome. J Neurol Neurosurg Psychiatry. 1994 Jun. 57(6):688-92. [Medline].
Wong DF, Singer HS, Brandt J, et al. D2-like dopamine receptor density in Tourette syndrome measured by PET. J Nucl Med. 1997 Aug. 38(8):1243-7. [Medline].
Wolf SS, Jones DW, Knable MB, et al. Tourette syndrome: prediction of phenotypic variation in monozygotic twins by caudate nucleus D2 receptor binding. Science. 1996 Aug 30. 273(5279):1225-7. [Medline].
Robertson MM. D2 be or not to be?. Nat Med. 1996 Oct. 2(10):1076-7. [Medline].
Ernst M, Zametkin AJ, Jons PH, et al. High presynaptic dopaminergic activity in children with Tourette''s disorder. J Am Acad Child Adolesc Psychiatry. 1999 Jan. 38(1):86-94. [Medline].
Malison RT, McDougle CJ, van Dyck CH, et al. [123I]beta-CIT SPECT imaging of striatal dopamine transporter binding in Tourette''s disorder. Am J Psychiatry. 1995 Sep. 152(9):1359-61. [Medline].
Meyer P, Bohnen NI, Minoshima S, et al. Striatal presynaptic monoaminergic vesicles are not increased in Tourette''s syndrome. Neurology. 1999 Jul 22. 53(2):371-4. [Medline].
Peterson BS. Neuroimaging studies of Tourette syndrome: a decade of progress. In: Cohen DJ, Jankovic J, Goetz CG, eds. Tourette Syndrome. Philadelphia: Lippincott Williams & Wilkins. 2001:179-96.
Serra-Mestres J, Ring HA, Costa DC, et al. Dopamine transporter binding in Gilles de la Tourette syndrome: a [123I]FP-CIT/SPECT study. Acta Psychiatr Scand. 2004 Feb. 109(2):140-6. [Medline].
Singer HS, Szymanski S, Giuliano J, et al. Elevated intrasynaptic dopamine release in Tourette''s syndrome measured by PET. Am J Psychiatry. 2002 Aug. 159(8):1329-36. [Medline].
Stamenkovic M, Schindler SD, Asenbaum S, et al. No change in striatal dopamine re-uptake site density in psychotropic drug naive and in currently treated Tourette''s disorder patients: a [(123)I]-beta-CIT SPECt-study. Eur Neuropsychopharmacol. 2001 Feb. 11(1):69-74. [Medline].
Wong D, Singer H, Marenco S. Dopamine transporter reuptake sites measured by [11C]WIN 35,428 PET imaging are elevated in Tourette syndrome. J Nucl Med. 1994. 35:130.
Cheon KA, Ryu YH, Namkoong K, et al. Dopamine transporter density of the basal ganglia assessed with [123I]IPT SPECT in drug-naive children with Tourette's disorder. Psychiatry Res. 2004 Jan 15. 130(1):85-95. [Medline].
Black KJ, Hershey T, Akbudak E, et al. Levodopa activation pharmacologic fMRI in Tourette syndrome. Abstract presented at: 34th Annual Meeting of the Society for Neuroscience. October 23-27, 2004;. San Diego, CA. [Full Text].
Channon S, Sinclair E, Waller D, et al. Social cognition in Tourette''s syndrome: intact theory of mind and impaired inhibitory functioning. J Autism Dev Disord. 2004 Dec. 34(6):669-77. [Medline].
Goudriaan AE, Oosterlaan J, de Beurs E, et al. Decision making in pathological gambling: a comparison between pathological gamblers, alcohol dependents, persons with Tourette syndrome, and normal controls. Brain Res Cogn Brain Res. 2005 Apr. 23(1):137-51. [Medline].
Serrien DJ, Orth M, Evans AH, et al. Motor inhibition in patients with Gilles de la Tourette syndrome: functional activation patterns as revealed by EEG coherence. Brain. 2005 Jan. 128(Pt 1):116-25. [Medline].
Hershey T, Black KJ, Hartlein J, Braver TS, Barch DM, Carl JL, et al. Dopaminergic modulation of response inhibition: an fMRI study. Brain Res Cogn Brain Res. 2004 Aug. 20(3):438-48. [Medline].
Braun AR, Stoetter B, Randolph C, et al. The functional neuroanatomy of Tourette''s syndrome: an FDG-PET study. I. Regional changes in cerebral glucose metabolism differentiating patients and controls. Neuropsychopharmacology. 1993 Dec. 9(4):277-91. [Medline].
Diler RS, Reyhanli M, Toros F, Kibar M, Avci A. Tc-99m-ECD SPECT brain imaging in children with Tourette's syndrome. Yonsei Med J. 2002 Aug. 43(4):403-10. [Medline].
George MS, Trimble MR, Costa DC, et al. Elevated frontal cerebral blood flow in Gilles de la Tourette syndrome: a 99Tcm-HMPAO SPECT study. Psychiatry Res. 1992 Nov. 45(3):143-51. [Medline].
Hall M, Costa DC, Shields J, et al. Brain perfusion patterns with Tc-99m-HMPAO/SPET in patients with Gilles de la Tourette syndrome. Eur J Nucl Med. 1990. 16:WP18.
