Abstract P063: Long-term Efficacy Of Atomoxetine For The Treatment Of Symptomatic Neurogenic Orthostatic Hypotension

Abstract

Patients with neurogenic orthostatic hypotension (NOH) are at risk for syncope, falls and have poor quality of life. Only two drugs (midodrine, droxidopa) are FDA-approved for the treatment of NOH. We previously reported that atomoxetine, a norepinephrine transporter inhibitor, acutely improved upright blood pressure and symptoms in NOH, mostly in multiple system atrophy (MSA) patients. However, the long-term efficacy of atomoxetine for the treatment of NOH is unknown. We hypothesize chronic treatment with atomoxetine improves pre-syncopal symptoms in NOH We conducted multicenter, randomized, double-blind, placebo-controlled, 2X2 crossover design with initial atomoxetine dose-titration phase. NOH patients were randomized to two, 4-week treatment sequence (period 1: atomoxetine (10 or 18 mg TID) followed by placebo) or vice versa (period 2). The primary outcome was a reduction in pre-syncopal symptoms using the orthostatic hypotension questionnaire (OHQ) composite score, calculated from the OH symptoms Assessment (OHSA) and the OH Daily Activity Scale (OHDAS). Secondary endpoints were orthostatic vital signs. We screened 68 patients, 48 were enrolled in the dose-titration and 40 were randomized (68 ± 8 yo, %60 males, BMI 26.2 ± 4.8 kg/m 2 ). We found no difference in the OHQ score between atomoxetine and placebo at 2-week (4.8±2.4 vs 4.5±2.1, P=0.73). Sub-analyses between MSA and non-MSA patients showed significant decline in OHSA with atomoxetine (2.6±1.8 vs 3.6±1.8, p=0.03) in non-MSA patients, specifically in vision disturbance (p=0.04) and in weakness (p=0.03). At 4-week, atomoxetine effect on upright SBP persisted (3.4±20.61 vs. -5.5±14.82 mm Hg, p=0.037). Atomoxetine was well-tolerated. Even though we found no significant reduction in OHQ with atomoxetine. Sub-analyses based on diagnosis, found that non-MSA patients had a significant improvement in OHSA. Atomoxetine effect on upright SBP persisted after 4-week treatment suggesting no tachyphylaxis.