Tourette’s disorder

Kasper S, Tauscher J, Willeit M, Stamenkovic M, Neumeister A, Kufferle B, Barnas C, Stastny J, Praschak-Rieder N, Pezawas L et al. (2002). Receptor and transport imaging studies in schizophrenia, depression, bulimia and Tourette s disorder Implications for psychopharmacology. World Journal of Biological Psychiatry, 3, 133-146. 

Vandenbergh, D. J., Thompson, M. D., Cook, E. H., et al. (2000) Human dopamine transporter gene coding region conservation among normal, Tourette s disorder, alcohol dependence and attention-deficit hyperactivity disorder populations. Mol. Psychiatry. 5, 283-292. 

Tourette s Disorder. The compulsions of OCD in many respects resemble the complex motor tics exhibited by patients with Tourette s disorder. However, although the tics of Tourette s disorder are preceded by an urgency to perform the motor tic, this irresistible urge is distinct from the obsessional fear that drives the compulsive behaviors of OCD. 

Children Although Tourette s disorder most often has its onset between the ages of 2 and 15 years, information on the use and efficacy of pimozide in patients less than 12 years of age is limited. 

Unlabeled Uses Chronic motor or vocal tic disorder, Tourette s disorder... 

Ziemann, U., Paulus, W., and Rothenberger, A. (1997) Decreased motor inhibition in Tourette s disorder evidence from transcran-ial magnetic stimulation. Am J Psychiatry 154 1277—1284. 

A child with Tourette s disorder is treated with a daily dose of 2 mg of pimozide for tics. A family doctor treats a streptococcal pharyngitis with clarithromycin, and 24 hours later the child develops palpitations. An electrocardiogram (ECG) reveals a QTc prolongation to 0.465 milliseconds. 

Bawden, H.N., Stokes, A., Camfield, C.S., Camfield, P.R., and Salisbury, S. (1998) Peer relationship problems in children with Tourette s disorder or diabetes mellitus. / Child Psychol Psychiatry 39 663—668. 

Ernst, M., Zametkin, A.J., Jons, P.H., Matochik, J.A., Pascualvaca, D., and Cohen, R.M. (1999) High presynaptic dopaminergic activity in children with Tourette s disorder. J Am Acad Child Ado-lesc Psychiatry 38 86—94. 

Kadesjo, B. and Gillberg, C. (2000) Tourette s disorder epidemiology and comorbidity in primary school children. J Am Acad Child Adolesc Psychiatry 39 548-555. 

Silva, R.R., Munoz, D.M., Barickman, J., and Friedhoff, A.J. (1995) Environmental factors and related fluctuation of symptoms in children and adolescents with Tourette s disorder. J Child Psychol Psychiatry 36 305-312. 

Murphy and colleagues (1997) compared 31 patients with childhood-onset OCD and Tourette s disorder with 21 healthy volunteers. The patient group had 100% positive expression the D8/17 marker, regardless of whether the symptoms were temporally related to... 

Relative efficacy of haloperidol and pimozide in children and adolescents with Tourette s disorder. Am J Psychiatry 154 1057-1062. 

A potential limitation of most of the controlled studies discussed above relates to the numerous exclusion criteria used for patient selection. For example, in order to find homogenous samples, major depression, bipolar disorder, Tourette s disorder, psychosis (clomipramine, fluvoxamine and fluoxetine trials), primary psychiatric disorder other than OCD (clomipramine and sertraline trials), and attention deficit/hyperactivity disorder (ADHD), autism, or other developmental disorders (clomipramine and fluoxetine trials) were excluded. Thus it remains unknown how well these controlled studies will generalize to more naturalistic clinical populations that are highly comorbid and where exclusion criteria are not applied. 

Treatment of the comorbid patient presents a number of challenges (Fig. 39.2). The phenotype of OCD and Tourette s disorder (TD) is encountered frequently as there is a bidirectional overlap between the two conditions. In a review of 11 clinical studies, TD was found in an average of 21% of juvenile OCD subjects (Geller et ah, 1998). These subjects are more often male with an earlier age at onset and positive family history of OCD and tics. Kurlan et al. (1993) suggested that obsessional symptoms might respond less well to the SSRIs in these subjects. 

