Efectos adversos a nivel cardiovascular y neurológico asociados al consumo de modafinilo

  • Diego Felipe Sanabria Lozano UNIVERSIDAD DE SANTANDER
  • Nefi Helaman Rodriguez Londoño UNIVERSIDAD DE SANTANDER
  • Dikson Jair Logreira Gonzalez UNIVERSIDAD DE SANTANDER
  • Andrea Marquez-Barbosa UNIVERSIDAD DE SANTANDER
  • Orlando Jose Mejia-Restrepo UNIVERSIDAD DE SANTANDER

Resumen

Introducción: el modafinilo es un fármaco neuroestimulante utilizado principalmente para promover estados de vigilia atención y disminuir la fatiga ante ciertos comportamientos que propician la somnolencia diurna excesiva. Objetivo: identificar en la literatura científica los efectos adversos neurológicos y cardiovasculares causados por el consumo del modafinilo. Materiales y Métodos: revisión bibliográfica de los artículos encontrados entre los meses de abril y julio de 2019 en las bases de datos PUBMED, SCOPUS, DIALNET. 51 artículos superaron la evaluación de calidad metodológica y se incluyeron en la revisión. Resultados: se identificaron que los principales efectos adversos a nivel cardiovascular son la cardiomiopatía Tako-Tsubo y la taquicardia ventricular polimórfica, mientras que a nivel neurológico puede generar insomnio y distonías. Conclusiones: El consumo del modafinilo genera  epercusiones en las funciones cognitivas y cardiovasculares por lo cual no es aconsejable su uso a largo plazo en personas sanas. MÉD. UIS.2020;33(1):31-8.

Palabras clave: Taquicardia ventricular, Distonía, Modafinilo, Estimulantes del sistema nervioso central ., Trastornos del Sueño-Vigilia, Narcolepsia

Descargas

La descarga de datos todavía no está disponible.

Referencias

1. TEVA, GmbH. (2015) Professional information of Vigil®, Ulm, Germany.

2. TEVA, Pharmaceuticals Inc. (2015) Prescribing information of Provigil®, USA.

3. Radünz L, Reuter H, Andresen-Streichert H. Modafinil in forensic and clinical toxicology- case reports, analytics and literature. J Anal Toxicol. 2018; 42: 353-359. doi:10.1093/jat/bky008

4. De la Garza R, Zorick T, London E, Newton T. Evaluation of modafinil effects on cardiovascular, subjective, and reinforcing effects of methamphetamine in methamphetamine-dependent volunteers. Drug Alcohol Depend. 2010; 106:173-80. doi:10.1016/j.drugalcdep.2009.08.013 2010

5. Loewe D. metilfenidato y modafinilo: justicia igualitaria ypolíticas de acceso al mejoramiento cognitivo farmacológico. Acta Bioethica. 2017; I(23).

6. Gobierno Nacional de Colombia. www.odc.gov.co. [Online].; 2013. Acceso 10 de octubre de 2019. Disponible en: https:// www.unodc.org/documents/colombia/2014/Julio/Estudio_de_Consumo_UNODC.pdf

7. CONACE: Boletín Biblioteca Virtual. 2009. Recuperado de: http://www.bibliodrogas.cl/bibliodrogas/boletines/BOLETIN%20 ENERO%202009.pdf)

8. Robertson P, Hellriegel ET. Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003; 42: 123-137. doi. org/10.2165/00003088-200342020-00002

9. Volkow N, Fowler J, Logan J., et al. Effects of modafinil on dopamine and dopamine transporters in the male human brain: Clinical Implications. JAMA. 2009; 301: 1148- 1154.

10. Funayama T, Ikeda Y, Suzuki H. Modafinil augments brain activation associated with reward anticipation in the nucleus accumbens. Psychopharmacology. 2014; 231: 3217-28. doi:10.1007/s00213-014-3499-0.

11. Ballon J, Feifel D. A systematic review of modafinil: Potencial clinical uses and mechanism of action. J Clin Psychiatry 2006; 67: 554 – 566.

12. Minzenberg M, Carter C. Modafinil: A review of neurochemical actions and effects on cognition. Neuropsychopharmacology 2008; 33: 1477-1502. doi: 10.1038/sj.npp.1301534

13. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and metaanalyses: the PRISMA statement. PLoS Med. 2009; 6.doi:
10.1371/journal.pmed.1000097.

14. Biederman J, Swanson J. M, Wigal S, Kratochvil C. J, Boellner S. W, Earl C. Q, Jiang J, Greenhill L. Efficacy and safety of modafinil film-coated tablets in children and adolescents with
ttentiondeficit/hyperactivity disorder: results of a randomized, doubleblind, placebo-controlled, flexible-dose study. Pediatrics. 2005; 116: 777-784. doi: 10.1542/peds.2005-0617

15. Roth T, Schwartz J. R, Hirshkowitz M, Erman M. K, Dayno J. M, Arora S. Evaluation of the Safety of Modafinil for Treatment of Excessive Sleepiness. J Clin Sleep Med. 2007; 3: 595–602.

