Citicoline for Hemorrhagic Stroke
Citicoline is not recommended for the treatment of hemorrhagic stroke based on current evidence, as there are no adequately powered trials demonstrating efficacy, and major stroke guidelines do not support its use in this setting.
Guideline Position
The American Heart Association/American Stroke Association guidelines explicitly state that citicoline cannot be recommended for acute stroke treatment due to lack of consistent efficacy, with this recommendation carrying Grade A strength of evidence based on multiple randomized controlled trials 1, 2. While these guidelines primarily address ischemic stroke, the absence of recommendation extends to hemorrhagic stroke given the paucity of definitive evidence 3.
Available Evidence for Hemorrhagic Stroke
The evidence base for citicoline in hemorrhagic stroke is extremely limited:
Only one small pilot study exists: A double-blind, randomized, placebo-controlled trial enrolled just 38 patients (19 per group) with intracerebral hemorrhage treated within 6 hours of symptom onset 4. While this study showed citicoline (1g every 12 hours for 2 weeks) appeared safe with similar rates of serious adverse events compared to placebo (4 patients in each group), the efficacy signal was weak and inconclusive 4.
Trend toward benefit but underpowered: In this pilot study, 5 patients in the citicoline group achieved independence (mRS ≤2) at 3 months compared to only 1 patient in the placebo group (OR 5.38,95% CI 0.55-52), but the wide confidence interval crossing 1.0 indicates this finding could easily be due to chance 4.
No definitive trials have followed: Despite the pilot study being published in 2006, no large-scale confirmatory trials have been completed to validate these preliminary findings 4.
Context from Ischemic Stroke Evidence
The failure of citicoline in ischemic stroke further undermines its potential role in hemorrhagic stroke:
The large International Citicoline Trial on Acute Stroke (ICTUS) enrolled 2,298 patients with moderate to severe ischemic stroke and found no difference in 90-day outcomes between citicoline and placebo (OR 1.03,95% CI 0.86-1.25, p=0.364) 1, 2.
This high-quality negative trial in ischemic stroke—where the theoretical neuroprotective mechanisms would be most applicable—suggests limited therapeutic potential 1.
Established Management Priorities
Focus on evidence-based interventions for hemorrhagic stroke instead:
Acute blood pressure management is critical, as hypertension increases the risk of hematoma expansion 3.
Reversal of anticoagulation when applicable, following established protocols 3.
Surgical evaluation for cerebellar hemorrhages causing brainstem compression or hydrocephalus, which can be life-saving 3.
Avoidance of hypotonic fluids (such as 5% dextrose in water) that may worsen cerebral edema; use isotonic saline instead 3.
Temperature and glucose management: maintain normothermia and avoid hyperglycemia (>180 mg/dL), as both are associated with worse outcomes 3.
Clinical Bottom Line
While experimental models suggested potential benefit of citicoline in hemorrhagic stroke 5, and one tiny pilot study showed a safety signal 4, there is insufficient evidence to recommend its use in clinical practice. The single pilot study was too small to draw meaningful conclusions about efficacy, and no confirmatory trials have emerged in nearly two decades 4. Given the failure of citicoline in the much larger ischemic stroke population where it was extensively studied 1, 2, pursuing this agent for hemorrhagic stroke lacks scientific justification.