• Witchakorn Trisukon Department of Psychiatry and Neurology, Phramongkutklao Hospital
  • Fadhil A-hamad Saleh-arong Division of Nephrology, Department of Medicine, Phramongkutklao hospital
  • Bancha Satirapoj Division of Nephrology, Department of Medicine, Phramongkutklao hospital
  • Nattaphon Chokemaitree Department of Psychiatry and Neurology, Phramongkutklao hospital
Keywords: Chronic kidney diseases, Depression, Sleep quality, Clinical trial, Agomelatine, Sertraline


Background: Depression is a common comorbid disease among patients with chronic kidney disease (CKD). Insomnia, a symptom related to these conditions, negatively impacts disease progression and quality of life. Unfortunately, no consensus has been reached concerning treatment guidelines and choices of antidepressants suitable for treating depression among patients with CKD.

Objectives: The study aimed to evaluate the efficacy to sleep quality, depressive symptoms, safety and tolerability of agomelatine and sertraline in treating major depressive disorder among patients with CKD.

Methods: A double-blinded randomized controlled trial was conducted in the Nephrology Unit, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand. Patients with CKD and a diagnosis of major depressive disorder were randomly assigned to receive once-daily, fixed-dose sertraline 50 mg/d and agomelatine 25 mg/d. The treatment outcome was evaluated at 4 and 8 weeks. The Pittsburgh Sleep Quality Index score (PSQI) was used to measure sleep quality, and the Hamilton rating scale of depression, the Thai version (Thai HRSD-17), was used to evaluate depressive symptoms. Other outcomes included overall quality of life, side effects and tolerability.

Results: Agomelatine significantly improved sleep quality based on PSQI score throughout the observed period (p=0.002). Also, agomelatine more efficiently reduced depressive symptoms than sertraline (p=<0.001). In addition, patients receiving agomelatine as a treatment could continue their medication, whereas 52% of patients receiving sertraline discontinued because of side effects.

Conclusion: Agomelatine significantly improved sleep quality and tolerated well compared to sertraline.

Trial registration: thaiclinicaltrials.org ID: TCTR20200319005


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American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5(TM)). 5th ed., American Psychiatric Publishing, 2013. https://doi.org/10.1176/appi.books.9780890425596

Hedayati SS, Minhajuddin AT, Afshar M, Toto RD, Trivedi MH, Rush AJ. Association between major depressive episodes in patients with chronic kidney disease and initiation of dialysis, hospitalization, or death. JAMA 2010; 303: 1946-53. https://doi.org/10.1001/jama.2010.619 PMid:20483971 PMCid:PMC3217259

Lee YJ, Kim MS, Cho S, Kim SR. Association of depression and anxiety with reduced quality of life in patients with predialysis chronic kidney disease. Int J Clin Pract 2013; 67: 363-8. https://doi.org/10.1111/ijcp.12020 PMid:23521328

Tsai YC, Chiu YW, Hung CC, Hwang SJ, Tsai JC, Wang SL, Lin MY, Chen HC. Association of symptoms of depression with progression of CKD. Am J Kidney Dis 2012; 60: 54-61. https://doi.org/10.1053/j.ajkd.2012.02.325 PMid:22495469

Kop WJ, Seliger SL, Fink JC, Katz R, Odden MC, Fried LF, et al. Longitudinal association of depressive symptoms with rapid kidney function decline and adverse clinical renal disease outcomes. Clin J Am Soc Nephrol 2011; 6: 834-44. https://doi.org/10.2215/CJN.03840510 PMid:21393483 PMCid:PMC3069377

Chiang HH, Guo HR, Livneh H, Lu MC, Yen ML, Tsai TY. Increased risk of progression to dialysis or death in CKD patients with depressive symptoms: A prospective 3-year follow-up cohort study. J Psychosom Res 2015; 79: 228-32. https://doi.org/10.1016/j.jpsychores.2015.01.009 PMid:25659439

Cukor D, Fruchter Y, Ver Halen N, Naidoo S, Patel A, Saggi SJ. A preliminary investigation of depression and kidney functioning in patients with chronic kidney disease. Nephron Clin Pract 2012; 122: 139-45. https://doi.org/10.1159/000349940 PMid:23736810

Yamamoto R, Shinzawa M, Isaka Y, Yamakoshi E, Imai E, Ohashi Y, et al. Sleep Quality and Sleep Duration with CKD are Associated with Progression to ESKD. Clin J Am Soc Nephrol 2018; 13: 1825-832. https://doi.org/10.2215/CJN.01340118 PMid:30442866 PMCid:PMC6302324

