Rosiglitazone Add-On in Treatment of Depressed Patients with Insulin Resistance: a Pilot Study

Abstract

A number of cross-sectional studies have suggested an association between insulin resistance (IR) and affective disorders. However, limited data exist on potential changes in IR in a prospective treatment of depression. The present pilot study tested the hypothesis that improvement of IR with the addition of an insulin-sensitizing agent would improve mood in nondiabetic patients with unipolar or bipolar depression, who had surrogate blood markers suggestive of IR. Surrogate IR-criteria blood markers were fasting plasma glucose >100 mg/dl or triglyceride (TG) to high density lipoprotein (HDL) ratio >3.0. Open-label rosiglitazone, titrated to a dose of 8 mg/day, was administered for 12 weeks to 12 patients with depressive disorder receiving treatment as usual (TAU). Eight patients who completed the 12-week study exhibited significant declines in both depression severity by the Hamilton Depression Rating Scale and the Clinical Global Impression scale, with moderate effect sizes noted. Modest improvement in Matsuda Index scores was also noted at 12 weeks, yet declines in depression severity scores were not associated with improvements in the endocrine markers (Matsuda Index, TG/HDL ratio, and body mass index). These results suggest the potential novel use for an insulin-sensitizing agent in the treatment of depressive disorders. Larger placebo-controlled studies are warranted.

Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression

“…Such effects were reported for the thiazolidinediones rosiglitazone and pioglitazone (Saubermann et al, 2002; Ali et al, 2006; Zhao et al, 2006; Asghar et al, 2007; Strum et al, 2007; Eissa Ahmed and Al-Rasheed, 2009; Mittal et al, 2009; Rasgon et al, 2010; Kemp et al, 2011). For instance, rosiglitazone, one of the insulin sensitizers of the thiazolidinedione class, induces an antidepressant-like effect in the tail suspension and forced swim tests in mice, reducing immobilization and floating behavior (Eissa Ahmed and Al-Rasheed, 2009).…”

Applications of blood-based protein biomarker strategies in the study of psychiatric disorders

“…A clinical trial in patients with mild Alzheimer disease and type 2 diabetes mellitus found that patients who received pioglitazone showed improved cognition, compared to patients who received placebo (Landreth et al, 2008). Another study has shown that addition of an insulin-sensitizing agent may improve mood in nondiabetic patients with major depressive disorder or bipolar disorder, who had blood biomarkers indicative of insulin resistance (Rasgon et al, 2010a). Further studies are warranted to determine if these findings can be validated.…”

Rhodiola crenulata root ameliorates derangements of glucose and lipid metabolism in a rat model of the metabolic syndrome and type 2 diabetes

“…It has been suggested that insulin resistance is a part of the pathophysiology of affective disorders, and that improvement of insulin resistance may reduce the severity of depressive symptoms (Rasgon et al, 2001;Rasgon and Jarvik, 2004). Treatments of type 2 diabetic patients with insulin sensitizers rosiglitazone and pioglitazone improve not only metabolic derangements, but also affective disorders (Kemp et al, 2009;Wagner et al, 2009;Rasgon et al, 2010;Kemp et al, 2012). Rhodila species have been used widely to treat fatigue and depression (Kelly, 2001;Panossian et al, 2010).…”