Pergolide improvement in neuroleptic-resistant Tourette cases: various mechanisms causing tics

Abstract

The objective was to report the possibility that in Tourette's disorder (TD) the same pathways may not be involved in all patients. Tics in three children affected with TD showed no improvement after treatment with several neuroleptic drugs (D2 blockers) at appropriate doses. However, they did improve greatly and persistently with pergolide treatment. One of the 3 patients showed a less usual tic feature, the most relevant of which resembled violent myoclonias of both upper limbs. This suggests that in these patients the improvement due to pergolide is not linked to an effect on D2-receptors-carrying GABAergic neurons, as usually assumed, because the patients did not respond to neuroleptics acting in this way. In these 3 cases, unlike in other TD patents, a prevalent action of pergolide by pre-synaptic inhibition of dopamine release on D1-receptors-carrying GABAergic neurons is suggested. Therefore, direct and indirect pathways could be differentially involved in different cases of TD.

Implementation of an OSCE at Kaohsiung Medical University

“…Several researchers have reported on many kinds of treatments for tics, including pharmacotherapy and non-pharmacotherapy [16][17][18]. Treatments for comorbid conditions are also important to mitigate tics.…”

Clinical Pharmacology of Dopamine-Modulating Agents in Tourette’s Syndrome

“…The authors suggest pergolide as a treatment option for TS (Lipinski et al, 1997). A relevant tic reduction could also be reported in three children (7, 8, and 11 years) using doses of 0.15, 0.20, and 0.25 mg/day, starting with 0.05 mg/day (Cianchetti et al, 2005).…”

“…Pergolide, an ergoline DA agonist has been suggested as a treatment option after three patients improved with pergolide (Cianchetti, Fratta, Pisano, & Minafra, 2005). The authors concluded that this improvement might not be associated with an effect on DA-D2-receptors-carrying GABAergic neurons.…”

“…One case series (Cianchetti et al, 2005), one open-label study (Lipinski, Sallee, Jackson, & Sethuraman, 1997), and two placebo-controlled trials (Gilbert, Sethuraman, Sine, Peters, & Sallee, 2000;Gilbert et al, 2003) on pergolide in patients with TS have been conducted, all showing pergolide to be efficacious in reducing tics. In a 16-week, randomized, double-blind, placebo-controlled, crossover trial with 24 children (aged 7-17 years), pergolide was found to be a safe and efficacious treatment for TS in children at doses up to 0.3 mg/day in a 6-week treatment period (Gilbert et al, 2000).…”

Treatment of Touretteʼs Syndrome

“…35,36 In the one controlled study of pergolide in TS, 24 youths took a mean dose of 0.2 mg daily for 6 weeks, an amount significantly less than that used in Parkinson's disease. Pergolide increases motor inhibition, decreasing locomotion in rats and restless leg syndrome in human beings.…”