Citicoline In Patients Research Articles

The role of citicoline in the correction of cerebral blood flow disorders in patients with coronary artery disease in combination with COVID-19

OBJECTIVE. To evaluate the effect of citicoline on cerebral blood flow and microembolic signals (MES) after 6 months of treatment in patients with coronary artery disease combined with coronavirus disease (COVID-19). MATERIALS AND METHODS. A prospective study of 68 patients with coronary artery disease with confirmed COVID-19 by PCR was conducted. Group I (n=35) included patients with coronary artery disease in combination with COVID-19, who, in addition to standard therapy of cerebrovascular disease, received citicoline (500 mg twice daily) for 6 months after discharge from the hospital. The comparison group (group II; n=33) consisted of patients who did not receive citicoline. Cerebral blood flow, peak systolic velocity in extracranial and intracranial vessels were determined, and 1-hour transcranial monitoring to detect MES were performed. Patients were re-examined in 6 months. RESULTS. At the initial examination of patients, cerebral blood flow and the number of MES did not differ significantly. After 6 months, there was an increase in cerebral blood flow in the cerebral arteries, as well as a decrease in MES in patients taking citicoline, whereas in group II there was no positive dynamics of this ratio. A direct correlation between plasma C-reactive protein, D-dimer and MES was found in patients of both groups. After 6 months of treatment, C-reactive protein and D-dimer decreased in both groups equally. CONCLUSIONS. The obtained results of improvement of cerebral perfusion, blood rheology, due to the anti-inflammatory effect, stabilising function of citicoline on phospholipid membranes of cerebral vascular endothelium, neurons and glial elements allow the use of citicoline in patients with coronary artery disease in combination with COVID-19 to reduce the negative impact of COVID-19 on the central nervous system.

Possibility of correction of cerebral blood flow disorders and central nervous system damage with citicoline in patients with coronary artery disease in combination with COVID-19

ABSTRACT. The review describes some pathogenetic mechanisms of central nervous system lesions in patients with coronary artery disease in combination with coronavirus disease (COVID-19) and presents the current possibilities of their pharmacotherapy. The analysis of experimental and clinical trials has shown that the multifactorial effect of citicoline on the main pathogenic links of brain damage in COVID-19 and numerous positive clinical effects make it a promising drug in the treatment of patients with coronary artery disease in combination with COVID-19 and post-COVID syndrome.

Role of Citicoline in Patients With Mild Cognitive Impairment.

The term mild cognitive impairment (MCI) defines an intermediate state between normal aging and dementia. Vascular cognitive impairment refers to a decline in cognitive function that is caused by or associated with vascular disease and comprises all the spectrum of cognitive impairments, from MCI of vascular origin to vascular dementia. One of the available treatments for cognitive impairment is cytidine diphosphate-choline (CDP-Choline), or citicoline. The objective of the present manuscript is to provide complete evidence about the efficacy of citicoline for MCI, especially of vascular origin, but also due to other neurodegenerative disorders. Citicoline is a pharmaceutical product constituted by the combination of 2 natural molecules (cytidine and choline) and is marketed as a food supplement. It has been proposed to provide neuroprotective effects through diverse mechanisms of action. Taking into account the available literature, citicoline has shown a consistent improvement in cognitive function in patients with MCI, especially of vascular origin. Moreover, it provides beneficial effects on vascular, Alzheimer, and mixed dementias, stroke sequelae, intracerebral hemorrhages, traumatic brain injuries, and neurodegenerative diseases. Long-term treatment with citicoline has also been demonstrated to be well-tolerated and has not been associated with severe adverse events. Citicoline is a safe, well-tolerated, and promising agent with evidenced neuroprotective properties.

Serum Levels of the Biomarkers Associated with Astrocytosis, Neurodegeneration, and Demyelination: Neurological Benefits of Citicoline Treatment of Patients with Ischemic Stroke and Atrial Fibrillation.

