Pioglitazone is an effective treatment for patients with post-stroke depression combined with type 2 diabetes mellitus

Abstract

The antidepressive effects of the antidiabetic medicine, pioglitazone, were recently reported in several studies. These effects may ameliorate the depressive symptoms of patients with post-stroke depression (PSD). The present study aimed to evaluate the antidepressive effect of pioglitazone in patients with PSD combined with type 2 diabetes. A total of 118 consecutive patients with stroke who had depression were studied for an average of 3 months. The Diagnostic and Statistical Manual of Mental Disorders (fourth edition) was used to assess whether a patient was depressed or not. The severity of depression was evaluated by the Hamilton depression rating scale (HAMD). In accordance with their HAMD scores, the 118 patients were divided into a severe depression group (n=40) and a mild and moderate (MM) depression group (n=78). These subjects were then divided into pioglitazone [30 mg once daily (qd)] and metformin (0.5 g twice daily) subgroups. All patients were given fluoxetine (20 mg qd). Follow-up evaluations, which included HAMD scores, activities of daily living (ADL) scores, fasting blood glucose (FBG) levels and fasting insulin (FINS) levels, were conducted on the first and third month following the beginning of the treatment. In the MM depression group, the HAMD score in the pioglitazone subgroup was lower than that in the metformin subgroup following treatment for 1 or 3 months. In the severe depression group, the HAMD score in the pioglitazone subgroup was lower than that in the metformin subgroup following 3 months of treatment. The FINS levels of the pioglitazone subgroup gradually decreased in the 3 months of treatment. No noticeable improvement was observed in the ADL scores and FBG values. In conclusion, the results of the current study demonstrate that pioglitazone effectively decreased HAMD scores and FINS values in patients with PSD, suggesting that pioglitazone may be useful for the treatment of patients with PSD combined with type 2 diabetes.

Repositioning of diabetes treatments for depressive symptoms: A systematic review and meta-analysis of clinical trials

“…Three trials of metformin used active controls. In the two aforementioned RCT's against pioglitazone, metformin was inferior in reducing depressive symptoms in patients with depression (Hu et al, 2015;Kashani et al, 2013). In a 12-week trial of women with polycystic ovarian syndrome, myo-inositol was marginally superior to metformin in reducing depressive symptoms.…”

“…Of the 8 RCTs testing pioglitazone, 6 were placebo-controlled (Calabrese, 2017;Lin et al, 2015;Roohafza et al, 2014;Sepanjnia et al, 2012;Simuni T., 2015;Zeinoddini et al, 2015) and two used metformin as a control (Hu et al, 2015;Kashani et al, 2013). Apart from one study (Lin et al, 2015), all RCTs selecting depressed patients at baseline reported significant reduction in depressive symptoms compared to controls.…”

Inflammation and the Silent Sequelae of Stroke

“…Non-SSRI antidepressants have not been widely studied in stroke, but drugs like agomelatine may be particularly attractive given that melatonin decreases central nervous system inflammation [107] and improves outcome in experimental models of cerebral ischemia [108,109]. Additional evidence for the role of inflammation in the genesis of PSD and as a viable target for the treatment of PSD includes the fact that treatment with pioglitazone, as opposed to metformin, decreases PSD in patients with diabetes [110]. Peroxisome proliferator-activated receptor-γ agonists like pioglitazone have both anti-inflammatory and neuroprotective properties [111,112].…”

PPAR-γ Agonists for the Treatment of Major Depression: A Review

“…In the 4 prospective open-label studies [34][35][36][37] (▶ table 1), 118 patients with a current MDE and metabolic disorders were assessed before the beginning and after 8 or 12 weeks of treatment with PPAR-γ agonists (pioglitazone or rosiglitazone) and 59 by metformin. For rosiglitazone [34], the starting dose, 4 mg/d, was increased after 4 weeks at 8 mg/d.…”