Citicoline Should Not Be Prescribed for Stroke Patients
Do not prescribe citicoline for acute ischemic stroke patients, as the American Heart Association/American Stroke Association explicitly states that no agent with putative neuroprotective effects, including citicoline, can be recommended for treatment of acute ischemic stroke (Grade A recommendation). 1, 2
Why Citicoline Is Not Recommended
The evidence against citicoline is definitive and based on high-quality randomized controlled trials:
The International Citicoline Trial on Acute Stroke (ICTUS), the largest and most recent definitive trial with 2,298 patients, found no difference in 90-day global outcomes between citicoline and placebo (OR 1.03,95% CI 0.86-1.25, p=0.364). 1
Multiple clinical trials have consistently failed to demonstrate efficacy in improving stroke outcomes, leading to the Grade A recommendation against its use. 1, 2
The planned primary analyses in major efficacy trials showed no benefit, with citicoline-treated patients showing identical recovery rates to placebo (both 40% achieving Barthel Index ≥95 at 12 weeks). 3
Understanding the Contradictory Evidence
While you may encounter older literature suggesting benefit, these findings do not hold up under scrutiny:
A 2002 pooled analysis suggested 25.2% recovery with citicoline versus 20.2% with placebo, but this was a post-hoc analysis that was not confirmed by subsequent definitive trials. 4
Post-hoc subgroup analyses in earlier trials suggested possible benefit in patients with moderate to severe strokes (NIHSS ≥8), but these were exploratory findings that failed validation in the properly powered ICTUS trial. 5, 3
The failure of the ICTUS trial in 2012 definitively closed the door on citicoline as a stroke treatment, superseding all earlier positive signals. 1
What You Should Prescribe Instead
Focus on evidence-based interventions with proven mortality and morbidity benefits:
Administer IV recombinant tissue plasminogen activator (r-tPA) within 3 hours (Grade 1A) or 4.5 hours (Grade 2C) of symptom onset for eligible patients. 2
Start aspirin 160-325 mg within 24-48 hours for patients not receiving thrombolysis, after excluding intracranial hemorrhage. 2
Consider endovascular thrombectomy for large vessel occlusions within appropriate time windows. 2
Admit patients to specialized stroke units with coordinated interdisciplinary care. 2
Critical Pitfall to Avoid
Do not be swayed by observational studies or drug surveillance reports showing apparent benefit (such as the 4,191-patient Korean surveillance study), as these lack the rigor of randomized controlled trials and are subject to selection bias and confounding. 6 The definitive randomized evidence is clear and negative. 1