Opioid Overdoses Tied to Lasting Cognitive Impairment

Jim Kling

September 17, 2021

Opioid overdoses usually aren't fatal, but a new review of numerous studies, mostly case reports and case series, suggests that they can have long-lasting effects on cognition, possibly because of hypoxia resulting from respiratory depression.

Erin L. Winstanley, PhD, MA, and associates noted in the review that opioids cause about 80% of worldwide deaths from illicit drug use, and the Centers for Disease Control and Prevention's provisional August 2021 number of more than 88,000 opioid-caused deaths in the United States is the highest ever recorded – a 27% increase over what was reported last December. That number suggests that the opioid epidemic continues to rage, but the study results also show that the neurological consequences of nonfatal overdoses are an important public health problem.

And that's something that may be overlooked, according to Mark S. Gold, MD, who was not involved with the study and was asked to comment on the review, which was published in the Journal of Addiction Science.

"Assuming that an overdose has no effect on the brain, mood, and behavior is not supported by experience or the literature. While reversing overdoses is life-saving, preventing overdose may be brain saving," said Gold. He is a University of Florida, Gainesville, Emeritus Eminent Scholar, adjunct professor of psychiatry at Washington University in St. Louis, and a member of the clinical council of Washington University's Public Health Institute.

common pattern among patients with opioid use disorder (OUD) is that they undergo treatment with medication-assisted therapy (MAT), only to drop out of treatment and then repeat the treatment at a later date. That suggests that physicians should take a harder look at the limitations of MAT and other treatments, Gold said.

Although the review found some associations between neurocognitive deficits and opioid overdose, the authors point out that it is difficult to make direct comparisons because of biases and differences in methodology among the included studies. They were not able to reach conclusions about the prevalence of brain injuries following nonfatal opioid overdoses. Few included studies controlled for confounding factors that might contribute to or explain neurocognitive impairments, reported Winstanley, associate professor in the department of behavioral medicine and psychiatry at the University of West Virginia, Morgantown, and associates.

Still, distinct patterns emerged from the analysis of almost 3,500 subjects in 79 studies in 21 countries. Twenty-nine studies reported diagnoses of leukoencephalopathy, which affects white matter. Spongiform leukoencephalopathy is known to occur secondarily after exposure to a variety of toxic agents, including carbon monoxide poisoning and drugs of abuse. The damage can lead to erosion of higher cerebral function. The condition can occur from 2 to 180 days after a hypoxic brain injury, potentially complicating efforts to attribute it specifically to an opioid overdose. Amnestic syndrome was also reported in some studies. One study found that about 39% of people seeking buprenorphine treatment suffered from neurocognitive impairment.

Gold called the study's findings novel and of public health importance. "Each overdose takes a toll on the body, and especially the brain," he said.

Better Documentation Needed

The variability in symptoms, as well as their timing, present challenges to initial treatment, which often occur before a patient reaches the hospital. This is a vital window because the length of time of inadequate respiration because of opioid overdose is likely to predict the extent of brain injury. The duration of inadequate respiration may not be captured in electronic medical records, and emergency departments don't typically collect toxicology information, which may lead health care providers to attribute neurocognitive impairments to ongoing drug use rather than an acute anoxic or hypoxic episode. Further neurocognitive damage may have a delayed onset, and better documentation of these events could help physicians determine whether those symptoms stem from the acute event.

Winstanley and associates called for more research, including prospective case-control studies to identify brain changes following opioid-related overdose.

The authors also suggested that physicians might want to consider screening patients who experience prolonged anoxia or hypoxia for neurocognitive impairments and brain injuries. Gold agreed.

"Clinicians working with OUD patients should take these data to heart and take a comprehensive history of previous overdoses, loss of consciousness, head trauma, and following up on the history with neuropsychological and other tests of brain function," Gold said. "After an assessment, rehabilitation and treatment might then be more personalized and effective."

Gold had no relevant financial disclosures.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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