Fluoxetine-related death in a child with cytochrome P450 2D6 genetic deficiency

[Guest guest]

I was wondering if you want to add this to the PubMed CYP2D6

Clinical Studies file on the site.--

Sallee F, DeVane C, Ferrell R: Fluoxetine-related death in a child with

cytochrome P450 2D6 genetic deficiency. Journal of Child and Adolescent

Psychopharmacology 2000;10 (Spring):27-34. From the University of

Cincinnati, Ohio; and other institutions. See Related Story in Psychiatry

Drug Alerts 1996;10 (June):48.

CYP2D6 Deficiency-Related Death

In 1995, the FDA reported on the death of a 9-year old boy who at various

times had received clonidine, fluoxetine, and methylphenidate, and who was

found to have extremely high fluoxetine blood levels. The medical examiner

concluded that an intentional fluoxetine overdose had been administered by

his adoptive parents.

Some follow-up information on this case concerning a psychopharmacologic

evaluation and genetic testing has been made available. It appears that the

boy had an autosomal recessive defect in cytochrome P450 2D6 (CYP2D6), which

can result in poor metabolism and elevated levels of fluoxetine. The

accusation of intentional overdose was subsequently abandoned.

The 9-year old (55-lb) boy died following the onset of nausea, flu-like

symptoms, and a seizure that led to cardiopulmonary arrest. The patient's

medical history shows that at age 5 he was diagnosed with fetal alcohol

syndrome, ADHD, and Tourette's disorder, and that he was treated with 0.6

mg/day clonidine for his tics. He was noted to be extremely hyperactive,

with violent outbursts. At age 6, fluoxetine, 5 mg/day was added to 0.9

mg/day clonidine, and fluoxetine was gradually increased to 30 mg/day. The

patient experienced vomiting and diarrhea at this dosage and was

hospitalized for dehydration. The combination was discontinued during

hospitalization and then resumed with a fluoxetine increase to 40 mg/day.

The patient experienced 2 more episodes of vomiting and diarrhea.

At age 8, the patient was receiving fluoxetine and clonidine for Tourette's

disorder and OCD, and 60 mg/day methylphenidate was added to treat ADHD. The

patient was also receiving

25 mg/day promethazine for nausea. Fluoxetine was increased to 80 mg/day,

and he experienced a seizure. One month later, fluoxetine was increased to

100 mg/day. Subsequently, 3 episodes of dizziness, nausea, and low-grade

fever occurred. He experienced 2 seizures, followed by status epilepticus

and cardiopulmonary arrest wherein he could not be resuscitated.

This appears to be the first report of toxicity and death in a child with

confirmed polymorphism of CYP2D6. About 7-10% of Caucasians are estimated to

be genetically deficient in CYP2D6. This deficiency, combined with the 100

mg/day dose of fluoxetine, probably contributed to fluoxetine toxicity and

death in this patient. The possible effect of the other medications is

unknown, and many questions remain about this unfortunate case.