The effect of melatonin in functional heartburn: A randomized, placebo-controlled clinical trial

Patrick P. Basu, Hemanth Hempole, Nitya Krishnaswamy, Niraj J. Shah, Mark M. Aloysius

Columbia University College of Physicians and Surgeons, New York, USA.
James J. Peters VA Medical Center, Mount Sinai School of Medicine, New York, USA.
King’s County Hospital, New York, USA.
North Shore University Hospital at Forest Hills, Forest Hills, USA.

DOI: 10.4236/ojgas.2014.42010                

Abstract

Background: Melatonin is a safe and effective treatment for patients with functional pain and gastrointestinal disorders. Objective: To evaluate the efficacy and safety of melatonin for 3 months in patients with functional heartburn. Methods: In the randomized, placebo-controlled pilot study, patients with functional heartburn were treated with omeprazole 20 mg before breakfast and randomized to receive either melatonin 6 mg (n = 20), nortripty line 25 mg (n = 20), or placebo (n = 20) at bedtime for 3 months. Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQOL) scores were assessed at baseline and at the end of the study. Results: Melatonin improved GERD-HRQOL scores compared with nortriptyline (P = 0.0015) and placebo (P < 0.0001). Fewer adverse events were reported by patients receiving melatonin compared with those receiving nortriptyline or placebo. Conclusions: Melatonin was a safe and effective treatment for functional heartburn.

