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Possible Biological Mechanisms of the Serotonin Reuptake Inhibitor Discontinuation Syndrome

Alan F. Schatzberg, M.D., Chair, Peter Haddad, M.D., Eric M. Kaplan, M.D., Michel Lejoyeux, M.D., Ph.D., Jerrold F. Rosenbaum, M.D., A. H. Young, M.D., Ph.D., and John Zajecka, M.D.

Published: May 1, 1997

Article Abstract

Although the number of documented serotonin reuptake inhibitor (SRI) discontinuation reactionsis increasing, to date no systematic studies have been completed; therefore the mechanism of actionfor these reactions is not clearly understood. However, several hypotheses have been proposed.Researchers have postulated that discontinuation events result from a sudden decrease in the availabilityof synaptic serotonin in the face of down-regulated serotonin receptors. In addition, otherneurotransmitters, such as dopamine, norepinephrine, or gamma-aminobutyric acid (GABA), mayalso be involved, although little research in this area has been published. Individual patient sensitivity,i.e., genetics or cognitive mindset, may also be a factor in SRI discontinuation phenomena. Finally,experts have hypothesized that since some symptoms associated with paroxetine withdrawal are similarto those of tricyclic antidepressant discontinuation, they may be caused by cholinergic rebound.

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Volume: 58

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