Fang H, Tu S, Sheng J, Shao A. Depression in sleep disturbance: A review on a bidirectional relationship, mechanisms and treatment. J Cell Mol Med 2019; 23: 2324-332. https://doi.org/10.1111/jcmm.14170 PMid:30734486 PMCid:PMC6433686

Furukawa TA, Streiner DL, Young LT. Is antidepressant-benzodiazepine combination therapy clinically more useful? A meta-analytic study. J Affect Disord 2001; 65: 173-7. https://doi.org/10.1016/S0165-0327(00)00254-8 PMid:11356241

Rizvi SJ, Sproule BA, Gallaugher L, McIntyre RS, Kennedy SH. Correlates of benzodiazepine use in major depressive disorder: The effect of anhedonia. J Affect Disord 2015; 187: 101-5. https://doi.org/10.1016/j.jad.2015.07.040 PMid:26331683

Winkelmayer WC, Mehta J, Wang PS. Benzodiazepine use and mortality of incident dialysis patients in the United States. Kidney Int 2007; 72: 1388-93. https://doi.org/10.1038/sj.ki.5002548 PMid:17851463

Fukuhara S, Green J, Albert J, Mihara H, Pisoni R, Yamazaki S, et al. Symptoms of depression, prescription of benzodiazepines, and the risk of death in hemodialysis patients in Japan. Kidney Int 2006; 70: 1866-72. https://doi.org/10.1038/sj.ki.5001832 PMid:17021611

Manikandan S. Agomelatine: A novel melatonergic antidepressant. J Pharmacol Pharmacother 2010; 1: 122-3. Erratum in: J Pharmacol Pharmacother 2011; 2: 58. https://doi.org/10.4103/0976-500X.72369 PMid:21350627 PMCid:PMC3043343

Talas A, Cerit C, Aslan EA. Comparison of the Effects of Sertraline and Agomelatine on Sleep Quality, Sexual Functioning and Metabolic Parameters in Patients With Major Depressive Disorder. Psychiatr. Clin. Psychopharmacol 2018; 29: 257-63. https://doi.org/10.1080/24750573.2018.1490096

Nagler EV, Webster AC, Vanholder R, Zoccali C. Antidepressants for depression in stage 3-5 chronic kidney disease: a systematic review of pharmacokinetics, efficacy and safety with recommendations by European Renal Best Practice (ERBP). Nephrol Dial Transplant 2012; 27:3736-45. https://doi.org/10.1093/ndt/gfs295 PMid:22859791

Hamilton M. Symptoms and assessment of depression. In: Paykel ES, editor. Handbook of affective disorders. Edinburgh: Churchill Livingstone, 1982: 3-11.

Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res 1989; 28: 193-213. https://doi.org/10.1016/0165-1781(89)90047-4 PMid:2748771

Sitasuwan T, Bussaratid S, Ruttanaumpawan P, Chotinaiwattarakul W. Reliability and validity of the Thai version of the Pittsburgh Sleep Quality Index. J Med Assoc Thai. 2014; 97 (Suppl 3): S57-67.

Palmer S, Vecchio M, Craig JC, Tonelli M, Johnson DW, Nicolucci A, et al. Prevalence of depression in chronic kidney disease: systematic review and meta-analysis of observational studies. Kidney Int. 2013; 84: 179-91. https://doi.org/10.1038/ki.2013.77 PMid:23486521

Waraich P, Goldner EM, Somers JM, Hsu L. Prevalence and incidence studies of mood disorders: a systematic review of the literature. Can J Psychiatry 2004; 49: 124-38. https://doi.org/10.1177/070674370404900208 PMid:15065747

Katon WJ. Epidemiology and treatment of depression in patients with chronic medical illness. Dialogues Clin Neurosci 2011; 13: 7-23. https://doi.org/10.31887/DCNS.2011.13.1/wkaton PMid:21485743 PMCid:PMC3181964

Maung, SC, El Sara A, Chapman C, Cohen D, Cukor Dl. "Sleep disorders and chronic kidney disease. World J Nephrol 2016; 5: 224-32. https://doi.org/10.5527/wjn.v5.i3.224 PMid:27152260 PMCid:PMC4848147

Koch BC, van der Putten K, Van Someren EJ, Wielders JP, Ter Wee PM, Nagtegaal JE, et al. Impairment of endogenous melatonin rhythm is related to the degree of chronic kidney disease (CREAM study). Nephrol Dial Transplant 2010; 25: 513-9. https://doi.org/10.1093/ndt/gfp493 PMid:19767630

Viljoen M, Steyn ME, van Rensburg BW, Reinach SG. Melatonin in chronic renal failure. Nephron 1992; 60: 138-43. https://doi.org/10.1159/000186729 PMid:1552997

