Stroke and head injury are neurological emergencies that often cause mortality, morbidity, and impaired life quality. Fast and accurate therapy is the key to successful management because there are about 2 million neuron deaths every minute. Therefore, neuroprotective and nootropic supplements, such as citicoline and piracetam, are often given to patients with acute ischemic stroke and head injuries. However, opinions regarding the administration of citicoline in stroke therapy and head injuries vary greatly.

Citicoline and Piracetam in Ischemic Stroke and Head Injuries

Decompression and reperfusion are definitive therapies for head injuries and ischemic strokes, but these are often too late to be carried out and cause extensive neurological damage. It makes many drugs that have neuroprotective effects developed and given. Piracetam and citicoline are often given in strokes and head injuries because they have a protective effect on neuron cells, improve nerve cell function, improve brain oxygenation, brain nutrition, improve brain perfusion, etc.

The therapeutic effects of Piracetam

Piracetam is a nootropic drug derived from gamma-aminobutyric acid (GABA). This drug has neuronal and vascular effects. Piracetam neuronal effects include increasing neuroplasticity, improving neurotransmission, neuroprotective, and anticonvulsant processes. Piracetam works by influencing serotonergic, noradrenergic, and glutamatergic neurotransmitters, especially in post-synapse receptors. This drug can also affect membrane fluidity and plasticity. Membrane fluidity and plasticity are important components in maintaining cell structure from damage (neuroprotection). Piracetam is beneficial in increasing glucose oxidation and producing ATP to protect nerve cells from hypoxia. Piracetam also has a vascular effect, which decreases vasospasm, reduces erythrocyte adhesion to the endothelium, increases brain vascularity and peripheral microcirculation. Piracetam also has an anticoagulation effect because it can reduce fibrinogen levels and von Willebrand factor. Vascular factors owned by piracetam are considered beneficial in the treatment of acute ischemic stroke.

The therapeutic effects of  Citicoline 

Citicoline is an exogenous cholinergic drug derived from cytidine-5-diphosphocholine (CDP-choline). CDP-Choline is one of the factors that play a role in cell membrane biosistence. CDP-choline plays a role in helping the synthesis of phosphatidylcholine. Phosphatidylcholine is a phospholipid needed for brain gray matter function. Citicoline increases acetylcholine synthesis, renews phospholipids in the brain, and minimizes brain ischemia by reducing free radicals (malondialdehyde). Therefore, citicoline considered to have neuroprotective and regenerative effects, so it is widely used in strokes and head injuries.

Studies Related to the Administration of Citicoline and Piracetam

Many studies exist regarding citicoline and piracetam's therapeutic effects, especially in acute ischemic strokes and head injuries.

One recent meta-analysis and systemic literature study on citicoline in head injuries among 1128 patients showed that citicoline administration in head injuries had no benefit. There was no difference in the Glasgow Outcome Scale (GOS) of patients given citicoline and not, especially in acute head injuries. Meanwhile, the benefits of citicoline in chronic head injuries are still questionable and require further research.
A meta-analysis of 12 previous clinical trials showed that citicoline could be useful in improving the Glasgow Coma Scale (GCS) when given to severe head injury patients (95% CI 1,302-2,530). Still, these results are very heterogeneous in cases of head injury.

In the case of ischemic stroke, the administration of citicoline is considered quite significant. Randomized controlled trial (RCT) clinical trials in 100 patients showed that patients are given citicoline experienced improved function in daily activities based on Barthel index at follow-up 1 month and 3 months after therapy (P <0.001 and P = 0.002 ). A meta-analysis of 10 RCTs also showed that citicoline administration was beneficial in improving the patient's neurological function, especially if given within 24 hours after the onset of the structure (OR 1.27 95% CI: 1.05-1.53). However, citicoline administration is not better than rtPA reperfusion. Other meta-analyzes assess that citicoline administration is not beneficial for reducing mortality (OR = 0.91, 95% CI: 0.07-1.09 with P = 0.3), but the administration of citicoline is safe.

Data on the use of piracetam for stroke and head injuries are quite limited. One of the literature shows that high-dose piracetam can improve aphasia on the stroke and improve clinical symptoms in trauma. A recent systematic, systemic literature review from Cochrane in 1002  patients showed that piracetam was not very useful in acute stroke therapy. Piracetam is associated with increased mortality, but this is not statistically significant (95% CI increase 81% - 5% decrease).

Considerations for Giving Citicoline and Piracetam

Administration of citicoline in head injuries or stroke generally shows improvement in patients' symptoms, although the benefits are limited and very dependent on the dose and time of administration. Available data indicate that therapeutic outcomes are better with citicoline administration. Giving citicoline is also safe to do and does not harm the patient. Citicoline is a supplement and cannot replace definitive therapies such as rtPA reperfusion or decompression. Piracetam is no better than citicoline, and in some cases, it can increase mortality.

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