Skip to main content Accessibility help

Use of antidepressants in patients with depression and comorbid diabetes mellitus: a systematic review

  • Subethini Roopan (a1) and Erik Roj Larsen (a2)



Depression may be difficult to treat and with comorbid diabetes mellitus (DM) it is an even bigger challenge. This article aims to evaluate antidepressants most suitable for patients with depression and comorbid DM.

Design and methods

Initially we searched for randomised, controlled double-blind trials of treatment with antidepressants in depressed with DM but there were only a few studies and many of them were small trials. Thus, we decided to include studies that were not only randomised-controlled trials. In total, we ended up with 18 articles for our purposes.


The combination of depression and DM may be harmful as depression has a strong impact on psychosocial and medical outcomes in patients with DM. Almost all of the trials in this review showed a reduction in depressive symptoms after treatment with an antidepressant in the acute as well as during maintenance phase. It showed that depression improvement had a favourable effect on glycaemic control that was weight independent. Some studies included only subjects with minor depression or with suboptimal-controlled diabetes making it difficult to show an effect.


From these data, we will recommend choosing an selective serotonin reuptake inhibitor (SSRI) if possible to treat a depression among patients with diabetes. If treatment with a tricyclic antidepressant is needed, closer glycaemic monitoring is recommended. Bear in mind that there is a possible risk of hypoglycemia when using SSRIs. Agomelatine and bupropion have shown promising results, but need to be investigated in more trials.


Corresponding author

Erik Roj Larsen, Department of Affective Disorders Q, Mood Disorders Research Unit, Aarhus University Hospital, Risskov DK-8240, Denmark. Tel: +45 78 47 21 30; E-mail:


