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Combination ergotamine and caffeine improves seated blood pressure and presyncopal symptoms in autonomic failure.

Arnold AC, Ramirez CE, Choi L, Okamoto LE, Gamboa A, Diedrich A, Raj SR, Robertson D, Biaggioni I, Shibao CA - Front Physiol (2014)

Bottom Line: Blood pressure was measured while patients were seated and after standing for up to 10 min, at baseline and at 1 h post-drug.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).

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Pharmacology, Department of Medicine, Autonomic Dysfunction Center, Vanderbilt University School of Medicine Nashville, TN, USA.

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.

No MeSH data available.


Related in: MedlinePlus

Changes in seated blood pressure following drug administration. The combination of 1 mg ergotamine and 100 mg caffeine increased seated systolic blood pressure over time compared with placebo in patients with severe autonomic failure (p = 0.003). Similarly, 5–10 mg midodrine increased seated systolic blood pressure in these patients (p = 0.015), but this effect was not different from ergotamine/caffeine (p = 0.621). Data are presented as mean ± 95% confidence interval.
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Figure 1: Changes in seated blood pressure following drug administration. The combination of 1 mg ergotamine and 100 mg caffeine increased seated systolic blood pressure over time compared with placebo in patients with severe autonomic failure (p = 0.003). Similarly, 5–10 mg midodrine increased seated systolic blood pressure in these patients (p = 0.015), but this effect was not different from ergotamine/caffeine (p = 0.621). Data are presented as mean ± 95% confidence interval.

Mentions: The average seated SBP during the 30-min baseline period was similar among placebo, ergotamine/caffeine, and midodrine study days (p = 0.441; Friedman test). Ergotamine/caffeine significantly increased seated SBP, the primary outcome, as a linear function of time compared with placebo (Figure 1; slope difference: 1.003; 95% CI: 1.001 to 1.005; p = 0.003; random effects model). Similarly, midodrine increased seated SBP compared with placebo (Figure 1; slope difference: 1.002; 95% CI: 1.001–1.004; p = 0.015; random effects model). The magnitude of the seated pressor response to midodrine was similar between patients receiving the 5 mg (median: 26; IQR: 14–36) and 10 mg (median: 23; IQR: 7–48) doses. There was no significant difference, however, in the seated pressor response between ergotamine/caffeine and midodrine (slope difference: 1.000; 95% CI: 0.998–1.001; p = 0.621; random effects model). In this study, 9 out of 12 (75%) patients exhibited an increase in seated SBP ≥ 20 mmHg with ergotamine/caffeine compared with 5 out of 12 (42%) patients for midodrine, a difference that was not significantly different (p = 0.125; McNemar test).


Combination ergotamine and caffeine improves seated blood pressure and presyncopal symptoms in autonomic failure.

Arnold AC, Ramirez CE, Choi L, Okamoto LE, Gamboa A, Diedrich A, Raj SR, Robertson D, Biaggioni I, Shibao CA - Front Physiol (2014)

Changes in seated blood pressure following drug administration. The combination of 1 mg ergotamine and 100 mg caffeine increased seated systolic blood pressure over time compared with placebo in patients with severe autonomic failure (p = 0.003). Similarly, 5–10 mg midodrine increased seated systolic blood pressure in these patients (p = 0.015), but this effect was not different from ergotamine/caffeine (p = 0.621). Data are presented as mean ± 95% confidence interval.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109567&req=5

Figure 1: Changes in seated blood pressure following drug administration. The combination of 1 mg ergotamine and 100 mg caffeine increased seated systolic blood pressure over time compared with placebo in patients with severe autonomic failure (p = 0.003). Similarly, 5–10 mg midodrine increased seated systolic blood pressure in these patients (p = 0.015), but this effect was not different from ergotamine/caffeine (p = 0.621). Data are presented as mean ± 95% confidence interval.
Mentions: The average seated SBP during the 30-min baseline period was similar among placebo, ergotamine/caffeine, and midodrine study days (p = 0.441; Friedman test). Ergotamine/caffeine significantly increased seated SBP, the primary outcome, as a linear function of time compared with placebo (Figure 1; slope difference: 1.003; 95% CI: 1.001 to 1.005; p = 0.003; random effects model). Similarly, midodrine increased seated SBP compared with placebo (Figure 1; slope difference: 1.002; 95% CI: 1.001–1.004; p = 0.015; random effects model). The magnitude of the seated pressor response to midodrine was similar between patients receiving the 5 mg (median: 26; IQR: 14–36) and 10 mg (median: 23; IQR: 7–48) doses. There was no significant difference, however, in the seated pressor response between ergotamine/caffeine and midodrine (slope difference: 1.000; 95% CI: 0.998–1.001; p = 0.621; random effects model). In this study, 9 out of 12 (75%) patients exhibited an increase in seated SBP ≥ 20 mmHg with ergotamine/caffeine compared with 5 out of 12 (42%) patients for midodrine, a difference that was not significantly different (p = 0.125; McNemar test).

Bottom Line: Blood pressure was measured while patients were seated and after standing for up to 10 min, at baseline and at 1 h post-drug.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).

View Article: PubMed Central - PubMed

Affiliation: Division of Clinical Pharmacology, Department of Medicine, Autonomic Dysfunction Center, Vanderbilt University School of Medicine Nashville, TN, USA.

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.

No MeSH data available.


Related in: MedlinePlus