Via Research Recognition Day 2024 VCOM-Carolinas

Clinical Case-Based Reports

Management of Prolonged Tricyclic Antidepressant Toxicity in a Pediatric Patient with Increased Body Habitus Mikayla Kidd, OMS-IV 1 ; Austin Peterson, OMS-IV 1 ; Hanna S. Sahhar, MD, FAAP, FACOP 1,2 ; David Eagerton, Ph.D, F-ABFT 1 1 Edward Via College of Osteopathic Medicine-Carolinas Campus, Spartanburg, South Carolina 2 Spartanburg Regional Healthcare System, Department of Pediatrics, Pediatric Intensive Care Unit, Spartanburg, SC

Abstract

Case Report

Discussion

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A 15-year-old female with PMHx of anxiety, depression, borderline personality disorder, and previous suicide attempts presented to the Emergency Department via EMS after ingesting approximately 30 Amitriptyline 25mg tablets in an attempt to overdose.

What are Tricyclic Antidepressants? Tricyclic antidepressants (TCAs) are used to manage disorders such as depression and anxiety. They work by inhibiting the reuptake of serotonin, dopamine, and norepinephrine in presynaptic terminals within the central nervous system 1,2 Metabolism of Tricyclic Antidepressants • Amitriptyline undergoes hepatic metabolism by the cytochrome P450 (CYP) enzyme system , mainly CYP2C19 and CYP2D6 pathways. 3 • Metabolism by CYP2C19 results in active metabolites, most notably, nortriptyline Factors Affecting Metabolism of Amitriptyline • Age, liver function, and the presence of additional medications that inhibit or induce the CYP enzymes and BMI 2 • Genetics: ultrarapid vs slow metabolizers 2,6 This case report describes a fifteen-year-old female with an extensive psychiatric history who presented to the Emergency Department after ingesting an overdose of Amitriptyline. The patient had an increased body habitus with a body mass index (BMI) of 36 kg/m 2 . The case highlights the deviations from expected pharmacokinetics and pharmacodynamics of tricyclic antidepressants (TCAs) in patients with increased adiposity. The patient exhibited clinical evidence of TCA overdose, including prolonged QRS duration (QRSD), seizures, tachycardia, and sedation. Electrocardiogram (ECG) findings showed a wide complex tachycardia and prolonged QRSD. Elevated levels of Amitriptyline were observed despite adequate time for drug metabolism, which can be attributed to the patient's increased BMI. The case underscores the impact of increased adiposity on drug metabolism, leading to higher drug levels in the bloodstream and a longer half-life, potentially increasing the risk of adverse effects. It also emphasizes the diverse symptoms of TCA toxicity, including anticholinergic effects, cardiovascular effects, seizures, and sedation. ECGs play a crucial role in assessing the cardiogenic effects of TCA toxicity. Monitoring drug levels in patients with increased adiposity and TCA toxicities is crucial due to altered and delayed drug metabolism. ECGs are essential for assessing the cardiovascular effects of TCA toxicity. This case report provides valuable insights into the clinical manifestations and potential complications of TCA toxicity, highlighting the need for careful management and monitoring in such cases. Introduction

This case demonstrates deviations from expected pharmacokinetics and pharmacodynamics of TCAs in an individual with a BMI of 36 kg/m 2 .

The patient in this case displayed clinical evidence of TCA overdose including prolonged QRS duration, seizures, tachycardia, and sedation. Prolonged QRS duration is used as a marker for patients at highest risk for seizures and lethal tachyarrhythmias.

Initial Emergency Room Presentation: • Vital Signs: BP: 137/85, HR: 132 bpm, Weight: 109 kg, BMI: 36 kg/m 2

• ED course : Patient presented unresponsive with GCS of 3 and no response to Narcan. She was tachycardic with signs of respiratory distress. Initial ECG obtained upon presentation can be seen in Figure 1(a). Sodium bicarbonate and magnesium sulfate were given emergently, and patient was subsequently intubated and admitted to the PICU for further management.

The patient continued to have elevated levels of amitriptyline despite adequate time for full drug metabolism to occur. The reported half-life of amitriptyline is reported to be between 10-26 hours for normal metabolizers. Based on the predicted half-life, the patient was expected to have cleared the drug in five half-lives based on the predicted pharmacokinetics. Drug levels were drawn on days seven and ten due to persistent ECG abnormalities . On day seven, the amitriptyline level was 301 ng/mL and nortriptyline level was 311 ng/mL, for a combined level of 612 ng/mL (reference range for the combined level is 80-200 ng/mL). On day ten, the amitriptyline level was 59 ng/mL, nortriptyline level was 72 ng/mL, for a combined level of 131 ng/mL There are known genetic factors that influence rate of metabolism by CYP enzymes. However, it is unlikely that a genetic abnormality is present in this patient due to the ratio of amitriptyline and nortriptyline levels seen on days seven and ten of admission. Amitriptyline and nortriptyline are being metabolized at a ratio of 1:1 indicating there is likely no alteration in the CYP2C19 or CYP2D6 metabolic pathways.

Figure 1: ECGs obtained during hospital course from day zero to day nine

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Given her liver function tests were within the normal range, age, ratio of metabolism, and no additional medications, her increased BMI likely explains how drug levels remained elevated for 10 days after ingestion.

References

(a) Day 0: Initial ECG upon arrival to the Emergency Department significant for a wide complex tachycardia with ventricular rate of 163 bpm, normal axis, normal R wave progression, QRSD 128 ms, QTc 504 ms. (b) Day 3 of Hospitalization: ECG obtained in the PICU significant for sinus tachycardia with a prolonged QRSD of 119 ms. (c) Day 6 of Hospitalization: ECG obtained on the general pediatric floor significant for sinus rhythm with persistent, prolonged QRSD of 102 ms. (d) Day 9 at Discharge: Final ECG indicating normal sinus rhythm with normal QRSD of 92 ms.

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Signs and Symptoms of Tricyclic Antidepressant Overdose • Blurred vision, dry mouth, drowsiness, and hypotension 4,7 • Tachyarrhythmias and prolongation of the QRS complexes 9 • Seizures and sedation 4,10

Table 1: TCA values obtained on days seven and ten

We thank Spartanburg Regional Healthcare System for their cooperation.

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2024 Research Recognition Day