Klieger PS, Fett KA, Dimitsopulos T, Karlan R. Asymmetry of basal ganglia perfusion in Tourette''s syndrome shown by technetium-99m-HMPAO SPECT. J Nucl Med. 1997 Feb. 38(2):188-91. [Medline].
Moriarty J, Costa DC, Schmitz B, et al. Brain perfusion abnormalities in Gilles de la Tourette''s syndrome. Br J Psychiatry. 1995 Aug. 167(2):249-54. [Medline].
Riddle MA, Rasmusson AM, Woods SW, Hoffer PB. SPECT imaging of cerebral blood flow in Tourette syndrome. Adv Neurol. 1992. 58:207-11. [Medline].
Braun AR, Randolph C, Stoetter B, et al. The functional neuroanatomy of Tourette''s syndrome: an FDG-PET Study. II: Relationships between regional cerebral metabolism and associated behavioral and cognitive features of the illness. Neuropsychopharmacology. 1995 Oct. 13(2):151-68. [Medline].
Crespo-Facorro B, Cabranes JA, Lopez-Ibor Alcocer MI, et al. Regional cerebral blood flow in obsessive-compulsive patients with and without a chronic tic disorder. A SPECT study. Eur Arch Psychiatry Clin Neurosci. 1999. 249(3):156-61. [Medline].
Eidelberg D, Moeller JR, Kazumata K, Antonini A, Sterio D, Dhawan V, et al. Metabolic correlates of pallidal neuronal activity in Parkinson's disease. Brain. 1997 Aug. 120 ( Pt 8):1315-24. [Medline].
Peterson BS, Skudlarski P, Anderson AW, et al. A functional magnetic resonance imaging study of tic suppression in Tourette syndrome. Arch Gen Psychiatry. 1998 Apr. 55(4):326-33. [Medline].
Stern E, Silbersweig DA, Chee KY, et al. A functional neuroanatomy of tics in Tourette syndrome. Arch Gen Psychiatry. 2000 Aug. 57(8):741-8. [Medline].
Jeffries KJ, Schooler C, Schoenbach C, et al. The functional neuroanatomy of Tourette''s syndrome: an FDG PET study III: functional coupling of regional cerebral metabolic rates. Neuropsychopharmacology. 2002 Jul. 27(1):92-104. [Medline].
Gates L, Clarke JR, Stokes A, et al. Neuroanatomy of coprolalia in Tourette syndrome using functional magnetic resonance imaging. Prog Neuropsychopharmacol Biol Psychiatry. 2004 Mar. 28(2):397-400. [Medline].
Biswal B, Ulmer JL, Krippendorf RL, et al. Abnormal cerebral activation associated with a motor task in Tourette syndrome. AJNR Am J Neuroradiol. 1998 Sep. 19(8):1509-12. [Medline].
Serrien DJ, Nirkko AC, Loher TJ, et al. Movement control of manipulative tasks in patients with Gilles de la Tourette syndrome. Brain. 2002 Feb. 125(Pt 2):290-300. [Medline].
Rauch SL, Whalen PJ, Curran T, et al. Probing striato-thalamic function in obsessive-compulsive disorder and Tourette syndrome using neuroimaging methods. Adv Neurol. 2001. 85:207-24. [Medline].
Swerdlow NR, Karban B, Ploum Y, et al. Tactile prepuff inhibition of startle in children with Tourette''s syndrome: in search of an "fMRI-friendly" startle paradigm. Biol Psychiatry. 2001 Oct 15. 50(8):578-85. [Medline].
Laplane D, Widlocher D, Pillon B, et al. [Obsessional-type compulsive behavior caused by bilateral circumscribed pallidostriatal necrosis. Encephalopathy caused by a wasp sting]. Rev Neurol (Paris). 1981. 137(4):269-76. [Medline].
Laplane D. [Obsessive-compulsive disorders caused by basal ganglia diseases]. Rev Neurol (Paris). 1994 Aug-Sep. 150(8-9):594-8. [Medline].
Peterson BS, Staib L, Scahill L, et al. Regional brain and ventricular volumes in Tourette syndrome. Arch Gen Psychiatry. 2001 May. 58(5):427-40. [Medline].
Peterson BS, Thomas P, Kane MJ, et al. Basal Ganglia volumes in patients with Gilles de la Tourette syndrome. Arch Gen Psychiatry. 2003 Apr. 60(4):415-24. [Medline].
Eichele H, Plessen KJ. Neural plasticity in functional and anatomical MRI studies of children with Tourette syndrome. Behav Neurol. 2013. 27(1):33-45. [Medline].
Bloch MH, Leckman JF, Zhu H, et al. Caudate volumes in childhood predict symptom severity in adults with Tourette syndrome. Neurology. 2005 Oct 25. 65(8):1253-8. [Medline].
Fredericksen KA, Cutting LE, Kates WR, et al. Disproportionate increases of white matter in right frontal lobe in Tourette syndrome. Neurology. 2002 Jan 8. 58(1):85-9. [Medline].
Hong KE, Ock SM, Kang MH, et al. The segmented regional volumes of the cerebrum and cerebellum in boys with Tourette syndrome. J Korean Med Sci. 2002 Aug. 17(4):530-6. [Medline].
