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Fluoxetine-related death in a
child with cytochrome P-450 2D6 genetic
deficiency.
Sallee FR, DeVane CL, Ferrell
RE.
Department of Psychiatry, University of Cincinnati, Ohio
45267, USA. salleefr@email.uc.edu
The clinical course of a
9-year-old diagnosed with attention-deficit hyperactivity disorder,
obsessive-compulsive disorder, and Tourette's disorder and treated with
a combination of methylphenidate, clonidine, and fluoxetine is
described. The patient experienced over a 10-month period, signs and
symptoms suggestive of metabolic toxicity marked by bouts of
gastrointestinal distress, low-grade fever, incoordination, and
disorientation. Generalized seizures were observed, and the patient
lapsed into status epilepticus followed by cardiac arrest and
subsequently expired. At autopsy, blood, brain, and other tissue
concentrations of fluoxetine and norfluoxetine were several-fold higher
than expected based on literature reports for overdose situations. The
medical examiner's report indicated death caused by fluoxetine toxicity.
As the child's adoptive parents controlled medication access, they were
investigated by social welfare agencies. Further genetic testing of
autopsy tissue revealed the presence of a gene defect at the cytochrome
P450 CYP2D locus, which results in poor metabolism of fluoxetine. As a
result of this and other evidence, the investigation of the adoptive
parents was terminated. This is the first report of a fluoxetine-related
death in a child with a confirmed genetic polymorphism of the CYP2D6
gene that results in impaired drug metabolism. Issues relevant to child
and adolescent psychopharmacology arising from this case are
discussed.
PMID: 10755579 [PubMed - indexed for MEDLINE]
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