Olanzapine Overdose Cause of Acute Extrapyramidal Symptoms
To the Editor: As one of the atypical antipsychotic agents, olanzapine has been considered to be similar to clozapine but free of the risk of agranulocytosis. The in vitro binding of olanzapine to dopamine (D1, D2, D4), serotonin (5-HT2a, 5-HT2c), a-adrenergic, histamine, and muscarinic receptors is comparable to the binding of clozapine (1). Neuroimaging studies have shown that the D2-receptor binding of olanzapine in therapeutic doses is similar to that of clozapine (2). Such preclinical studies would predict that olanzapine and clozapine are similar in their lack of propensity to cause extrapyramidal symptoms. Broad-based clinical trials have found that olanzapine, in doses up to 20 mg/day, produces extrapyramidal symptoms at rates approximating those of placebo (3). Sheitman et al. recently reported that olanzapine becomes more distinct from clozapine and is associated with more extrapyramidal symptoms at doses above those most often prescribed (20mg/day) (4). We present the first reported case in which an overdose of olanzapine produced acute extrapyramidal symptoms.
Quentin, a 9-year-old boy who weighed 64 lb and had no prior exposure to psychotropic medication, took 100 mg of his mother"s olanzapine and an indeterminate amount of acetominophen in an apparent suicide attempt. At presentation in the emergency department about 2 hours after ingestion, Quentin was combative and unable to follow commands. He also had tachycardia, hypotension, and decreased gastrointestinal motility. He was treated with elective intubation for airway management and with intravenous fluids and norepinephrine for pressure support. Activated charcoal and n-acetyl cysteine were used to prevent further drug toxicity. Cisapride, ondansetron, and metoclopramide were given for promotility effects. Significant laboratory abnormalities during his hospitalization included peak levels of the following: acetaminophen (158 mg/ml), aspartate aminotransferase (93 U/liter), alanine aminotransferase (47 U/liter), and lactate dehydrogenase (434 U/liter). Quentin’s platelets were elevated (502,000/mm3). Quentin did well with treatment and was extubated within 15 hours of admission. By about 36 hours after ingestion and after resolution of his presenting symptoms Quentin developed “jitteriness” and hyperreflexia followed by tremors of the extremities, cogwheel rigidity, a stiff jaw, oculogyric signs, and severe dystonia of the neck. These symptoms were treated with intravenous diphenhydramine for 24 hours and then with oral diphenhydramine for 9 days thereafter. During the course of this treatment, his extrapyramidal symptoms improved significantly. At 13 days after ingestion, Quentin had only a slight upper extremity tremor and no subjective complaints.
Hoffman and Donovan have found that in rats, olanzapine, like risperidone, loses its atypical properties in higher doses by producing catalepsy, not unlike haloperidol at therapeutic doses (5). This effect was not observed with clozapine at any dose, suggesting that clozapine remains unique in its lack of association with extrapyramidal symptoms relative even to the newer atypical antipsychotics.
1. Bymaster FP, Calligaro DO, Falcone JF, Marsh RD, Moore NA, Tye NC, Seeman P, Wong DT: Radioreceptor binding profile of the atypical antipsychotic agent olanzapine. Neuropsychopharmacology 1996; 14:87–96Crossref, Medline, Google Scholar
2. Pilowsky L, Busatto G, Taylor M, Costa CD, Sharma T, Sigmundsson T, Ell PJ, Nohria V, Kerwin RW: Dopamine D2 receptor occupancy in vivo by the novel atypical antipsychotic olanzapine--a 123I single photon emission tomography (SPET) study. Psychopharmacology 1996; 124:148–53Crossref, Medline, Google Scholar
3. Beasley C, Tollefson G, Tran P: Safety of olanzapine. J Clin Psychiatry 1997; 58(suppl 10):13–17Google Scholar
4. Sheitman BB, Lindgren JC, Early J, Sved M: High-dose olanzapine for treatment-refractory schizophrenia (letter). Am J Psychiatry 1997; 154:1626Link, Google Scholar
5. Hoffman D, Donovan H: Catalepsy as a rodent model for detecting antipsychotic drugs with extrapyramidal liability. Psychopharmacology 1995; 120:128–133Crossref, Medline, Google Scholar