Hyde TM, Stacey ME, Coppola R, et al. Cerebral morphometric abnormalities in Tourette''s syndrome: a quantitative MRI study of monozygotic twins. Neurology. 1995 Jun. 45(6):1176-82. [Medline].
Peterson BS, Gore JC, Riddle MA, et al. Abnormal magnetic resonance imaging T2 relaxation time asymmetries in Tourette''s syndrome. Psychiatry Res. 1994 Dec. 55(4):205-21. [Medline].
Giedd JN, Rapoport JL, Leonard HL, et al. Case study: acute basal ganglia enlargement and obsessive-compulsive symptoms in an adolescent boy. J Am Acad Child Adolesc Psychiatry. 1996 Jul. 35(7):913-5. [Medline].
Castellanos FX, Giedd JN, Hamburger SD, et al. Brain morphometry in Tourette''s syndrome: the influence of comorbid attention-deficit/hyperactivity disorder. Neurology. 1996 Dec. 47(6):1581-3. [Medline].
Peterson BS, Leckman JF, Tucker D, et al. Preliminary findings of antistreptococcal antibody titers and basal ganglia volumes in tic, obsessive-compulsive, and attention deficit/hyperactivity disorders. Arch Gen Psychiatry. 2000 Apr. 57(4):364-72. [Medline].
Hallett M. Neurophysiology of tics. Adv Neurol. 2001. 85:237-44. [Medline].
Johannes S, Wieringa BM, Nager W, et al. Tourette syndrome and obsessive-compulsive disorder: event-related brain potentials show similar mechanisms [correction of mechansims] of frontal inhibition but dissimilar target evaluation processes. Behav Neurol. 2003. 14(1-2):9-17. [Medline].
Johannes S, Wieringa BM, Nager W, et al. Excessive action monitoring in Tourette syndrome. J Neurol. 2002 Aug. 249(8):961-6. [Medline].
O''Connor K, Lavoie ME, Robert M. Preparation and motor potentials in chronic tic and Tourette syndromes. Brain Cogn. 2001 Jun-Jul. 46(1-2):224-6. [Medline].
Ziemann U, Paulus W, Rothenberger A. Decreased motor inhibition in Tourette''s disorder: evidence from transcranial magnetic stimulation. Am J Psychiatry. 1997 Sep. 154(9):1277-84. [Medline].
Moll GH, Heinrich H, Trott GE, et al. Children with comorbid attention-deficit-hyperactivity disorder and tic disorder: evidence for additive inhibitory deficits within the motor system. Ann Neurol. 2001 Mar. 49(3):393-6. [Medline].
Gilbert DL, Bansal AS, Sethuraman G, et al. Association of cortical disinhibition with tic, ADHD, and OCD severity in Tourette syndrome. Mov Disord. 2004 Apr. 19(4):416-25. [Medline].
Gilbert DL, Sallee FR, Zhang J, et al. Transcranial magnetic stimulation-evoked cortical inhibition: a consistent marker of attention-deficit/hyperactivity disorder scores in tourette syndrome. Biol Psychiatry. 2005 Jun 15. 57(12):1597-600. [Medline].
Orth M, Amann B, Robertson MM, et al. Excitability of motor cortex inhibitory circuits in Tourette syndrome before and after single dose nicotine. Brain. 2005 Jun. 128(Pt 6):1292-300. [Medline].
Como PG. Neuropsychological function in Tourette syndrome. Adv Neurol. 2001. 85:103-11. [Medline].
Keri S, Szlobodnyik C, Benedek G, et al. Probabilistic classification learning in Tourette syndrome. Neuropsychologia. 2002. 40(8):1356-62. [Medline].
Marsh R, Alexander GM, Packard MG, et al. Habit learning in Tourette syndrome: a translational neuroscience approach to a developmental psychopathology. Arch Gen Psychiatry. 2004 Dec. 61(12):1259-68. [Medline].
Marsh R, Alexander GM, Packard MG, et al. Perceptual-motor skill learning in Gilles de la Tourette syndrome. Evidence for multiple procedural learning and memory systems. Neuropsychologia. 2005. 43(10):1456-65. [Medline].
LeVasseur AL, Flanagan JR, Riopelle RJ, Munoz DP. Control of volitional and reflexive saccades in Tourette''s syndrome. Brain. 2001 Oct. 124(Pt 10):2045-58. [Medline].
Leckman JF, Katsovich L, Kawikova I, et al. Increased serum levels of interleukin-12 and tumor necrosis factor-alpha in Tourette's syndrome. Biol Psychiatry. 2005 Mar 15. 57(6):667-73. [Medline].
Tang Y, Gilbert DL, Glauser TA, et al. Blood gene expression profiling of neurologic diseases: a pilot microarray study. Arch Neurol. 2005 Feb. 62(2):210-5. [Medline].
Hong JJ, Loiselle CR, Yoon DY, et al. Microarray analysis in Tourette syndrome postmortem putamen. J Neurol Sci. 2004 Oct 15. 225(1-2):57-64. [Medline].
Alexander GM, Peterson BS. Testing the prenatal hormone hypothesis of tic-related disorders: gender identity and gender role behavior. Dev Psychopathol. 2004. 16(2):407-20. [Medline].
