LAMOTRIGINE TRIAL IN IDIOPATHIC PARKINSONISM - A DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSSOVER STUDY

Increased glutamatergic transmission in the basal ganglia is implicate d in the pathophysiology of idiopathic parkinsonism (IF). We investiga ted the effects of lamotrigine (LTG), a glutamate-release inhibitor, i n the symptomatic treatment of IP in two double-blind, placebo-control led studies. Single doses of L-dopa/carbidopa (equal to 50% of the usu al morning dose) were administered together with either LTG (100, 200, or 400 mg) or two random placebo doses in 14 patients with IF. The pa tients were assessed using the Modified Columbia Rating Scale (MCRS) a nd the Purdue Pegboard Test (PPBT) at multiple intervals over 8 hours. There were no significant differences between the placebo doses and t he three doses of LTG: on the MCRS and PPBT scores. In a 3-month study , 12 patients took LTG titrated up to 400 mg or placebo with their ant iparkinsonian medication for 3 months and were then crossed over. Nine of 12 patients did not complete the study because of dyskinesia (n = 2), hallucinations (n = 3), and deterioration of parkinsonian symptoms (n = 4) on LTG. There was no significant difference between placebo a nd LTG on the MCRS and PPBT in the three patients who completed the st udy. The results failed to demonstrate any symptomatically beneficial effects of LTG in IP.