Citiholin u neurologiji i psihijatriji:

Aleksandra Pavlovic; Dragan  Pavlovic; Sanja Totic; Maja Lackovic; Marija Bozic; Jelena Djordjevic

doi:10.5937/engrami45-44417

Aleksandra Pavlovic Faculty of Special Education and Rehabilitation, University of Belgrade
Dragan Pavlovic Poliklinika Antamedica, Beograd, Srbija
Sanja Totic Medicinski fakultet u Beogradu, Univerzitet u Beogradu, Beograd, Srbija Klinika za psihijatriju, Univerzitetski klinički centar Srbije, Beograd, Srbija
Maja Lackovic Medicinski fakultet u Beogradu, Univerzitet u Beogradu, Beograd, Srbija Klinika za psihijatriju, Univerzitetski klinički centar Srbije, Beograd, Srbija
Marija Bozic Medicinski fakultet u Beogradu, Univerzitet u Beogradu, Beograd, Srbija Klinika za oftalmologiju, Univerzitetski klinički centar Srbije, Beograd, Srbij
Jelena Djordjevic Fakultet medicinskih nauka, Univerzitet u Kragujevcu, Kragujevac, Srbija Klinika za neurologiju i psihijatriju za decu i omladinu, Beograd, Srbija

DOI: https://doi.org/10.5937/engrami45-44417

Keywords: Citicoline, acethylcholine, stroke, dementia, cognition, psychiatry

Abstract

Citicoline is a supplement-nootropic with potential applications in treating various neurological, psychiatric, and other conditions. There is experimental and clinical evidence of the benefits of citicoline in individuals after stroke, traumatic brain injury, and cognitive decline of various etiologies. Preclinical studies suggest that citicoline has neuroprotective and neurorestorative effects, which can be explained by its antioxidant, anti-inflammatory, and metabolic actions. Citicoline is necessary for the synthesis and stabilization of biological membranes, improves mitochondrial function, and is crucial in the synthesis of acetylcholine and other neurotransmitters in the central nervous system. No specific drugs are available for treating cognitive sequelae of stroke and traumatic brain injury. In experimental and clinical studies, citicoline has shown a safe profile with positive clinical effects on overall cognitive abilities, attention, executive function, and mood. There are also positive results of its use in patients with neurodegenerative diseases, although on a small number of participants. In psychiatry, the beneficial effects of citicoline on depression, negative symptoms of schizophrenia, and substance use disorders are described. This review provides an overview of the mechanisms of action of citicoline and summarizes the published research on its use in neurology and psychiatry.

References

Synoradzki K, Grieb P. Citicoline: A Superior Form of Choline? Nutrients 2019;11(7):1569. doi:10.3390/nu11071569. PMID:31336819.

Pavlović DM, Pavlović AM. Više kortikalne funkcije. Beograd. Orion Art; 2016.

Abdel-Aziz N, Moustafa EM, Saada HN. The impact of citicoline on brain injury in rats subjected to head irradiation. Environ Sci Pollut Res Int 2021;28(8):9742-52. doi: 10.1007/s11356-020-11101-7. PMID: 33155111.

Jasielski P, Piędel F, Piwek M, Rocka A, Petit V, Rejdak K. Application of Citicoline in Neurological Disorders: A Systematic Review. Nutrients 2020;12(10):3113. doi: 10.3390/nu12103113. PMID: 33053828.

Abdolmaleki A, Moghimi A, Ghayour MB, Rassouli MB. Evaluation of neuroprotective, anticonvulsant, sedative and anxiolytic activity of citicoline in rats. Eur J Pharmacol 2016 15;789:275-9. doi: 10.1016/j.ejphar.2016.07.048. PMID: 27475676.

Faiq MA, Wollstein G, Schuman JS, Chan KC. Cholinergic nervous system and glaucoma: From basic science to clinical applications. Prog Retin Eye Res 2019;72:100767. doi: 10.1016/j.preteyeres.2019.06.003. PMID: 31242454.

Al-Kuraishy HM, Al-Buhadily AK, Al-Gareeb AI, et al. Citicoline and COVID-19: vis-à-vis conjectured. Naunyn Schmiedebergs Arch Pharmacol 2022;395(12):1463-75. doi: 10.1007/s00210-022-02284-6. PMID: 36063198.

Cho JH, Kim JY. Efficacy and safety of oral citicoline in acute ischemic stroke: drug surveillance study in 4,191 cases. Methods Find Exp Clin Pharmaco 2009;31(03):171–6. doi: 10.1358/mf.2009.31.3.1364241. PMID: 19536360.