Peterson BS, Leckman JF. The temporal dynamics of tics in Gilles de la Tourette syndrome. Biol Psychiatry. 1998 Dec 15. 44(12):1337-48. [Medline].
Jankovic J. Stereotypies. In: Marsden CD, Fahn S, eds. Movement Disorders 3. Boston: Mass. Butterworth-Heinemann. 1994:503-17.
Mink JW. Basal ganglia dysfunction in Tourette''s syndrome: a new hypothesis. Pediatr Neurol. 2001 Sep. 25(3):190-8. [Medline].
Mink JW. Neurobiology of basal ganglia circuits in Tourette syndrome: faulty inhibition of unwanted motor patterns?. Adv Neurol. 2001. 85:113-22. [Medline].
Mink JW. The basal ganglia: focused selection and inhibition of competing motor programs. Prog Neurobiol. 1996 Nov. 50(4):381-425. [Medline].
Flaherty AW, Graybiel AM. Input-output organization of the sensorimotor striatum in the squirrel monkey. J Neurosci. 1994 Feb. 14(2):599-610. [Medline].
Price RA, Kidd KK, Cohen DJ, et al. A twin study of Tourette syndrome. Arch Gen Psychiatry. 1985 Aug. 42(8):815-20. [Medline].
Devor EJ. Untying the gordian knot: the genetics of Tourette syndrome. J Nerv Ment Dis. 1990 Nov. 178(11):669-79. [Medline].
Pauls DL. Issues in genetic linkage studies of Tourette syndrome. Phenotypic spectrum and genetic model parameters. Adv Neurol. 1992. 58:151-7. [Medline].
State MW, Pauls DL, Leckman JF. Tourette''s syndrome and related disorders. Child Adolesc Psychiatr Clin N Am. 2001 Apr. 10(2):317-31, ix. [Medline].
Pauls D. Genome scans in sibpairs and trios: new data. Presented at: 4th International Scientific Symposium on Tourette Syndrome; June 25-27, 2004; Cleveland, OH.
Crane J, Fagerness J, Osiecki L, Gunnell B, Stewart SE, Pauls DL, et al. Family-based genetic association study of DLGAP3 in Tourette Syndrome. Am J Med Genet B Neuropsychiatr Genet. 2011 Jan. 156(1):108-14. [Medline]. [Full Text].
State MW, Greally JM, Cuker A, et al. Epigenetic abnormalities associated with a chromosome 18(q21-q22) inversion and a Gilles de la Tourette syndrome phenotype. Proc Natl Acad Sci U S A. 2003 Apr 15. 100(8):4684-9. [Medline].
Abelson JF, Kwan KY, O'Roak BJ, et al. Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science. 2005 Oct 14. 310(5746):317-20. [Medline].
Hyde TM, Aaronson BA, Randolph C, et al. Relationship of birth weight to the phenotypic expression of Gilles de la Tourette''s syndrome in monozygotic twins. Neurology. 1992 Mar. 42(3 Pt 1):652-8. [Medline].
Kirvan CA, Swedo SE, Heuser JS, Cunningham MW. Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea. Nat Med. 2003 Jul. 9(7):914-20. [Medline].
Snider LA, Swedo SE. Post-streptococcal autoimmune disorders of the central nervous system. Curr Opin Neurol. 2003 Jun. 16(3):359-65. [Medline].
Swedo SE, Leonard HL, Rapoport JL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) subgroup: separating fact from fiction. Pediatrics. 2004 Apr. 113(4):907-11. [Medline].
Asbahr FR, Ramos RT, Negrao AB, Gentil V. Case series: increased vulnerability to obsessive-compulsive symptoms with repeated episodes of Sydenham chorea. J Am Acad Child Adolesc Psychiatry. 1999 Dec. 38(12):1522-5. [Medline].
Mell LK, Davis RL, Owens D, et al. Association between streptococcal infection and obsessive-compulsive disorder, Tourette's syndrome, and tic disorder. Pediatrics. 2005 Jul. 116(1):56-60. [Medline].
Murphy TK, Benson N, Zaytoun A, et al. Progress toward analysis of D8/17 binding to B cells in children with obsessive compulsive disorder and/or chronic tic disorder. J Neuroimmunol. 2001 Nov 1. 120(1-2):146-51. [Medline].
Church AJ, Dale RC, Lees AJ, et al. Tourette''s syndrome: a cross sectional study to examine the PANDAS hypothesis. J Neurol Neurosurg Psychiatry. 2003 May. 74(5):602-7. [Medline].
Kiessling LS, Marcotte AC, Culpepper L. Antineuronal antibodies in movement disorders. Pediatrics. 1993 Jul. 92(1):39-43. [Medline].
Pavone P, Bianchini R, Parano E, et al. Anti-brain antibodies in PANDAS versus uncomplicated streptococcal infection. Pediatr Neurol. 2004 Feb. 30(2):107-10. [Medline].
Wendlandt JT, Grus FH, Hansen BH, Singer HS. Striatal antibodies in children with Tourette''s syndrome: multivariate discriminant analysis of IgG repertoires. J Neuroimmunol. 2001 Sep 3. 119(1):106-13. [Medline].
