A double-blind, placebo-controlled study of intranasal apomorphine spray as a rescue agent for off-states in Parkinson's disease

Nine patients with advanced levodopa-responsive Parkinson's disease were enrolled in a double-blind, placebo-controlled crossover trial of intranasal apomorphine as rescue therapy for parkinsonian off-states. Patients were assigned in random order to each of four possible combinations of apomorphine, trimethobenzamide antiemetic, and their matched placebos and received detailed in-office motor scoring during each of the four study periods. Patients also completed diaries describing the effectiveness of the nasal spray for reversing off-states. A statistically significant reduction in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score was seen following active apomorphine during in-office evaluation visits but not following placebo nasal spray. Patient diaries revealed that active apomorphine had a latency to onset of 11 minutes and a duration of 50 minutes. Significant nausea from apomorphine spray was seen in only one patient whereas nasal irritation was disabling in three and mild in two. We conclude that intranasal apomorphine is an effective rescue agent for parkinsonian off-states although nasal irritation is a limiting factor.