Chemistry:Melatonin treatments for major depressive disorder

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Melatonin is a hormone typically associated with the regulation of circadian rhythms,[1][2] blood pressure,[2][3] seasonal reproduction[4] and ovarian[5] and retinal[6] physiologies. It is hypothesized that the use of melatonin to restore circadian rhythms can reduce depressive symptoms.[7][8][9]

Melatonin and its relationship with major depressive disorder

It has been estimated that between 8 and 12% of UK residents will experience some form of depression within any given year,[10] however statistically depression within women occurs at a higher prevalence, with 1 in 4 women suffering from clinical depression compared to 1 in 10 men.[11] While there are many forms of treatment available that involve pharmaceutical medications and psychological therapies, they are not always successful, which has resulted in research looking into alternative treatments. One such alternative treatment that is being explored is of that using the hormone melatonin.

Melatonin is a naturally occurring hormone that is synthesised and secreted during nighttime from the pineal gland, when melatonin receptors (M1 and M2) throughout the brain are activated.[12] Melatonin is typically associated with the regulation of circadian rhythms, blood pressure, seasonal reproduction and ovarian and retinal physiologies.[13] Major depressive disorders are frequently associated with circadian dis-regulations which have been known to bring on depressive behaviours and symptoms, disrupted sleep and poor regulation of hormones such as cortisol and serotonin,[14] which leads to the hypothesis that if circadian rhythms are restored (through melatonin based treatments) that depressive symptoms will reduce.

Recent studies have heavily suggested that the use of melatonin has been successful in treating symptoms of major depressive disorders, as discussed by Plesničar (2014).[15] This review article discusses new types of antidepressants (such as agomelatine) that target melatonergic systems (agonists of M1 and M2 receptors) and serotonergic systems, in particular 5-HT2C receptor antagonists. Administration of these new types of medications result in secretions of dopamine and norepinephrine neurotransmitters, while not significantly disrupting serotonin secretions.

One study that has been able to demonstrate small success in reducing depressive symptoms in treatment-resistant depression was that conducted by Dalton, Rotondi, Kennedy and Brown (2000).[16] Here, 8 adults between the ages of 22-73 were initially prescribed 5 mg of SR-Melatonin, which increased to 10 mg. Depressive symptoms were measured using the Hamilton Rating Scale for Depression (HRSD) both pre and post treatment. Overall patients presented a 20% reduction in their HRSD scores, with a range of 0-45%. Due to the small sample and no reduction of 50%, these results are not sufficient to suggest that melatonin treatments should be a replacement therapy for treatment-resistant depression and more common forms of depression. But the results do suggest that this alternative treatment can stabilise symptoms and/or be used in conjunction with other more successful treatments and medications.


  1. S. R. Pandi-Perumal; Daniel P. Cardinali (2007). Melatonin: From Molecules to Therapy. Nova Publishers. p. 633. ISBN 978-1-60021-121-8. 
  2. 2.0 2.1 William B. White (16 November 2007). Blood Pressure Monitoring in Cardiovascular Medicine and Therapeutics. Springer Science & Business Media. pp. 138–140. ISBN 978-1-59259-978-3. 
  3. Ellis D. Avner; William Harmon; Patrick Niaudet (2004). Pediatric Nephrology. Lippincott Williams & Wilkins. p. 1155. ISBN 978-0-7817-3545-2. 
  4. Hing-Sing Yu; Russel J. Reiter (21 December 1992). Melatonin: Biosynthesis, Physiological Effects, and Clinical Applications. CRC Press. p. 188. ISBN 978-0-8493-6900-1. 
  5. Peter C.K. Leung; Eli Y. Adashi (18 December 2003). The Ovary. Academic Press. p. 292. ISBN 978-0-08-054258-4. 
  6. Joseph Besharse; Dean Bok (19 April 2011). The Retina and its Disorders. Academic Press. p. 502. ISBN 978-0-12-382199-7. 
  7. Depression: New Insights for the Healthcare Professional: 2011 Edition. ScholarlyEditions. 9 January 2012. pp. 108–109. ISBN 978-1-4649-0024-2. 
  8. Barry, A. L.; Fuchs, P. C.; Jones, R. N. (1989). "Statistical criteria for selecting quality control limits for broth microdilution susceptibility tests with 39 different antimicrobial agents. Collaborative Antimicrobial Susceptibility Testing Group". Diagnostic Microbiology and Infectious Disease 12 (5): 413–20. doi:10.1016/0732-8893(89)90112-0. PMID 2612129. 
  9. Dolberg, O. T.; Hirschmann, S; Grunhaus, L (1998). "Melatonin for the treatment of sleep disturbances in major depressive disorder". The American Journal of Psychiatry 155 (8): 1119–21. doi:10.1176/ajp.155.8.1119. PMID 9699707. 
  10. Singleton et al. 2001
  11. National Institute For Clinical Excellence, 2003
  12. Hickie and Rogers, 2011
  13. Altun and Ugur-Altun, 2007
  14. de Bodinat et al. 2010
  15. Plesničar 2014
  16. Dalton, Rotondi, Kennedy and Brown 2000


  • Singleton, N., Bumpstead, R., O’Brien, M., Lee, A., & Meltzer, H. (2001). Psychiatric morbidity among adults living in private households.
  • National Institute for Health and Clinical Excellence. (2003). Depression, NICE Guideline, Second Consultation. London: NHS p. 19.
  • Hickie, I. B.; Rogers, N. L. (2011). "Novel melatonin-based therapies: potential advances in the treatment of major depression". The Lancet 378 (9791): 621–631. doi:10.1016/s0140-6736(11)60095-0. PMID 21596429. 
  • Altun, A.; Ugur-Altun, B. (2007). "Melatonin: therapeutic and clinical utilization". International Journal of Clinical Practice 61 (5): 835–845. doi:10.1111/j.1742-1241.2006.01191.x. PMID 17298593. 
  • de Bodinat, C.; Mocaër, E.; Renard, P.; Muñoz, C.; Millan, M. J. (2010). "Agomelatine, the first melatonergic antidepressant: discovery, characterization and development". Nature Reviews Drug Discovery 9 (8): 628–642. doi:10.1038/nrd3140. PMID 20577266. 
  • Plesničar, B. K. (2014). "Efficacy and tolerability of agomelatine in the treatment of depression". Patient Preference and Adherence 8: 603. 
  • Dalton, E. J.; Rotondi, D.; Levitan, R. D.; Kennedy, S. H.; Brown, G. (2000). "Use of slow-release melatonin in treatment-resistant depression". Journal of Psychiatry and Neuroscience 25 (1): 48. 

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