Toxicology experts say death from medications in Nex Benedict case ‘very, very uncommon’

The death of Nex Benedict, a 16-year-old transgender student of Indigenous heritage from Oklahoma who used he, him, they, and them pronouns, has ignited a nationwide debate on several issues, including the rampant bullying faced by LGBTQ+ students in schools and the manner of Benedict’s death.

A one-page summary autopsy report released by the Oklahoma Office of the Chief Medical Examiner on Wednesday, attributing Benedict’s death to suicide through combined toxicity from fluoxetine (Prozac) and diphenhydramine (Benadryl), has led to public skepticism and demands for more detailed information because of the report’s brevity. Benedict died February 8, one day after he was assaulted by a group of girls in an Owasso High School bathroom. A full report is expected to be released March 27.

In their response to the summary report from the medical examiner, Benedict’s family, through their legal representation, sought to bring attention to details of physical injuries not fully covered by the initial classification of Benedict’s death. They pointed out details from the full autopsy report that, while it stated “No lethal trauma,” listed several significant injuries. These included bruises around Benedict’s right eye and on the right side of their face, minor cuts on their right cheek and ear, and scrapes on both ears and the left cheek, along with bleeding under the scalp. On the teen’s chest, there was a scrape and a contusion, which, along with a specific type of bruising, was likely from attempts to save his life through CPR. Additionally, Benedict’s limbs showed a mix of fresh and healing bruises, scrapes, and scars, particularly noticeable on the back of their left hand, according to the family. By sharing these details, the family aimed to highlight the extent of physical harm Benedict experienced, countering any suggestions that the assault he faced was minor and urging for a fuller examination of the events leading to his death.

GLAAD President and CEO Sarah Kate Ellis urged restraint in reporting findings without the full context of the report.

The Advocate spoke to Dr. Joshua King, medical director of the Maryland Poison Center at the University of Maryland School of Pharmacy, and Dr. Masha Yemets, a clinical toxicology fellow at the same institution, to gain insights into the risks associated with fluoxetine and diphenhydramine, particularly in overdose scenarios.

Both said they couldn’t comment definitively on Benedict’s death — “Without the full autopsy report and associated toxicology data, we couldn’t comment about the medical examiner’s determination,” Yemets cautioned — but they agreed that both of the medications reported to be in Benedict’s system are commonly taken and pose a low risk of dangerous interactions when used correctly. Diphenhydramine is an antihistamine taken for allergies and fluoxetine is used for depression and anxiety. Because diphenhydramine can make a person drowsy, it is also a common ingredient in over-the-counter sleep aids.

“In general, in therapeutic use, meaning taking it as prescribed or directed, death, while not an impossibility, would be very, very uncommon,” King said, noting that while most overdoses do not lead to death, they can cause significant harm, sometimes causing the patient to require hospitalization.

“Diphenhydramine and fluoxetine are part of a larger group of medications that, in the vast majority of cases, are used safely by millions of people. The risk of death from these medications, especially when used as directed, is extraordinarily low,” he added.

King explained that while most people would be unlikely to suffer adverse effects from these medications, those with underlying conditions could be at risk.

“It is possible that the medications could interact in someone who had an undiagnosed heart condition, meaning that these medications can cause a particular type of heart arrhythmia called torsades, but that would be very, very, very rare in normal use. I’m not going to say it’s impossible," King said, pointing out that such cases often come to light posthumously when an investigation reveals a previously unknown congenital or inherited heart condition. He emphasized the rarity of fatal outcomes in normal therapeutic use but acknowledged the serious risks associated with overdoses, including serotonin syndrome, which can lead to confusion, hallucinations, agitation, and, in severe cases, seizures and potentially fatal respiratory complications. “Most of those overdoses are treated. This is something we do fairly commonly at the poison center,” he added. “The vast majority don’t result in death, but if you take enough of it, especially with a confounding factor such as another sedative medication, it’s possible.”