Kurlan R, Kaplan EL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) etiology for tics and obsessive-compulsive symptoms: hypothesis or entity? Practical considerations for the clinician. Pediatrics. 2004 Apr. 113(4):883-6. [Medline].
Kurlan R. The PANDAS hypothesis: losing its bite?. Mov Disord. 2004 Apr. 19(4):371-4. [Medline].
Muller N, Riedel M, Blendinger C, et al. Mycoplasma pneumoniae infection and Tourette's syndrome. Psychiatry Res. 2004 Dec 15. 129(2):119-25. [Medline].
Perlmutter SJ, Leitman SF, Garvey MA, et al. Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood. Lancet. 1999 Oct 2. 354(9185):1153-8. [Medline].
Loiselle CR, Lee O, Moran TH, Singer HS. Striatal microinfusion of Tourette syndrome and PANDAS sera: failure to induce behavioral changes. Mov Disord. 2004 Apr. 19(4):390-6. [Medline].
Singer HS, Loiselle CR, Lee O, et al. Anti-basal ganglia antibodies in PANDAS. Mov Disord. 2004 Apr. 19(4):406-15. [Medline].
Singer HS, Hong JJ, Yoon DY, et al. Serum autoantibodies do not differentiate PANDAS and Tourette syndrome from controls. Neurology. 2005 Dec 13. 65(11):1701-7. [Medline].
Robertson MM. The prevalence and epidemiology of Gilles de la Tourette syndrome. Part 1: the epidemiological and prevalence studies. J Psychosom Res. 2008 Nov. 65(5):461-72. [Medline].
Robertson MM. The prevalence and epidemiology of Gilles de la Tourette syndrome. Part 2: tentative explanations for differing prevalence figures in GTS, including the possible effects of psychopathology, aetiology, cultural differences, and differing phenotypes. J Psychosom Res. 2008 Nov. 65(5):473-86. [Medline].
Hebebrand J, Klug B, Fimmers R, et al. Rates for tic disorders and obsessive compulsive symptomatology in families of children and adolescents with Gilles de la Tourette syndrome. J Psychiatr Res. 1997 Sep-Oct. 31(5):519-30. [Medline].
Leckman JF. Phenomenology of tics and natural history of tic disorders. Brain Dev. 2003 Dec. 25 Suppl 1:S24-8. [Medline].
Carter AS, O''Donnell DA, Schultz RT, et al. Social and emotional adjustment in children affected with Gilles de la Tourette''s syndrome: associations with ADHD and family functioning. Attention Deficit Hyperactivity Disorder. J Child Psychol Psychiatry. 2000 Feb. 41(2):215-23. [Medline].
Martinez D, Slifstein M, Broft A, et al. Imaging human mesolimbic dopamine transmission with positron emission tomography. Part II: amphetamine-induced dopamine release in the functional subdivisions of the striatum. J Cereb Blood Flow Metab. 2003 Mar. 23(3):285-300. [Medline].
Cath DC, Spinhoven P, Hoogduin CA, et al. Repetitive behaviors in Tourette''s syndrome and OCD with and without tics: what are the differences?. Psychiatry Res. 2001 Mar 25. 101(2):171-85. [Medline].
Robertson MM, Gourdie A. Familial Tourette''s syndrome in a large British pedigree. Associated psychopathology, severity, and potential for linkage analysis. Br J Psychiatry. 1990 Apr. 156:515-21. [Medline].
Burd L, Freeman RD, Klug MG, et al. Tourette Syndrome and learning disabilities. BMC Pediatr. 2005 Sep 1. 5:34. [Medline].
Albin R. Neurobiology of basal ganglia and TS: neurotransmitters and neurochemistry overview. Presented at: 4th International Scientific Symposium on Tourette Syndrome;. June 25-27, 2004; Cleveland, Ohio.
Woods DW, Watson TS, Wolfe E, et al. Analyzing the influence of tic-related talk on vocal and motor tics in children with Tourette''s syndrome. J Appl Behav Anal. 2001 Fall. 34(3):353-6. [Medline].
Meidinger AL, Miltenberger RG, Himle M, et al. An investigation of tic suppression and the rebound effect in Tourette's disorder. Behav Modif. 2005 Sep. 29(5):716-45. [Medline].
Kwak C, Dat Vuong K, Jankovic J. Premonitory sensory phenomenon in Tourette's syndrome. Mov Disord. 2003 Dec. 18(12):1530-3. [Medline].
Coffey BJ, Miguel EC, Biederman J, et al. Tourette''s disorder with and without obsessive-compulsive disorder in adults: are they different?. J Nerv Ment Dis. 1998 Apr. 186(4):201-6. [Medline].
Leckman JF, Walker DE, Goodman WK, Pauls DL, Cohen DJ. "Just right" perceptions associated with compulsive behavior in Tourette's syndrome. Am J Psychiatry. 1994 May. 151(5):675-80. [Medline].
Miguel EC, do Rosario-Campos MC, Prado HS, et al. Sensory phenomena in obsessive-compulsive disorder and Tourette''s disorder. J Clin Psychiatry. 2000 Feb. 61(2):150-6; quiz 157. [Medline].
