Abrupt cessation of
clonidine treatment in hypertensive patients may precipitate a withdrawal syndrome. Since this
drug is likely to be more widely prescribed to normotensive patients with neuropsychiatric diseases, we studied neurochemical, cardiovascular, and behavioral changes upon placebo substitution in seven patients receiving
clonidine (6 micrograms/kg/day for 3 weeks) for treatment of
alcohol amnestic disorder. Urinary excretion of all major
catecholamine metabolites returned to pretreatment levels 3-5 days after discontinuing
clonidine, without significant overshoot. The percentage increase during
clonidine withdrawal of the
norepinephrine metabolite
normetanephrine was greater than were those of
vanillylmandelic acid, 3-methoxy-4-hydroxyphenylglycol (
MHPG), or the
epinephrine metabolite
metanephrine. Excretion of the
dopamine metabolites
homovanillic acid and
3-methoxytyramine did not change. Total plasma
MHPG, heart rate, and mean arterial pressure were significantly elevated above pretreatment values 72 h after the last dose of
clonidine. There was an enhancement of episodic memory compared to predrug values but no other behavioral changes were noted during
clonidine withdrawal. These findings are consistent with augmented
catecholamine release and central noradrenergic activation which may produce psychopathology in some psychiatric patients during
clonidine withdrawal.