Efficacy of Midodrine Hydrochloride in Neurocardiogenic Syncope Refractory to Standard Therapy

INTRODUCTION: Some patients with neurocardiogenic syncope continue to have recurrent syncope or presyncope despite the use of currently available drug therapy. The purpose of this study was to determine whether midodrine hydrochloride, a selective adrenergic agonist, could be effective in patients resistant to, or intolerant of, currently used medications in the treatment of neurocardiogenic syncope. METHODS AND RESULTS: Eleven patients with a history of recurrent syncope or presyncope in whom hypotension with syncope or presyncope could be provoked during head-up tilt testing were included. There were 4 men and 7 women with a mean age (+/-SD) age of 34 +/- 13 years. In all patients, standard therapy with beta-adrenergic receptor blocking agents, ephedrine, theophylline, disopyramide, fludrocortisone, and sertraline hydrochloride, was either ineffective, poorly tolerated, or contraindicated. Midodrine was initially administered orally at a dose of 2.5 mg three times daily. After adjustment of dosage over 2 to 4 weeks, patients were followed-up clinically. Midodrine was discontinued in one patient because of side effects. Frequency of syncope or presyncope during the 3 months prior to starting treatment was compared during a mean follow-up of 17 +/- 4 weeks after starting treatment with midodrine. There was significant (P < 0.01) reduction in syncopal and presyncopal episodes on midodrine. Five patients had complete resolution of symptoms, while four patients had significant improvement. Symptoms did not improve in one patient. CONCLUSIONS: Midodrine hydrochloride can be effective in preventing recurrent symptoms in selected patients with neurocardiogenic syncope unresponsive to, or intolerant of, standard drug therapy.