Adibhatla RM, Hatcher JF, Dempsey RJ. Effects of citicoline on phospholipid and glutathione levels in transient cerebral ischemia. Stroke 2001;32(10):2376-81. doi: 10.1161/hs1001.096010. PMID: 11588329.

Adibhatla RM, Hatcher JF. Citicoline mechanisms and clinical efficacy in cerebral ischemia. J Neurosci Res 2002;70(2):133-9. doi: 10.1002/jnr.10403. PMID: 12271462.

Gutiérrez-Fernández M, Rodríguez-Frutos B, Fuentes B et al. CDP-choline treatment induces brain plasticity markers expression in experimental animal stroke. Neurochem Int 2012;60(03):310–7. doi: 10.1016/j.neuint.2011.12.015. PMID: 22226841.

Piamonte BLC, Espiritu AI, Anlacan VMM. Effects of Citicoline as an Adjunct Treatment for Alzheimer's Disease: A Systematic Review. J Alzheimers Dis 2020;76(2):725-32. doi: 10.3233/JAD-200378. PMID: 32538854.

Krupinski J, Ferrer I, Barrachina M, Secades JJ, Mercadal J, Lozano R. CDP-choline reduces pro-caspase and cleaved caspase-3 expression, nuclear DNA fragmentation, and specific PARP-cleaved products of caspase activation following middle cerebral artery occlusion in the rat. Neuropharmacology 2002;42(6):846-54. doi: 10.1016/s0028-3908(02)00032-1. PMID: 12015211.

Ma X, Zhang H, Pan Q, et al. Hypoxia/Aglycemia-induced endothelial barrier dysfunction and tight junction protein downregulation can be ameliorated by citicoline. PLoS One 2013;8(12):e82604. doi: 10.1371/journal.pone.0082604. PMID: 24358213.

Hurtado O, Moro MA, Cárdenas A, et al. Neuroprotection afforded by prior citicoline administration in experimental brain ischemia: effects on glutamate transport. Neurobiol Dis 2005;18(2):336-45. doi: 10.1016/j.nbd.2004.10.006. PMID: 15686962.

Secades JJ. Role of citicoline in the management of traumatic brain injury. Pharmaceuticals (Basel) 2021;14(5):410. doi: 10.3390/ph14050410. PMID: 33926011.

Martynov MY, Gusev EI. Current knowledge on the neuroprotective and neuroregenerative properties of citicoline in acute ischemic stroke. J Exp Pharmacol 2015;7:17-28. doi: 10.2147/JEP.S63544. PMID: 27186142.

Grieb P. Neuroprotective properties of citicoline: facts, doubts and unresolved issues. CNS Drugs 2014;28(3):185-93. doi: 10.1007/s40263-014-0144-8. PMID: 24504829.

Alshammari D. Role of citicoline in modulation of angiogenesis and apoptosis in vascular/human brain microvessel endothelial cells. Ph. D. Thesis. School of Healthcare Sciences Manchester Metropolitan University; 2014.

Warach S, Pettigrew LC, Dashe JF, et al. Effect of citicoline on ischemic lesions as measured by diffusion-weighted magnetic resonance imaging. Citicoline 010 Investigators. Ann Neurol 2000;48(5):713-22. PMID: 11079534.

Dávalos A, Alvarez-Sabín J, Castillo J, et al; International Citicoline Trial on acUte Stroke (ICTUS) trial investigators. Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial). Lancet 2012;380(9839):349-57. doi: 10.1016/S0140-6736(12)60813-7. PMID: 22691567.

Mehta A, Mahale R, Buddaraju K, Javali M, Acharya P, Srinivasa R. Efficacy of Neuroprotective Drugs in Acute Ischemic Stroke: Is It Helpful? J Neurosci Rural Pract 2019;10(4):576-81. doi: 10.1055/s-0039-1700790. PMID: 31831974.

Ghosh S, Das SK, Nath T, Ghosh KC, Bhattacharyya R, Mondal GP. The effect of citicoline on stroke: A comparative study from the Eastern part of India. Neurol India 2015;63(5):697-701. doi: 10.4103/0028-3886.166538. PMID: 26448227.

Martí-Carvajal AJ, Valli C, Martí-Amarista CE, Solà I, Martí-Fàbregas J, Bonfill Cosp X. Citicoline for treating people with acute ischemic stroke. Cochrane Database Syst Rev 2020;8(8):CD013066. doi: 10.1002/14651858.CD013066.pub2. PMID: 32860632.