Scahill LD, Leckman JF, Marek KL. Sensory phenomena in Tourette''s syndrome. Adv Neurol. 1995. 65:273-80. [Medline].
Bliss J. Sensory experiences of Gilles de la Tourette syndrome. Arch Gen Psychiatry. 1980 Dec. 37(12):1343-7. [Medline].
Chappell P, Leckman J, Goodman W, et al. Elevated cerebrospinal fluid corticotropin-releasing factor in Tourette''s syndrome: comparison to obsessive compulsive disorder and normal controls. Biol Psychiatry. 1996 May 1. 39(9):776-83. [Medline].
Morris HR, Thacker AJ, Newman PK, Lees AJ. Sign language tics in a prelingually deaf man. Mov Disord. 2000 Mar. 15(2):318-20. [Medline].
Chabane N, Delorme R, Millet B, et al. Early-onset obsessive-compulsive disorder: a subgroup with a specific clinical and familial pattern?. J Child Psychol Psychiatry. 2005 Aug. 46(8):881-7. [Medline].
do Rosario-Campos MC, Leckman JF, Curi M, et al. A family study of early-onset obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet. 2005 Jul 5. 136(1):92-7. [Medline].
Miguel EC. Co-morbid OCD. Presented at: 4th International Scientific Symposium on Tourette Syndrome; June 25-27, 2004; Cleveland, OH.
Block MH. Presentation at: 4th International Scientific Symposium on Tourette Syndrome. June 25-27, 2004; Cleveland, OH.
Bockner S. Gilles de la Tourette''s disease. J Ment Sci. 1959 Oct. 105:1078-81. [Medline].
Kurlan R, Trinidad KS. Treatment of tics. In: Kurlan R, ed. Treatment of Movement Disorders. Philadelphia, PA:. JB Lippincott. 1995: 365-406.
McCracken JT, Suddath R, Chang S, Thakur S, Piacentini J. Effectiveness and tolerability of open label olanzapine in children and adolescents with Tourette syndrome. J Child Adolesc Psychopharmacol. 2008 Oct. 18(5):501-8. [Medline].
Bruggeman R, van der Linden C, Buitelaar JK, et al. Risperidone versus pimozide in Tourette''s disorder: a comparative double-blind parallel-group study. J Clin Psychiatry. 2001 Jan. 62(1):50-6. [Medline].
Onofrj M, Paci C, D''Andreamatteo G, Toma L. Olanzapine in severe Gilles de la Tourette syndrome: a 52-week double-blind cross-over study vs. low-dose pimozide. J Neurol. 2000 Jun. 247(6):443-6. [Medline].
Sallee FR, Kurlan R, Goetz CG, et al. Ziprasidone treatment of children and adolescents with Tourette''s syndrome: a pilot study. J Am Acad Child Adolesc Psychiatry. 2000 Mar. 39(3):292-9. [Medline].
Caine ED, Polinsky RJ, Kartzinel R, Ebert MH. The trial use of clozapine for abnormal involuntary movement disorders. Am J Psychiatry. 1979 Mar. 136(3):317-20. [Medline].
Murphy TK, Bengtson MA, Soto O, et al. Case series on the use of aripiprazole for Tourette syndrome. Int J Neuropsychopharmacol. 2005 Sep. 8(3):489-90. [Medline].
Seo WS, Sung HM, Sea HS, Bai DS. Aripiprazole treatment of children and adolescents with Tourette disorder or chronic tic disorder. J Child Adolesc Psychopharmacol. 2008 Apr. 18(2):197-205. [Medline].
Acosta MT, Castellanos FX. Use of the "inverse neuroleptic" metoclopramide in Tourette syndrome: an open case series. J Child Adolesc Psychopharmacol. 2004 Spring. 14(1):123-8. [Medline].
Nicolson R, Craven-Thuss B, Smith J, et al. A randomized, double-blind, placebo-controlled trial of metoclopramide for the treatment of Tourette's disorder. J Am Acad Child Adolesc Psychiatry. 2005 Jul. 44(7):640-6. [Medline].
Gilbert DL, Sethuraman G, Sine L, et al. Tourette''s syndrome improvement with pergolide in a randomized, double-blind, crossover trial. Neurology. 2000 Mar 28. 54(6):1310-5. [Medline].
Black KJ, Hartlein JM, Schlaggar BL. Levodopa treatment for tics: preliminary report. J Neuropsychiatry Clin Neurosci. 14:102.
Azrin NH, Nunn RG, Frantz SE. Habit reversal vs. negative practice treatment of nervous tics. Behav Res Ther. 1980. 11:169-78.
Azrin NH, Peterson AL. Habit reversal for the treatment of Tourette syndrome. Behav Res Ther. 1988. 26(4):347-51. [Medline].
Wilhelm S, Deckersbach T, Coffey BJ, et al. Habit reversal versus supportive psychotherapy for Tourette''s disorder: a randomized controlled trial. Am J Psychiatry. 2003 Jun. 160(6):1175-7. [Medline].
Deckersbach T, Rauch S, Buhlmann U, et al. Habit reversal versus supportive psychotherapy in Tourette's disorder: A randomized controlled trial and predictors of treatment response. Behav Res Ther. 2005 Oct 28. [Medline].
