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Postmortem forensic toxicology of
selective serotonin reuptake inhibitors: a review of pharmacology and
report of 168 cases.
Goeringer KE, Raymon L,
Christian GD, Logan BK.
Washington State Toxicology
Laboratory, Department of Laboratory Medicine, Seattle, WA 98134,
USA.
This paper reviews the complex pharmacology of the new class
of antidepressant medications exhibiting selective inhibition of
serotonin reuptake. The four selective serotonin reuptake inhibitors
(SSRIs) considered--fluoxetine, fluvoxamine, sertraline and
paroxetine--can result in toxicity and death through contributing to
serotonergic excess resulting in serotonin syndrome, inhibiting the
metabolism of other centrally acting drugs, leading to accumulation of
toxic concentrations, and exerting complex vasoactive effects on the
vascular smooth muscle. This latter feature is of particular concern in
patients with preexisting heart disease. An analytical method involving
isolation of the drugs by liquid/liquid extraction at alkaline pH into
n-butyl chloride, and analysis by gas chromatography/mass spectrometry
(GC/MS) is described, together with some of its limitations. Toxicologic
and cause and manner of death data were examined in 60 deaths involving
fluoxetine, 5 involving fluvoxamine, 75 involving sertraline, and 28
involving paroxetine. Deaths involving drug toxicity were generally a
result of ingestion of multiple drugs, and in only a small number of the
cases was death attributed principally to the SSRI involved. The
potential for drug interactions between members of this class of drugs
is discussed as well as their metabolites and a variety of other
therapeutic and abused drugs which can contribute to their toxicity. In
the absence of other risk factors, the lowest concentrations determined
to have resulted in death were 0.63 mg/L for fluoxetine, 0.4 mg/L for
paroxetine, and 1.5 mg/L for sertraline. We had insufficient data to
make even this crude assessment for fluvoxamine. Drug-induced elevation
of serotonin concentrations may be a significant risk factor for
patients with atherosclerotic cardiovascular disease (ASCVD). Other
factors including preexisting disease and the presence of other drugs
and their pharmacology need to be carefully considered before
determining the appropriate cause and manner of death in these
cases.
Publication Types:
- Review
- Review of Reported Cases
PMID: 10855970 [PubMed -
indexed for MEDLINE]
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