Giakas, W.J. (1995) Risperidone treatment for a Tourette s disorder patient with comorbid obsessive-compulsive disorder. Am ] Psychiatry 152 1097-1098. 

Bruggeman, R., van der Linden, C., Buitelaar, J.K., Gericke, G.S., Hawkridge, S.M., and Temlett, J.A. (2001) Risperidone versus pimozide in Tourette s disorder a comparative double-blind parallel-group study. / Clin Psychiatry 62 50—56. 

Budman, C.L., Gayer, A., Lesser, M., Shi, Q., and Bruun, R.D. (2001) An open-label study of the treatment efficacy of olanzapine for Tourette s disorder. / Clin Psychiatry 62 290—294. 

Hoopes, S.P. (1999) Donepezil for Tourette s disorder and ADHD./ Clin Psychopharmacol 19 381—382. 

Sallee, F.R., Nesbitt, L., Jackson, C., Sine, L., and Sethuraman, G. (1997) Relative efficacy of haloperidol and pimozide in children and adolescents with Tourette s disorder. Am Psychiatry 154 1057-1062. 

Silver, A.A., Shytle, R.D., Philipp, M.K., Wilkinson, B.J., McConville, B., and Sanberg, P.R. (2001a) Transdermal nicotine and haloperidol in Tourette s disorder a double-blind placebo-controlled study. / Clin Psychiatry 62 707-714. 

Stamenkovic, M., Schindler, S.D., Aschauser, H.N., DeZwaan, M., Willinger, U., Resinger, E., and Kasper, S. (2000) Effective open-lahel treatment of Tourette s disorder with olanzapine. Int Clin Psychopharmacol 15 23—28. 

Budman, C., Brunn, R.D., Park, K.S., Lesser, M., and Olson, M. (2000) Explosive outbursts in children with Tourette s disorder./ Am Acad Child Adolesc Psychiatry 39 1270-1276. 

Pimozide is FDA-labeled for Tourette s disorder and is particularly interesting in that it is a highly specific DA antagonist that may produce fewer adverse effects than haloperidol. In open studies with adequate doses, this agent has demonstrated efficacy for acute schizophrenia. Several double-blind trials comparing pimozide with other neuroleptics also found it to be an equally effective maintenance therapy ( 34, 35, 36, 37 and 38). We consider this agent to be as effective as the other standard agents, with the same, but perhaps less severe, side effects. 

The association with Gilles de la Tourette s disorder is particularly important. Although only a few OCD patients have tics, the prevalence is much higher than in the general population. Conversely, obsessive-compulsive symptoms are common in Tourette s patients. Thus, there is a clear association between Tourette s disorder and OCD. Tourette s is familial, and most likely genetically transmitted ( 157). Less is known about the heritability of OCD, but there is some suggestion that it is, at least in part, genetically determined (158, 159 and 160). 

Several large studies have investigated the prevalence of both Tourette s disorder and OCD in index cases having Tourette s disease ( 161, 162). In the cases of Tourette s disorder with OCD symptoms, the age-corrected ratio is 18%, with relatives having Tourette s disorder, chronic tics, or OCD (10%). in relatives of patients that have Tourette s symptoms only, 17% have either Tourette s disorder or chronic tic disorder and 14% have OCD. Thus, the incidence of OCD in relatives is identical in index cases of those with Tourette s disorder with OCD and index cases of Tourette s disorder only. Finally, follow-up studies find that Tourette s disorder develops in a significant percentage of children with OCD (163). 

As noted earlier, there is also a genetic association between OCD and Tourette s disorder, with many Tourette s patients experiencing OCD symptoms ( 183, 184 and 185). Tourette s disorder is thought to be an autosomal dominant disease, and although it has not been localized as yet, studies are actively in process, with at least 50% of the autosomal genome excluded as the locus (186, 187). 

Shapiro AK, Shapiro E. Evaluation of the reported association of obsessive compulsive symptoms or disorders with Tourette s disorder. Compr Psychiatry 1992 23 152-165. 

Both typical (e.g., haloperidol) and atypical (e.g., clozapine) antipsychotics are used in children and adolescents, primarily to treat schizophrenia, psychotic mood disorder, and pervasive developmental disorders. These agents are also used on occasion to treat a range of other conditions including conduct disorder, impulsive and aggressive disorders, Tourette s disorder, and ADHD. 

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