Experimental Dyskinesia Treatments

Subject: Experimental Dyskinesia Treatments

Date: 9/1/2005

1. Effect of serotonin 5-HT1A agonist in advanced Parkinson’s disease
W Bara-Jiminez, F Bibbiani, MJ Morris, T Dimitrova, A Sherzai, MM Mouradian, TN Chase
Movement Disorders 2005;20:932-936

The experimental serotonin 5-HT1A agonist sarizotan reduces dyskinesias without decreasing antiparkinson effects of levodopa, according to this study.

Eighteen PD patients (mean age 58, off-state H&Y 2.5-4.0) with motor fluctuations and peak-dose dyskinesias were randomized to receive placebo or placebo followed by sarizotan twice daily. After a one-week placebo run-in, patients received 2 mg of study drug for one week, and 5 mg for one week. Dyskinesia severity was rated with the UPDRS Item 33, modified to assess each body part.

Sarizotan by itself had no antiparkinsonian effect, and did not affect levodopa’s antiparkinsonian effect. Low-dose sarizotan did not reduce dyskinesias. High-dose sarizotan reduced mean dyskinesia severity from 7.5 to 4.5 (p<0.05 compared to placebo), and increased the half-time of levodopa efficacy from 87 minutes to 121 minutes. Most adverse events occurred during the placebo period.

2. rTMS of supplementary motor area modulates therapy-induced dyskinesias in Parkinson disease
G Koch, L Brusa, C Caltagirone, A Peppe, M Oliveri, P Stanzione, D Centonze
Neurology 2005;65:623-625

Low-frequency repetitive transcranial magnetic stimulation can reduce dyskinesias, according to this study.

Eight advanced PD patients with disabling dyskinesias received either sham or real rTMS over the supplementary motor area. Sham rTMS was delivered using a coil held close to the SMA but oriented to prevent induction of current in the brain. Real rTMS was delivered at either low or high frequency. Low frequency (1 Hz) stimulation was applied continuously for 15 minutes at 90% of resting motor excitability threshold, while high frequency (5 Hz) was applied for 10 seconds on, 40 seconds off, for 15 minutes, at 110% of resting motor excitability threshold. Dyskinesias were assessed by blinded videotape analysis using the Abnormal Involuntary Movements Scale.

No effect was seen for sham or high frequency rTMS. For low frequency rTMS, mean AIMS score fell from 6.75 to 2.25 (p<0.001) immediately after stimulation, and remained significantly lowered at 15 minutes (4.00) but not at 30 minutes (7.03) afterward.

The authors conclude, “these results are consistent with the hypothesis that SMA plays a central role in the developing of dyskinesia by dopaminergic stimulation…Further studies with repeated rTMS sessions could evaluate possible long-lasting beneficial effects of 1-Hz rTMS on drug-induced dyskinesias.”