Electroencephalographic and Psychometric Assessment of the CNS Effects of Single Doses of Guanfacine Hydrochloride (Estulic®) and Clonidine (Catapres®)

Abstract

A double-blind, placebo-controlled study was carried out in 10 young healthy volunteers to investigate the effects of single doses of 1 and 2 mg guanfacine hydrochloride (Estulic®) and 0.15 and 0.3 mg clonidine (Catapres®) on the electroencephalogram (EEG), subjective mental and emotional state, blood pressure and heart rate. These doses are considered to be equipotent with regard to their antihypertensive effects, as shown in long-term therapeutic trials. Each subject received all five treatments in random sequence at intervals of 1 week. The EEG tracings were evaluated quantitatively by spectral analysis. Procedures were carried out before and at 1, 2, 4, 6 and 8 h after drug administration. After clonidine the EEG showed increased slow-wave activity and decreased alpha activity, these effects being dose-dependent. They were of the sedative type and did not clearly indicate specific psychotropic properties. The subjective mental and emotional state questionnaire indicated a decrease of alertness, extroversion, concentration and mood (in that order), changes which paralleled the EEG changes. The changes observed after guanfacine were qualitatively similar to those after clonidine, but were of considerably lower intensity. Our data suggest that guanfacine has less central nervous system-depressant activity than clonidine.

Effects of d-Methylphenidate, Guanfacine, and Their Combination on Electroencephalogram Resting State Spectral Power in Attention-Deficit/Hyperactivity Disorder

“…Behaviorally, GUAN leads to improvement in ADHD symptoms 8,11,12 ; however, neurophysiologically, guanfacine appeared to lower alpha power, which was subsequently associated with slower reaction time, higher reaction time variability, and a trend towards lower performance on tasks measuring inhibition. This result is similar to the only previous study examining EEG correlates of guanfacine among humans 22 . Among 10 healthy adults, guanfacine resulted in alpha power decrease with concomitant participant report of significantly reduced alertness, both of which were interpreted as being consistent with a central nervous system depressant effect.…”

Quantitative Electroencephalographic Correlates of Steroid Administration in Man

“…Martin and Kay [31] also reviewed evidence that morphine induces a slowing o f alpha waves and an increase in theta and delta waves in animals and man, and Oliverio et al [32] reported that BE administration resulted in increased high-voltage low-frequency E E G activity in rats, findings that may be consistent with our observed correlation between prednisone-induced changes in C S F BE and slowing o f brain wave activity. Lastly, Yamadera et al [33] and Fink and Irwin [34] reported that acute doses of the central alpha-2-receptor agonist drugs, clonidine and guanfacine (both o f which lower N E release), increase slow wave activity and de crease alpha activity in man, findings consistent with our observed relationship between decreased C S F levels of N E and decreased alpha activity. Our results, although preliminary and based on a relative ly small sample, suggest that relatively brief courses of exogenous corticosteroid administration are associated with significant brain electrophysiologic changes.…”

Changes of Sleep Architecture, Spectral Composition of Sleep EEG, the Nocturnal Secretion of Cortisol, ACTH, GH, Prolactin, Melatonin, Ghrelin, and Leptin, and the DEX-CRH Test in Depressed Patients during Treatment with Mirtazapine

“…Clonidine, an agonist at presynaptic adrenergic alpha 2 receptors, has a potent influence on alpha activity. In healthy volunteers, clonidine suppresses alpha activity in wake EEG (Yamadera et al, 1985;Bischoff et al, 1998). In accordance with these studies, the blockade of alpha 2 receptors with mirtazapine results in the increase of alpha power.…”