Carolinas Research Day 2021

Introducing Two New Toxidromes: Antipsychotics and Atypical Antidepressants Mya Lor OMS-IV; Erica Rubin OMS-IV; Hanna S. Sahhar, MD, FAAP, FACOP Edward Via College of Osteopathic Medicine, Spartanburg, SC Abstract Antipsychotic Case Report Antidepressant Case Report

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References these toxidromes occur without any prior history of ingestion. • Further research can be done on the potential different presentations of toxidromes in children versus adults. • Signs and symptoms of antipsychotic and atypical antidepressant overdoses have historically been established, but they have never been introduced as toxidromes before. [1] Brett J. Concerns about quetiapine. Aust Prescr . 2015;38(3):95-97. doi:10.18773/austprescr.2015.032 [2] Cooper WO, Hickson GB, Fuchs C, Arbogast PG, Ray WA. New users of antipsychotic medications among children enrolled in TennCare. Arch Pediatr Adolesc Med . 2004;158(8):753-759. doi:10.1001/archpedi.158.8.753 [3] Judge, B. S., & Rentmeester, L. L. (2011). Antidepressant overdose-induced seizures. Neurologic Clinics , 29 (3), 565–80 [4] Kim S, Lee G, Kim E, Jung H, Chang J. Quetiapine Misuse and Abuse: Is it an Atypical Paradigm of Drug Seeking Behavior?. J Res Pharm Pract . 2017;6(1):12-15. doi:10.4103/2279-042X.200987 [5] Murray, B., Carpenter, J., Dunkley, C., Moran, T. P., Kiernan, E. A., Rianprakaisang, T., Alsukaiti, W. S., Calello, D. P., Kazzi, Z., & Toxicology Investigators Consortium (ToxIC) (2020). Single-Agent Bupropion Exposures: Clinical Characteristics and an Atypical Cause of Serotonin Toxicity. Journal of medic l toxicology : official journal of the American College of Medical Toxicology , 16 (1), 12–16. [6] Rasimas JJ, Liebelt EL. Adverse Effects and Toxicity of the Atypical Antipsychotics: What is Important for the Pediatric Emergency Medicine Practitioner. Clin Pediatr Emerg Med . 2012;13(4):300-310. doi:10.1016/j.cpem.2012.09.005 [7] Santarsieri, D., & Schwartz, T. L. (2015). Antidepressant efficacy and side-effect burden: a quick guide for clinicians. Drugs in context , 4 , 212290. [8] Teo DCL, Wong HK, Tan SN. Atypical Neuroleptic Malignant Syndrome Precipitated by Clozapine and Quetiapine Overdose: A Diagnostic Challenge. Innov Clin Neurosci . 2018;15(7-8):20-22. Published 2018 Aug 1. [9] Vo KT, Merriman AJ, Wang RC. Seizure in venlafaxine overdose: a 10-year retrospective review of the California poison control system. Clinical toxicology (Philadelphia, Pa) . 2020;58(10):984-990 [10] Volpi-Abadie, J., Kaye, A. M., & Kaye, A. D. (2013). Serotonin syndrome. The Ochsner journal , 13 (4), 533–540 Conclusion A 13-year.-old female with no significant medical history presented to the Emergency Department (ED) after intentionally ingesting 15 tablets of Bupropion. The patient had one episode of seizure activity in the waiting room that was treated with Ativan. She does not have a history of seizures, outside of a febrile seizure when she was a small child. She reported that she was stressed out which is why she took the medication. The patient’s mother noted that the patient was also dealing with the death of her grandmother and moving to a new location. In the ED, the patient was complaining of “pain all over''. The history was limited due to the altered mental status of the patient. Physical examination was notable for injected conjunctiva, pupils that were equal, round and reactive at 3mm bilaterally, tachycardia, skin unremarkable, normal muscle tone, alter and delirious. Initial EKG shows QRS of 82 and normal QTC. The patient was given IV fluids, Ativan and potassium repletion. The patient was then given Zofran for vomiting. The patient was then admitted to the Pediatric Intensive Care Unit for further management. The patient has an inpatient psychiatry consultation on hospital day two. Psychiatry impression was that of major depressive disorder, ruling out bereavement and unspecified anxiety disorder, ruling out PTSD. Psychiatry also recommended initiating involuntary commitment. On hospital day three, the patient was medically cleared and back to baseline. The patient was later discharged to an inpatient psychiatry unit. • We propose two new toxidromes with defined characteristics to help healthcare providers identify and treat these toxidromes efficiently and effectively. Recognition of these toxidromes can lead to more effective and efficient patient management. • Healthcare providers should have a high index of suspicion for antipsychotic and atypical antidepressant overdoses, especially when patient’s exhibit signs and symptoms of these toxidromes • One limitation to the toxidrome presentations is that most patients do not exhibit all the classic signs and symptoms. This poses a challenge to determine if

