Does fentanyl increase the risk of seizures?

From the Guidelines

Fentanyl does not have a significant association with an increased risk of seizures at therapeutic doses, according to the most recent and highest quality evidence available. The provided evidence [ 1 ] discusses the management of cancer pain with opioids, including fentanyl, but does not specifically mention fentanyl as a cause of seizures. However, it does mention that hydromorphone, another opioid, may lead to opioid neurotoxicity, including myoclonus, hyperalgesia, and seizures [ 1 ].

Key points to be aware of:

• The risk of seizures with fentanyl is not well-established in the provided evidence [ 1 ].
• Fentanyl is a highly lipid-soluble opioid that can be administered via various routes, including parenteral, spinal, transdermal, transmucosal, buccal, and intranasal [ 1 ].
• The evidence suggests that other opioids, such as hydromorphone, may have a higher risk of neurotoxicity, including seizures [ 1 ].
• Patients with a history of seizures or epilepsy may still require caution when using fentanyl, although the evidence does not specifically support an increased risk [ 1 ].

When using fentanyl, it is essential to monitor for signs of seizure activity, such as sudden body stiffness, loss of consciousness, or jerking movements, and seek immediate medical attention if these occur. However, based on the available evidence [ 1 ], fentanyl does not appear to have a significant association with an increased risk of seizures at therapeutic doses.

From the FDA Drug Label

Fentanyl transdermal system is a skin patch that contains fentanyl. Fentanyl is a very strong opioid narcotic pain medicine that can cause serious and life-threatening breathing problems ... have a seizure

• Seizure risk: Fentanyl transdermal system can cause seizures.
• Key consideration: The drug label explicitly mentions seizures as a potential side effect of fentanyl transdermal system 2.

From the Research

Fentanyl and Seizure Risk

• Fentanyl has been shown to increase the risk of seizures in certain individuals, particularly those with a history of complex partial seizures 3.
• A study published in the Journal of Neurosurgery found that moderate doses of fentanyl can evoke electrical seizure activity in patients with complex partial seizures 3.
• Another study published in Der Anaesthesist found that the combination of fentanyl and droperidol lowered the threshold for both clonic and tonic convulsions in mice, suggesting a potential proconvulsant effect 4.
• High doses of fentanyl have been shown to depress cerebral blood flow and metabolism in rats, and seizures were observed in about 25% of rats receiving high doses of fentanyl 5.

Comparison to Other Substances

• A study published in Epilepsia found that antidepressant drugs, which are sometimes compared to fentanyl in terms of their potential to induce seizures, exhibit a seizure risk close to that reported for the first spontaneous seizure in the general population at therapeutic dosages 6.
• However, the study also found that high doses of antidepressant drugs can increase the risk of seizures, and that certain drugs such as maprotiline and amoxapine may exhibit a greater seizure risk than others 6.
• A study published in Archives of Academic Emergency Medicine found that tramadol, a substance related to fentanyl, can cause seizures even at therapeutic doses, and that the risk of seizure increases with higher doses and in individuals with a history of seizure 7.

Key Findings

• Fentanyl can increase the risk of seizures in certain individuals, particularly those with a history of complex partial seizures 3, 4, 5.
• The risk of seizure associated with fentanyl may be dose-dependent, with higher doses increasing the risk of seizure 4, 5, 7.
• Fentanyl may have a proconvulsant effect, particularly when combined with other substances such as droperidol 4.