Letters to the Editor
Seizures, Coma, and Coagulopathy Following Olanzapine Overdose
Dear Editor:
Olanzapine is an atypical antipsychotic with few overdose cases reported (1). We describe new-onset seizures and a hypercoagulable state following a suicidal olanzapine overdose.
Case Report
A man aged 32 years was brought to the emergency department (ER) following olanzapine overdose. He had a 12-year history of schizophrenia, paranoid subtype. His pertinent history was notable for obesity (body mass index 32) and negative for underlying seizure disorder or alcohol use. Prior to admission, his treatment had for 3 months consisted of olanzapine 10 mg daily, with limited response. For several days preceding presentation, he reported hearing accusatory hallucinations commanding him to kill himself. On the day of admission, he took his total olanzapine supply (70 tablets, equal to 700 mg) all at once.
The patient was found unresponsive and brought to the ER. He was stuporous and hypertensive and had miosis. A toxicologic workup was negative for other substances. Naloxone administration failed to lead to pupillary dilatation. Over the following 3 hours, 2 partial complex seizures involving his left upper extremity were observed; intravenous (IV) lorazepam promptly stopped them. Neurological examination, EEG and brain CT scans were noncontributory and failed to reveal other etiologic processes. Bloodwork was notable for a slightly elevated activated partial thromboplastin time (43.6 seconds, range 28.1 to 42.1 seconds), with normal platelet count, prothrombin time, and international normalized ratio.
Owing to his obtunded state, he was intubated and admitted to the intensive care unit. He required IV antibiotics for aspiration pneumonia. Four days later, because he had difficulties weaning off the ventilator, a ventilation-perfusion lung scan was ordered and revealed multiple disseminated pulmonary emboli. Further workup also found bilateral deep venous thromboses. Hematological consultation confirmed the presence of anticardiolipin antibodies, leading to a diagnosis of underlying antiphospholipid syndrome and recommendation that he receive lifetime warfarin therapy. Because his psychosis persisted, haloperidol 2 mg daily was initiated, with beneficial effect. Following discharge, the patient was lost to follow-up.
Discussion
Common adverse effects of olanzapine include dizziness, somnolence, increased appetite, and weight gain. Although the drug has an overall favourable safety profile, experience with toxicity is still emerging (1). Weight gain over long-term use, combined with prolonged stupor and immobility following the overdose, may have contributed to our patient’s thrombosis. The underlying antiphospholipid syndrome further elevated his risk (2). Although not routinely tested, up to one-third of patients presenting with psychosis have an underlying antiphospholipid syndrome (4). Other relevant risk factors for clot formation in psychiatric patients (which did not occur in this patient) include smoking, phenothiazine prescription, and use of restraints (3).
One other death has been described in a patient receiving olanzapine (10 mg daily). This patient died from disseminated intravascular coagulation following prolonged status epilepticus (5). Although an autopsy was performed, testing for anticardiolipin antibodies was not reported (4). Some authors have dismissed convulsions and clotting abnormalities as unlikely following olanzapine intoxication (6). However, olanzapine is structurally related to clozapine, which has one of the highest incidences of seizure occurrence among the atypical antipsychotics (1). Therefore, on the basis of emerging data, we recommend vigilance for seizures and clotting abnormalities with high dosages of olanzapine and in patients with underlying coagulopathies.
References
1. Capel MM, Colbridge MG, Henry JA. Overdose profiles of new antipsychotic agents. Int J Neuropsychopharmacol 2000;3:51–4.
2. Heit JA. Risk factors for venous thromboembolism. Clin Chest Med 2003;24:1–12.
3. Gelenberg AJ. Venous thromboembolism and antipsychotic drugs. Biol Ther Psychiatry 2003;26:9–12.
4. Schwartz M, Rochas M, Weller B, Sheinkman A, Tal I, Golan D, and others. High association of anticardiolipin antibodies with psychosis. J Clin Psychiatry 1998;59: 20–3.
5. Wyderski RJ, Starrett WG, Abou-Saif A. Fatal status epilepticus associated with olanzapine therapy. Ann Pharmacother 1999;33:787–9.
6. Isbister GK, Whyte IM, Smith AJ. Olanzapine overdose. Anaesthesia 2001;56:400.
Nadeem H Bhanji, BScPharm, MD
Guy Chouinard, MD, MSc, FRCPC
Lawrence Hoffman, MD, CM, FRCPC
Howard C Margolese, MD, CM, MSc, FRCPC
Montreal, Quebec
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