Am J Psychiatry 1991; 148:1060-1063
Copyright © 1991 by American Psychiatric Association
Comparison of the effects of hydrochlorothiazide and furosemide on lithium disposition
BL Crabtree, JE Mack, CD Johnson and BC Amyx
Department of Clinical Pharmacy Practice, University of Mississippi Medical Center, Jackson 39216.
OBJECTIVE: This study examined the interaction between lithium and
diuretics, comparing both the pharmacokinetic and the pharmacodynamic
variable of hydrochlorothiazide, furosemide, and placebo. METHOD: The
study, which took place in an outpatient research clinic of a university
hospital, used a double-blind, placebo-controlled crossover design. The
subjects were normal, healthy male volunteers who responded to recruitment
announcements. Thirteen subjects entered and completed the study. All
subjects took lithium, 300 mg b.i.d., for 6 weeks. Hydrochlorothiazide, 25
mg b.i.d.; furosemide, 20 mg b.i.d.; and placebo were given during weeks 2,
4, and 6 in a random order of assignment. Serum lithium levels and indices
of diuretic activity were measured during each week. RESULTS: The subjects'
serum lithium levels after 5 days of taking hydrochlorothiazide were
significantly higher than after 5 days of taking furosemide and placebo. At
the doses studied, hydrochlorothiazide was also more potent than furosemide
in increasing plasma renin activity, increasing sodium excretion, and
decreasing lithium excretion. CONCLUSIONS: The observed differences between
diuretics in effects on serum lithium may have been due to differences in
the potency of the diuretics at the doses studied as well as in the site of
action of the diuretic effect. The results must be interpreted cautiously,
however, because the effects were small and of questionable clinical
significance, and the study used healthy volunteers and low doses of
lithium instead of psychiatric patients and the usual therapeutic levels of
lithium.