Keywords

Melatonin; Functional Heartburn; Nortriptyline; HRQOL

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Galmiche, J.P., Clouse, R.E., Balint, A., Cook, I.J., Kahrilas, P.J., Paterson, W.G., et al. (2006) Functional esophageal disorders. Gastroenterology, 130, 1459-1465.
[2]	Martinez, S.D., Malagon, I.B., Garewal, H.S., Cui, H. and Fass, R. (2003) Nonerosive reflux disease (NERD)-acid reflux and symptom patterns. Alimentary Pharmacology & Therapeutics, 17, 537-545.
[3]	Hershcovici, T. and Fass, R. (2010) Nonerosive Reflux Disease (NERD)—An update. Journal of Neurogastroenterology and Motility, 16, 8-21.
[4]	Lu, W.Z., Song, G.H., Gwee, K.A. and Ho, K.Y. (2008) The effects of melatonin on colonic transit time in normal controls and IBS patients. Digestive Diseases Sciences, 54, 1087-1093.
[5]	Raikhlin, N.T. and Kvetnoy, I.M. (1976) Melatonin and enterochromaffine cells. Acta Histochemica, 55, 19-24.
[6]	Bubenik, G.A. (2008) Thirty four years since the discovery of gastrointestinal melatonin. Journal of Physiology and Pharmacology, 59, 33-51.
[7]	Kasimay, O., Cakir, B., Devseren, E. and Yegen, B.C. (2005) Exogenous melatonin delays gastric emptying rate in rats: Role of CCK2 and 5-HT3 receptors. Journal of Physiology and Pharmacology, 56, 543-553.
[8]	Cho, C.H., Pang, S.F., Chen, B.W. and Pfeiffer, C.J. (1989) Modulating action of melatonin on serotonin-induced aggravation of ethanol ulceration and changes of mucosal blood flow in rat stomachs. Journal of Pineal Research, 6, 89-97.
[9]	Kato, K., Murai, I., Asai, S., Komuro, S., Matsuno, Y., Matsukawa, Y., et al. (1997) Central effect of melatonin against stress-induced gastric ulcers in rats. Neuroreport, 8, 2305-2309.
[10]	Pieri, C., Marra, M., Moroni, F., Recchioni, R. and Marcheselli, F. (1994) Melatonin: A peroxyl radical scavenger more effective than vitamin E. Life Science, 55, PL271-PL276.
[11]	Bubenik, G.A. (2002) Gastrointestinal melatonin: Localization, function, and clinical relevance. Digestive Diseases Sciences, 47, 2336-2348.
[12]	Mantovani, M., Kaster, M.P., Pertile, R., Calixto, J.B., Rodrigues, A.L. and Santos, A.R. (2006) Mechanisms involved in the antinociception caused by melatonin in mice. Journal of Pineal Research, 41, 382-389.
[13]	Ray, M., Mediratta, P.K., Mahajan, P. and Sharma, K.K. (2004) Evaluation of the role of melatonin in formalin-induced pain response in mice. Indian Journal of Medical Sciences, 58, 122-130.
[14]	Mickle, A., Sood, M., Zhang, Z., Shahmohammadi, G., Sengupta, J.N. and Miranda, A. (2010) Antinociceptive effects of melatonin in a rat model of post-inflammatory visceral hyperalgesia: A centrally mediated process. Pain, 149, 555-564.
[15]	Song, G.H., Leng, P.H., Gwee, K.A., Moochhala, S.M. and Ho, K.Y. (2005) Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: A randomised, double blind, placebo controlled study. Gut, 54, 1402-1407.
[16]	Esposito, E., Paterniti, I., Mazzon, E., Bramanti, P. and Cuzzocrea, S. (2010) Melatonin reduces hyperalgesia associated with inflammation. Journal of Pineal Research, 49, 321-331.
[17]	Wilhelmsen, M., Amirian, I., Reiter, R.J., Rosenberg, J. and Gogenur, I. (2011) Analgesic effects of melatonin: A review of current evidence from experimental and clinical studies. Journal of Pineal Research, 51, 270-277.
[18]	Ambriz-Tututi, M., Rocha-Gonzalez, H.I., Cruz, S.L. and Granados-Soto, V. (2009) Melatonin: A hormone that modulates pain. Life Science, 84, 489-498.
[19]	Gagnier, J.J. (2001) The therapeutic potential of melatonin in migraines and other headache types. Alternative Medicine Review, 6, 383-389.
[20]	Mozaffari, S., Rahimi, R. and Abdollahi, M. (2010) Implications of melatonin therapy in irritable bowel syndrome: A systematic review. Current Pharmaceutical Design, 16, 3646-3655.
[21]	Velanovich, V. (2007) The development of the GERD-HRQL symptom severity instrument. Diseases of the Esophagus, 20, 130-134.
[22]	Kandil, T.S., Mousa, A.A., El-Gendy, A.A. and Abbas, A.M. (2010) The potential therapeutic effect of melatonin in gastroesophageal reflux disease. BMC Gastroenterology, 10, 7.
[23]	Pereira Rde, S. (2006) Regression of gastroesophageal reflux disease symptoms using dietary supplementation with melatonin, vitamins and aminoacids: Comparison with omeprazole. Journal of Pineal Research, 41, 195-200.
[24]	Smith, B., Peterson, K., Fu, R., McDonagh, M. and Thakurta, S. (2011) Drug class review: Drugs for fibromyalgia: Final original report [Internet]. Oregon Health & Science University, Portland, 2011.
[25]	Jackson, J.L., Shimeall, W., Sessums, L., Dezee, K.J., Becher, D., Diemer, M., et al. (2010) Tricyclic antidepressants and headaches: Systematic review and meta-analysis. BMJ, 341, c5222.
[26]	Jackson, J.L., O’Malley, P.G., Tomkins, G., Balden, E., Santoro, J. and Kroenke, K. (2000) Treatment of functional gastrointestinal disorders with antidepressant medications: A meta-analysis. American Journal of Medicine, 108, 65-72.
[27]	Olden, K.W. (2005) The use of antidepressants in functional gastrointestinal disorders: New uses for old drugs. CNS Spectrums, 10, 891-896.
[28]	Chakravarty, S. and Rizvi, S.I. (2011) Day and night GSH and MDA levels in healthy adults and effects of different doses of melatonin on these parameters. International Journal of Cell Biology, 2011, 404591.
[29]	Pandi-Perumal, S.R., Srinivasan, V., Maestroni, G.J., Cardinali, D.P., Poeggeler, B. and Hardeland, R. (2006) Melatonin: Nature’s most versatile biological signal? Febs Journal, 273, 2813-2838.
[30]	Chassany, O., Holtmann, G., Malagelada, J., Gebauer, U., Doerfler, H. and Devault, K. (2008) Systematic review: Health-related quality of life (HRQOL) questionnaires in gastrooesophageal reflux disease. Alimentary Pharmacology & Therapeutics, 27, 1053-1070.
[31]	Barion, A. and Zee, P.C. (2007) A clinical approach to circadian rhythm sleep disorders. Sleep Medicine, 8, 566-577.
[32]	Wade, A.G., Ford, I., Crawford, G., McConnachie, A., Nir, T., Laudon, M., et al. (2010) Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: A randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety. BMC Medicine, 8, 51.
[33]	Zhdanova, I.V., Wurtman, R.J., Regan, M.M., Taylor, J.A., Shi, J.P. and Leclair, O.U. (2001) Melatonin treatment for age-related insomnia. The Journal of Clinical Endocrinology and Metabolism, 86, 4727-4730.