Ischemic stroke is a main complication of atrial fibrillation (cardiac arrhythmia). The aim of our study was to estimate the effects of citicoline (CDP-choline) therapy on the levels of circulating neurospecific protein markers in serum of the patients with ischemic stroke and atrial fibrillation. Fiftyfour patients (mean age 76 years) treated with citicoline in a dose of 2.0 g daily intravenously for 12 to 14 days in addition to basic treatment formed the examined group. Thirty-two patients (mean age 68.5 years) obtained only standard therapy and formed the control group. Serum levels of neuronal and glial protein markers, including glial fibrillary acidic protein (GFAP), a neurofilament light subunit (NF-L), myelin basic protein (MBP), and ionized calcium-binding adaptor molecule 1 (Iba1), were measured in patients of both groups before and after treatment; an immunoblotting technique followed by densitometry analysis were used. Supplementary citicoline treatment provided significant reductions of the levels of GFAP (33%, P = 0.034), NF-L (27%, P = 0.019), and MBP (32%, P = 0.018), as compared to the initial values, while there were no marked changes in the studied parameters in the control group. The results obtained allow us to hypothesize that therapeutic benefit of citicoline in patients with ischemic stroke and atrial fibrillation can be mediated through increasing neuronal viability, protecting against axonal injury, decreasing the level of reactive astrogliosis, preventing deficiencies in the blood-brain integrity, and reducing the intensity of demyelination. However, citicoline administration exerted no effect on the blood content of microglial marker Iba-1, thus possibly preserving an important functional significance of microglia, which is needed to resolve local inflammation and clear cellular debris, and also provide protective factors to reduce cell injury in the ischemic brain. The obtained results indicate that serum levels of neurospecific biomarkers are significant and clinically relevant indices of the efficiency of treatment of the above-mentioned pathologies and can be used for further investigations of the stroke pathophysiology and molecular mechanisms of nootropic-mediated neuroprotection.

Experience with citicoline in patients with post-stroke cognitive impairment

Objective: to investigate the efficacy and safety of citicoline (Ceresil® Canon) in patients with post-stroke cognitive impairment.Patients and methods. Examinations were made in 33 patients aged 45 years and older who had experienced primary ischemic hemispheric stroke with complaints of a decline in memory or other cognitive functions. The cognitive status was assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The presence of anxiety-depressive spectrum disorders was determined on the Hospital Anxiety and Depression Scale. All the patients received citicoline (Ceresil® Canon) oral solution at a dose of 1000 mg/day for 3 months.Results and discussion. Citicoline administration showed a statistically significant reduction in the severity of cognitive impairment (p<0.001). The time course of positive changes in the cognitive status of patients was reflected by an increase in the median score on the MMSE from 26 [25; 27.5] to 28 [26.5; 29] and on MoCA from 23 [21; 25] to 25 [22; 26]. There was a decline in the number of patients with anxiety-depressive disorders. No adverse events or side effects were found in the patients.Conclusion. The findings suggest that citicoline (Ceresil® Canon) produced as an oral solution is well tolerated and improves cognitive functions and affective sphere in patients in the recovery period of ischemic stroke.

Comparison of two different doses of citicoline in patients with traumatic brain injury

Introduction: The ever-increasing and common occurrence of head traumas highlight the importance of adopting therapeutic measures for the reduction of the associated morbidity and mortality. Citicoline, as a safe medicine with positive effects on improving traumatic injuries, has been proven to be useful in various studies. However, there are still no data on the specific standard method and dosage of citicoline for the treatment of patients with traumatic head injuries. Regarding this, the present study was performed to determine the effective therapeutic dosage of citicoline and its impact on patients with traumatic head injuries. Methods: This double-blind clinical trial was performed on 30 patients with traumatic concussion (a Glasgow coma scale [GCS] of ≤8) admitted to the intensive care unit and neurosurgery department. The patients were randomly divided into three groups of A (control), B (citicoline with a dosage of 0.5 g/twice a day), and C (citicoline with a dosage of 1.5 g/twice a day). The GCS, degree of muscle strength, Glasgow outcome score (GOS), contusion volume, and cerebral edema (based on brain CT scans) were calculated at specific times and intervals. In addition, the patients' dependency on a ventilator and their length of ICU stay were registered. Results: Mean GCS on the first day of stay, GCS changes on the third and fourth days of stay, first and seventh days of stay, seventh and fourteenth days of stay, and first and fourteenth days of stay in the three study groups showed the significant statistical difference (P<0.05). Significant statistical differences were seen between the GOS of the 30th day of stay in the three study groups (P<0.05). The contusion volume difference was only significant between the first and seventh days of stay in groups A and C (P<0.05). No significant difference was observed in the mean length of stay in ICU and duration of dependency on a ventilator in the three study groups (P<0.05). The mean degree of muscle strength was only significantly different on the first day of stay between groups B and C (P=0.008). Conclusions: In contrary to similar studies, the results of the current study revealed that citicoline had no positive effect on patient healing. This result may be due to the small sample size and the inconsistent first-day GCSs of the patients in all three groups. Therefore, given the confirmation of the effectiveness of citicoline even at higher dosages in other studies in future studies, it is recommended to use populations with a larger number of patients.

