title: Hemodynamic profiles and tolerability of modafinil in the treatment of postural tachycardia syndrome: a randomized, placebo-controlled trial.
abstract: BACKGROUND
  Postural tachycardia syndrome (POTS) is characterized clinically not only by an exaggerated increase in heart rate (HR), but an associated cognitive impairment that disables many patients. Modafinil might be effective in improving the cognitive symptoms, but modafinil may stimulate the sympathetic nervous system and worsen tachycardia in POTS. We tested the hypothesis that modafinil would worsen tachycardia and orthostatic symptoms in POTS.
  
  
  METHODS
  Patients with POTS (n = 54) underwent a randomized crossover trial with modafinil 100 mg versus placebo. Heart rate and systolic blood pressure (SBP) were measured seated and standing before modafinil or placebo administration and then hourly for 4 hours.
  
  
  RESULTS
  Over 4 hours, standing HR was not significantly different between the modafinil and placebo groups (analysis of variance [ANOVA] Pdrug = 0.328), but seated SBP was significantly higher in the modafinil group (mean [SD], 109 [12] mm Hg vs 104 [10] mm Hg; P = 0.004). Modafinil also significantly increased both the seated SBP (ANOVA Pdrug = 0.004) and the standing SBP (ANOVA Pdrug = 0.041) over time. There was no significant difference between modafinil and placebo over the 4-hour period with regard to POTS symptom burden scores (14 [12] vs 14 [12]; P = 0.962).
  
  
  CONCLUSIONS
  Modafinil did not significantly worsen standing HR or acute orthostatic symptoms in patients with POTS compared with the placebo group and improved upright blood pressure. Therefore, modafinil could be tested as a potential treatment for the cognitive impairment in POTS.
authors.affiliation: From the Departments of *Medicine, †Psychiatry, ‡Pharmacology, §Biostatistics, ∥Neurology, Autonomic Dysfunction Center, Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN; and ¶Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Kpaeyeh
authors.forename: Philip L
authors.initials: PL
authors.lastname: Mar
authors.forename: Vidya
authors.initials: V
authors.lastname: Raj
authors.forename: Bonnie K
authors.initials: BK
authors.lastname: Black
authors.forename: Amy C
authors.initials: AC
authors.lastname: Arnold
authors.forename: Italo
authors.initials: I
authors.lastname: Biaggioni
authors.forename: Cyndya A
authors.initials: CA
authors.lastname: Shibao
authors.forename: Sachin Y
authors.initials: SY
authors.lastname: Paranjape
authors.forename: William D
authors.initials: WD
authors.lastname: Dupont
authors.forename: David
authors.initials: D
authors.lastname: Robertson
authors.forename: Satish R
authors.initials: SR
authors.lastname: Raj
mesh_terms: D000328:Adult; D001559:Benzhydryl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D005260:Female; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D000077408:Modafinil; D054972:Postural Orthostatic Tachycardia Syndrome / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001559:Benzhydryl Compounds; D000077408:Modafinil