Hemodynamic profiles and tolerability of modafinil in the treatment of postural tachycardia syndrome: a randomized, placebo-controlled trial.

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.

Sotalol.

Sotalol is effective for treating atrial fibrillation (AF), ventricular tachycardia, premature ventricular contractions, and supraventricular tachycardia. Racemic (DL) sotalol inhibits the rapid component of the delayed rectifier potassium current. There is a near linear relationship between sotalol dosage and QT interval prolongation. However, in dose ranging trials in patients with AF, low-dose sotalol was not more effective than placebo. Orally administered sotalol has a bioavailability of nearly 100%. The only significant drug interactions are the need to avoid or limit use of concomitant drugs that cause QT prolongation, bradycardia, and/or hypotension.