Depression in Patients With Type 2 Diabetes Mellitus: Currently Most Beneficial Therapeutic Options

Dear Editor, Type 2 diabetes mellitus (T2DM) is an extremely common health issue in today’s population. Moreover, patients with T2DM are at an increased risk of developing mental health disorders, including depression. Research studies suggest that approximately 15% of patients with T2DM meet the diagnostic criteria for depression.[1] Depression, as an independent condition, requires appropriate treatment, and when it coexists with diabetes, it is associated with reduced treatment adherence, increased diabetes-related fatalism, and a lower quality of life.[1] Therefore, it is essential to identify an antidepressant that does not negatively impact glucose metabolism and allows patients to effectively manage both conditions. Studies indicate that older antidepressants, such as tricyclic antidepressants, are associated with weight gain and an increased risk of developing T2DM. Therefore, their use in patients already suffering from T2DM is not a beneficial treatment. Regarding selective serotonin reuptake inhibitors (SSRIs), some studies also report potential adverse effects on T2DM. For instance, sertraline may promote beta-cell damage and apoptosis.[2] However, a substantial body of research indicates that certain SSRIs may confer benefits in T2DM patients. For example, fluoxetine has been found to regulate glycemic indices and lipid profiles in T2DM patients.[2] A meta-analysis involving five randomized, placebo-controlled trials demonstrated that short-term fluoxetine therapy can lead to weight loss, and reduction in glycated hemoglobin (HbA1c) and triglyceride levels in T2DM patients.[2] In addition, various studies have indicated that citalopram also positively influences blood glucose levels and HbA1c. Moreover, citalopram’s anti-inflammatory and antioxidant effects are also important in the management of T2DM.[3] Although SSRIs are effective in treating depression in patients with T2DM, recent studies report that agomelatine may represent an even more advantageous therapeutic option. Agomelatine is a structural analog of melatonin. It is a relatively new drug with a unique mechanism. It functions as an agonist at melatonergic MT1 and MT2 receptors, whereas acting as an antagonist at serotonergic 5-HT2C receptors.[4] A two-arm, single-blind, randomized controlled trial comparing the effects of fluoxetine and agomelatine in patients with T2DM found that both medications were effective. However, compared with fluoxetine, patients treated with agomelatine had a significantly lower average Hamilton Rating Scale for Anxiety score after 12 weeks of treatment. The HbA1c levels were also significantly lower in the agomelatine group. Additionally, agomelatine was less likely to cause weight gain.[5] Another study demonstrated that agomelatine is at least as effective as escitalopram and fluoxetine in treating patients with T2DM and depression.[5] A study comparing paroxetine and agomelatine revealed similar efficacy in treating depression in patients with T2DM. However, among patients with treatment-resistant depression, the remission rate for agomelatine was significantly higher (43%). Furthermore, agomelatine was associated with fewer withdrawal symptoms and sexual side effects.[6] It is also worth emphasizing the importance of coordinated patient care, which combines the treatment process by physicians with support from non-physician care providers in decision-making and treatment adjustment. The independent randomized clinical trial conducted in India showed significant improvement in diabetes treatment outcomes in patients receiving coordinated care, compared with those receiving standard care.[7] In conclusion, both SSRIs and agomelatine have demonstrated good results in treating depression in patients with T2DM. However, recent studies indicate that agomelatine may offer better outcomes with fewer side effects and should be further investigated [Figure 1].Figure 1: The mutual influence of depression and T2DM.Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.