Yemets added, “The majority of the time, whenever poison centers are called, there’s something that was found on the scene or something that was reported by the family member, caregiver, the patient themselves, which elucidates that there has been an exposure or ingestion.” This information allows medical professionals to assess the situation and tailor their responses accordingly and accurately. She pointed out that without such initial reports, determining the exact cause of symptoms can be challenging, though the absence of this information doesn’t prevent the use of standard medical interventions.

King provided a nuanced explanation regarding the progression of deterioration following an overdose involving medications like those in question. “Death again is very rare from these poisons, but we would say, in the case of an overdose, general complications can lead to seizures and aspiration. Aspiration means that vomit goes down into the lungs, which can quickly lead to death. The quickest cause of death, however, could be arrhythmia,” King said, indicating the rapid onset of severe symptoms that could occur within an hour or two of ingestion.

He emphasized the importance of thorough medical examinations and toxicology reports in such cases: “I think no matter how you slice it, it is a terrible tragedy. It’s crucial to determine how much of this tragedy is due to the circumstances we’ve heard about or how much is a matter of suicide prevention.”

In the wake of Benedict’s death, the Rainbow Youth Project, a nonprofit that supports LGBTQ+ young people, has seen an exponential increase in calls to crisis lines by LGBTQ+ youth seeking support.

Regarding young people being prescribed antidepressants such as fluoxetine, in addition to those possibly using diphenhydramine for allergies, King emphasized the need to avoid causing alarm among patients and their guardians. Discontinuing prescribed medications due to fear stirred by individual cases might lead to more harm than the medication itself, he noted. “It would be more dangerous if someone were prescribed this medication for depression and heard about this case and said, ‘This is dangerous. I’m going to stop taking it,’ and then ended up having a complication due to untreated depression,” he said.

He also stressed the necessity of waiting for the full autopsy report for a more accurate understanding, “It seems unlikely that such findings would be in the medical examiner’s report without some access to analytic data. The levels found typically give us an indication of whether there was an overdose or regular use, information crucial yet not reported as of yet,” he said.

The danger level of overdoses varies significantly from person to person, he added. “It’s different for everyone, and it depends on the person. But in general, we’re talking about taking multiple times the prescribed dose,” King explained. He cautioned against the misconception that doubling a dose might be safe, clarifying that there’s a substantial difference between accidentally taking two or three times the prescribed dose and consuming a handful of pills. “Most serious poisonings we see involve taking 10 times or more than the prescribed dose. However, it’s impossible to predict exactly how someone will react because different bodies respond in different ways,” he said.

Overdoses on medications such as diphenhydramine and fluoxetine are a weekly occurrence at the poison control center where he works, King pointed out

An April 2023 Morbidity and Mortality Weekly Report by the Centers for Disease Control and Prevention sheds light on the alarming trend of suspected suicide attempts by poisoning among young people since the COVID-19 pandemic, highlighting the involvement of common medications such as fluoxetine and diphenhydramine. These two medications were among the top substances contributing to these overdose incidents. The analysis reveals a significant uptick in overdoses involving these medications, with diphenhydramine-involved overdoses increasing by 24.2 percent in 2021 and 35.8 percent into 2022.

This frequent reporting is influenced by how commonly these medications are prescribed and used, King explained. The regular appearance of these drugs on lists does not necessarily indicate they are more dangerous than others, he said. Instead, he suggested that their prevalence in overdose reports is mainly due to how accessible they are. “People will generally overdose on what they have available,” he said.

As the Benedict family calls for action against bullying and hate in schools, the community awaits the full autopsy report for more definitive answers.

If you or someone you know needs mental health resources and support, please call, text, or chat with the 988 Suicide & Crisis Lifeline or visit988lifeline.org for 24/7 access to free and confidential services. Trans Lifeline, designed for transgender or gender-nonconforming people, can be reached at (877) 565-8860. The lifeline also provides resources to help with other crises, such as domestic violence situations. The Trevor Project Lifeline, for LGBTQ+ youth (ages 24 and younger), can be reached at (866) 488-7386. Users can also access chat services at TheTrevorProject.org/Help or text START to 678678.