Dutta N, Cavanna AE. The effectiveness of habit reversal therapy in the treatment of Tourette syndrome and other chronic tic disorders: a systematic review. Funct Neurol. 2013 Jan-Mar. 28(1):7-12. [Medline].
Black KJ. Habit Reversal Therapy for Tourette Syndrome. Available at http://www.nil.wustl.edu/labs/kevin/move/HRT.htm. Accessed: August 31, 2009.
Miltenberger RG, Fuqua RW, Woods DW. Applying behavior analysis to clinical problems: review and analysis of habit reversal. J Appl Behav Anal. 1998 Fall. 31(3):447-69. [Medline].
Jenkins BG, Chen YI, Sanchez Pernaute R, et al. Mapping dopaminergic function in normal and MPTP treated monkeys with pharmacologic MRI and PET. Presented at: Annual Meeting of the Society of Neuroscience; November 10-15, 2001; San Diego, CA.
Woods DW, Hook SS, Spellman DF, Friman PC. Case study: Exposure and response prevention for an adolescent with Tourette''s syndrome and OCD. J Am Acad Child Adolesc Psychiatry. 2000 Jul. 39(7):904-7. [Medline].
Scahill L, Chappell PB, Kim YS, et al. A placebo-controlled study of guanfacine in the treatment of children with tic disorders and attention deficit hyperactivity disorder. Am J Psychiatry. 2001 Jul. 158(7):1067-74. [Medline].
The Tourette''s Syndrome Study Group. Treatment of ADHD in children with tics: a randomized controlled trial. Neurology. 2002 Feb 26. 58(4):527-36. [Medline].
Spencer T, Biederman J, Coffey B, et al. A double-blind comparison of desipramine and placebo in children and adolescents with chronic tic disorder and comorbid attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 2002 Jul. 59(7):649-56. [Medline].
Allen AJ, Kurlan RM, Gilbert DL, et al. Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders. Neurology. 2005 Dec 27. 65(12):1941-9. [Medline].
Marras C, Andrews D, Sime E, Lang AE. Botulinum toxin for simple motor tics: a randomized, double-blind, controlled clinical trial. Neurology. 2001 Mar 13. 56(5):605-10. [Medline].
Jankovic J, Beach J. Long-term effects of tetrabenazine in hyperkinetic movement disorders. Neurology. 1997 Feb. 48(2):358-62. [Medline].
U.S. Food and Drug Administration. FDA Approves First Drug for Treatment of Chorea in Huntington's Disease. FDA. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116936.htm. Accessed: August 31, 2009.
Singer HS, Wendlandt J, Krieger M, Giuliano J. Baclofen treatment in Tourette syndrome: a double-blind, placebo-controlled, crossover trial. Neurology. 2001 Mar 13. 56(5):599-604. [Medline].
Awaad Y, Michon AM, Minarik S, et al. Use of levetiracetam to treat tics in children and adolescents with Tourette syndrome. Mov Disord. 2005 Jun. 20(6):714-8. [Medline].
Hedderick EF, Morris CM, Singer HS. Double-blind, crossover study of clonidine and levetiracetam in Tourette syndrome. Pediatr Neurol. 2009 Jun. 40(6):420-5. [Medline].
Smith-Hicks CL, Bridges DD, Paynter NP, Singer HS. A double blind randomized placebo control trial of levetiracetam in Tourette syndrome. Mov Disord. 2007 Sep 15. 22(12):1764-70. [Medline].
Bruun RD, Budman CL. Paroxetine treatment of episodic rages associated with Tourette''s disorder. J Clin Psychiatry. 1998 Nov. 59(11):581-4. [Medline].
Iancu I, Kotler M, Bleich A, Lepkifker E. Clomipramine efficacy for Tourette syndrome and major depression: a case study. Biol Psychiatry. 1995 Sep 15. 38(6):407-9. [Medline].
Kurlan R, Como PG, Deeley C, et al. A pilot controlled study of fluoxetine for obsessive-compulsive symptoms in children with Tourette''s syndrome. Clin Neuropharmacol. 1993 Apr. 16(2):167-72. [Medline].
Scahill L, Riddle MA, King RA, et al. Fluoxetine has no marked effect on tic symptoms in patients with Tourette''s syndrome: a double-blind placebo-controlled study. J Child Adolesc Psychopharmacol. 1997 Summer. 7(2):75-85. [Medline].
Chappell PB, Leckman JF, Riddle MA, et al. Neuroendocrine and behavioral effects of naloxone in Tourette syndrome. Adv Neurol. 1992. 58:253-62. [Medline].
Erenberg G, Lederman RJ. Naltrexone and Tourette''s syndrome. Ann Neurol. 1992 May. 31(5):574. [Medline].
van Wattum PJ, Chappell PB, Zelterman D, et al. Patterns of response to acute naloxone infusion in Tourette''s syndrome. Mov Disord. 2000 Nov. 15(6):1252-4. [Medline].
Chappell PB, Leckman JF, Scahill LD, et al. Neuroendocrine and behavioral effects of the selective kappa agonist spiradoline in Tourette''s syndrome: a pilot study. Psychiatry Res. 1993 Jun. 47(3):267-80. [Medline].
