NEW ORLEANS—Droxidopa reduces dizziness and lightheadedness on standing in patients with orthostatic hypotension, compared with placebo, according to a study reported at the 64th Annual Meeting of the American Academy of Neurology. The drug also increases patients’ standing blood pressure and modestly increases their supine blood pressure.
Patients treated with droxidopa reported fewer falls than controls did, according to Horacio Kaufmann, MD, Professor of Neurology at New York University Langone Medical Center in New York City. The drug was well tolerated and was not associated with serious adverse events.
A Large Study of Patients With Autonomic Failure
Dr. Kaufmann and colleagues assessed the efficacy of droxidopa for the treatment of neurogenic orthostatic hypotension in patients with autonomic failure. The double-blind, randomized, placebo-controlled study was conducted at 74 centers in nine countries. The researchers enrolled 263 patients with neurogenic orthostatic hypotension resulting from primary autonomic failure (eg, Parkinson’s disease or multiple system atrophy).
The primary end point of the four-week study was a change in symptoms, as measured by the Orthostatic Hypotension Questionnaire (OHQ). The OHQ asks patients to rate the severity of symptoms (eg, dizziness, lightheadedness, and feeling faint) on a scale of 1 to 10, and it also collects information about daily activities affected by the symptoms. The study’s secondary end point was change in blood pressure.
The trial began with an open-label dose-optimization phase that identified responders—patients whose systolic standing blood pressure increased by 10 mm Hg and whose OHQ scores improved in response to the drug. Nonresponders were dropped from the study. The optimal dose of the drug was determined by forced titration of as much as 600 mg of droxidopa three times per day. After a one-week washout period, 162 patients filled out OHQ questionnaires and were randomized in a double-blind fashion to receive either droxidopa or placebo for seven days. At the end of the seven days, patients filled out OHQ questionnaires again.
Patients’ mean age was 57, and gender distribution was roughly equal. Approximately 41% of patients had Parkinson’s disease, 33% had pure autonomic failure, 16% had multiple system atrophy, and 10% had other disorders such as nondiabetic autonomic neuropathies.
Increased Standing and Supine Blood Pressure
At the end of the study, the OHQ score of patients receiving droxidopa decreased by 1.83 points, compared with a reduction of 0.93 points for patients receiving placebo. Scores for dizziness and lightheadedness on standing decreased by 2.4 points among patients receiving droxidopa, compared with a decrease of approximately one point in patients receiving placebo. Vision disturbances and weakness also decreased, and daily activities improved, among patients taking droxidopa, noted Dr. Kaufmann.
Droxidopa was associated with an 11.2–mm Hg increase in standing systolic blood pressure, compared with an increase of 3.9 mm Hg in patients receiving placebo. Supine blood pressure increased by 7.6 mm Hg in patients receiving droxidopa, compared with an increase of less than 1 mm Hg in patients receiving placebo.
Because supine hypertension occurs in nearly half of patients with neurogenic orthostatic hypotension, the finding that droxidopa increased standing blood pressure more than supine blood pressure is “reassuring,” Dr. Kaufmann told Neurology Reviews. “The preferential effect on standing blood pressure is likely a consequence of the drug’s mechanism of action,” he explained. The enzyme dopa decarboxylase converts droxidopa into norepinephrine, and the process partially restores a state of normal neural functionality.
The investigators did not observe any serious adverse events during the trial. Approximately 11% of patients receiving droxidopa had headaches, 8% had dizziness, 5% had nausea, 4% had fatigue, and 2.5% had hypertension. Patients receiving droxidopa reported significantly fewer falls than patients receiving placebo. “We believe that this is something quite interesting that we will be exploring,” said Dr. Kaufmann.
—Erik Greb