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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

Effect of drugs on orthostatic presyncopal symptoms. Data represent changes in orthostatic symptom scores from baseline (left bar) to 60 min post-administration (right bar), with comparisons made for each individual drug. (A) Combination 1 mg ergotamine and 100 mg caffeine reduced the orthostatic symptom composite score in autonomic failure patients, suggesting an improvement in presyncopal symptom burden. In contrast, there was no effect of 5–10 mg midodrine or placebo on this composite score. (B) Combination ergotamine and caffeine also reduced the lightheadedness component (Question 1) of the orthostatic symptoms score in these patients, with no significant effect of midodrine or placebo. Data are presented as mean ± 95% confidence interval.
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Figure 3: Effect of drugs on orthostatic presyncopal symptoms. Data represent changes in orthostatic symptom scores from baseline (left bar) to 60 min post-administration (right bar), with comparisons made for each individual drug. (A) Combination 1 mg ergotamine and 100 mg caffeine reduced the orthostatic symptom composite score in autonomic failure patients, suggesting an improvement in presyncopal symptom burden. In contrast, there was no effect of 5–10 mg midodrine or placebo on this composite score. (B) Combination ergotamine and caffeine also reduced the lightheadedness component (Question 1) of the orthostatic symptoms score in these patients, with no significant effect of midodrine or placebo. Data are presented as mean ± 95% confidence interval.

Mentions: As shown in Figure 2, at 60 min after placebo administration 5 out of 12 (42%) autonomic failure patients could stand for 10 min, compared with 8 out of 12 (67%) after ergotamine/caffeine and 6 out of 12 (50%) after midodrine. There was no significant difference, however, in orthostatic tolerance between ergotamine/caffeine and placebo (ΔAUCSBP: 248; 95% CI: −73 to 568; p = 0.130; random effects model), between midodrine and placebo (ΔAUCSBP: 85; 95% CI: −141 to 311; p = 0.461), or between ergotamine/caffeine and midodrine (ΔAUCSBP: −163; 95% CI: −387 to 62; p = 0.155). The orthostatic symptom composite score, as well as the lightheadedness component of this score (Question 1), were reduced at 60 min following ergotamine/caffeine administration (Figure 3; p = 0.034 and 0.040, respectively; Wilcoxon signed-rank test) when compared with baseline. In contrast, there was no significant effect of either midodrine or placebo on orthostatic symptom scores (Figure 3).


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)

Effect of drugs on orthostatic presyncopal symptoms. Data represent changes in orthostatic symptom scores from baseline (left bar) to 60 min post-administration (right bar), with comparisons made for each individual drug. (A) Combination 1 mg ergotamine and 100 mg caffeine reduced the orthostatic symptom composite score in autonomic failure patients, suggesting an improvement in presyncopal symptom burden. In contrast, there was no effect of 5–10 mg midodrine or placebo on this composite score. (B) Combination ergotamine and caffeine also reduced the lightheadedness component (Question 1) of the orthostatic symptoms score in these patients, with no significant effect of midodrine or placebo. 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 3: Effect of drugs on orthostatic presyncopal symptoms. Data represent changes in orthostatic symptom scores from baseline (left bar) to 60 min post-administration (right bar), with comparisons made for each individual drug. (A) Combination 1 mg ergotamine and 100 mg caffeine reduced the orthostatic symptom composite score in autonomic failure patients, suggesting an improvement in presyncopal symptom burden. In contrast, there was no effect of 5–10 mg midodrine or placebo on this composite score. (B) Combination ergotamine and caffeine also reduced the lightheadedness component (Question 1) of the orthostatic symptoms score in these patients, with no significant effect of midodrine or placebo. Data are presented as mean ± 95% confidence interval.
Mentions: As shown in Figure 2, at 60 min after placebo administration 5 out of 12 (42%) autonomic failure patients could stand for 10 min, compared with 8 out of 12 (67%) after ergotamine/caffeine and 6 out of 12 (50%) after midodrine. There was no significant difference, however, in orthostatic tolerance between ergotamine/caffeine and placebo (ΔAUCSBP: 248; 95% CI: −73 to 568; p = 0.130; random effects model), between midodrine and placebo (ΔAUCSBP: 85; 95% CI: −141 to 311; p = 0.461), or between ergotamine/caffeine and midodrine (ΔAUCSBP: −163; 95% CI: −387 to 62; p = 0.155). The orthostatic symptom composite score, as well as the lightheadedness component of this score (Question 1), were reduced at 60 min following ergotamine/caffeine administration (Figure 3; p = 0.034 and 0.040, respectively; Wilcoxon signed-rank test) when compared with baseline. In contrast, there was no significant effect of either midodrine or placebo on orthostatic symptom scores (Figure 3).

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