TIME-COURSE OF PHYSICAL AND PSYCHOLOGICAL RESPONSES TO SELEGILINE MONOTHERAPY IN NEWLY-DIAGNOSED, IDIOPATHIC PARKINOSONISM

Rationale: Poor specificity of face-value endpoints and the poor sensi tivity of gross clinical examination may have militated against demons trating prophylaxis by selegiline. Methods: Objective measures of the four cardinal signs were used as primary outcome criteria in a randomi sed, double-blind, placebo-controlled, parallel group study of selegil ine monotherapy in 25 newly diagnosed elderly sufferers from idiopathi c parkinsonism, stratified for sex and Hoehn and Yahr functional stagi ng. Results: There was a significant interaction between time and natu re of treatment with respect to rigidity. The effect of time during ac tive treatment was highly significant: rigidity decreased by 1.3 % per week. The worsening of rigidity on placebo was not statistically sign ificant. Neuronal rescue is a possible explanation for the long term, progressive improvement produced by selegiline. No significant treatme nt effect was seen on the other cardinal signs. However, there was a s ignificant quadratic time trend for arousal on active treatment sugges ting tolerance to this effect. Conclusion: The difference in time cour se between the psychostimulant and physical effects suggests more than one mode of action.