Efficacy and safety of clonazepam in refractory neurally mediated syncope

Neurally mediated syncope is a complex syndrome that-is often difficult to manage using currently available treatment strategies. The efficacy and saf ety of clonazepam was evaluated in 35 patients with refractory neurally med iated syncope. All patients had syncope (n=33) or disabling presyncope (n=2 ) and a positive head-up tilt table test (HUTT) despite treatment with one or more of the following therapies: beta-blocker, high-salt diet, fludrocor tisone, elastic compression stockings, and disopyramide. Clonazepam was ini tiated at 0.5 mg/day and titrated in 0.25-0.5 mg/day increments for symptom control. Early (first 8 weeks) symptomatic response was achieved in 31 of 35 (89%) patients. Early HUTT reverted to negative in 29 of 35 (83%) patien ts. Two patients discontinued clonazepam during early follow-up due to side effects. Thirty-three patients received long-term clonazepam therapy. Twen ty-five patients had late HUTT with 21 remaining negative. Of the eight pat ients who did not have late HUTT, one patient discontinued clonazepam prior to HUTT due to side effects. Seven patients refused late HUTT. All seven p atients achieved symptomatic control on clonazepam with two requiring dose titration. Of the 21 patients with a negative late HUTT, 18 achieved sympto matic control with true of these patients requiring dose titration. Two pat ients who had only partial symptom control despite dose titration achieved total symptomatic control with the addition of disopyramide and beta-blocke rs. Two patients with a negative late HUTT dis continued clonazepam due to side effects. One patient had been symptomatically controlled while the oth er had recurrent symptoms with dose limiting side effects occurring after c lonazepam dose titration. In the 4 patients with a positive late HUTT, 2 pa tients were symptomatically controlled, 1 patient required combination ther apy with a beta-blocker to achieve symptomatic control, and 1 patient disco ntinued therapy due to side effects. Overall, 29 of 35 (83%) patients conti nue to receive clonazepam with symptom control. Based on intention-to-treat HUTT results, 21 of 35 (60%) patients were responders. Four patients requi red clonazepam dose titration and three required combination therapy with c lonazepam plus disopyramide and/or a beta-blocker to achieve control. Clona zepam was discontinued in 6 patients, 5 for side effects and 1 following a transient ischemic attack. Clonazepam appears to be an effective therapeuti c alternative in patients with refractory neurally mediated syncope. Based on our preliminary findings, a placebo controlled evaluation of clonazepam in neurally mediated syncope is warranted.