Human vitreous concentrations of citicoline following topical application of citicoline 2% ophthalmic solution.

PurposeTo evaluate the presence and concentration of citicoline and its metabolites (choline, cytidine and uridine) in the vitreous body in human eyes after topical application of an ophthalmic solution of citicoline 2%, in vivo.MethodsTwenty-one subjects affected by epiretinal membrane with surgical indication for pars-plana vitrectomy underwent treatment with 1 drop 3 times/day of a solution of citicoline 2%, 0.2% high molecular weight hyaluronic acid and 0.01% benzalkonium chloride (OMK1, Omikron Italia s.r.l., Rome, Italy) 14 days before surgery and 2 hours prior to surgery. Five additional patients served as controls and received an OMK1 vehicle solution without citicoline. The vitreous samples were taken at the beginning of the pars-plana vitrectomy and analyzed for qualitative/quantitative determination of vitreous concentration of citicoline and its metabolites by means of high performance liquid chromatography.ResultsThe overall mean concentration of citicoline in patients treated with citicoline 2% solution was 406.72 ± 52.99 μg/mL, while the mean concentration of choline, cytidine and uridine was 180.88 ± 41.49 μg/mL, 44.45 ± 10.19 μg/mL and 330.41 ± 75.8 μg/mL, respectively. The concentration of citicoline in phakic eyes (n = 13, 366.61 ± 129.61 μg/mL) was lower compared to that found in pseudophakic eyes (n = 8, 435.89 ± 131.42 μg/mL) and the difference was not statistically significant. The concentration of citicoline in the control eyes was 45.66 ± 26.36 μg/mL, while the concentration of choline, cytidine and uridine were 17.21 ± 9.93 μg/mL, 6.24 ± 3.6 μg/mL and 172.80 ± 99.76 μg/mL, respectively.ConclusionCiticoline can reach the human vitreous in high concentration when administered in ophthalmic solution. This evidence contributes to the build-up of the pyramid of the evidences required for determining the role of citicoline administered in ophthalmic formulation in retinal and optic nerve neurodegenerative diseases.

A Randomized, Double-Blind, Placebo-Controlled Trial of Citicoline in Patients with Alcohol Use Disorder.

Alcohol use disorder is a major societal and individual burden that exacerbates health outcomes, decreases quality of life, and negatively affects U.S. healthcare spending. Although pharmacological treatments are available for alcohol use disorder, many of them are limited by small effect sizes and used infrequently. Citicoline is a widely available over-the-counter supplement with a favorable side effect profile. It acts through cholinergic pathways and phospholipid metabolism. The current report examines the effect of oral citicoline on alcohol use, craving, depressive symptoms, and cognitive outcomes in individuals with alcohol use disorder. A 12-week, randomized, double-blind, parallel-group, placebo-controlled, pilot study of citicoline (titrated to 2,000mg/d) in 62 adults (age 18 to 75) with alcohol use disorder was conducted. Alcohol use, such as number of drinking days, amount used, and number of heavy drinking days, was assessed using the Timeline Followback method and liver enzymes, while alcohol craving was measured using the Penn Alcohol Craving Scale. A neurocognitive battery (e.g., Rey Auditory Verbal Learning Test) and depressive symptoms scale (e.g., Inventory of Depressive Symptomatology Self-Report) scores were also collected. Data were analyzed using a random regression analysis. The primary outcome analysis was conducted in the intent-to-treat sample and consisted of 55 participants (78.2% men and 21.8% women, mean age of 46.47 ± 9.15 years). In the assessment period, the drinking days, on average, represented 77% of the assessed days. Significant between-group differences were not observed on alcohol use, craving, and cognitive or depressive symptom measures. Citicoline was well tolerated. This proof-of-concept study observed that citicoline was well tolerated, but was not associated with a reduction in alcohol use or other outcomes, as compared to placebo. The favorable effects reported with citicoline for cocaine use, cognitive disorders, and other conditions do not appear to extend to alcohol use disorder.

