Metformin for the Improvement of Comorbid Depression Symptoms in Diabetic Patients: A Systematic Review

Abstract

Diabetes mellitus and depression are chronic debilitating disorders and can occur comorbidly. They are thought to be linked not only through environmental and behavioral factors but through molecular mechanisms as well. Antidepressant medication and psychological therapy, standard treatments for depressive symptoms in Type 2 diabetes mellitus, are linked to high rates of treatment failure and nonadherence; therefore, understanding the molecular mechanisms linking diabetes and depression could lead to discovering new targets and developing novel therapeutics. Metformin is considered a first-line antidiabetic medication for Type 2 diabetes mellitus, and several studies have discussed its antidepressant effect. Metformin is thought to promote neurogenesis, enhance spatial memory function and protect the brain against oxidative imbalance. This systematic review aims to compile information on metformin's effect on depression symptoms and assess current knowledge on the relationship between depression and diabetes. After reviewing several studies, we concluded that metformin might help treat comorbid depression in diabetic patients, but before it can be recommended as a depression medication, more extensive and betterdesigned trials are needed.

Does Better Diet Quality Offset the Association between Depression and Metabolic Syndrome?

“…Lastly, the lack of data about medication use may also be a major limitation. Metformin, a major medication for type 2 diabetes, has been proposed to treat comorbid depression and diabetic patients [ 68 ]. Several studies have suggested that antidepressants can induce (Mirtazapine (SNRI), TCAs amitriptyline and nortriptyline) and reduce (selective Serotonin re-uptake inhibitors) weight gain as a side effect [ 69 , 70 , 71 ], although results vary depending on the duration of exposure and types of medication [ 72 ].…”

Considerations in the Treatment of Depression and Anxiety in Women with PCOS

“…In the general population of diabetic patients, there is no clear consensus on whether anti-diabetic agents reduce depression, with some supporting metformin or pioglitazone use but others not finding consistent associations, and positive findings not correlating with HOMA-IR. 37,38 A pilot trial of 19 adolescents and 25 adults with PCOS found that after 3 months of metformin 1,500 mg/day, the severity of depression symptoms as measured by the Beck Depression Inventory-II (BDI-II) decreased significantly in both the adolescent and adult groups, with 70.5% of patients having a decrease of 2 points or more (p < 0.001). 39 However, prior meta-analyses have not shown improvements in PCOS quality of life with the addition of metformin to lifestyle interventions.…”

“…59,60 A randomized clinical trial of 72 women with PCOS assigned to 16 weeks of acupuncture, exercise, or control groups found reductions in Montgomery Asberg Depression Rating Scale (À1.00 AE 8.07) and Brief Scale for Anxiety (À1.74 AE 7.88) in the acupuncture group at week 32. 27 A secondary analysis of a pilot randomized trial in China conducted over 16 weeks in 54 women with PCOS found that those in the electroacupuncture arm had significantly decreased depression scores as measured by the Zung-SDS (median: 33 [IQR: [31][32][33][34][35][36][37][38][39][40] vs. 42 [IQR: 37-50], p ¼ 0.004) and significantly improved total Chinese Quality of Life scores (median: 198 [IQR: 175-210] vs. 176 [IQR: 173-187], p ¼ 0.023). 61 Dietary modifications targeting insulin-sensitizing and inflammatory pathways have also been evaluated.…”

“…In the secondary analysis of Chinese randomized trial of 16 weeks of electroacupuncture in women with PCOS, those in the intervention arm had significant reductions in anxiety symptoms as measured by the Zang-SAS compared to the control group (median: 35 [IQR: [32][33][34][35][36][37][38] vs. 43 [IQR: [38][39][40][41][42][43][44][45][46][47][48], p ¼ 0.003). 61 The randomized placebo-controlled trial of 55 women with PCOS receiving CoQ10 or placebo also found significant reductions in the Beck Anxiety Inventory (BAI) compared to the placebo group (p ¼ 0.01).…”

Severe depressive symptoms in patients with hypertension: Are antihypertensive medications implicated?

“…22 Preclinical and clinical data suggest a potential role of metformin in improving depressive symptoms: however, the data is, as yet, inconclusive. 23 Dyslipidemia patients are at higher risk of developing cardiovascular diseases (CVD), and patients with CVD are at higher risk for depression. 24…”