Koch BC, Nagtegaal JE, Hagen EC, Wee PM, Kerkhof GA. Different melatonin rhythms and sleep-wake rhythms in patients on peritoneal dialysis, daytime hemodialysis and nocturnal hemodialysis. Sleep Med 2010; 11: 242-6. https://doi.org/10.1016/j.sleep.2009.04.006 PMid:19596605

Corruble E, de Bodinat C, Belaïdi C, Goodwin GM; agomelatine study group. Efficacy of agomelatine and escitalopram on depression, subjective sleep and emotional experiences in patients with major depressive disorder: a 24-wk randomized, controlled, double-blind trial. Int J Neuropsychopharmacol 2013; 16: 2219-34. https://doi.org/10.1017/S1461145713000679 PMid:23823799

Kasper S, Hajak G, Wulff K, Hoogendijk WJ, Montejo AL, Smeraldi E, et al. Efficacy of the novel antidepressant agomelatine on the circadian rest-activity cycle and depressive and anxiety symptoms in patients with major depressive disorder: a randomized, double-blind comparison with sertraline. J Clin Psychiatry 2010; 71: 109-20. https://doi.org/10.4088/JCP.09m05347blu PMid:20193645

Quera-Salva MA, Hajak G, Philip P, Montplaisir J, Keufer-Le Gall S, Laredo J, Guilleminault C. Comparison of agomelatine and escitalopram on nighttime sleep and daytime condition and efficacy in major depressive disorder patients. Int Clin Psychopharmacol 2011; 26: 252-62. d https://doi.org/10.1097/YIC.0b013e328349b117 PMid:21829106

Quera Salva MA, Hartley S, Barbot F, Alvarez JC, Lofaso F, Guilleminault C. Circadian rhythms, melatonin and depression. Curr Pharm Des 2011; 17: 1459-70. https://doi.org/10.2174/138161211796197188 PMid:21476953

Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, et al. Comparative Efficacy and Acceptability of 21 Antidepressant Drugs for the Acute Treatment of Adults With Major Depressive Disorder: A Systematic Review and Network Meta-Analysis. Focus (Am Psychiatr Publ) 2018; 16: 420-29. https://doi.org/10.1176/appi.focus.16407 PMid:32021580 PMCid:PMC6996085

Hedayati SS, Yalamanchili V, Finkelstein FO. A practical approach to the treatment of depression in patients with chronic kidney disease and end-stage renal disease. Kidney Int 2012; 81: 247-55. https://doi.org/10.1038/ki.2011.358 PMid:22012131 PMCid:PMC3258342

Nagler EV, Webster AC, Vanholder R, Zoccali C. Antidepressants for depression in stage 3-5 chronic kidney disease: a systematic review of pharmacokinetics, efficacy and safety with recommendations by European Renal Best Practice (ERBP). Nephrol Dial Transplant 2012; 27: 3736-45. https://doi.org/10.1093/ndt/gfs295 PMid:22859791

Hedayati SS, Gregg LP, Carmody T, Jain N, Toups M, Rush AJ, et al. Effect of Sertraline on Depressive Symptoms in Patients With Chronic Kidney Disease Without Dialysis Dependence: The CAST Randomized Clinical Trial. JAMA 2017; 318: 1876-90. https://doi.org/10.1001/jama.2017.17131 PMid:29101402 PMCid:PMC5710375

Palmer SC, Natale P, Ruospo M, Saglimbene VM, Rabindranath KS, Craig JC, et al. Antidepressants for treating depression in adults with end-stage kidney disease treated with dialysis. Cochrane Database Syst Rev 2016; 2016: CD004541. https://doi.org/10.1002/14651858.CD004541.pub3

Mehrotra R, Cukor D, Unruh M, Rue T, Heagerty P, Cohen SD, et al. Comparative Efficacy of Therapies for Treatment of Depression for Patients Undergoing Maintenance Hemodialysis: A Randomized Clinical Trial. Ann Intern Med 2019;170: 369-79. https://doi.org/10.7326/M18-2229 PMid:30802897

How to Cite
Trisukon W, Saleh-arong FA- hamad, Satirapoj B, Chokemaitree N. EFFECT OF AGOMELATINE AND SERTRALINE ON SLEEP QUALITY AMONG PATIENTS WITH CHRONIC KIDNEY DISEASE AND MAJOR DEPRESSIVE DISORDER: A DOUBLE-BLINDED RANDOMIZED CONTROLLED TRIAL. J Southeast Asian Med Res [Internet]. 2023May16 [cited 2023Jun.5];70:e0148. Available from: https://www.jseamed.org/index.php/jseamed/article/view/148
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