IS THERE ANY BENEFIT OF CITICOLINE FOR ACUTE ISCHEMIC STROKE ? SYSTEMATIC REVIEW OF CURRENT EVIDENCES

Two main strategies have been suggested for the treatment of ischemic stroke including reperfusion and neuroprotection. Citicoline is one of neuroprotector agent that commonly used in ischemic stroke. A systematic review of citicoline focusing only on ischemic stroke has not yet performed. This systematic review aimed to identify the effectiveness of citicoline in patients with ischemic stroke history. A systematic research was performed using PubMed and Cochrane Library as the database. Keywords were: “citicoline and stroke”, “citicoline and ischemic stroke”, and “randomized controlled trial citicoline. The inclusion criteria were: (i) the trials conducted between 2007 to 2017, (ii) written in English, (iii) the studies performed in human, (iv) patients had ischemic stroke history, (v) citicoline was the main drug assessed in the study. The exclusion criteria i.e.: (i) the study was not a randomized controlled trial (RCT) and (ii) the full text was not available. The quality of RCT was determined by using Jadad score. A literature search revealed 541 journals from PubMed and Cochrane Library. After screening the title and abstract, adjusting for inclusion and exclusion criteria, adjusting for the irrelevant topic, and duplication the final result was 4 RCT studies. All studies had a good quality, indicated by Jadad score of 3 or more. Three studies conclude that no statistically significant difference in treatment outcome between citicoline and other groups. The last study revealed citicoline is effective in preventing post-stroke cognitive impairment.

Использование цитиколина у пациентов с нарушением двигательных функций после инсульта

Использование цитиколина у пациентов с нарушением двигательных функций после инсульта

Citicoline for Acute Ischemic Stroke: A Systematic Review and Formal Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Trials

Citicoline is a drug approved for the treatment of acute ischemic stroke. Although evidence of its efficacy has been reported, recently published results of a large placebo-controlled clinical trial did not show differences. This study aims to assess whether starting citicoline treatment within 14 days after stroke onset improves the outcome in patients with acute ischemic stroke, as compared with placebo. A systematic search was performed to identify all published, unconfounded, randomized, double-blind, and placebo-controlled clinical trials of citicoline in acute ischemic stroke. Ten randomized clinical trials met our inclusion criteria. The administration of citicoline was associated with a significant higher rate of independence, independently of the method of evaluation used (odds ratio [OR] 1.56, 95% confidence interval [CI] = 1.12-2.16 under random effects; OR 1.20, 95% CI = 1.06-1.36 under fixed effects). After studying the cumulative meta-analysis, and with the results obtained with the subgroup of patients who were not treated with recombinant tissue plasminogen activator (rtPA) (OR 1.63, 95% CI = 1.18-2.24 under random effects; OR 1.42, 95% CI = 1.22-1.66 under fixed effects), our hypothesis of dilution of the effect of citicoline was confirmed. When we analyzed the effect of citicoline in patients who were not treated with rtPA and were receiving the highest dose of citicoline started in the first 24 hours after onset, based on more recent trials, there was no heterogeneity, and the size of the effect has an OR of 1.27 (95% CI = 1.05-1.53). This systematic review supports some benefits of citicoline in the treatment of acute ischemic stroke. But, on top of the best treatment available (rtPA), citicoline offers a limited benefit.

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

Although drug dependence is common in patients with bipolar disorder, minimal data are available on the treatment of drug dependence in this patient population. The authors previously reported a decreased risk of relapse to cocaine use in a pilot study of citicoline in patients with bipolar disorder and cocaine dependence. The primary aim of the present study was to determine whether citicoline reduces cocaine use in outpatients with bipolar I disorder and current cocaine dependence and active cocaine use. A total of 130 outpatients with bipolar I disorder (depressed or mixed mood state) and cocaine dependence received citicoline or placebo add-on therapy for 12 weeks. Results of thrice-weekly urine drug screens were analyzed using a generalized linear mixed model that was fitted to the binary outcome of cocaine-positive screens at each measurement occasion for 12 weeks. Mood was assessed with the Inventory of Depressive Symptomatology-Self Report, the Hamilton Depression Rating Scale, and the Young Mania Rating Scale. In the intent-to-treat sample (N=61 in both groups), significant treatment group and group-by-time effects were observed, whether or not missing urine screens were imputed as cocaine positive. The group effect was greatest early in the study and tended to decline with time. No between-group differences in mood symptoms or side effects were observed. Citicoline was well tolerated for treatment of cocaine dependence in patients with bipolar disorder. Cocaine use was significantly reduced with citicoline initially, although treatment effects diminished over time, suggesting the need for augmentation strategies to optimize long-term benefit.

