Does citicoline (cytidine diphosphate-choline) cause seizures?

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Last updated: October 19, 2025View editorial policy

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Citicoline and Seizure Risk

Based on the available evidence, citicoline does not appear to cause seizures in humans and may actually have anticonvulsant properties in some experimental models.

Evidence on Citicoline and Seizures

  • No guidelines or clinical evidence indicate that citicoline (cytidine diphosphate-choline) causes seizures in humans 1
  • Citicoline has been studied as a neuroprotective agent for ischemic stroke, with no reports of seizure induction in clinical guidelines 1
  • Unlike medications such as metronidazole that are known to reduce seizure threshold, citicoline is not contraindicated in patients with seizure disorders 2

Experimental Studies on Citicoline and Seizures

  • Several animal studies have actually demonstrated potential anticonvulsant effects of citicoline:

    • Citicoline at doses of 100 and 150 mg/kg significantly delayed seizure onset in pentylenetetrazole seizure models 3
    • Administration of citicoline (500 and 1000 mg/kg) increased the threshold for clonic seizures and the tonic phase of seizures in mice 4
    • The anticonvulsant effect of citicoline persisted for up to 6 hours after injection in experimental models 4
  • One contradictory study found that citicoline treatment enhanced seizure-induced neuronal death and microglial activation in a pilocarpine-induced epilepsy model, suggesting potential adverse effects in that specific model 5

Mechanism of Action

  • Citicoline serves as a choline donor in the biosynthesis of acetylcholine and neuronal membrane phospholipids, primarily phosphatidylcholine 5
  • Some research suggests citicoline's anticonvulsant effects may involve nitric oxide pathways 6

Clinical Implications

  • Unlike amantadine and rimantadine, which have documented increased risk of seizures in patients with seizure disorders, citicoline has not been associated with increased seizure risk in clinical guidelines 1
  • Citicoline has been studied extensively as a neuroprotective agent for stroke patients without reports of increased seizure risk 1

Monitoring Recommendations

  • While specific monitoring for seizures is not indicated based on current evidence, standard clinical vigilance is appropriate when administering any medication 1
  • The contradictory findings in one animal model suggest caution may be warranted in patients with active epilepsy until more clinical data becomes available 5

Summary

  • Current clinical guidelines and research do not support citicoline as a seizure-inducing agent 1
  • Most experimental evidence suggests potential anticonvulsant rather than proconvulsant properties 3, 7, 4
  • Unlike certain medications (amantadine, rimantadine, metronidazole) that carry warnings about seizure risk, citicoline does not have such contraindications in clinical guidelines 1, 2

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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