Moreover, studies have shown that not only streptococci but also other infectious agents such as Borellia Burgdorferi or Mycoplasma Pneumoniae are associated with tics, ie, the association of tics and infectious agents is not restricted

to streptococci. A broader concept of this association, however, would more fulfill the needs for an infectious concept of TS. Conventional pharmacotherapeutic concepts of TS There is no doubt that dopaminergic neurotransmission is involved in the pathophysiology of TS. Dopamine (D2) receptor Inhibitors,research,lifescience,medical blocking agents such as haloperidol or pimozide have been shown to be effective in TS in several studies.79 Haloperidol showed an efficacy between 78% and 91% in 41 reports over a 14-year period.4 Many patients, however, discontinue haloperidol due to extrapyramidal side effects, while pimozide showed a superior profile regarding side effects. Pimozide was effective in several doubleblind, placebo-controlled studies.80 There are also reports of effective treatment with Inhibitors,research,lifescience,medical drugs such as fluphenazine, penfluridol, trifluoperazine, and flupenthixol.81 In the meantime, atypical antipsychotics such as risperidone, which is not only a D2 receptor antagonist, but also a serotonin (5-HT)2 antagonist, has been shown to be effective in TS.82,83 Clozapine

was observed to be effective against tics,84 although there have also been negative results reported.81 A partial Inhibitors,research,lifescience,medical control of tics during therapy with olanzapine at a dose of 5 to 10 mg/day was reported, as well as a reduction in tics in a controlled study (n=4).85 Ziprasidone, at a dose of 5 to 40 mg/day, was shown to be significantly more effective than placebo in 28 patients (7 to 17 years old) in a double-blind, randomized study, and was well tolerated.86 It should be noted, however, that Inhibitors,research,lifescience,medical the sudden death of a TS patient under therapy with ziprasidone during a clinical trial was reported.87 Aripiprazole, a new atypical antipsychotic that acts as a dopaminergic modulator showing mixed

dopamine antagonistic Inhibitors,research,lifescience,medical and agonistic effects, may take a special position in the therapy of TS. Effective treatment of TS using aripiprazole was reported repeatedly, in contrast to those treated with other antipsychotics, a also number of patients showed complete recovery from tics without significant high throughput screening adverse effects.88-90 The drug of first choice, for therapy of tics, particularly for children in many European countries, is tiapride, a benzamide derivate, which selectively blocks dopamine in the basal ganglia. Although only double-blind, placebo-controlled studies show beneficial effects on movement disorders and tics,91,92 tiapride is widely used in countries such as Germany, France, and others. It is one of the few drugs which is prescribed not only in adults, but also in children. In contrast to several antipsychotics, however, no adverse effects on cognitive performance in children have been observed.