Our first case is a 17-year-old Caucasian male with a past medical history of seizures, depression, anxiety, attention deficit hyperactivity disorder, and asthma who presented to the Emergency Department (ED) for evaluation of altered mental status. The patient was unconscious with pinpoint pupils, demonstrated decerebrate posturing, and had agonal and irregular breathing with diminished lung sounds bilaterally. The patient’s Glasgow Coma Scale was less than eight and immediately intubated for airway protection. On physical examination, the patient’s skin appeared pale and cool to the touch. He was afebrile, tachycardic at 144 beats/minute, hypertensive at 164/110 mmHg, and had a respiratory rate of 13 breaths/minute with oxygen saturation at 100% on the non-rebreather mask. In an attempt to mitigate the decerebrate posturing, he was given levetiracetam, four doses of lorazepam, and two doses of propofol without resolution. Urine drug screen was positive for marijuana. EKG showed a moderately extended QTc interval measuring 441 ms. Later that afternoon, the patient exhibited a high fever of 105.2°F. He was given acetaminophen suppository 650 mg to decrease his fever with no response. Supportive care was continued until his fever subsided. The patient was extubated on day three and admitted to overdosing on quetiapine in an attempt to get high. The patient was discharged home on the fourth day with fluoxetine for anxiety.

Typical and atypical antipsychotic medications have been available since the 1950s and 1970s, respectively, and have been approved to treat psychiatric and several mood disorders. Atypical antidepressants were designed to more effectively treat major depressive disorder. The use of these medications has become more prevalent leading to abuse and overdose. The two case reports highlight the toxicities of antipsychotics and atypical antidepressants and introduce two new toxidromes. Case one is a 17-year-old male with a past medical history of seizures, anxiety, and asthma presented to the emergency department (ED) with altered mental status. The patient was suspected of ingesting a large dose of an atypical antipsychotic medication due to his initial presentation of seizure, central nervous system depression, miosis, hypotension, tachycardia, and acute dystonia that was initially mistaken as decerebrate posturing. Within two days, hyperthermia was evident, and an electrocardiogram (EKG) showed prolongation of QTc interval. We can establish a distinguished group of initial signs and symptoms associated with an exposure to a dangerous level of antipsychotic using the medications' affinity to certain receptors. Similar to our patient’s initial presentation, an antipsychotic toxidrome would present with hypotension with reflex tachycardia due to the inhibition of alpha-adrenergic receptors. Miosis of the pupils may also be observed due to an unopposed parasympathetic system because of the alpha-adrenergic receptor blockade. Antipsychotics also have a high affinity for dopamine receptors that can lead to extrapyramidal symptoms and neuroleptic malignant syndrome. Case two is a 13-year-old female with no significant medical history presented to the ED with seizure activity after intentionally ingesting 15 tablets of Bupropion. Physical examination was notable for injected conjunctiva, equal, round, and reactive pupils at 3 mm bilaterally, tachycardia, skin unremarkable, confusion, and delirium. Within three days, the patient recovered fully and was admitted to an adolescent psychiatric unit for further evaluation. Like our patient’s initial presentation, an atypical antidepressant toxidrome may present with seizure activity due to inhibition of the reuptake of dopamine at the presynaptic cleft. Tachycardia can also be observed due to the inhibition of the norepinephrine reuptake. Serotonin syndrome may also be seen due to a variety of atypical antidepressants acting on the serotonin receptors. Signs and symptoms of antipsychotic and atypical antidepressant overdoses have historically been established, but they have never been introduced as toxidromes before. Toxidromes are medical emergencies that require immediate attention and treatment, but it can be challenging to recognize. Therefore, we propose two new toxidromes with defined characteristics to help healthcare providers identify and treat these toxidromes efficiently and effectively. Typical and atypical antipsychotics have been available since the 1950s and 1970s, respectively 2 . Antipsychotics have been approved to treat psychiatric disorders such as psychosis and several mood disorders. Treatment for major depression disorder has been available since the 1950’s 7 . Atypical antidepressants such as Bupropion and Venlafaxine have been available since the 1980’s and 1990’s respectively 7 . They were approved to treat major depressive disorder, generalized anxiety disorder, panic disorder and other mood disorders that did not respond to the traditional treatment of selective serotonin receptor inhibitors. The use of antipsychotics and atypical antidepressants has become much more prevalent as well as the potential to abuse these drugs leading to an increased incidence of overdose 5 7 . Typical and atypical antipsychotics and atypical antidepressants demonstrate affinity for specific neurotransmitter receptors manifesting as symptoms that when combined, can be recognized as a toxidrome. Introduction

PRESENTATION

TOXIDROME AGENT/DRUG VITALS

SKIN PUPILS ME NTAL STATUS

TREATMENT/ ANTIDOTE

Antipsychotics Typical:

Hypotension, Tachycardia, Hyperthermia (NMS)

Normal

Miosis or Variable

More EPS symptoms, Sedation, Coma, Seizures

Benztropine, Diphenhydramine, Supportive Care

Haloperidol, Risperidone

Atypical: Quetiapine, Clozapine

Less EPS symptoms, Sedation, Coma, Seizures

Atypical Antidepressants

Bupropion

Hypertension, Tachycardia, Normal Temperature or Hyperthermia

Normal or Diaphoretic

Normal or Mydriasis

Seizures, Sedation, Agitation

Supportive Care

Serotonin and Norepinephrine receptor inhibitors: Venlafaxine

Table 1: This demonstrates the potential signs and symptoms a patient would exhibit with an antipsychotic toxidrome or atypical antidepressant toxidrome.

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