Hide All
1. Ali, S, Stone, MA, Peters, JL, Davies, MJ, Khunti, K. The prevalence of co-morbid depression in adults with Type 2 diabetes: a systematic review and meta-analysis. Diabet Med 2006;23:11651173.
2. Petrak, F, Herpertz, S. Treatment of depression in diabetes: an update. Curr Opin Psychiatry 2009;22:211217.
3. Lustman, PJ, Clouse, RE, Freedland, KE. Management of major depression in adults with diabetes: implications of recent clinical trials. Semin Clin Neuropsychiatry 1998;3:102114.
4. Chamberlain, JJ, Rhinehart, AS, Shaefer, CF Jr, Neuman, A. Diagnosis and management of diabetes: synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes. Ann Intern Med 2016;164:542552.
5. WHO. WHO guidelines approved by the Guidelines Review Committee, in use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus: abbreviated report of a WHO consultation. Geneva: World Health Organization, 2011.
6. Nathan, DM, Turgeon, H, Regan, S. Relationship between glycated haemoglobin levels and mean glucose levels over time. Diabetologia 2007;50:22392244.
7. Knol, MJ, Derijks, HJ, Geerlings, MI, et al. Influence of antidepressants on glycaemic control in patients with diabetes mellitus. Pharmacoepidemiol Drug Saf 2008;17:577586.
8. Weber-Hamann, B, Hentschel, F, Kniest, A, et al. Hypercortisolemic depression is associated with increased intra-abdominal fat. Psychosom Med 2002;64:274277.
9. Andreoulakis, E, Hyphantis, T, Kandylis, D, Iacovides, A. Depression in diabetes mellitus: a comprehensive review. Hippokratia 2012;16:205214.
10. Barnard, K, Peveler, RC, Holt, RI. Antidepressant medication as a risk factor for type 2 diabetes and impaired glucose regulation: systematic review. Diabetes Care 2013;36:33373345.
11. van der Feltz-Cornelis, CM, Nuyen, J, Stoop, C, et al. Effect of interventions for major depressive disorder and significant depressive symptoms in patients with diabetes mellitus: a systematic review and meta-analysis. Gen Hosp Psychiatry 2010;32:380395.
12. Baumeister, H, Hutter, N, Bengel, J. Psychological and pharmacological interventions for depression in patients with diabetes mellitus: an abridged Cochrane review. Diabet Med 2014;31:773786.
13. Petrak, F, Baumeister, H, Skinner, TC, Brown, A, Holt, RI. Depression and diabetes: treatment and health-care delivery. Lancet Diabetes Endocrinol 2015;3:472485.
14. Erenmemisoglu, A, Ozdogan, UK, Saraymen, R, Tutus, A. Effect of some antidepressants on glycaemia and insulin levels of normoglycaemic and alloxan-induced hyperglycaemic mice. J Pharm Pharmacol 1999;51:741743.
15. Mahmood, D, Akhtar, M, Vohora, D, Khanam, R. Comparison of antinociceptive and antidiabetic effects of sertraline and amitriptyline on streptozotocin-induced diabetic rats. Hum Exp Toxicol 2010;29:881886.
16. Gupta, B, Awasthi, A, Jaju, BP. Effect of acute & chronic imipramine treatment on glucose homeostasis. Indian J Med Res 1992;96:6571.
17. Andersohn, F, Schade, R, Suissa, S, Garbe, E. Long-term use of antidepressants for depressive disorders and the risk of diabetes mellitus. Am J Psychiatry 2009;166:591598.
18. Brown, LC, Majumdar, SR, Johnson, JA. Type of antidepressant therapy and risk of type 2 diabetes in people with depression. Diabetes Res Clin Pract 2008;79:6167.
19. Kesim, M., Tiryaki, A, Kadioglu, M, Muci, E, Kalyoncu, NI, Yaris, E. The effects of sertraline on blood lipids, glucose, insulin and HBA1C levels: a prospective clinical trial on depressive patients. J Res Med Sci 2011;16:15251531.
20. Weber-Hamann, B, Gilles, M, Lederbogen, F, Heuser, I, Deuschle, M. Improved insulin sensitivity in 80 nondiabetic patients with MDD after clinical remission in a double-blind, randomized trial of amitriptyline and paroxetine. J Clin Psychiatry 2006;67:18561861.
21. Ghaeli, P, Shahsavand, E, Mesbahi, M, Kamkar, MZ, Sadeghi, M, Dashti-Khavidaki, S. Comparing the effects of 8-week treatment with fluoxetine and imipramine on fasting blood glucose of patients with major depressive disorder. J Clin Psychopharmacol 2004;24:386388.
22. Filipcic, I, Margetic, B, Simunovic, I, Jakovljevic, M. Depression treatment and its impact upon the quality of life in patients with diabetes type 2 – the Croatian study. Psychiatr Danub 2010;22:231235.
23. Amsterdam, JD, Shults, J, Rutherford, N, Schwartz, S. Safety and efficacy of s-citalopram in patients with co-morbid major depression and diabetes mellitus. Neuropsychobiology 2006;54:208214.
24. Goodnick, PJ, Kumar, A, Henry, JH, Buki, VM, Goldberg, RB. Sertraline in coexisting major depression and diabetes mellitus. Psychopharmacol Bull 1997;33:261264.
25. Gehlawat, P, Gupta, R, Rajput, R, Gahlan, D, Gehlawat, VK. Diabetes with comorbid depression: role of SSRI in better glycemic control. Asian J Psychiatr 2013;6:364368.
26. Paile-Hyvarinen, M, Wahlbeck, K, Eriksson, JG. Quality of life and metabolic status in mildly depressed women with type 2 diabetes treated with paroxetine: a single-blind randomised placebo controlled trial. BMC Fam Pract 2003;4:7.
27. Karaiskos, D, Tzavellas, E, Ilias, I, Liappas, I, Paparrigopoulos, T. Agomelatine and sertraline for the treatment of depression in type 2 diabetes mellitus. Int J Clin Pract 2013;67:257260.
28. Barragan-Rodriguez, L, Rodriguez-Moran, M, Guerrero-Romero, F. Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: a randomized, equivalent trial. Magnes Res 2008;21:218223.
29. Gulseren, L, Gulseren, S, Hekimsoy, Z, Mete, L. Comparison of fluoxetine and paroxetine in type II diabetes mellitus patients. Arch Med Res 2005;36:159165.
30. Vasile, D, Vasiliu, O, Vasile, ML, Terpan, M, Ojog, DG. P.2.c.002 Agomelatine versus selective serotoninergic reuptake inhibitors in major depressive disorder and comorbid diabetes mellitus. European Neuropsychopharmacology 2011;21 (Suppl. 3):S383S384.
31. Khazaie, H, Rahimi, M, Tatari, F, Rezaei, M, Najafi, F, Tahmasian, M. Treatment of depression in type 2 diabetes with fluoxetine or citalopram? Neurosciences (Riyadh) 2011;16:4245.
32. Lustman, PJ, Griffith, LS, Clouse, RE, et al. Effects of nortriptyline on depression and glycemic control in diabetes: results of a double-blind, placebo-controlled trial. Psychosom Med 1997;59:241250.
33. Lustman, PJ, Freedland, KE, Griffith, LS, Clouse, RE. Fluoxetine for depression in diabetes: a randomized double-blind placebo-controlled trial. Diabetes Care 2000;23:618623.
34. Paile-Hyvarinen, M, Wahlbeck, K, Eriksson, JG. Quality of life and metabolic status in mildly depressed patients with type 2 diabetes treated with paroxetine: a double-blind randomised placebo controlled 6-month trial. BMC Fam Pract 2007;8:34.
35. Echeverry, D, Duran, P, Bonds, C, Lee, M, Davidson, MB. Effect of pharmacological treatment of depression on A1C and quality of life in low-income Hispanics and African Americans with diabetes: a randomized, double-blind, placebo-controlled trial. Diabetes Care 2009;32:21562160.
36. Lustman, PJ, Clouse, RE, Nix, BD, et al. Sertraline for prevention of depression recurrence in diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Arch Gen Psychiatry 2006;63:521529.
37. Lustman, PJ, Williams, MM, Sayuk, GS, Nix, BD, Clouse, RE. Factors influencing glycemic control in type 2 diabetes during acute- and maintenance-phase treatment of major depressive disorder with bupropion. Diabetes Care 2007;30:459466.
38. Komorousova, J, Beran, J, Rusavy, Z, Jankovec, Z. Glycemic control improvement through treatment of depression using antidepressant drugs in patients with diabetes mellitus type 1. Neuro Endocrinol Lett 2010;31:801806.
39. Derijks, HJ, Heerdink, ER, De Koning, FH, Janknegt, R, Klungel, OH, Egberts, AC. The association between antidepressant use and hypoglycaemia in diabetic patients: a nested case-control study. Pharmacoepidemiol Drug Saf 2008;17:336344.


Related content

Powered by UNSILO

Use of antidepressants in patients with depression and comorbid diabetes mellitus: a systematic review

  • Subethini Roopan (a1) and Erik Roj Larsen (a2)


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.