The clinical course of a 9-year-old diagnosed with attention-deficit hypera
ctivity disorder, obsessive-compulsive disorder, and Tourette's disorder an
d treated with a combination of methylphenidate, clonidine, and fluoxetine
is described. The patient experienced over a 10-month period, signs and sym
ptoms 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 foll
owed by cardiac arrest and subsequently expired. At autopsy, blood, brain,
and other tissue concentrations of fluoxetine and norfluoxetine were severa
l-fold higher than expected based on literature reports for overdose situat
ions. The medical examiner's report indicated death caused by fluoxetine to
xicity. As the child's adoptive parents controlled medication access, they
were investigated by social welfare agencies. Further genetic testing of au
topsy 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 ter
minated. 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 im
paired drug metabolism. Issues relevant to child and adolescent psychopharm
acology arising from this case are discussed.