Evidence-Based Reviews

Tics and tourette’s disorder: Which therapies, and when to use them

Current Psychiatry. 2003 October;2(10):45-56

References

1. Sukhodolsky DG, Scahill L, Zhang H, et al. Disruptive behavior in children with Tourette’s syndrome: association with ADHD comorbidity, tic severity, and functional impairment. J Am Acad Child Adolesc Psychiatry 2003;42(1):98-105.

2. Jankovic J. Tourette’s syndrome. N Engl J Med 2001;345(16):1184-92.

3. Leckman JF, Goodman WK, Anderson GM, et al. CSF biogenic amines in obsessive-compulsive disorder and Tourette’s syndrome. Neuropsychopharmacology 1995;12:73-86.

4. 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;9:277-91.

5. Moriarty J, Campos D, Schmitz B, et al. Brain perfusion abnormalities in Gilles de la Tourette’s syndrome. Br J Psychiatry 1995;167:249-54.

6. Leckman JF. Cohen DJ (eds). Tourette’s syndrome. Tics, obsessions, compulsions: developmental psychopathology and clinical care. New York: John Wiley & Sons, 1999.

7. Budman C, Bruun R, Park K, Olson M. Rage attacks in children and adolescents with Tourette’s disorder: a pilot study. J Clin Psychiatry 1998;59(11):576-80.

8. Leckman JF, Riddle MA, Hardin MT, et al. The Yale Global Tic Severity Scale: Initial testing of a clinician-rated scale of tic severity. J Am Acad Child Adolesc Psychiatry 1989;28(4):566-73.

9. Spencer T, Biederman J, Harding M, et al. Disentangling the overlap between Tourette’s disorder and ADHD. J Child Psychol Psychiatry 1999;39:1037-44.

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12. Leckman JF, Hardin MT, Riddle MA, et al. Clonidine treatment of Gilles de la Tourette’s syndrome. Arch Gen Psychiatry 1991;48(4):324-8.

13. Dion Y, Annable L, Sandor P, Chouinard G. Risperidone in the treatment of Tourette syndrome: a double-blind, placebo-controlled trial. J Clin Psychopharmacology 2002;22(1):31-9.

14. 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;62(1):50-6.

15. 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;247:443-6.

16. Sallee FR, Kurlan R, Goetz, et al. Ziprasidone treatment of children and adolescents with Tourette’s syndrome: a pilot study. J Am Acad Child Adolesc Psychiatry 2000;39(3):292-9.

17. Parraga HC, Parraga MI, Woodward RL, Fenning PA. Quetiapine treatment of children with Tourette’s syndrome: report of two cases. J Child Adolesc Psychopharmacology 2001;11(2):187-91.

18. Sallee FR, Nesbitt L, Jackson C, et al. Relative efficacy of haloperidol and pimozide in children and adolescents with Tourette’s disorder. Am J Psychiatry 1997;154(8):1057-62.

19. 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;59(7):649-56.

20. Kurlan R. for the Tourette’s Syndrome Study Group. Treatment of ADHD in children with tics: A randomized controlled trial. Neurology 2002;58:527-36.

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22. Singer HS, Brown J, Quaskey S, et al. The treatment of attentiondeficit hyperactivity disorder in Tourette’s syndrome: A double-blind, placebo-controlled study with clonidine and desipramine. Pediatrics 1995;95(1):74-81.

In controlled trials, haloperidol improved symptoms by 43 to 66%,¹⁸ which was greater than placebo and equal to the effect of fluphenazine and trifluoperazine. Haloperidol, however, demonstrated a higher rate of EPS.

Pimozide’s indication for pediatric Tourette’s disorder applies only to treatmentrefractory cases. In controlled studies, pimozide was at least as effective as haloperidol,¹⁸ equal to risperidone¹⁴ and less effective than olanzapine.¹⁵ Pimozide caused fewer side effects than haloperidol but more than atypical antipsychotics. Pimozide may cause QTc prolongation, and regular ECG monitoring is required.

Despite their efficacy, typical antipsychotics are associated with common and occasionally severe side effects that limit their long-term tolerability.⁶ Fear of tardive dyskinesia generally limits their use to only severe and treatmentresistant cases.

Step 5: Benzodiazepines. Although controlled trials of tic disorders have not evaluated benzodiazepines, these drugs were effective adjuncts in one case series using haloperidol.⁶ Anecdotal reports suggest they may reduce tics indirectly by lessening anxiety. Many experienced clinicians use clonazepam, 0.5 to 3 mg/d, or lorazepam, 0.5 to 4 mg/d, to treat Tourette’s disorder. Aside from its anxiolytic effects, clonazepam is also considered a minor mood stabilizer.

