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Olanzapine Toxicity in a Toddler

1998; American Academy of Pediatrics; Volume: 102; Issue: 6 Linguagem: Inglês

10.1542/peds.102.6.1494b

1098-4275

Luke Yip, Richard C. Dart, Kathleen Graham,

Alcoholism and Thiamine Deficiency

To the Editor. Olanzapine (Zyprexa, Eli Lilly) is an atypical antipsychotic approved in 1996 for clinical use in Europe and the United States. There is no recommended pediatric dose for olanzapine or any information on its effect on children.The mother of a 2½-year-old boy discovered that one or two of her 7.5 mg olanzapine tablets were missing. Within 1 hour the boy was found sleeping and difficult to arouse. Over the next several hours he intermittently awoke. During these times he refused to interact (kiss, speak, play, dance) with family members and remained slow to respond. He was described as glassy-eyed, hostile, agitated, appeared in pain, violent towards family members, and refusing to eat. There was no history of recent illness, head trauma, or seizures. Past medical and surgical history were unremarkable. The child was not on any medications.The child was evaluated 9.5 hours postingestion because of persistent abnormal behavior. He was a well-nourished, well-developed 13.5-kg male. His blood pressure was 100/60; respiratory rate, 28; heart rate, 120–180; temperature (rectal) 36.9°C; pulse oximetry 98%. HEENT: normal cephalic, atraumatic, pupils 1 to 2 mm and reactive, no nystagmus. Hypersalivation without apparent oropharyngeal lesions was noted. Neck: supple. Lungs: clear with equal breath sounds. Cor: regular tachycardia. Abdomen: normal bowel sounds, soft, and nontender. Neurologic: somnolent and stuporous, yet irritable, agitated, and hostile when aroused. He did not seem to be hallucinating and followed some commands. He was ataxic but muscle tone and reflexes were normal and without clonus.Complete blood count, electrolytes, anion gap, renal function, urinalysis, head computed tomography scan, and lumbar puncture were normal. Urine toxicology ADX panel was negative for cocaine metabolites, opiates, barbiturates, and benzodiazepines. Serum toxicology 10 hours postingestion was positive for olanzapine by GC-MS: 11 ng/mL (adult therapeutic range 9–23 ng/mL). Electrocardiogram: sinus tachycardia with normal QRS and QTC intervals. The patient gradually improved to normal during a 24-hour period.We believe this to be the first report of pediatric olanzapine intoxication. Our patient exhibited agitation, aggressive behavior, miosis, hypersalivation, tachycardia, and ataxia. Adverse effects of olanzapine in adults include somnolence, asthenia, nervousness, insomnia, anxiety, akathisia, tremor, anticholinergic effects, and increased liver function tests.1 During premarketing trials, overdose of olanzapine was associated with drowsiness and slurred speech.The onset and duration of clinical effects in our patient were 1 hour and 24 hours, respectively; consistent with olanzapine's peak plasma concentrations (6 hours) and half-life (27–31 hours).2Olanzapine is structurally and chemically related to clozapine. The pediatric overdose effects of clozapine are similar in duration (24 hours) and signs and symptoms (ataxia, tachycardia, confusion, hypersalivation, and stupor).3,4 A prolonged clinical course should be anticipated with olanzapine or clozapine toxicity.