Secades JJ, Alvarez-Sabín J, Rubio F, Lozano R, Dávalos A, Castillo J; Trial Investigators. Citicoline in intracerebral haemorrhage: a double-blind, randomized, placebo-controlled, multi-centre pilot study. Cerebrovasc Dis 2006;21(5-6):380-5. doi: 10.1159/000091547. PMID: 16490951.

Bonvicini M, Travaglini S, Lelli D, Antonelli Incalzi R, Pedone C. Is Citicoline Effective in Preventing and Slowing Down Dementia?-A Systematic Review and a Meta-Analysis. Nutrients 2023;15(2):386. doi: 10.3390/nu15020386. PMID: 36678257.

Verdelho A, Biessels GJ, Chabriat H, et al. Cerebrovascular disease in patients with cognitive impairment: A white paper from the ESO dementia committee – A practical point of view with suggestions for the management of cerebrovascular diseases in memory clinics. Eur Stroke J 2021a;6(2):111-119. doi: 10.1177/2396987321994294.

Mijajlović MD, Pavlović A, Brainin M, et al. Post-stroke dementia - a comprehensive review. BMC Med 2017;15(1):11.

Verdelho A, Wardlaw J, Pavlovic A, et al. Cognitive impairment in patients with cerebrovascular disease: A white paper from the ESO Dementia Committee. A practical point of view for stroke clinicians from the ESO Dementia Committee. Eur Stroke J 2021b;6(1):5-17. doi: 10.1177/23969873211000258. PMID: 33817330.

Alvarez-Sabín J, Ortega G, Jacas C, et al. Long-term treatment with citicoline may improve poststroke vascular cognitive impairment. Cerebrovasc Dis 2013;35(2):146-54. doi: 10.1159/000346602. PMID: 23406981.

Pavlović A, Pavlović D, Aleksić V, Šternić N. Vaskulna demencija: istine i kontroverze. Srp Arh Celok Lek 2013;141(3-4):247-55. doi: 10.2298/sarh1304247p. PMID: 23745353.

Gareri P, Cotroneo AM, Orsitto G, Putignano S. The Importance of Citicoline in Combined Treatment in Dementia: What did the Citimem Study Teach us? Rev Recent Clin Trials 2021;16(2):126-30. doi: 10.2174/1574887115999201126205538. PMID: 33243132.

Castagna A, Manzo C, Fabbo A, Lacava R, Ruberto C, Ruotolo G. The CITIMERIVA Study: CITIcoline plus MEmantina plus RIVAstigmine in Older Patients Affected with Alzheimer's Disease. Clin Drug Investig 2021;41(2):177-82. doi: 10.1007/s40261-020-00996-2. Erratum in: Clin Drug Investig. 2021 Apr;41(4):413. PMID: 33484469.

Nakazaki E, Mah E, Sanoshy K, Citrolo D, Watanabe F. Citicoline and memory function in healthy older adults: A randomized, double-blind, placebo-controlled clinical trial. J Nutr 2021;151(8):2153-60. doi: 10.1093/jn/nxab119. PMID: 33978188.

Que DS, Jamora RDG. Citicoline as Adjuvant Therapy in Parkinson's Disease: A Systematic Review. Clin Ther 2021;43(1):e19-e31. doi: 10.1016/j.clinthera.2020.11.009. PMID: 33279231.

Pavlovic D, Pekic S, Stojanovic M, Popovic V. Traumatic brain injury: neuropathological, neurocognitive and neurobehavioral sequelae. Pituitary 2019;22(3):270-82. doi: 10.1007/s11102-019-00957-9. PMID: 30929221.

Puffer RC, Yue JK, Mesley M, et al. Recovery Trajectories and Long-Term Outcomes in Traumatic Brain Injury: A Secondary Analysis of the Phase 3 Citicoline Brain Injury Treatment Clinical Trial. World Neurosurg 2019;125:e909-e915. doi: 10.1016/j.wneu.2019.01.207. PMID: 30763755.

Arcadi FA, Corallo F, Torrisi M, et al. Role of citicoline and choline in the treatment of post-stroke depression: an exploratory study. J Int Med Res 2021;49(11):3000605211055036. doi: 10.1177/03000605211055036. PMID: 34727752.

Pavlović DM. Ortomolekularna neurologija i psihijatrija. Kako pobolјšati rad mozga uz pomoć suplemenata/mikronutrijenata. Beograd. OrionArt; 2019.

