Posted by Phillipa on December 6, 2012, at 23:16:38
Medscape Medical News > Psychiatry
Diabetes Drugs May Reduce Risk for Affective Disorders
Dec 05, 2012Authors & Disclosures
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The increased risk for depression and other affective disorders seen in patients with type 2 diabetes (T2DM) is minimized by oral antihyperglycemic treatment with sulfonylurea and metformin, a new study suggests.
The findings build on prior research that has shown that mood disorders, including depression as well as the neurodegenerative diseases dementia and Parkinson's disease, are more common among patients with T2DM and that treatment with metformin may help reduce the risk.
Dr. Mark Wahlqvist
"We wondered if there might be some common underlying mechanism which predisposes to neurodegenerative disease and depression or affective disorders," Mark L. Wahlqvist, MD, professor emeritus, Monash University and the Monash Asia Institute, Victoria, Australia, who led the new study, told Medscape Medical News.
"Since we have now found that metformin usage is associated with less affective disorder, we think our hypothesis has considerable merit. It also points to problems of energy regulation in the brain, as elsewhere in the body, as a mechanism," he said.
The study was published online November 29 in BMC Medicine.
Mental Health Impact Underestimated
To determine the effect on risk for affective disorder with T2DM, with and without oral antihyperglycemic agents (OAA), Dr. Wahlqvist and colleagues followed a representative sample of 762,753 Taiwanese adults for 12 years using the Taiwanese National Health Insurance database.
For patients with T2DM aged 50 years and older, having no OAA therapy was a risk factor for affective disorder, with an overall hazard ratio (HR) of 2.62 (95% confidence interval [CI], 2.31 - 2.98), they report.
This finding, researchers note, "suggests that available studies have grossly underestimated the potential effect of diabetes in this area of mental health."
They also report that the combination of sulfonylurea and metformin (but not either one alone) significantly reduced both the incidence and relative risk for affective disorder in association with T2DM, irrespective of sex.
The HR for affective disorder was 0.92 (95% CI, 0.59 - 1.45) for patients receiving metformin alone, 1.08 (95% CI, 0.84 - 1.38) for those receiving sulfonylurea alone, and 0.40 (95% CI, 0.32 - 0.50) for those receiving combined treatment. These findings are "consistent with synergistic or complimentary mechanisms of action" of the 2 agents, the authors write.
Drug Discovery Crisis
The finding that the incidence of affective disorder was lower for patients with T2DM taking sulfonylurea and metformin than it was for their peers who were not taking these agents is "not entirely unexpected," adds Michael Berk, MD, PhD, from Deakin University School of Medicine, Barwon Health, Geelong, Victoria, Australia, in a linked commentary. In addition, there are published data suggesting that pioglitazone also has antidepressant properties, he notes.
"As the global burden of diabetes increases, these findings may be relevant to the reduction of its mental-health consequences," the researchers write.
"The case for routine and first-line use of metformin in the pharmacotherapeutic management of diabetes is strengthened by our observations," Dr. Wahlqvist told Medscape Medical News. "But so also is the case for personal behaviors, which include regular physical activity and [healthy] eating patterns," he said.
According to Dr. Berk, there is a "crisis in drug discovery for neuropsychiatric disorders, with a profound, yet unexpected drought in new drug development across the spectrum."
"Historically," he writes, "the vast majority of agents have been discovered serendipitously or have been modifications of existing agents."
The finding by Dr. Wahlqvist and colleagues that treatment with sulfonylurea and metformin reduces the risk for affective disorder illustrates that "serendipitous discoveries, based on astute clinical observation or data mining, remain a valid option," he concludes.
Dr. Wahlqvist and coauthors report no relevant financial relationships. Dr. Berk has received grant/research support from Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Organon, Novartis, Mayne Pharma, and Servier; he has been a speaker for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, and Solvay and Wyeth; and he has served as a consultant to AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen Cilag, Lundbeck Merck, and Servier.