Neuroprotective Effects of Citicoline in Diffuse Axonal Injuries

Citicoline is a neuroprotective agent and fundamental item of phospholipid biosynthesis in cell walls. In this study, we aimed at examining the effect of citicoline in patients suffering from traumatic brain injury with Glasgow Coma Score (GCS) ≤ 8, and diffuse axonal injury (DAI) diagnosis. Efficacy of citicoline was evaluated by measurement of malondialdehyde (MDA) plasma levels as a marker of oxidative stress. Forty patients were randomly divided into two groups of cases (treated with citicoline) and controls (treated without citicoline). The duration of study was 15 days and 13 blood samplings were performed on the 1st, 10th and12th days of admission to evaluate the plasma levels of MDA. Citicoline was administered intravenously with dosage of 500mg/6h. In the control group, the mean plasma levels of MDA were 2.54±0.83, 2.43±0.79 and 2.39±0.97 ng/dL in first, second, and third blood samplings, respectively (P=0.85). In the case group, the mean plasma levels of MDA were 2.46±1.08, 1.99± 0.81 and 1.60±0.6 ng/dL in first, second and third blood samplings, respectively (P=0.01). The mean total plasma levels of MDA were comparable in the case (2.64±1.08 ng/dL) and control groups (2.54±0.83 ng/dL) (P=0.78). The results of this study suggest that citicoline is an effective neuroprotective agent which might be used in order to reduce MDA levels. Keywords: Citicoline; malondialdehyde; traumatic brain injury

Effective Treatment of Traumatic Brain Injury

IN THIS ISSUE OF JAMA, ZAFONTE AND COLLEAGUES 1 PREsent the findings of the Citicoline Brain Injury Treatment Trial (COBRIT), a phase 3, double-blind study comparing citicoline vs placebo. In this trial, 1213 study participants with complicated mild, moderate, or severe traumatic brain injury (TBI) were randomized to receive 2000 mg of citicoline or placebo daily for 90 days. The study, which did not demonstrate any benefits of citicholine treatment, is likely to have implications not only for the use of citicoline in patients with TBI but also for the design of future trials of TBI therapies. Traumatic brain injury is an important national and global health issue for civilian and military populations. Recent estimates for the United States indicate that each year 235 000 patients are hospitalized for nonfatal TBI, 1.1 million are treated in emergency departments, and 53 000 die. Trauma, which often includes TBI, is the leading cause of non–cancerrelated deaths among Americans younger than 40 years. A population-based study conducted in Olmsted County, Minnesota, found that the incidence of TBI requiring medical attention was 558 per 100 000 person-years. Following hospitalization for TBI, approximately 43% of patients in the United States have residual disability; 3.2 million Americans are now living with disability following hospitalization for TBI. A birth cohort study in New Zealand indicated that 32% of people had experienced an episode of TBI requiring medical attention by age 25 years. Clearly, TBI is a potentially severe and disabling health condition, but these estimates of morbidity, mortality, and disability do not consider the large number of mild TBI events for which patients do not seek immediate medical attention but can be associated with persistent problems such as headache. Moreover, US veterans with combat-associated mild TBI often have posttraumatic stress disorder, which can complicate reentry into civilian life. The main causes of TBI are motor vehicle crashes, sports injuries, falls, work-related injuries, assaults, and intentional and unintentional injuries involving firearms, explosives, and other weapons. Traumatic brain injury–related fatalities have declined the past 10 to 15 years in part because of improvements in protection of occupants in motor vehicles, protective helmet design, and other preventive measures. However, there remains an imperative need to further reduce the incidence of TBI. In addition, reducing the severity of TBI morbidity once trauma has occurred and improving the rate and extent of recovery from TBI are major challenges. Experimental therapies have shown some promise. For example, among a few carefully selected individuals with severe TBI who were in a state of minimal consciousness, electrical stimulation of the interstitial thalamic nuclei was associated with improved ability to participate and respond to cognitive and motor therapy. In a double-blind, placebo-controlled trial, amantadine improved the rate of recovery from severe TBI, although improvement attributed to amantadine was incomplete and only applicable for patients with severe TBI. There currently are no effective treatments to reduce the severity of TBI-related deficits among patients with complicated mild or moderate TBI. Therefore, the results of the COBRIT study of citicoline therapy were anticipated with great hope. Citicoline is an intermediate in the generation of phosphatidylcholine from choline. The brain uses choline to synthesize the neurotransmitter acetylcholine and the essential membrane components phosphatidylcholine and sphingomyelin. Citicoline increases choline availability for acetylcholine synthesis and membrane synthesis and repair. Citicoline has little toxicity in humans at doses up to 2000 mg daily. There have been encouraging findings in animal studies and preliminary clinical pilot studies using citicoline to reduce cerebral injury caused by TBI, ischemia, and aging. However, similar to the TBI study by Zafonte et al, a multicenter placebo-controlled study found that citicoline did not improve the extent or speed of recovery following acute stroke. There are several possible explanations for differences in the results of animal and human clinical studies in the efficacy of citicoline to reduce brain injury associated with trauma or ischemia. First, differences between animal and

