Citicoline

Citicoline in the Treatment of Acute Ischaemic Stroke: An International, Randomised, Multicentre, Placebo-Controlled Study (ICTUS Trial)

Study: This 2012 international, randomized, double-blind, placebo-controlled trial (NCT01189045) involved 2,298 patients with moderate-to-severe acute ischemic stroke (AIS) within 24 hours of onset. Patients received 2,000 mg/day citicoline (1,000 mg IV every 12 hours for 3 days, then 1,000 mg oral twice daily) or placebo for 6 weeks. The primary endpoint was global recovery at 90 days (combined NIHSS ≤1, mRS ≤1, and Barthel Index ≥95).

Findings: Citicoline showed no significant benefit over placebo for global recovery (odds ratio [OR] 1.03, 95% CI 0.86–1.25, p=0.364). Subgroup analyses suggested potential benefits in patients over 70, those with NIHSS <14, or those not receiving thrombolytic therapy, but the overall trial concluded citicoline was not efficacious for AIS. Side effects were similar between groups, with mild digestive disturbances in <5%.

Link: The Lancet

Citicoline Brain Injury Treatment Trial (COBRIT)

Study: This 2012 phase III, double-blind, randomized, placebo-controlled trial (NCT00545662) involved 1,213 patients with traumatic brain injury (TBI) classified as complicated mild, moderate, or severe. Patients received 2,000 mg/day oral citicoline or placebo for 90 days. Outcomes included functional and cognitive status assessed by the TBI Clinical Trials Network Core Battery, including Glasgow Outcome Scale–Extended (GOS-E).

Findings: Citicoline did not significantly improve functional or cognitive outcomes compared to placebo at 90 days (OR 0.98, 95% CI 0.83–1.15) or 180 days (OR 0.87, 95% CI 0.72–1.04). Improvements in GOS-E were similar (35.4% citicoline vs. 35.6% placebo). The treatment was safe, with rare mild side effects (e.g., diarrhea, headache).

Link: JAMA

Citicoline and Memory Function in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Study: This 2021 randomized, double-blind, placebo-controlled trial involved 100 healthy older adults (aged 50–85) with age-associated memory impairment (AAMI). Participants received 500 mg/day Cognizin® citicoline or placebo for 12 weeks. Outcomes included memory performance (episodic and overall memory) assessed using standardized tests like the Paired Associates and Logical Memory subtests.

Findings: Citicoline significantly improved overall memory performance (p<0.05), particularly episodic memory, compared to placebo. Motor speed and reduced impulsivity were also noted. The supplement was well-tolerated with no serious adverse effects.

Link: The Journal of Nutrition

Effectiveness and Safety of Citicoline in Mild Vascular Cognitive Impairment: The IDEALE Study

Study: This 2013 open-label, non-randomized, parallel trial involved 349 patients with mild vascular cognitive impairment. Patients received 1,000 mg/day citicoline (500 mg twice daily) or no treatment for 9 months. Outcomes included Mini-Mental State Examination (MMSE) scores, activities of daily living, and brain MRI changes.

Findings: Citicoline improved MMSE scores (p<0.05) compared to the control group, which showed a decline. Functional and cognitive improvements were sustained at 9 months. No significant adverse effects were reported, though the non-randomized design limits conclusions.

Link: Clinical Interventions in Aging

Double-Blind Placebo-Controlled Study with Citicoline in APOE Genotyped Alzheimer’s Disease Patients: Effects on Cognitive Performance, Brain Bioelectrical Activity, and Cerebral Perfusion

Study: This 1999 randomized, double-blind, placebo-controlled trial involved 30 Alzheimer’s disease patients stratified by APOE genotype. Participants received 1,000 mg/day citicoline or placebo for 12 weeks. Outcomes included cognitive performance (ADAS-Cog), EEG activity, and cerebral blood flow (SPECT).

Findings: Citicoline improved cognitive performance (ADAS-Cog, p<0.05) and increased cerebral blood flow, particularly in APOE ε4 non-carriers. EEG showed improved brain bioelectrical activity. No significant side effects were reported.

Link: Methods and Findings in Experimental and Clinical Pharmacology

A Randomized, Double-Blind, Placebo-Controlled Trial of Citicoline for Cocaine Dependence in Bipolar I Disorder

Study: This 2015 randomized, double-blind, placebo-controlled trial involved 130 outpatients with bipolar I disorder and cocaine dependence. Participants received 2,000 mg/day citicoline or placebo for 12 weeks alongside standard treatment. Outcomes included cocaine use (urine tests) and mood symptoms (Hamilton Depression Rating Scale).

Findings: Citicoline significantly reduced cocaine use (p=0.026) compared to placebo, with no significant effect on mood symptoms. The treatment was well-tolerated, with mild side effects (e.g., stomach pain) in <10% of participants.

Link: American Journal of Psychiatry

Can Treatment with Citicoline Eyedrops Reduce Progression in Glaucoma? The Results of a Randomized Placebo-Controlled Clinical Trial

Study: This 2020 randomized, double-blind, placebo-controlled trial involved 78 patients with progressive glaucoma. Participants received 2% citicoline eyedrops or placebo three times daily for 3 years. Outcomes included visual field progression and retinal function (pattern electroretinogram, PERG).

Findings: Citicoline eyedrops significantly reduced visual field progression (p<0.05) and improved PERG amplitudes compared to placebo, suggesting neuroprotective effects. No significant ocular or systemic side effects were reported.

Link: Journal of Glaucoma

Assessing the Acute Effects of CDP-Choline on Sensory Gating in Schizophrenia: A Pilot Study

Study: This 2018 randomized, double-blind, placebo-controlled, crossover trial involved 24 healthy males (mean age 21.3) to assess citicoline’s effects on sensory gating and cognition. Participants received a single dose of 500 mg or 1,000 mg citicoline or placebo. Outcomes included P50 event-related potential (ERP) suppression and EEG oscillations.

Findings: Citicoline (500 mg and 1,000 mg) improved sensory gating (P50 suppression, p<0.05) and EEG oscillations, particularly in low-gating individuals, suggesting potential benefits for schizophrenia-related cognitive deficits. No adverse effects were reported.

Link: Journal of Psychopharmacology

Citicoline on the Barthel Index: Severe and Moderate Brain Injury

Study: This 2023 randomized, controlled trial involved 40 patients with severe or moderate TBI. Patients received 2,000 mg/day citicoline or standard treatment for 14 days. Outcomes included Barthel Index scores, NIHSS, and Glasgow Coma Scale (GCS).

Findings: Citicoline significantly improved Barthel Index scores (p=0.02) and NIHSS (p=0.03) compared to controls, indicating better functional recovery. No significant differences in GCS or adverse effects were noted.

Link: Indian Journal of Pharmacology

Efficacy of Citicoline as a Neuroprotector in Children with Post-Cardiac Arrest: A Randomized Controlled Clinical Trial

Study: This 2021 randomized, controlled trial involved 60 children post-cardiac arrest. Patients received 100 mg/kg/day citicoline IV or placebo for 7 days. Outcomes included neurological status (Pediatric Cerebral Performance Category, PCPC) and survival at 3 months.

Findings: We found that Citicoline is a promising neuroprotective drug in children with post-cardiac arrest.

Link: Pubmed