Step 6: Other options. Numerous novel medications have been studied in trials of tics and Tourette’s, although most—including the mixed D1/D2 agonist pergolide—have not been proven effective. In an uncontrolled study, the parenteral opioid antagonist naloxone decreased tics at low doses and increased them at higher doses. Botulinum toxin, nicotine, mecamylamine (a nicotine antagonist), baclofen, and flutamide have not proven efficacy in placebo-controlled trials.

Transcranial magnetic stimulation and neurosurgery have been used in patients with severe refractory tics and Tourette’s disorder but are not well-established treatments.

TICS AND COMORBIDITIES

ADHD. When it presents with tics, ADHD is frequently an independent target—or even the main target—of management. Because stimulants may exacerbate tics, nonstimulant medications such as clonidine, guanfacine, or desipramine could be tried first.¹⁹ Clonidine has been shown to ameliorate aggression, hyperactivity, and impulsivity but has sedating side effects. Atomoxetine—a nonstimulant ADHD medication—is another option for youth with comorbid tics and ADHD.

In our experience, carefully monitored stimulant trials may also be tried. A recent controlled trial showed that methylphenidate and clonidine, separately and combined, are effective for ADHD and comorbid Tourette’s disorder.²⁰ Stimulants of potential benefit include methylphenidate and amphetamine (not just dextroamphetamine), including their long-acting formulations. Combining stimulants with antipsychotics or clonidine may also be useful.

Table 2

Recommended drugs and dosages for pediatric tics and Tourette’s disorder*

Class/drug	Starting dosage (mg/d)	Dosage increase interval	Dosage range (mg/d)	Dosing regime	Potency/CYP-450 pathway	Delay to onset
Alpha2 agonists
Clonidine	0.025-0.05	5 to 7 days	0.1-0.3	bid or tid (patch every 5 to 7 days)	N/A	2 to 8 wks
Guanfacine	0.5	5 to 7 days	0.5-4	bid to tid	N/A	2 to 8 wks
Side effects	Common: dry mouth, drowsiness, dizziness, sedation, weakness, skin rashes (patch) Rare: hypotension, bradycardia, conduction delay, rebound symptoms
Atypical antipsychotics
Risperidone	0.25-1	7 to 21 days	0.5-6	qd to bid	high/ 2D6, 3A4	2 to 4 wks
Olanzapine	2.5-5	7 to 21 days	2.5-10	qd to bid	medium/ 1A2, 2D6	2 to 4 wks
Ziprasidone	20	7 to 21 days	40-160	qd to bid	medium/ 3A4	2 to 4 wks
Quetiapine	12.5-25	7 to 21 days	100-600	qd to bid	low/ 3A4	2 to 4 wks
Side effects	Common: weight gain (especially in youth), sedation Rare: hepatic enzyme elevation, extrapyramidal symptoms (EPS), increased QTc interval (ziprasidone)
Typical antipsychotics
Haloperidol	0.25-0.5	7 to 21 days	2-10 mg	qd to tid	high/ 2D6, 3A4	2 to 4 wks
Pimozide	0.5	7 to 21 days	1-8 mg	qd to tid	high/ 1A2, 2D6, 3A4	2 to 4 wks
Side effects	Common: EPS (acute dystonia, akathisia, parkinsonism), sedation, weight gain, dysphoria, cognitive dulling, increased plasma prolactin Rare: neuroleptic malignant syndrome (potentially fatal: autonomic instability, hyperthermia and muscular rigidity); tardive dyskinesia; increased QTc interval (pimozide)
Tricyclic antidepressants
Desipramine	25	5 to 7 days	2.5-5 /kg/d	qd to bid	2D6	3 to 6 wks
Nortriptyline	10	5 to 7 days	0.5-3 /kg/d	qd to bid	2D6	3 to 6 wks
Imipramine	25	5 to 7 days	2.5-5 /kg/d	qd to bid	2C19, 2D6, 3A4	3 to 6 wks
Clomipramine	25	5 to 7 days	3 /kg/d	qd to bid	2C19, 2D6, 3A4	3 to 6 wks
Side effects	Common: anticholinergic (dry mouth, blurred vision, constipation); antihistaminic (sedation, weight gain); and antialpha adrenergic (dizziness) Rare: heart palpitations, seizures, hepatic enzyme elevations, increased QTc interval
* Benzodiazepines (clonazepam or lorazepam) may be useful adjuncts; see text for side effects and dosages. Source: Adapted from DSM-IV-TR

To control rage attacks, a trial of mood stabilizers or atypical antipsychotics may be combined with standard tic medications.

Tricyclic antidepressants have been used to treat tics—especially in children with comorbid ADHD.²¹ A case series and controlled study by Singer et al of desipramine and clonidine found no significant impact on tics,²² although this trial was limited by a fixed dose design and few assessment points.

More recently, a double-blind, placebo-controlled trial found a 58% decrease in tic symptoms with desipramine (mean dosage 3.4 mg/kg/d) in patients with tics and ADHD.¹⁹ This effect was associated with small increases in heart rate and blood pressure.