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June 4, 1997

Fatality Associated With Combined Fluoxetine-Amitriptyline Therapy

Author Affiliations

University of Kansas School of Medicine
Psychiatric Research Institute Wichita, Kan

JAMA. 1997;277(21):1682. doi:10.1001/jama.1997.03540450038031

To the Editor.  —To our knowledge, this is the first published report of a death associated with fluoxetine—tricyclic antidepressant (TCA) interaction.

Report of a Case.  —A 36-year-old man with recurrent major depression was prescribed amitriptyline, 150 mg/d, and fluoxetine, 40 mg/d. He died approximately 6 weeks later, and his body was found in his house several weeks after death. An autopsy revealed no anatomical cause of death. Investigation revealed no evidence of suicide by an acute overdose.Toxicological testing revealed only amitriptyline, fluoxetine, their respective metabolites, nortriptyline and norfluoxetine, and ethanol, the level of which was 9 mg/dL (and could be solely because of postmortem formation by microorganisms). Analyses were performed on gastric contents and on samples from the liver, kidney, and brain (Table).

Comment.  —Given these findings, the most plausible explanation for the death of this patient is chronic intoxication with amitriptyline because of a reduction in its clearance