Analysis of Therapeutic Efficacy of Citicoline in Patients with Vertigo of Central Origin and Vascular Aetiology

Analysis of Therapeutic Efficacy of Citicoline in Patients with Vertigo of Central Origin and Vascular Aetiology

PCV52 COST-EFFECTIVNESS STUDY OF CITICOLINE IN PATIENTS WITH ACUTE ISCHEMIC STROKE IN RUSSIA

Cerebrovascular diseases are on the second place among all causes of death in Russia. Neuroprotective therapy is one of the main approaches of therapy in patients with acute ischemic stroke in Russia despite the absence of this group of medicines in the recommendations of national standard of care in stroke (GOST R 200). The objective of this research was to evaluate cost-effectiveness ratio for the use of citicolin (a neuroprotective agent widely used in some EU countries, South Korea, Russia and some other countries) in patients treated according to the national standard of care in stroke (GOST R 200). The data on the efficacy of citicolin in patients with acute ischemic stroke were extracted from pooling analysis of clinical trials “Oral citicolin in acute stroke” (Davalos A. et al., 2002) The clinical effect was measured as global recovery index (proportion of patients with full recovery during 3 months). Cost of treatment with citicolin and cost-effectiveness ratio (CER) were calculated from the point of view of the Russian state health care system. According to the results of the above mentioned pooling analysis, the use of citicoline in stroke patients was associated with significantly greater rate of recovery than placebo (OR,1.33; 95% CI, 1.10 to 1.62). Costs of treatment of acute ischemic stroke according to recommendations of the national standard plus citicolin was 1 715.5 USD per 3 months. Costs of the treatment without citicolin was 1 289 USD per 3 months. CER (i.e. direct costs per one fully recovery patient) treated with citicolin and placebo were 6 354 USD and 6 384 USD respectively. Incremental CER was 6 264 USD. According to the applied model a treatment, citicolin appeared to demonstrate its clinically efficacy and cost-effectiveness in treatment of the patients with acute ischemic stroke, compared to placebo.

Oral Citicoline in Acute Ischemic Stroke

No single neuroprotective agent has been shown to influence outcome after acute stroke. Citicoline has been studied worldwide in many clinical trials with positive findings, but only 1 trial has obtained significant results in the primary efficacy variables. Our objective was to evaluate the effects of oral citicoline in patients with acute ischemic stroke by a data pooling analysis of clinical trials. The primary efficacy end point chosen was the common evaluation of recovery, combining National Institutes of Health Stroke Scale </=1, modified Rankin Scale score </=1, and Barthel Index >/=95 at 3 months using the generalized estimating equations analysis. A systematic search of all prospective, randomized, placebo-controlled, double-blind clinical trials with oral citicoline (MEDLINE, Cochrane, and Ferrer Group bibliographic databases) was undertaken. Individual patient data were extracted from each study and pooled in a single data file. The main inclusion criteria included compatible neuroimaging with ischemic stroke, National Institutes of Health Stroke Scale >/=8, and prior modified Rankin Scale score </=1. Four clinical trials using various doses of oral citicoline (500, 1000, and 2000 mg) were identified. Of 1652 randomized patients, 1372 fulfilled the inclusion criteria (583 received placebo, 789 received citicoline). Recovery at 3 months was 25.2% in citicoline-treated patients and 20.2% in placebo-treated patients (odds ratio [OR], 1.33; 95% CI, 1.10 to 1.62; P=0.0034). The dose showing the largest difference with placebo was 2000 mg, with 27.9% of patients achieving recovery (OR, 1.38; 95% CI, 1.10 to 1.72; P=0.0043). The overall safety of citicoline was similar to placebo. Treatment with oral citicoline within the first 24 hours after onset in patients with moderate to severe stroke increases the probability of complete recovery at 3 months.

A randomized efficacy trial of citicoline in patients with acute ischemic stroke.

Department of Anesthesiology; Duke University; Durham, North Carolina Department of Anesthesiology; Wake Forest University of School of Medicine; Winston-Salem, North Carolina