Adding pioglitazone, an insulin-sensitizing agent with anti-inflammatory properties, to usual antidepressant treatment relieved unremitting depression in a small clinical trial, but only in patients who had insulin resistance, a report published online Nov. 18 shows.
The association between insulin resistance and depressive symptoms has been well documented but remains poorly understood. “A better understanding of the reciprocal links between depression and insulin resistance may lead to a dramatic shift in the way in which depression is conceptualized and treated, with a greater focus on treating and/or preventing metabolic dysfunction,” said Kathleen Watson Lin of the department of psychiatry and behavioral sciences, Stanford (Calif.) University, and her associates.
The investigators previously found that rosiglitazone, a related insulin-sensitizing agent, improved depression severity in an open-label pilot study. Now they report the results of a double-blind randomized trial involving 37 men and women aged 23-71 years (mean age, 43-49 years) who had unremitting depression despite receiving a variety of standard treatments. These study participants had a range of insulin sensitivities, including 20 who had insulin resistance, but none had frank diabetes. Nineteen were randomly assigned to receive pioglitazone and 18 to receive a matching placebo pill for 12 weeks.
Pioglitazone improved depressive symptoms only in the subgroup of patients who had insulin resistance. Their scores on the Hamilton Depression Rating Scale-21 declined an average of 7.15 points more than did the scores of patients with insulin resistance who received placebo. In contrast, among patients who did not have insulin resistance, there was no difference in the decline of HDRS-21 scores between those who received pioglitazone and those who received placebo, the investigators said (Psychiatry Res. 2015 Nov 18).
This treatment response was the most pronounced in younger patients.
The study findings suggest that pioglitazone may be an effective adjuvant therapy for unremitting depression, at least in patients who have insulin resistance and especially in those who are younger. However, given the small size of this study population, larger clinical trials are needed to examine this possibility, Ms. Watson Lin and her associates said.
This study was funded by the National Institutes of Health. Ms. Watson Lin reported having no financial disclosures. One of her associates reported serving as a consultant to Shire and Sunovion, and receiving research support from Magceutics and Corcept.