Atomoxetine as an adjunct to nonpharmacological treatments for preventing vasovagal attacks in patients with recurrent vasovagal syncope: A pilot randomized-controlled trial

BACKGROUND: Despite the reduced quality of life in patients with recurrent vasovagal syncope (VVS), pharmacologic treatment options remain limited. Studies indicate that norepinephrine reuptake inhibition reduces tilt-induced syncope/pre-syncope. This study aimed to evaluate the effects of atomoxetine on syncopal/pre-syncopal episodes in patients with recurrent VVS. METHODS: In a placebo-controlled trial, we randomized patients with newly diagnosed VVS who experienced ≥3 syncopal episodes in the past three months to receive either atomoxetine (20 mg daily for two weeks followed by 40 mg daily for two weeks) or placebo. The primary endpoint was the combined number of syncopal and pre-syncopal episodes. RESULTS: Among 843 patients initially screened, 46 were randomized (N = 23 in each group) and reevaluated at one and three months. Compared to placebo, atomoxetine significantly reduced the primary endpoint after three months (P < 0.001). In the atomoxetine arm, the median time to first pre-syncopal episode was 55 days (95% confidence interval (CI): 41.21–68.79), while this was 27 days (95% CI: 14.48–39.52) for the placebo group (P < 0.001). In a subgroup analysis of patients with systolic blood pressure < 110 mmHg, atomoxetine reduced the primary endpoint, and the number of syncopal and pre-syncopal episodes after one and three months. In this subgroup, the median time to first pre-syncopal attack was 56 days in the atomoxetine group as opposed to 9 days in the placebo group. CONCLUSIONS: In this pilot study, the promising effects of atomoxetine in reducing syncopal/pre-syncopal episodes in recurrent VVS, especially with low blood pressure phenotype, warrant the conduction of future randomized trials.