Delayed presentation of an aripiprazole overdose

Delayed presentation of an aripiprazole overdose

To the Editor:

Aripiprazole is an atypical antipsychotic that is used to treat schizophrenia and bipolar disorders. Its therapeutic effects are largely the result of partial dopamine agonism. It also affects multiple serotonin receptors as well as histamine-1 receptors and alpha-1 adrenergic receptors (1). The latter is responsible for causing orthostatic hypotension. There has been limited experience with overdose, with the most common side effect seen being sedation (1–4). Even though supratherapeutic ingestions have resulted in persistent symptoms for days, the symptom onset is typically seen within three hours of the ingestion as reported in multiple cases (1,4). We present a case where the patient became symptomatic after an intentional overdose 9 hours after ingestion.

A 25-year-old woman was brought to the Emergency Department (ED) by the police approximately 30 minutes after taking an intentional overdose of aripiprazole. She reported taking fifteen 15 mg (patient weight 50 kg) aripiprazole (Abilify®) pills after breaking up with her boyfriend. She denied any other ingestion. Her past medical history is only significant for bipolar disorder which she was prescribed aripiprazole. A thorough search of her home by the police and her family found the bottle of aripiprazole and bottles of celecoxib and metronidazole, which the patient was taking after an elective abortion six days prior. No other pill bottles or drugs were found. The amount ingested was consistent with the pill count based on the bottles brought in with the patient. Although no drug levels were sent, the patient remained consistent in her story in the amount ingested. She denied any alcohol or illicit drug use. She denied having any other complaints. Because the amount ingested was thought to be benign, charcoal was not administered.

Her initial vital signs included heart rate 70 beats/minute, blood pressure 119/76 mm Hg, temperature 98.4^oF, and a pulse oximetry of 100% on room air. She was alert and oriented (to person, place and time), and had a normal neurological exam, including a normal gait. Laboratory investigations were performed and showed normal electrolytes and complete blood count. Urinalysis and a urine immunoassay drug screen (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates) were negative. Serum ethanol, acetaminophen and salicylate concentrations were non-detectable. A 12-lead EKG showed a heart rate of 60, PR interval of 130, QRS interval of 73, and a QTc of 396. The patient was observed in the ED for three hours, during which she voiced no complaints, and then was sent to the psychiatric holding unit for evaluation.

In the psychiatric holding unit, the patient completed a full psychiatric evaluation by the psychiatric nurse without difficulty. After the evaluation, it was decided that patient should be admitted for inpatient treatment for her suicidal ideation. Patient was transferred to the inpatient psychiatric unit three hours after her emergency department discharge and was noted to have no complaints and have stable vital signs. In the psychiatric unit, 30 minute visual checks were performed and the patient was noted to be awake and alert and in no distress. Two hours after admission to the psychiatric inpatient unit, the patient was found difficult to be aroused. Her blood pressure was 80/40 mmHg with a heart rate of 50 beats/minute. The medical team was contacted and transferred her to the Intensive Care Unit (ICU) for observation. For the next two hours, the patient remained difficult to arouse, but protecting her airway. Her systolic blood pressure remained around 85 mmHg with a heart rate around 55 beats/minute. Repeat EKG as well as electrolytes, liver function tests, and complete blood count were normal and unchanged. Intravenous fluids were administered and patient's blood pressure gradually improved as well as her mental status. Patient's systolic blood pressure stabilized around 110 mm Hg. After 24 hours with stable vital signs and improved neurological status, she was transferred back to the psychiatric inpatient unit. Patient did not sustain any permanent sequelae from the overdose.

While this patient had somnolence consistent with previous reports of aripiprazole overdose, there have been no reports of symptom onset nine hours post-ingestion. Aripiprazole primarily undergoes hepatic metabolism via two P450 isozymes, CYP2D6 and CYP3A4, with elimination of metabolites primarily in the urine and feces (5). Because of the long elimination half-life (75 hours) of the parent compound and its active metabolite, dehydro-aripiprazole (elimination half-life of 95 hours) (5), a longer observation period may be necessary after an overdose to look for clinical manifestations.

Notes

5. Bristol-Myers Squibb Company and Otsuka America Pharmaceutical, Inc. Abilify (aripiprazole) tablets package insert, 2004.