Comparison of the Melatonin Receptor Agonist Ramelteon and the Non-Benzodiazepine Hypnotic Zolpidem for Nocturia

Full-Text HTML Download Download as PDF (Size:268KB) PP. 293-298
DOI: 10.4236/oju.2013.38055    2,507 Downloads   4,027 Views  


To examine the efficacy of the melatonin receptor agonist ramelteon for nocturia, it was compared with zolpidem, a conventional non-benzodiazepine hypnotic. A total of 50 patients with nocturia (32 urinations/night) were enrolled. Subjects assigned odd numbers or even numbers were respectively prescribed 8 mg of ramelteon (n = 27; mean age: 75 years) or 5 mg of zolpidem (n = 23; mean age: 73 years) once a day before sleeping for 4 weeks. The daytime and nighttime frequencies of urination, as well as the results of global self-assessment by the patients, were compared between the two groups before and after 4 weeks of treatment. Both ramelteon and zolpidem caused a significant decrease of nocturia to about once per night after 4 weeks. The global self-assessment rating at 4 weeks was “good” or “fair” for more patients in the zolpidem group than in the ramelteon group, while the rating was “excellent” or “no change” for more patients in the ramelteon group. There were no serious adverse events in either group. Ramelteon was safe and effective for nocturia, achieving similar results to zolpidem. However, responders and non-responders to ramelteon were more clearly distinguished. Ramelteon might be effective for patients with sleep disturbance and nocturia because of low melatonin levels. Therefore, as diagnostic therapy for identification of nocturia caused by sleep disturbance and melatonin deficiency, ramelteon should be administered to patients who do not respond to alpha-1 antagonists and/or anticholinergic agents.

Cite this paper

H. Mukouyama, K. Sugaya, S. Nishijima, H. Naka, M. Sakumoto, T. Onaga, K. Kadekawa and K. Ashitomi, "Comparison of the Melatonin Receptor Agonist Ramelteon and the Non-Benzodiazepine Hypnotic Zolpidem for Nocturia," Open Journal of Urology, Vol. 3 No. 8, 2013, pp. 293-298. doi: 10.4236/oju.2013.38055.


