Psychostimulants Tied to 1 in 5 Fatal Strokes in Young Adults

Psychostimulants including methamphetamine, cocaine, and 3,4-methylenedioxymethamphetamine (MDMA), as well some legally available agents in this drug class, have been tied to a significantly increased risk of fatal stroke in young adults, new research shows.

Among fatal stroke in young adults, investigators found almost 20% occurred in psychostimulant users, the majority of whom had evidence of consumption of such agents immediately prior to stroke onset.

"Two things emerged of significance. Firstly, one fifth of all fatal strokes among young adults were related to psychostimulant use. We did not expect these drugs to contribute so much to stroke-related mortality," lead author Shane Darke, PhD, who is affiliated with the National Drug & Alcohol Research Centre at the University of New South Wales in Sydney, Australia, told Medscape Medical News.

"Secondly, psychostimulant strokes were more likely to be intracerebral, while strokes in non-users were more likely to be subarachnoid," he added.

This finding, he said, may explain why strokes following psychostimulant use were more likely to be deadly "as intracerebral strokes have the highest mortality rate."

The study was published online April 2 in the Journal of Forensic Sciences.

A Growing Concern

Worldwide psychostimulant use is increasing, the investigators note. With an estimated 37 million users globally, the most commonly used agent in this class is methamphetamine.

In addition to hemorrhagic stroke, psychostimulants such as cocaine can also elevate ischemic stroke risk. Although the evidence is more limited, some researchers also believe there may be an association between MDMA and adverse intracerebral events.

To learn more, the investigators examined all fatal strokes in young individuals ages 15 to 44 years in what the investigators believe is the first study to assess national data of fatal stroke in psychostimulant users vs nonusers.

Investigators assessed 2009–2016 data from the National Coronial Information System database in Australia. They examined 205 coroner reports and 242 police reports related to the 279 fatal strokes.

The investigators considered toxicology results for methamphetamine, cocaine/benzoylecgonine, and MDMA, as well as data for the prescription medication phentermine and dimethylamylamine (DMAA), an over-the-counter stimulant found in a variety of supplement types.

They also collected data on stroke type — hemorrhagic, ischemic, thrombotic, mycotic, and embolic — as well as the location of the initial hemorrhage/ischemia (the subarachnoid space or intraparenchymal).

A total of 279 cases of fatal stroke were identified – 259 hemorrhagic, 8 ischemic, 8 thrombotic and 4 mycotic. Fifty individuals were psychostimulant users and 229 were not.

Hemorrhagic strokes accounted for the majority of neurovascular diagnoses. A total of 48 of the 50 fatal strokes in psychostimulant users were hemorrhagic and the remaining 2 ischemic.

Among non-users, 211 of 229 fatal strokes were hemorrhagic. Another 8 individuals died from thrombotic stroke, 6 from ischemic stroke, and 4 from mycotic stroke.

There were no embolic strokes reported in either group.

Location Differences

Although hemorrhagic stroke was common in both groups, there was a significant difference between groups. Whereas the majority of psychostimulant users had an intraparenchymal stroke (which carries a high mortality rate), non-users were more likely to have a hemorrhagic stroke in the subarachnoid space.

Psychostimulants were reported in 37 of the 45 toxicology analyses available in the psychostimulant user group. Methamphetamines were most common, present in 32 cases, followed by DMAA in 2 cases, and cocaine, MDMA, or phentermine in 1 case each.

The researchers also found that the majority of psychostimulant users had evidence of consumption immediately before fatal stroke.

The researchers also took other stroke risk factors into account. However, only tobacco use emerged as more common among the psychostimulant group vs the non-psychostimulant group.

Approximately 15% of the study population had a history of injection drug use, but it was more likely among the psychostimulant users (odds ratio, 10.20; 95% confidence interval, 4.93 - 21.10).

The researchers also found among this young cohort a daunting statistic: there were 12,574 years of potential life lost.

Not an Overdose

Interestingly, the dose of psychostimulant use did not contribute to stroke risk. The median methamphetamine concentration in the study was similar to that reported for all methamphetamine-related deaths in Australia over a similar period. In addition, median consumption was still less than half that of deaths attributed solely to methamphetamine toxicity.

"These results suggest that high concentrations are not essential to cause a methamphetamine-related stroke," the researchers note.

Multiple mechanisms may underlie the association. Psychostimulants could increase the risk for hemorrhagic strokes secondary to transient psychostimulant-induced hypertension.

Chronic use of these agents can cause long-term systemic hypertension, which, in turn, can cause vascular fatigue and vessel wall rupture. In addition, chronic psychostimulant use may be a significant factor in the development of aneurysms related to a hypertensive crisis.

The investigators noted a couple of caveats. All cases were referrals to a coroner, so the research may not have captured all fatal strokes in this age group. Also, use of toxicology and other reports to identify psychostimulant users likely underestimated use in this population.

Darke said he would like to expand on the current findings.

"Ideally, a longitudinal cohort of psychostimulant [users] would provide data on the risk factors for stroke in this population. Factors such as route of administration, frequency of use, and length of drug use career," he said.

Useful Data

Commenting on the findings for Medscape Medical News, John C.M. Brust, MD, professor of neurology at Columbia University Medical Center in New York City, said the study adds "useful support that these drugs cause stroke, and there is bioplausibility."

"It’s interesting such a large percentage young people with emergent strokes have recently used psychostimulants," added Brust, who published a review article on neurologic complications of illicit drug abuse. Brust was not associated with the current study.

However, he cautioned that the investigators found an association, not causality. The study was also retrospective, he added, and there is a need for more rigorous, prospective epidemiologic studies to confirm the findings of the current study.

The Australian government provides funding for the National Drug & Alcohol Research Centre at the University of New South Wales. Darke and Brust have disclosed no relevant financial relationships.

J. Forensic Sci. Published online April 2, 2019. Abstract

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