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.