title: Combination ergotamine and caffeine improves seated blood pressure and presyncopal symptoms in autonomic failure.
abstract: Severely affected patients with autonomic failure require pressor agents to counteract the blood pressure fall and improve presyncopal symptoms upon standing. Previous studies suggest that combination ergotamine and caffeine may be effective in the treatment of autonomic failure, but the efficacy of this drug has not been evaluated in controlled trials. Therefore, we compared the effects of ergotamine/caffeine on seated blood pressure and orthostatic tolerance and symptoms in 12 primary autonomic failure patients without history of coronary artery disease. Patients were randomized to receive a single oral dose of placebo, midodrine (5-10 mg), or ergotamine and caffeine (1 and 100 mg, respectively) in a single-blind, crossover study. Blood pressure was measured while patients were seated and after standing for up to 10 min, at baseline and at 1 h post-drug. Ergotamine/caffeine increased seated systolic blood pressure (SBP), the primary outcome, compared with placebo (131 ± 19 and 95 ± 12 mmHg, respectively, at 1 h post-drug; p = 0.003 for time effect). Midodrine also significantly increased seated SBP (121 ± 19 mmHg at 1 h post-drug; p = 0.015 for time effect vs. placebo), but this effect was not different from ergotamine/caffeine (p = 0.621). There was no significant effect of either medication on orthostatic tolerance; however, ergotamine/caffeine improved presyncopal symptoms (p = 0.034). These findings suggest that combination ergotamine and caffeine elicits a seated pressor response that is similar in magnitude to midodrine, and improves symptoms in autonomic failure. Thus, ergotamine/caffeine could be used as an alternate treatment for autonomic failure, in carefully selected patients without comorbid coronary artery disease.
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Autonomic Dysfunction Center, Vanderbilt University School of Medicine Nashville, TN, USA.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Arnold
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Autonomic Dysfunction Center, Vanderbilt University School of Medicine Nashville, TN, USA.
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Ramirez
authors.affiliation: Department of Biostatistics, Vanderbilt University School of Medicine Nashville, TN, USA.
authors.forename: Leena
authors.initials: L
authors.lastname: Choi
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Autonomic Dysfunction Center, Vanderbilt University School of Medicine Nashville, TN, USA.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Okamoto
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Autonomic Dysfunction Center, Vanderbilt University School of Medicine Nashville, TN, USA.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Gamboa
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Autonomic Dysfunction Center, Vanderbilt University School of Medicine Nashville, TN, USA.
authors.forename: André
authors.initials: A
authors.lastname: Diedrich
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Autonomic Dysfunction Center, Vanderbilt University School of Medicine Nashville, TN, USA.
authors.forename: Satish R
authors.initials: SR
authors.lastname: Raj
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Autonomic Dysfunction Center, Vanderbilt University School of Medicine Nashville, TN, USA.
authors.forename: David
authors.initials: D
authors.lastname: Robertson
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Autonomic Dysfunction Center, Vanderbilt University School of Medicine Nashville, TN, USA.
authors.forename: Italo
authors.initials: I
authors.lastname: Biaggioni
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Autonomic Dysfunction Center, Vanderbilt University School of Medicine Nashville, TN, USA.
authors.forename: Cyndya A
authors.initials: CA
authors.lastname: Shibao
keywords: autonomic failure; caffeine; ergotamine; orthostatic hypotension; pressor agent
references.citation: Am J Med. 1993 Jul;95(1):38-48
references.pmid: 7687093
references.citation: Neurology. 1998 Jul;51(1):120-4
references.pmid: 9674789
references.citation: Br Med J. 1979 Aug 4;2(6185):307
references.pmid: 476438
references.citation: Hypertension. 2012 Mar;59(3):650-6
references.pmid: 22311903
references.citation: Control Clin Trials. 1990 Apr;11(2):116-28
references.pmid: 2161310
references.citation: Eur J Neurol. 1998 Nov;5(6):593-599
references.pmid: 10210895
references.citation: Curr Hypertens Rep. 2013 Aug;15(4):304-12
references.pmid: 23832761
references.citation: Eur J Clin Pharmacol. 1974;7(3):213-6
references.pmid: 4851611
references.citation: J Clin Pharmacol. 1994 May;34(5):375-86
references.pmid: 8089249
references.citation: Headache. 2003 Feb;43(2):144-66
references.pmid: 12558771
references.citation: Pharmacol Ther. 2012 Jun;134(3):279-86
references.pmid: 21664375
references.citation: J Clin Invest. 1988 Jan;81(1):213-20
references.pmid: 3335637
references.citation: Acta Med Scand. 1974 Dec;196(6):473-7
references.pmid: 4456977
references.citation: Circulation. 1983 Mar;67(3):602-9
references.pmid: 6295662
references.citation: Am J Cardiol. 1990 Jan 1;65(1):89-92
references.pmid: 2104735
references.citation: Ann Intern Med. 1986 Aug;105(2):168-73
references.pmid: 3729199
references.citation: Semin Neurol. 2003 Dec;23(4):407-21
references.pmid: 15088262
references.citation: Cardiol Clin. 2002 May;20(2):291-301, vii
references.pmid: 12119802
references.citation: Ann Intern Med. 1980 Mar;92(3):387-8
references.pmid: 7356234
references.citation: Auton Neurosci. 2013 Oct;177(2):291-6
references.pmid: 24008021
references.citation: Clin Auton Res. 2004 Jun;14(3):146-7
references.pmid: 15241642
references.citation: Auton Neurosci. 2011 Apr 26;161(1-2):46-8
references.pmid: 21393070
references.citation: Mayo Clin Proc. 1981 Jul;56(7):429-33
references.pmid: 6166817
references.citation: Am J Med. 1995 Dec;99(6):604-10
references.pmid: 7503082
references.citation: JAMA. 1997 Apr 2;277(13):1046-51
references.pmid: 9091692
references.citation: JAMA. 2010 Nov 17;304(19):2172-3
references.pmid: 21081731
references.citation: Clin Pharmacol Ther. 1981 Dec;30(6):782-9
references.pmid: 7030580
references.citation: Neurology. 1988 Jun;38(6):951-6
references.pmid: 2452997
references.citation: N Engl J Med. 1985 Aug 29;313(9):549-54
references.pmid: 3894971
references.citation: Br Med J. 1980 Jul 26;281(6235):275-6
references.pmid: 7427244
references.citation: Am J Med. 1998 Aug;105(2):116-24
references.pmid: 9727818
references.citation: J Clin Hypertens (Greenwich). 2013 Mar;15(3):147-53
references.pmid: 23458585
references.citation: Hypertension. 2010 Nov;56(5):847-51
references.pmid: 20837887
references.citation: Clin Auton Res. 2012 Apr;22(2):79-90
references.pmid: 22045363
references.citation: Curr Pain Headache Rep. 2003 Feb;7(1):55-62
references.pmid: 12525272