McConville BJ, Norman AB, Fogelson MH, Erenberg G. Sequential use of opioid antagonists and agonists in Tourette''s syndrome. Lancet. 1994 Mar 5. 343(8897):601. [Medline].
Silver AA, Shytle RD, Philipp MK, et al. Transdermal nicotine and haloperidol in Tourette''s disorder: a double-blind placebo-controlled study. J Clin Psychiatry. 2001 Sep. 62(9):707-14. [Medline].
Silver AA, Shytle RD, Sheehan KH, Sheehan DV, Ramos A, Sanberg PR. Multicenter, double-blind, placebo-controlled study of mecamylamine monotherapy for Tourette's disorder. J Am Acad Child Adolesc Psychiatry. 2001 Sep. 40(9):1103-10. [Medline].
Orth M, Kirby R, Richardson MP, et al. Subthreshold rTMS over pre-motor cortex has no effect on tics in patients with Gilles de la Tourette syndrome. Clin Neurophysiol. 2005 Apr. 116(4):764-8. [Medline].
Hembree EA, Riggs DS, Kozak MJ, et al. Long-term efficacy of exposure and ritual prevention therapy and serotonergic medications for obsessive-compulsive disorder. CNS Spectr. 2003 May. 8(5):363-71, 381. [Medline].
McDougle CJ, Goodman WK, Leckman JF, et al. Haloperidol addition in fluvoxamine-refractory obsessive-compulsive disorder. A double-blind, placebo-controlled study in patients with and without tics. Arch Gen Psychiatry. 1994 Apr. 51(4):302-8. [Medline].
Miguel EC, Shavitt RG, Ferrao YA, et al. How to treat OCD in patients with Tourette syndrome. J Psychosom Res. 2003 Jul. 55(1):49-57. [Medline].
Castellanos FX, Giedd JN, Elia J, et al. Controlled stimulant treatment of ADHD and comorbid Tourette''s syndrome: effects of stimulant and dose. J Am Acad Child Adolesc Psychiatry. 1997 May. 36(5):589-96. [Medline].
Biederman J, Wilens T, Mick E, et al. Pharmacotherapy of attention-deficit/hyperactivity disorder reduces risk for substance use disorder. Pediatrics. 1999 Aug. 104(2):e20. [Medline].
Kurlan R. Tourette''s syndrome: are stimulants safe?. Curr Neurol Neurosci Rep. 2003 Jul. 3(4):285-8. [Medline].
Gadow KD, Nolan EE, Sverd J. Methylphenidate in hyperactive boys with comorbid tic disorder: II. Short-term behavioral effects in school settings. J Am Acad Child Adolesc Psychiatry. 1992 May. 31(3):462-71. [Medline].
Gadow KD, Sverd J, Sprafkin J, et al. Long-term methylphenidate therapy in children with comorbid attention-deficit hyperactivity disorder and chronic multiple tic disorder. Arch Gen Psychiatry. 1999 Apr. 56(4):330-6. [Medline].
Sverd J, Gadow KD, Paolicelli LM. Methylphenidate treatment of attention-deficit hyperactivity disorder in boys with Tourette''s syndrome. J Am Acad Child Adolesc Psychiatry. 1989 Jul. 28(4):574-9; discussion 580-2. [Medline].
Feigin A, Kurlan R, McDermott MP, et al. A controlled trial of deprenyl in children with Tourette''s syndrome and attention deficit hyperactivity disorder. Neurology. 1996 Apr. 46(4):965-8. [Medline].
Spencer T, Biederman J, Steingard R, Wilens T. Bupropion exacerbates tics in children with attention-deficit hyperactivity disorder and Tourette''s syndrome. J Am Acad Child Adolesc Psychiatry. 1993 Jan. 32(1):211-4. [Medline].
Donovan SJ, Stewart JW, Nunes EV, et al. Divalproex treatment for youth with explosive temper and mood lability: a double-blind, placebo-controlled crossover design. Am J Psychiatry. 2000 May. 157(5):818-20. [Medline].
Budman C, Coffey BJ, Shechter R, Schrock M, Wieland N, Spirgel A, et al. Aripiprazole in children and adolescents with Tourette disorder with and without explosive outbursts. J Child Adolesc Psychopharmacol. 2008 Oct. 18(5):509-15. [Medline].
Ackermans L, Duits A, van der Linden C, et al. Double-blind clinical trial of thalamic stimulation in patients with Tourette syndrome. Brain. 2011 Mar. 134:832-44. [Medline].
Woods DW, Marcks BA. Controlled evaluation of an educational intervention used to modify peer attitudes and behavior toward persons with Tourette's Syndrome. Behav Modif. 2005 Nov. 29(6):900-12. [Medline].
Brauser D. Potential New Risk Factors for Tourette's, Tics Identified. Available at http://www.medscape.com/viewarticle/819287. Accessed: January 19, 2014.
Mathews CA, Scharf JM, Miller LL, Macdonald-Wallis C, Lawlor DA, Ben-Shlomo Y. Association between pre- and perinatal exposures and Tourette syndrome or chronic tic disorder in the ALSPAC cohort. Br J Psychiatry. 2014 Jan. 204:40-5. [Medline]. [Full Text].
|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|
|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.|