[1] M. H. Blanker, A. M. Bohnen, F. P. Groeneveld, R. M. Bernsen, A. Prins and J. L. Ruud Bosch, “Normal Voiding Patterns and Determinants of Increased Diurnal and Nocturnal Voiding Frequency in Elderly Men,” Journal of Urology, Vol. 164, No. 4, 2000, pp. 1201-1205.
[2] M. H. Blanker, R. M. Bernsen, J. L. Bosch, S. Thomas, F. P. Groeneveld, A. D. Prins and A. M. Bohnen, “Relation between Nocturnal Voiding Frequency and Nocturnal Urine Production in Older Men,” Urology, Vol. 60, No. 4, 2002, pp. 612-616.
[3] K. Yoshimura, “Correlates for Nocturia: A Review of Epidemiological Studies,” Journal of Urology, Vol. 19, No. 4, 2012, pp. 317-329.
[4] J. P. Weiss, J. G. Blaivas, D. S. Stember and M. M. Brooks, “Nocturia in Adults. Etiology and Classification,” Neurourology and Urodynamics, Vol. 17, No. 5, 1998, pp. 467-472.<467::AID-NAU2>3.0.CO;2-B
[5] J. P. Weiss, J. G. Blaivas, D. S. Stember and D. C. Chaikin, “Evaluation of the Etiology of Nocturia in Men: The Nocturia and Nocturnal Bladder Capacity Indices,” Neurourology and Urodynamics, Vol. 18, No. 6, 1999, pp. 559-565.<559::AID-NAU6>3.0.CO;2-D
[6] K. Yoshimura, N. Terada, Y. Matsui, A. Terai, N. Kinukawa and Y. Arai, “Prevalence of and Risk Factors for Nocturia: Analysis of a Health Screening Program,” International Journal of Urology, Vol. 11, No. 5, 2004, pp. 282-287.
[7] L. W. Gourova, C. van de Beek, M. G. Spigt, F. H. Nieman and P. E. van Kerrebroeck, “Predictive Factors for Nocturia in Elderly Men: A Cross-Sectional Study in 21 General Practices,” BJU International, Vol. 97, No. 3, 2006, pp. 528-532. 2006.06029.x
[8] K. Sugaya S. Nishijima, M. Miyazato, K. Kadekawa and Y. Ogawa, “Effects of Melatonin and Rilmazafone on Nocturia in the Elderly,” Journal of International Medical Research, Vol. 35, No. 5, 2007, pp. 685-691.
[9] O. Nishizawa, I. Araki, O. Ishizuka, N. Uchimura, H. Oh-oka, S. Ozono, H. Kakizaki, M. Kasahara, M. Gotoh, R. Sakakibara, H. Shinbo, K. Sugaya, Y. Suzuki, A. Sone, M. Takei, M. Takeda, A. Hirayama, Y. Homma, O. Yamaguchi, T. Yamanishi, O. Yokoyama and M. Yoshida, “Clinical Guidelines for Nocturia,” International Journal of Urology, Vol. 17, No. 5, 2010, pp. 379-409.
[10] G. Zammit, S. Wang-Weigand, M. Rosenthal and X. Peng, “Effect of Ramelteon on Middle-of-the-Night Balance in Older Adults with Chronic Insomnia,” Journal of Clinical Sleep Medicine, Vol. 15, No. 1, 2009, pp. 34-40.
[11] S. R. Pandi-Perumal, V. Srinivasan, D. W. Spence, A. Moscovitch, R. Hardeland, G. M. Brown and D. P. Cardinali, “Ramelteon: A Review of Its Therapeutic Potential in Sleep Disorders,” Advances in Therapy, Vol. 26, No. 6, 2009, pp. 613-626.
[12] Y. S. Song and J. H. Ku, “Zolpidem Pharmacotherapy Combined with Alpha-Blocker Therapy for Nocturia Unresponsive to Alpha-Blocker Monotherapy in Men with Lower Urinary Tract Symptoms: A Preliminary Study,” International Urology and Nephrology, Vol. 39, No. 4, 2007, pp. 1147-1152.
[13] P. Abrams, L. Cardozo, M. Fall, D. Griffiths, P. Rosier, U. Ulmsten, P. Van Kerrebroeck, A. Victor and A. Wein, “Standardisation Sub-Committee of the International Continence Society: The Standardisation of Terminology in Lower Urinary Tract Function: Report from the Standardisation Sub-Committee of the International Continence Society,” Urology, Vol. 61, No. 1, 2003, pp. 37-49.
[14] K. Sugaya, S. Nishijima, M. Oda, T. Owan, M. Miyazato and Y. Ogawa, “Biochemical and Body Composition Analysis of Nocturia in the Elderly,” Neurourology and Urodynamics, Vol. 27, No. 3, 2008, pp. 205-211.
[15] K. Fujikawa, M. Kasahara, Y. Matsui and H. Takeuchi, “Human Atrial Natriuretic Peptide Is a Useful Criterion in Treatment of Nocturia,” Scandinavian Journal of Urology and Nephrology, Vol. 35, No. 4, 2001, pp. 310-313.
[16] N. Shimizu, M. Nozawa, Y. Itami, Y. Yamamoto and Y. Hayashi, “A Study on Efficacy of Ramelteon in Patients with Insomnia and Nocturia,” Japanese Journal of Urological Surgery, Vol. 24, 2011, pp. 1473-1479.
[17] K. Sugaya, S. Nishijima, M. Miyazato, T. Owan, Y. Oshiro, A. Uchida, S. Hokama and Y. Ogawa, “Investigation of Biochemical Factors Related to Non-Bothersome Nocturnal Urination,” BioMed Research, Vol. 28, No. 4, 2007, pp. 458-460.
[18] J. H. Han, I. H. Chang, S. C. Myung, M. Y. Lee, W. Y. Kim, S. Y. Lee, S. W. Lee and K. D. Kim, “A Novel Pathway Underlying the Inhibitory Effects of Melatonin on Isolated Rat Urinary Bladder Contraction,” The Korean Journal of Physiology & Pharmacology, Vol. 16, No. 1, 2012, pp. 37-42.
[19] Y. Matsuta, A. Yusup, K. Tanase, H. Ishida, H. Akino and O. Yokoyama, “Melatonin Increases Bladder Capacity via GABAergic System and Decreases Urine Volume in Rats,” Journal of Urology, Vol. 184, No. 1, 2010, pp. 386-391.

comments powered by Disqus

Copyright © 2017 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.