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Atomoxetine for the prevention of vasovagal syncope: A new and emerging therapy
Dr Satish R Raj MD MSCI, Lucy Lei BSc, Professor Robert S Sheldon MD PhD
Libin Cardiovascular Institute of Alberta, Department of Cardiac Sciences, Cumming School of Medicine, University of Calgary, Canada
There are few effective therapies for vasovagal syncope (VVS). Pharmacological norepinephrine transporter (NET) inhibition increases sympathetic nervous system tone and decreases tilt-induced syncope in healthy subjects. Atomoxetine is a potent, and highly selective NET inhibitor. We tested the hypothesis that atomoxetine prevents tilt-induced syncope. We also report on an open-label experience with atomoxetine in patients with frequent VVS.
Methods & Results
We designed and conducted a proof-of-principle, randomized, placebo-controlled trial of the efficacy of atomoxetine to prevent VVS on tilt tests. VVS patients (n=56; 35±14 years [73% F]) underwent tilt testing having received either atomoxetine 40 mg x 2 doses, or placebo. Continuous non-invasive beat-to-beat blood pressure monitoring allowed us to assess the mechanism of atomoxetine’s efficacy. Fewer VVS patients fainted with atomoxetine than with placebo 10/29 vs. 19/27; p=0.012 (Figure left). The benefit of atomoxetine was not due to an effect on vascular resistance or on stroke volume, but to preserve blood pressure by preventing bradycardia, in turn preserving cardiac index.
Atomoxetine basically prevented cardioinhibitory (VASIS 2B) syncope. NET inhibition signifi cantly decreased the risk of tilt-induced syncope in VVS subjects by blunting reflex bradycardia, and maintaining cardiac index and
blood pressure. Following the tilt-based study, we have started using off - label atomoxetine in some of our refractory VVS patients. Atomoxetine 60-80 mg daily.
To date, 13 VVS patients (8F; median 56.5 yr) have been treated, with a decrease from a median of 4.5 faints/yr PRE-atomoxetine to a median of 0.34 faints/yr WITH-atomoxetine. 10 patients were “responders”.
We conclude that atomoxetine seems to be a very promising medication to prevent VVS. These fi ndings need to be confi rmed in a placebo-controlled randomized control trial.