Al-Kuraishy HM, Al-Gareeb AI. Citicoline Improves Human Vigilance and Visual Working Memory: The Role of Neuronal Activation and Oxidative Stress. Basic Clin Neurosci 2020;11(4):423-32. doi: 10.32598/bcn.11.4.1097.1. PMID: 33613880.

Silveri MM, Dikan J, Ross AJ, et al. Citicoline enhances frontal lobe bioenergetics as measured by phosphorus magnetic resonance spectroscopy. NMR Biomed 2008;21(10):1066-75. doi: 10.1002/nbm.1281. PMID: 18816480.

Ghajar A, Gholamian F, Tabatabei-Motlagh M, et al. Citicoline (CDP-choline) add-on therapy to risperidone for treatment of negative symptoms in patients with stable schizophrenia: A double-blind, randomized placebo-controlled trial. Hum Psychopharmacol 2018;33(4):e2662. doi: 10.1002/hup.2662. PMID: 29901250.

Jeong H, Yoon S, Sung YH, et al. Effects of cytidine-5'-diphosphate choline on gray matter volumes in methamphetamine-dependent patients: A randomized, double-blind, placebo-controlled study. J Psychiatr Res 2021;143:215-21. doi: 10.1016/j.jpsychires.2021.09.006. PMID: 34507102.

Lassi DLS, Malbergier A, Negrão AB, Florio L, De Aquino JP, Castaldelli-Maia JM. Pharmacological Treatments for Cocaine Craving: What Is the Way Forward? A Systematic Review. Brain Sci 2022;12(11):1546. doi: 10.3390/brainsci12111546. PMID: 36421870.

Fischler PV, Soyka M, Seifritz E, Mutschler J. Off-label and investigational drugs in the treatment of alcohol use disorder: A critical review. Front Pharmacol 2022;13:927703. doi: 10.3389/fphar.2022.927703. PMID: 36263121.

Skripuletz T, Manzel A, Gropengießer K, et al. Pivotal role of choline metabolites in remyelination. Brain 2015;138(Pt 2):398-413. doi: 10.1093/brain/awu358. PMID: 25524711.

Aslan E, Kocaeli H, Bekar A, Tolunay S, Ulus IH. CDP-choline and its endogenous metabolites, cytidine and choline, promote the nerve regeneration and improve the functional recovery of injured rat sciatic nerves. Neurol Res 2011;33(7):766-73. doi: 10.1179/1743132811Y.0000000004. PMID: 21756558.

Gundogdu EB, Bekar A, Turkyilmaz M, Gumus A, Kafa IM, Cansev M. CDP-choline modulates matrix metalloproteinases in rat sciatic injury. J Surg Res 2016;200(2):655-63. doi: 10.1016/j.jss.2015.10.003. PMID: 26521098.

Kanat O, Bagdas D, Ozboluk HY, Gurun MS. Preclinical evidence for the antihyperalgesic activity of CDP-choline in oxaliplatin-induced neuropathic pain. J BUON 2013;18(4):1012-8. Erratum in: J BUON. 2014 Jan-Mar;19(1):323. Kanat, D [corrected to Kanat, O]. PMID: 24344031.

Bagdas D, Sonat FA, Hamurtekin E, Sonal S, Gurun MS. The antihyperalgesic effect of cytidine-5'-diphosphate-choline in neuropathic and inflammatory pain models. Behav Pharmacol 2011p;22(5-6):589-98. doi: 10.1097/FBP.0b013e32834a1efb. PMID: 21836465.

Gandolfi S, Marchini G, Caporossi A, Scuderi G, Tomasso L, Brunoro A. Cytidine 5'-Diphosphocholine (Citicoline): Evidence for a Neuroprotective Role in Glaucoma. Nutrients 2020;12(3):793. doi: 10.3390/nu12030793. PMID: 32197303.

Rossetti L, Iester M, Tranchina L, et al. Can Treatment With Citicoline Eyedrops Reduce Progression in Glaucoma? The Results of a Randomized Placebo-controlled Clinical Trial. J Glaucoma 2020;29(7):513-20. doi: 10.1097/IJG.0000000000001565. PMID: 32541370.

Gareri P, Castagna A, Cotroneo AM, Putignano S, De Sarro G, Bruni AC. The role of citicoline in cognitive impairment: pharmacological characteristics, possible advantages, and doubts for an old drug with new perspectives. Clin Interv Aging 2015;10:1421-9. doi: 10.2147/CIA.S87886. Erratum in: Clin Interv Aging. 2015;10:1625. PMID: 26366063.

Citicoline in neurology and psychiatry

Citicoline in medicine

Abstract

References