Clinical Trials and Therapeutics
Clinical Pharmacology & Therapeutics (1999) 65, 328–335; doi:
Does short-term treatment with modafinil affect blood pressure in patients with obstructive sleep apnea?*
Jörg Heitmann MD1, Werner Cassel DiplPsych1, Ludger Grote MD1, Ulrich Bickel MD, PhD1, Udo Hartlaub DiplBiol1, Thomas Penzel PhD1 and Jörg Hermann Peter MD, PhD1
1Sleep Laboratory, Department of Medicine, Marburg University, and the Department of Physiology, Philipps-Universität Marburg University, Marburg, Germany, and Merckle GmbH, Clinical Research Department, Ulm, Germany.
Correspondence: Jörg Heitmann, MD, Medizinische Poliklinik, Schlafmedizinisches Labor, Klinikum der Philipps-Universität Marburg, Baldingerstrasse, D-35033 Marburg, Germany. E-mail: heitmanj@mailer.uni-marburg.de
*Supported by a grant from Merckle GmbH, Ulm, Germany.
Received 1 April 1998; Accepted 21 October 1998.
Abstract
Objective: To investigate the effects of modafinil, a central nonamphetamine awakening substance, on blood pressure and heart rate in hypersomnolent patients with obstructive sleep apnea.
Design: This double-blind, randomized, placebo-controlled crossover trial was performed over 2 days and 3 nights in a single-center study of hospitalized patients from a referred care center. Twenty-six otherwise healthy men (age range, 30 to 60 years) with mild to moderate obstructive sleep apnea were recruited by the outpatient department of the Marburg University Sleep Laboratory. Patients were given 200 mg oral modafinil in the morning and 100 mg at midday. Placebo was given in the same manner in a crossover design. Mean arterial (radial) blood pressure was monitored continuously during nocturnal sleep and during a series of standardized daytime physical and psychologic performance tests.
Results: The difference in the main end point between the treatment with modafinil and placebo was 1.17 
0.83 (mean SE) mm Hg (95% confidence interval: -0.56 to 2.91 mm Hg). The maximal differences in blood pressure values occurred under loaded conditions (systolic blood pressure, ergometry: 5.62 1.13 mm Hg; mental stress test: 6.19 1.33 mm Hg).
Conclusion: Short-term administration of modafinil did not elicit a significant response with regard to the main end point. However, cardiovascular effects during mental and physical load were observed. Long-term studies that include subjects with hypertension are necessary to investigate the clinical relevance of the cardiovascular effects of modafinil.
