Citicoline, Widely Administered to Brain-Injured Patients, Fails in Clinical Trials
A new study shows that the organic compound does not improve cognitive function in patients with traumatic brain injuries.
-- by Joann Jovinelly
Traumatic brain injury (TBI) is a major cause of death and disability in the United States with more than 1.4 million cases annually. Of those, more than 90,000 patients are left with permanent brain injuries and they remain disabled—a condition currently affecting about 5.3 Americans.
Citicoline, an organic compound already present in the body, especially in the brain, is currently used in nearly 60 countries to help restore brain function in those with TBIs. When administered quickly after the initial injury, citicoline, or CDPC, is thought to enhance recovery by reducing inflammation, possibly shortening the length of time a patient spends in a coma, as well as improving blood flow to damaged areas.
Now, in a study conducted by Ross D. Zafonte, D.O., of Harvard Medical School, Spaulding Rehabilitation and Massachusetts General Hospital, Boston, the use of citicoline in a randomized trial of 1,200 TBI participants showed that the compound, when used as a monotherapy, did not result in any cognitive improvements. Those results appear in the November issue of the Journal of the American Medical Association (JAMA).
Citicoline is presently used in the United States as a nutraceutical (that is, a food product that reportedly provides both health and medical benefits) and has been given to patients with Alzheimer’s disease, dementia, and those with brain injuries that result in memory loss. Citicoline is also an additive in a variety of commercial beverage products that make claims of improving cognitive performance and memory.
The Expert Take
“Despite considerable advances in emergency and critical care management of TBI as well as decades of research on potential agents for neuroprotection or enhanced recovery, no effective pharmacotherapy has yet been identified,” said Robert L. Ruff, M.D., Ph.D., of the Cleveland VA Medical Center and Case Western Reserve University.
“It is unlikely that [the study’s findings] can be accounted for by limitations in the study design or conduct,” Ruff concludes. “The broader implication of the COBRIT [Citicoline Brain Injury Treatment Trial] study may be that no single therapeutic agent is likely to be sufficient to improve functional outcomes for patients with TBI.”
Ruff suggests that future studies with TBI patients include multiple treatment interventions and rehabilitation strategies “either as components of the intervention or standardized across study treatment groups.”
Source and Method
The COBRIT study included 1,213 patients with varying degrees of TBI at eight different trauma centers across the United States. Zafonte and his colleagues examined the effects of 2,000 milligrams of oral citicoline versus placebo, all first administered within 24 hours of the initial injuries, and all given as regular doses over the course of 90 days.
Results from the citicoline groups did not differ from the placebo groups after the 90-day administration period.
According to study authors, “The COBRIT study indicates that citicoline was not superior to placebo as an acute and post-acute therapy among participants with a broad range of severity of TBI. The worldwide use of citicoline should now be questioned.”
Many factors influence the efficacy of medical treatments following a TBI, including the immediacy of treatment, location and extent of injury, and other health problems that may affect the speed and completeness of recovery.
Citicoline is unlikely to harm patients because it is a substance already present in the brain, and its use will most likely continue as one aspect of drug therapy following a TBI, often in conjunction with other drugs.
In a 2000 study published in the Journal of Neurosurgery, citicoline produced positive results on secondary brain injuries such as brain edema (increase in water retention in the injured cortex).
In that study, “[Citicoline] demonstrated neuroprotective effects on brain edema and blood-brain barrier breakdown in the injured cortex and hippocampus after brain injury in lab rats” and “appeared to exert neuroprotective effects through different pathways.”
Another study from 2009 published in the Journal of Neurotrauma showed citicoline’s positive results in improving cerebral blood flow, memory, and focal motor deficits in those patients classified with “mild” TBIs.