PEDIATRICS Vol. 114 No. 6 December 2004, pp. 1743 (doi:10.1542/peds.2004-1268)
Severe Extrapyramidal Symptoms in a 3-Year-Old Boy After Accidental Ingestion of the New Antipsychotic Drug Aripiprazole
Robert B. Schonberger, MAYale University School of Medicine
New Haven, CT 06510
Lindsey Douglas, MD
Carl R. Baum, MD, FAAP, FACMT
Department of Pediatrics
Yale University School of Medicine
New Haven, CT 06510
To the Editor.—
Aripiprazole is a new type of antipsychotic medication exhibiting high-affinity partial agonist activity at D2-dopamine receptors.1,2 When used in adults for the treatment of schizophrenia and schizoaffective disorder, aripiprazole has been associated with extrapyramidal symptoms (EPS) at a rate similar to that of placebo.3 Although it has been used in children, aripiprazole's safety profile in pediatric age groups is unknown.2,4 We report a case of severe EPS in a 3-year-old boy after accidental ingestion of a single dose of <15 mg of aripiprazole.
The patient was an otherwise healthy boy found by his mother holding an open bottle of his older sibling's aripiprazole. After inspection, one half of a 15-mg pill was missing. The child presented as a transfer to our hospital 
48 hours after the suspected ingestion with extreme lethargy, flat affect, intention tremor, truncal ataxia, and a Parkinsonian gait. Extensive work-up was notable only for a serum aripiprazole concentration of 63 ng/ml, collected 87 hours after ingestion. The patient's hospital course was characterized by slow improvement in mental status, tremor, and Parkinsonian symptoms, which resolved completely 7 days after ingestion.
We approximated the patient's initial dose and peak serum concentration of aripiprazole assuming the following pharmacokinetic properties known for adults: volume of distribution = 4.9 L/kg,4 half-life = 75 hours,4,5 bioavailability = 87%,4 and peak concentration 3 to 5 hours after ingestion.4,5 The estimated ingested dose in this 15.5-kg patient was 11.9 mg. Given that aripiprazole's pharmacokinetic profile in children is poorly defined, the estimated ingested dose using adult pharmacokinetic values seemed reasonably consistent with the pill count showing one half of a 15-mg pill missing. The peak serum concentration was estimated at 136 µg/L. Adults taking therapeutic doses of aripiprazole reached mean steady-state serum concentrations from 98 to 452 µg/L.5 Even accounting for a wide range of half-lives of aripiprazole secondary to variations in cytochrome P-450 isoenzymes,2,4,5 our patient's peak serum level was well within the adult therapeutic range.
We found 2 references in the literature regarding aripiprazole ingestion in young children. An 18-month-old child ingested 15 mg of the drug without apparent incident, and a 2.5-year-old child exhibited central nervous system depression and mild tachycardia after ingesting 225 mg of the drug.4 Severe EPS associated with aripiprazole were reported in an adolescent with a previous history of such symptoms.2 It is unknown whether our patient's adverse response represents an idiosyncratic sensitivity to the drug or whether it indicates a more general vulnerability to EPS in young children taking aripiprazole.2 This case underscores the need for caution in treating young children with dopamine receptor partial agonists.
REFERENCES
1. Burris KD, Molski TF, Xu C, et al. Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors.
J Pharmacol Exp Ther. 2002;302
:381
–389
2. Lindsey RL, Kaplan D, Koliatsos V, Walters JK, Sandson NB. Aripiprazole and extrapyramidal symptoms. J Am Acad Child Adolesc Psychiatry. 1268;42 :1268 –1269
3. Kane JM, Carson WH, Saha AR, et al. Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry. 2002;63 :763 –771[Web of Science][Medline]
4. Levine M, Traub S, Burns MJ. The pharmacology and toxicology of aripiprazole. Internet J Med Toxicol. 2004;7(1) :5
5. Mallikaarjun S, Salazar DE, Bramer SL. Pharmacokinetics, tolerability, and safety of aripiprazole following multiple oral dosing in normal healthy volunteers.
J Clin Pharmacol. 2004;44
:179
–187
PEDIATRICS (ISSN 1098-4275). ©2004 by the American Academy of Pediatrics
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