Briefly, while β-blockers have been used to prevent neurocardiogenic syncope, some studies have cast doubt on their effectiveness. While most studies have used metoprolol, we prefer nebivolol due to is low side effect profile. Fludrocortisone is a synthetic mineral corticoid that promotes retention of sodium as well as the expansion of central blood volume and sensitization of α-receptors in the peripheral vasculature. Midodrine hydrochloride is a direct α-1 receptor agonist which exerts direct vasoconstrictive effects (methylphenidate may be an acceptable alternative agent). The selective serotonin reuptake inhibitors are sometimes helpful, presumably by their desensitization of central reflexes.

Other treatments undergoing evaluation for refractory patients include octreotide, desmopression, and erythropoietin.

Permanent cardiac pacemaker placement has been advocated as a treatment for medically refractory patients based on the finding that up to one-third of these patients may experience severe bradycardia or asystole during either tilt-induced or spontaneously occurring syncope. While initial controlled studies of pacing were disappointing, it was realized that when pacemakers were placed in patients in whom asystole or bradycardia was documented during syncope using an implantable loop recorder the success rate was much higher (see Chapter 49, The Implantable Loop Recorder).

The recent ISSUE-3 trial was a randomized, double-blind, placebo-controlled trial of pacing in syncope patients with periods of asystole or profound bradycardia documented by an implantable loop recorder.¹⁰ Patients were randomized to pacing “on” or pacing “off.” At the end of 2 years, the acute recurrence in the pacemaker “off” group was 57% while the recurrence rate in the pacemaker on group was 25%.

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