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In Cryptogenic Stroke, Think Stimulants?

— Hospital saw three adult ADHD patients with ischemic stroke in one week

Last Updated October 19, 2016
MedpageToday

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BALTIMORE -- Stimulants prescribed for adult attention deficit hyperactivity disorder (ADHD) were associated with ischemic stroke in case reports presented here.

Of the three cases who were taking ADHD drugs and presented to the emergency department with ischemic stroke, two were taking dextroamphetamine/amphetamine (Adderall) and one was on lisdexamfetamine (Vyvanse), , of Loyola University in Chicago, and colleagues reported at the .

Action Points

  • Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • Note that stimulants prescribed for adult attention deficit hyperactivity disorder (ADHD) were associated with ischemic stroke, in reports of three cases occurring within a week of each other.
  • Be aware that causality could not be proved, and the cause of the strokes was ultimately labeled "indeterminate," or cryptogenic, but the major risk factor in all three cases was being on these medications.

Ortiz said the three cases all occurred within just one week of each other.

"We recommended that these patients stop their medications, and get a second opinion from the psychiatrist or other doctor who prescribed the medication about an alternative for their ADHD," Ortiz told ֱ.

He cautioned that his team couldn't prove causality in these cases, and that the cause of their stroke was ultimately labeled "indeterminate," or cryptogenic. But he noted that the major risk factor in all three cases was being on these medications.

"Amphetamines should be considered in patients who present with stroke-like symptoms," he said.

, of Loyola University in Chicago, who was a co-author on the paper, noted that physicians should remain vigilant about this potential risk as more adults are being prescribed drugs for ADHD.

"This is an association, it doesn't establish causality, but I think it's worthy of further investigation because some physicians may not pay attention" to the potential risks of prescribing these drugs, Biller told ֱ.

Some three million children in the U.S. are prescribed amphetamines for ADHD, and the drugs are being increasingly prescribed for adult ADHD, the researchers noted. New prevalence estimates have suggested that some 3% to 5% of adults have the condition -- although some experts have questioned whether the disease exists at all, according to a recent investigation by ֱ/Milwaukee Journal Sentinel.

As adult ADHD diagnoses increased stimulant overdoses also increased, the investigation found.

The drugs have been associated with cardiac problems, including tachycardia, myocardial infarction, and sudden death -- as well as cardiovascular issues such as stroke. And those side effects become more of a concern when these drugs are increasingly used in an older population, the researchers said.

Among these three ischemic stroke patients, two had some traditional stroke risk factors, but no firm etiology could be established, so they were labeled as cryptogenic.

In one case, a 37-year-old male was on 15 mg dextroamphetamine/amphetamine daily. He had a history of hypertension and dyslipidemia.

In another, a 35-year-old woman was taking 30 mg of dextroamphetamine/amphetamine a day. She had a history of hypertension and reactive thrombocytosis, and she'd been a smoker.

In the third case a 23-year-old male was taking lisdexamfetamine, and he only had a history of major depressive disorder.

"Amphetamine use may have been an etiological factor or potentiated other underlying vascular risk factors, leading to ischemic stroke," the researchers wrote.

A separate poster presented here by , of the University of Miami, and colleagues, reported a case of hemorrhagic stroke that occurred in a 36-year-old male who was on dextroamphetamine/amphetamine. The case was particularly unusual because the bleed in the basal ganglia was bilateral and symmetric, the researchers said.

"Amphetamine-related damage to striatal dopamine transporter axons have been variously described, but it is unknown if this is coincidental or if there exists a curious link to the susceptibility of bilateral basal ganglia to amphetamine-related intracerebral hemorrhage," they wrote.

There are several mechanisms by which the association between amphetamines and stroke risk could be tied, including a rise in catecholamine levels, extracranial and intracranial vasoconstriction, or cerebral vasculitis. Ortiz said his team suspects that the relationship is due to transient vasospasm produced by the amphetamine.

He noted that although no clear link between ADHD medications and stroke can be unequivocally established, patients with one or more cardiovascular risk factors could be carefully assessed prior to initiating stimulant therapy. And while those patients are taking the drugs, they should be monitored closely for any blood pressure and heart rate changes, he said.

The potential link needs to be explored further, he added: "Both population-based studies and randomized controlled trials need to be done in order to find whether the cause of stroke is related to amphetamines."

Biller called for increased vigilance "particularly when these patients may have other risk factors. One should be careful when putting patients on these drugs."

Disclosures

Ortiz disclosed no financial relationships with industry.

Primary Source

American Neurological Association

Orjuela K, et al "Amphetamine use in adults with ADHD and embolic strokes of undetermined source; a casual or causal relationship?" ANA 2016; Abstract S305.