MSACL 2024 Abstract

Case Description:

A 16-year-old male with a medical history of anxiety, ADHD, and multiple prior episodes of altered mental status (AMS) with no resolved etiology presents to the emergency department (ED) with AMS. He was in his baseline state at home, then went to school and was noted to exhibit extreme somnolence. He was unable to be woken up, and EMS was called. Of note, the patient had had two similar presentations to the ED over the previous two weeks. He received Narcan with no improvement. He was admitted to the neurology service and had an EEG that did not show epileptiform activity, similarly to his previous episodes when he was discharged home without any antiepileptic drugs. Other labs were unremarkable. A comprehensive drug screen was ordered and was unexpectedly positive for clozapine.

Background:

Extreme somnolence can be caused by an overdose or as a side effect of a variety of medications: antihistamines, antiemetics, antipsychotics, anticonvulsants, barbiturates, benzodiazepines and opioids to name a few. Adding to that sedatives like xylazine, a known contaminant of the illicit drug supply, along with non-toxic etiologies such as seizures and other neurological conditions, and the diagnosis of an AMS episode involving somnolence becomes more complex than what typical immunoassay drug screens can handle. Unintentional clozapine ingestions are rare. Clozapine is a second generation antipsychotic which has been used as an effective treatment alternative to traditional antipsychotics and has been deemed relatively safe in overdose. However, toxic effects in pediatric patients have been recorded and include hypersalivation, tachycardia, hypotension, sedation, delirium, leading to severe effects such as coma, respiratory depression, and even respiratory failure.

MS Method and Results:

A clinically validated comprehensive drug screen test using LC-QTOF-MS was used. The urine specimen was centrifuged to remove particulates, diluted with solvent and injected onto a SCIEX X500R platform. The untargeted data collection was performed using a positive-ion mode TOF-MS survey scan with IDA-triggered collection of high-resolution product ion spectra (20 dependent scans). The data was analyzed against an in-house validated library of 318 drugs and metabolites spanning multiple drug classes. The specimen was found positive for amphetamine, trazodone, citalopram (prescribed medications), naloxone, lorazepam (administered in the field and trauma room), and clozapine, an unexpected finding.

Discussion and Conclusion:

The patient's presentation was consistent with previously reported clozapine toxicity symptoms. However, the clozapine toxidrome includes many symptoms that are not all present concomitantly in exposed individuals. AMS in the form of extreme sedation can be attributed to other toxic agents as well as neurologic etiologies. This patient had alternative workups for this presentation in two other AMS episodes. Immunoassay drug screens were positive for amphetamine, known prescribed medication. Clozapine was not on the home medications list. Physicians and parents were notified of the comprehensive drug test result. The patient's older brother had been prescribed clozapine some months back, with discontinuation due to severe somnolence as a side effect. Patient denied taking clozapine intentionally. His symptoms improved with supportive care and the patient was discharged. Upon further investigation, the parents realized they mixed up medications and had given the patient the doses intended for his brother. Post correction, the patient's symptoms resolved permanently. Comprehensive drug testing by LC-QTOF-MS was the key to resolving this case. Had this test been employed in earlier episodes, rehospitalization of patient could have been prevented.