Acute overdose of enteric-coated valproic acid and olanzapine: Unusual presentation and delayed toxicity

To the Editor:

The importance of a prolonged observation period following asymptomatic enteric-coated valproic acid acute overdose, because of its delayed peak levels and potential to induce coma, has already been reported.^1–4 Nevertheless, when precise data for the ingestion (amount and nature) are unknown with an unusual clinical scenario, and when initial valproic acid serum concentration is undetectable, physicians might be misled. We present a case of delayed toxicity due to valproic acid after a suicide attempt with an unknown acute overdose of olanzapine.

A 32-year-old woman, with a history of bipolar disorder untreated since 2 months, was brought in by ambulance to the Emergency Department (ED) 3 h after intentional ingestion of 50 valproic acid tablets (500 mg-Depakote®). On initial assessment in the ED, she was agitated and confused with a Glasgow Coma Scale of 10/15. Her initial vital signs were blood pressure 139/59 mmHg, pulse rate 120 beats/min, respiratory rate 17 breaths/min, and oxygen saturation 95% on room air. Physical examination was normal except bilateral miosis. The electrocardiogram showed no abnormalities except tachycardia. Her blood sugar was 6.8 mmol/L, and she had hypokalemia (3 mmol/L). Otherwise her full blood count, other electrolytes, liver function tests, and renal function tests were within normal range. The patient's valproic acid concentration was found to be undetectable (< 2.8mg/L) as was her ethanol level. Immunological screening in blood and urine for barbiturates, benzodiazepines, tricyclic antidepressants, opiates, and cannabinoids was negative. Brain computed tomography was unremarkable.

As the Depakote® formulation is designed to have a very long absorption phase, the patient was not discharged and remained under extended observation. But, as the clinical presentation did not fit with valproic acid overdose, the patient was not administered activated charcoal. Her conscious level gradually deteriorated, and 11 h after ingestion, she was unresponsive with a Glasgow Coma Scale of 3/15. Complementary investigations were performed; cerebral spinal fluid study was normal and electroencephalography had no significant results. Her serum valproic acid concentration peaked at 1.160 mg/L (therapeutic level 50–100 mg/L). Blood laboratory results revealed lactic acidosis (pH: 7.31, lactic acid level: 4.3 mmol/L) and hyperammonemia. As the initial presentation remained unexplained, a detailed interrogation of the parents was carried out, and it was found that several hours before admission, the patient had ingested an overdose of olanzapine. Its level turned out to be 557.6 μg/L on hospital arrival (therapeutic level 5–100 μg/L), and 8 h later was almost in the therapeutic range. Chromatographic screening confirmed olanzapine and valproic acid kinetics, and no other substances were detected. Haemodialysis was performed, and the patient regained consciousness. She was discharged to a psychiatric facility.

In conclusion, we would like to highlight the importance for physicians to be aware of the specific management required for assumed valproic acid ingestions, including close and extended observation and, where necessary, serial valproic acid measurements. The presence of co-ingestants such as other CNS depressants should be suspected when the presentation is unusual.