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Serotonin Reuptake Inhibitor Discontinuation Syndrome: A Hypothetical Definition

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: February 1, 1997

Article Abstract

Adverse events following discontinuation from serotonin reuptake inhibitors (SRIs) are being reportedin the literature with increasing frequency; the frequency and severity of these symptoms appearto vary according to the half-life of the SRI, e.g., the incidence appears higher with the shorterhalf-life agents than with fluoxetine, which has an extended half-life. Yet, there have been no systematicstudies of the phenomenon to date. Therefore, a group of experts convened in Phoenix, Arizona, todevelop a clear description or definition of the phenomenon based on these reports. The SRI discontinuationsyndrome, referred to as "withdrawal symptoms" in many anecdotal case reports, is distinctlydifferent from the classic withdrawal syndrome associated with alcohol and barbiturates. Antidepressantsare not associated with dependence or drug-seeking behavior. SRI discontinuation symptomstend to be short-lived and self-limiting, but can be troublesome. They may emerge when an SRIis abruptly discontinued, when doses are missed, and less frequently, during dosage reduction. In addition,the symptoms are not attributable to any other cause and can be reversed when the originalagent is reinstituted, or one that is pharmacologically similar is substituted. SRI discontinuationsymptoms, in most cases, may be minimized by slowly tapering antidepressant therapy, but there havebeen several case reports where symptoms occurred consistently even through repeated attempts totaper therapy. Physical symptoms include problems with balance, gastrointestinal and flu-like symptoms,and sensory and sleep disturbances. Psychological symptoms include anxiety and/or agitation,crying spells, and irritability. Further analyses of data bases and clinical studies are needed to definethis proposed syndrome more clearly.

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Volume: 58

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