Polydrug Use and Diagnostic Challenges in Emergency Departments

Ran in Today's Clinical Lab, 6 May 2026

By Jared Jaeger, PhD, Clinical Science Liaison, QuidelOrtho

When a patient comes into the emergency department experiencing acute intoxication, every second matters to save their lives. If a patient has taken multiple drugs like opioids and stimulants at once, knowingly or unknowingly, treatment can be even more complicated. 

Rapid, accurate diagnostics and continuous monitoring are among the best tools emergency departments have to help patients who may be experiencing an overdose caused by more than one drug receive the care they need.

Polydrug use, sometimes known as the “fourth wave” of America’s opioid epidemic, is a critical public health issue. One study, which analyzed urine drug test results from more than 4 million patients who tested positive for fentanyl, found that 93% of samples also tested positive for other substances. According to the Centers for Disease Control and Prevention, 43% of overdose deaths from 2021 to 2024 involved both opioids and stimulants. In 2010, that percentage was 0.6%, according to one study.

For example, “pink cocaine,” also known as tusi, is increasingly appearing in US clubs and drug busts, worrying officials because it is not actually cocaine but an unpredictable mix of drugs: most commonly ketamine and MDMA, and sometimes methamphetamine or fentanyl, which can sharply increase overdose risk. Since May 2024, 18 pink cocaine exposures reported by U.S. Poison Centers across four states have been documented by America’s Poison Centers National Poison Data System®, and 83% of patients received medical treatment.

Counterfeit pills, like Adderall or Xanax, are also being increasingly laced with synthetic opioids, such as fentanyl, meaning users may be taking multiple drugs at once without realizing it. The increase in polydrug use is putting more pressure on emergency departments to quickly and effectively treat overdoses. 

Emergency departments can implement diagnostics to support immediate clinical decision-making through ongoing monitoring. Overdoses from polydrug use can be dynamic, with symptoms masked or altered, and patients may need more aggressive treatment depending on the combination of drugs. The risk of fatality can also increase, so healthcare providers must have access to rapid and broad toxicology diagnostics at the point of care to quickly identify potential culprits and treat patients experiencing an overdose.

Because symptoms may return or worsen after initial stabilization, emergency departments can pair rapid initial diagnostics with continuous monitoring for patients with suspected or confirmed polydrug use. Regular reassessment and follow-up testing can help clinicians identify delayed symptoms and intervene.  

Frequently, patients who come into the emergency room with a suspected overdose do not realize what substances they have taken. Emergency departments can ensure their drug screening diagnostic panels are regularly reassessed and updated to encompass emerging substances, so clinicians have access to the most up-to-date panels when making time-critical treatment decisions. 

Integrating access to advanced testing methods, such as mass spectrometry, can also help support accurate diagnosis and tailored treatment, as many emerging synthetic opioids can go undetected by traditional toxicology panels.

In addition to specific rapid diagnostic tools, emergency departments can also routinely update staff training to help clinicians and laboratory teams make informed decisions when implementing testing protocols and determining care plans.

Finally, emergency departments can align rapid diagnostic and monitoring strategies within care pathways that emphasize enabling timely intervention, reducing the risk of fatal outcomes, and opening the door to substance use disorder treatment and recovery.

As the drug landscape continues to evolve and polydrug use becomes increasingly prevalent and complex, our testing strategies must also adapt to ensure clinicians have the timely, actionable information they need to effectively treat patients and save lives.