Citicoline for Unilateral Weakness After Stroke
Citicoline is not recommended for the treatment of acute ischemic stroke causing unilateral weakness, as the American Heart Association/American Stroke Association issues a Grade A (strong) recommendation against its use based on definitive evidence showing no clinical benefit. 1, 2, 3
Why Citicoline Should Not Be Used
The highest quality evidence comes from the International Citicoline Trial on Acute Stroke (ICTUS), which enrolled 2,298 patients with moderate-to-severe ischemic stroke and found no difference in 90-day global outcomes between citicoline and placebo (odds ratio 1.03; 95% CI 0.86-1.25; p=0.364). 1, 3 This large, definitive European multicenter trial provides conclusive evidence that citicoline does not improve recovery from stroke-related weakness. 3
Critical Pitfall to Avoid
Do not be misled by older positive studies or pooled analyses. 3 While an earlier patient-level pooled analysis suggested 25.2% recovery with citicoline versus 20.2% with placebo when started within 24 hours, 4 this finding was definitively refuted by the subsequent ICTUS trial. 1, 3 The large sample size and rigorous methodology of ICTUS (2,298 patients) supersedes earlier smaller trials. 3
What You Should Do Instead for Unilateral Weakness
Acute Phase (First Hours)
Administer IV alteplase (rtPA) within 3-4.5 hours of symptom onset for eligible patients after excluding intracranial hemorrhage on CT/MRI. 3
Consider endovascular thrombectomy for large-vessel occlusions within guideline-specified time windows. 3
Maintain blood pressure <180/105 mmHg for 24 hours after reperfusion therapy to reduce hemorrhagic transformation risk. 3
Within 24-48 Hours
- Start aspirin 160-325 mg daily within 24-48 hours for patients not receiving thrombolysis, after excluding intracranial hemorrhage. 5, 2, 3 This is the only antiplatelet agent with proven efficacy in acute stroke, showing modest but statistically significant benefit primarily through prevention of early recurrent events. 5
General Management
Admit to a dedicated stroke unit with coordinated interdisciplinary care, which improves outcomes. 1, 3
Manage physiological parameters including blood pressure control (only lower if >220/120 mmHg in non-thrombolyzed patients, with modest 10-15% reduction). 2
The Evidence Hierarchy
The American Heart Association/American Stroke Association explicitly states that no agent with putative neuroprotective effects, including citicoline, can be recommended for acute ischemic stroke treatment (Grade A recommendation). 1, 2 This recommendation is based on multiple randomized controlled trials that failed to demonstrate consistent efficacy. 1
Even a 2016 meta-analysis that suggested some benefit acknowledged the effect was diluted when patients received rtPA, and any potential benefit was limited to those not receiving the best available treatment. 6 Since rtPA is now standard care for eligible patients, this further undermines any rationale for citicoline use. 6
Focus resources and time on proven therapies—rapid imaging, thrombolysis eligibility assessment, and early aspirin—rather than unproven neuroprotective agents. 3