Article date: June 2003
By: Michiel J. B. Kemme, Jeroen P. vd Post, Rik C. Schoemaker, Matthias Straub, Adam F. Cohen, Joop M. A. Van Gerven, in Volume 55, Issue 6, pages 518-525
Objectives The primary aim was to demonstrate that moxonidine, given in an experimental sustained release (SR) formulation, had no clinically relevant central nervous system (CNS) effects after 4 weeks of treatment. A clinically relevant CNS effect was predefined as more than 45° s−1 reduction in saccadic peak velocity (SPV), corresponding to the effects of one night's sleep deprivation.
Methods In a randomized, double‐blind fashion, 35 patients with mild to moderate essential hypertension received placebo run‐in medication for 2 weeks, followed by 4 weeks’ moxonidine sustained release (1.5 mg o.d.) or placebo. On the first day and 1 and 4 weeks following the start of treatment, blood pressure was measured and CNS effects were assessed using SPV, visual analogue scales and EEG.
Results On day 1 there was a significant, but not clinically relevant, reduction in the time‐corrected area under the effect curve (AUEC) for SPV in the moxonidine group compared with placebo [difference of 38° s−1; 95% confidence interval (CI) 23, 52]. This difference was no longer significant after one (9° s−1; 95% CI −17, 35) and 4 weeks (6.9° s−1; 95% CI −16, 30). Visual analogue scales for alertness showed similar results. A decrease in EEG α‐ and β‐power and an increase in δ‐power were only found on day 1 of moxonidine treatment. The AUEC for systolic/diastolic blood pressure relative to placebo was 23 (95% CI 17, 29)/13 (9, 16) mmHg lower on day 1 and remained reduced by 20 (11, 30)/12 (6, 17) and 15 (6, 25)/9 (3, 15) mmHg after 1 and 4 weeks’ moxonidine treatment.
Conclusions Four weeks’ treatment with an experimental SR formulation resulted in tolerance to CNS effects (equivalence to placebo) while blood pressure‐lowering effects remained adequate. The tolerance to CNS effects was already observed after 1 week of treatment.
DOI: 10.1046/j.1365-2125.2003.01796.x
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