Brainstorms August 31, 2000

Blue Genes and the Mechanism of Action of Antidepressants

Stephen M. Stahl

J Clin Psychiatry 2000;61(3):164-165

Article Abstract

All antidepressants increase neurotransmission for one or more of the monoamines—serotonin, norepinephrine, or dopamine. One problem with the monoamine hypothesis is that the timing of antidepressant effects on neurotransmitters is generally
faster (within minutes) than the timing of the antidepressant effects on mood (reaching maximal effect in days to weeks). One theory to
explain the ultimate mechanism of delayed therapeutic action of antidepressants is the "neurotransmitter receptor hypothesis of antidepressant action," which proposes that antidepressants, no matter what their initial actions on receptors and enzymes, eventually cause a desensitization or "down-regulation" of key neurotransmitter receptors in a time course consistent with the delayed onset of
antidepressant action of these drugs.