Droxidopa for the Treatment of Parkinson’s Disease

Droxidopa is a prodrug of noradrenaline that is available for the treatment of symptomatic neurogenic orthostatic hypotension (nOH) caused by primary autonomic failure, including Parkinson’s disease (PD). On the basis of limited but encouraging evidence from case series and small numbers of patients, droxidopa has been available for more than 20 years in Japan. Two recent large randomized placebo-controlled trials confirmed the short-lasting effect of droxidopa as assessed by the Orthostatic Hypotension Questionnaire composite score, lightheadedness/ dizziness score, and standing blood pressure in patients presenting with nOH; as such, the United States Food and Drug Administration has approved the use of droxidopa. Subsequent integrated post hoc analyses revealed that droxidopa is well-tolerated for the treatment of symptomatic nOH in patients with PD, and as such it might provide valid clinical advantages. With respect to long-term outcomes, a non-interventional prospective study revealed that fewer nOH patients reported having sustained a fall when evaluated after 6 months of droxidopa treatment compared to baseline; improvements in nOH symptoms, functionality, and quality of life were all sustained for 6 months. However, two out of four trials present conflicting results. Further placebo-controlled clinical trials with better objective outcomes will be needed in order to validate the efficacy of droxidopa for nOH in patients with PD.