16. Spiller H. A, Borys D, Griffith J, Klein-Schwartz W, Aleguas A, Sollee D, Anderson D. A, Sawyer T. S. Toxicity from modafinil ingestion. Clinical Toxicology. 2009; 47: 153-156. doi:10.1080/15563650802175595

17. Olivares J, González-Hernández J. Eficacia del modafinilo como potenciador cognitivo en sujetos sanos. Rev. Memoriza.com. 2009; 2: 39-43.

18. Aytas Ö, Dílek H. Modafinil-induced psychosis: A case report. Noro Psikiyatr Ars. 2015; 52: 99-101. doi: 10.5152/npa.2015.7160

19. Younes D, Asch F. Tako‐Tsubo Cardiomyopathy Following Modafinil Use. J Clin Pharmacol. 2013; 53: 662-664. doi: 10.1002/ jcph.77

20. Binnenmars H, Idzerda H, Tan H, Linssen G. Ventricular tachycardia during treatment with modafinil for narcolepsy: a case report. International Journal of Clinical Medicine. 2012; 3: 513-517. doi: 0.4236/ijcm.2012.36092

21. Amariles, P. A comprehensive literature search: drugs as possibletriggers of takotsubo cardiomyopathy. Curr Clin Pharmacol. 2011; 6: 1–11. doi: 10.2174/157488411794941340

22. Kpaeyeh, J, Mar P, Raj V, Black B, Arnold A, Biaggioni I, Shibao C, Paranjape S, Dupont W, Robertson D, Raj S. Hemodynamic Profiles and Tolerability of Modafinil in the Treatment of POTS: a randomized placebo-controlled trial. J Clin Psychopharmacol. 2014; 34: 738-741. doi: 10.1097/JCP.0000000000000221

23. Taneja I, Diedrich A, Black B, Byrne D, Paranjape S, Robertson D. Modafinil elicits sympathomedullary activation. Hypertension. 2005; 45: 612-618. doi:10.1161/01.hyp.0000158267.66763

24. Rattray B, Martin K, Hewitt A, Cooper G, McDonald W. Effect of acute modafinil ingestion on cognitive an physical performance folloeing mental exertion. Hum Psychopharmacol Clin Exp. 2019; 34: e2700.

25. Kaplan S, Goehring E, Melamed-Gal S, Nguyen-Khoa B, Knebel H, Jones J. Modafinil and the risk of cardiovascular events: findings from three US claims databases. Pharmacoepidemiol Drug Saf. 2018; 27: 1-9. doi: 10.1002/pds.4642

26. Mo Y, Thomas M, Miano T, Stemp L, Bonacum J, Hutchins K, Karras G. Effect of Modafinil on cognitive function in intensive care unit patients: A retrospective cohort study. The Journal of Clinical Pharmacology. 2018; 58: 152-157. doi: 10.1002/jcph.1002

27. Scammell T, Estabrooke I, McCarthy M, Chemelli R, Yanagisawa M, Miller M, Saper C. Hypothalamic Arousal Regions Are Activated during Modafinil Induced Wakefulness. J Neurosci. 2000; 20:
620-8628. https://doi.org/10.1523/ JNEUROSCI.20-22-08620.2000

28. Gallopin T, Luppi P, Rambert F, Frydman A, Fort P. Effect of the Wake-Promoting Agent Modafinil on Sleep-Promoting Neurons from the Ventrolateral Preoptic Nucleus: an In Vitro Pharmacologic
tudy. Sleep. 2004; 27: 19-25.

29. Urbano F, Leznik E, Llinás R. Modafinil enhances thalamocortical activity by increasing neuronal electrotonic coupling. Proc Natl Acad Sci U S A. 2007; 104: 12554-12559. doi: 10.1073/ pnas.0705087104

30. Webb I, Pollock M, Mistlberger R. Modafinil [2-[(Diphenylmethyl) sulfinyl]acetamide] and Circadian Rhythms in Syrian Hamsters: Assessment of the Chronobiotic Potential of a Novel Alerting Compound. J Pharmacol Exp Ther. 2006; 317: 882-889. doi:10.1124/jpet.105.099010

31. Volkow N, Fowler J, Logan J, Alexoff D, Zhu W, Telang F, Wang G, Jayne M, Hooker J, Wong C, Hubbard B, Carter P, Warner D, King P, Shea C, Xu Y, Muench L, Apelskog-Torres K. Effects of
odafinil on Dopamine and Dopamine Transporters in the Male Human Brain. JAMA. 2009; 301: 1148-1154. doi: 10.1001/ jama.2009.351

32. Wisor J. Modafinil as a catecholaminergic agent: empirical evidence and unanswered questions. Front Neurol. 2013; 4: 139. doi: 10.3389/fneur.2013.00139

33. Mereu M, Chun L, Prisinzano T, ewman A, Katz J, Tanda G. The Unique Psychostimulant Profile of (±)-Modafinil: Investigation of Behavioral and Neurochemical Effects in Mice. 2017; 45: 67174. doi: 10.1111/ejn.13376

