Lamotrigine trial in idiopathic parkinsonism: a double-blind, placebo-controlled, crossover study

Increased glutamatergic transmission in the basal ganglia is implicated in the pathophysiology of idiopathic parkinsonism (IP). We investigated the effects of lamotrigine (LTG), a glutamate-release inhibitor, in the symptomatic treatment of IP in two double-blind, placebo-controlled studies. Single doses of L-dopa/carbidopa (equal to 50% of the usual morning dose) were administered together with either LTG (100, 200, or 400 mg) or two random placebo doses in 14 patients with IP. The patients were assessed using the Modified Columbia Rating Scale (MCRS) and the Purdue Pegboard Test (PPBT) at multiple intervals over 8 hours. There were no significant differences between the placebo doses and the 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 antiparkinsonian 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 and LTG on the MCRS and PPBT in the three patients who completed the study. The results failed to demonstrate any symptomatically beneficial effects of LTG in IP.