title: Possible monoamine oxidase inhibitor-serotonin uptake inhibitor interaction: fluoxetine clinical data and preclinical findings.
abstract: The primary objective of this article is to review information pertinent to and emphasize the seriousness of a potential adverse monoamine oxidase inhibitor (MAOI)-serotonin uptake inhibitor interaction by considering, within the context of preclinical data, clinical cases in which an MAOI and fluoxetine hydrochloride, a specific serotonin uptake inhibitor, were administered in close temporal proximity. Clinical cases were identified by a review of spontaneous adverse event reports submitted voluntarily to Eli Lilly and Company through its drug surveillance program and by a review of reports of MAOI interactions published in the scientific literature. A discussion of eight selected clinical cases of acute adverse reactions (seven with fatal outcomes; one with a favorable response after cyproheptadine therapy) reported to Eli Lilly and Company in which an MAOI was initiated concurrently or shortly after the discontinuation of fluoxetine and a review of preclinical data suggest a possible role of serotonin and/or serotonin-dopamine interactions in the hypermetabolic state that may occur when a serotonin uptake inhibitor and an MAOI are coadministered, although alternative etiologic processes are possible as well. Data reviewed reinforce the idea that the administration of an MAOI in close temporal proximity to fluoxetine is contraindicated.
authors.affiliation: Psychopharmacology Division, Lilly Corporate Center, Indianapolis, Indiana 46285.
authors.forename: C M
authors.initials: CM
authors.lastname: Beasley
authors.forename: D N
authors.initials: DN
authors.lastname: Masica
authors.forename: J H
authors.initials: JH
authors.lastname: Heiligenstein
authors.forename: D E
authors.initials: DE
authors.lastname: Wheadon
authors.forename: R L
authors.initials: RL
authors.lastname: Zerbe
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D017809:Fatal Outcome; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D009460:Neurologic Examination / Q000187:drug effects; D010624:Phenelzine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011358:Product Surveillance, Postmarketing; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D014191:Tranylcypromine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D008996:Monoamine Oxidase Inhibitors; D011985:Receptors, Serotonin; D005473:Fluoxetine; D014191:Tranylcypromine; D010624:Phenelzine