34. Burrows B, Watterson L, Johnson M, Olive M. Effects of Modafinil and R-Modafinil on Brain Stimulation Reward Thresholds: Implications for Their Use in the Treatment of Psychostimulant Dependence. J Drug Alcohol Res. 2015; 4: 235958. doi: 10.4303/ jdar/235958

35. Dias V, Rosa H, D’avila L, Vey L, Barcelos R, Burger M.Modafinil reduces amphetamine preference and prevents anxiety-like symptoms during drug withdrawal in young rats: Involvement of
opaminergic targets in VTA and striatum. Prog Neuropsychopharmacol Biol Psychiatry. 2019; 92: 199-206. doi: 10.1016/j.pnpbp.2019.01.007

36. Karabacak Y, Sase S, Aher Y, Sase A, Saroja S, Cicvaric A, Höger H, Berger M, Bakulev V, Sitte H, Leban J, Monje F, Lubec G. The effect of modafinil on the rat dopamine transporter and dopamine receptors D1-D3 paralleling cognitive enhancement in the radial arm maze. Front Behav Neurosci. 2015; 9: 215. doi: 10.3389/fnbeh.2015.00215

37. Fernández A, Mascayano F, Lips W, Painel A, Norambuena J, Madrid E. Effects of modafinil on attention performance, shortterm memory and executive function in university students. A randomized trial. Medwave. 2015; 15: 6166. doi: 10.5867/ medwave.2015.05.6166

38. Bellebaum C, Kuchinke L, Roser P. Modafinil alters decision making based on feedback history – a randomized placebocontrolled double blind study in human. J Psychopharmacol. 2017; 31: 243- 49. doi: 10.1177/0269881116668591

39. Turner D, Robbins T W, Clark L, Aron A R, Dowson J, Sahakian B J. Cognitive enhancing effects of modafinil in healthy volunteers. Psychopharmacology. 2003; 165: 260-269. doi
0.1007/s00213002-1250-8

40. Punzi M, Gili T, Petrosini L, Caltagirone C, Spalletta G, Sensi S L. Modafinil-induced changes in functional connectivity in the cortex and cerebellum of healthy elderly subjects. Frontiers in aging
euroscience. 2017; 9: 1-9. doi: 10.3389/ fnagi.2017.00085

41. Ghahremani D G, Tabibnia G, Monterosso J, Hellemann G, Poldrack R A, London E D. Effect of modafinil on learning and task-related brain activity in methamphetamine-dependent and healthy
ndividuals. Neuropsychopharmacology. 2011; 36: 950959. DOI:10.1038/npp.2010.233

42. Del Percio C, Derambure P, Noce G, Lizio R, Bartrés D, Blin O, Payoux P, et al. Sleep deprivation and nodafinil effect cortical sources of resting state electroencephalographic rhythms in healthy
oung adults. Clinical Neurophysiology. 2019; 130: 1488-1498.

43. Müller U, Rowe J B, Rittman T, Lewis C, Robbins T W, Sahakian B J. Effects of modafinil on non-verbal cognition, task enjoyment and creative thinking in healthy volunteers. Neuropharmacology. 2013; 64: 490-495. 44. Gilleen J, Michalopoulou P G, Reichenberg A, Drake R, Wykes T, Lewis S W, Kapur S. Modafinil combined with cognitive training is associated with improved learning in healthy volunteers- A randomised controlled trial. European Neuropsychopharmacology. 2014; 24: 529-539.

45. Repantis D, Schlattmann P, Laisney O, et al. Modafinil and methylphenidate for neuroanhancement in healthy individuals: A systematic review. Pharmacological Research 2010; 62: 187-206. 46.
ees J, Michalopoulou P G, Lewis S W, Preston S, Bamford C, Collier T, Kalpakidou A, Wykes T, Emsley R, Pandina G, Kapur S, Drake R J. Modafinil and cognitive enhancement in schizophrenia and
ealthy volunteers: the effects of test battery in a randomized controlled trial. Psychological Medicine. 2017; 47: 2358-2368.

47. Battleday R M, Brem A K. Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review. European Neuropsychopharmacology. 2015; 25: 1865-1881.

48. amada Y, Inagawa T, Sueyoshi K, Sugawara N, Ueda N, Omachi Y, et al. Social cognition deficits as a target of early intervention for psychoses: a systematic review. Frontiers of Psychiatry. 019;
0: 333.

49. Kaser M, Deakin J B, Michael A, Zapata C, Bansal R, Ryan D, Cormack F, Rowe J B, Sahakian B J. Modafinil improves episodic memory and working memory cognition in patients with remitted depression: a double-blind, randomized, placebo-controlled study. Biological Psychiatry: Cognitive Neuroscienceand Neuroimaging. 2017; 2: 115-122.

50. Ojeda N., Del Pino R., Ibarretxe-Bilbao N., Schretlen D. J., & Pena J. (2016). [Montreal Cognitive Assessment Test: Normalization and standardization for Spanish population]. Revista de Neurologia, 63, 488–496. [PubMed]
Publicado
2020-06-10
Sección
Revisión de tema