Low-Dose Pergolide in Tourette Syndrome
abstract & commentary
Source: Gilbert DL, et al. Tourette’s syndrome improvement with pergolide in a randomized, double-blind, crossover trial. Neurology 2000;54:1310-1315.
Pharmacologic agents that block d2-dopaminergic neurotransmission (such as haloperidol or pimozide) have been among the most effective and widely used treatments for tics and Tourette syndrome (TS). It is therefore surprising to find a report claiming successful use of pergolide, which, in its more common use in treating parkinsonism, is generally regarded as a dopamine agonist.
Pergolide appears somewhat unique among readily available dopamine agonists in that it has considerable affinity for D1, D2, and D3 dopamine receptors. Its most potent effect is as a D2-agonist, and it seems to have about a 10-fold higher affinity at presynaptic-D2 receptors in binding studies. Presynaptic-D2 dopamine receptor activation generally results in reduced dopamine release. Therefore, extremely low doses of pergolide could conceivably act as a dopamine release blocker and thereby result in an improvement of tics.
In order to test this hypothesis, Gilbert and colleagues enrolled 24 children (aged 7-17 years) with chronic motor tic disorder, chronic vocal tic disorder, or chronic vocal and motor tic disorder (i.e., TS) in a randomized, double-blind, crossover trial. Pergolide, at a dose of 0.15-0.3 mg/day (about 10% of the typical dose used in treating parkinsonism), resulted in a 50% improvement in a standardized measure of tic severity, according to the Yale Global Tic Severity Scale. No serious adverse effects were encountered in this trial, which lasted several weeks.
COMMENTARY
This paper illustrates how basic pharmacological principles can guide rational use of drugs for seemingly paradoxical indications. This report confirms findings of a previous open-label study from this same group regarding efficacy of low-dose pergolide in TS (Lipinski et al. Mov Dis 1997;12:402-407). In the prior open-label study, a somewhat older (17-19 years old) population was examined. Interestingly, Lipinski et al found about 60% of TS patients had restless legs comorbidity, suggesting that it was a strong predictor of response of tics to pergolide; no mention of follow-up of this observation is made in the current paper.
Drugs that block dopaminergic neurotransmission are well known to have a wide array of long-term side effects, especially tardive movement disorders. This study only examined the short-term effects of low-dose pergolide; the long-term effects of low-dose pergolide in children are unknown. It would not be reasonable to assume that these effects might be the same as those seen in long-term pergolide use in Parkinson’s disease patients, as different doses are used and designed to produce different neurochemical effects. —rt
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