Megan Brooks

May 15, 2011

May 15, 2011 (Honolulu, Hawaii) — The insulin-releasing properties of sulphonylureas may include antidepressant effects, according to a large retrospective study reported here Sunday at the American Psychiatric Association (APA) 2011 Annual Meeting.

In the study, diabetes patients prescribed a sulphonylurea alone had the lowest likelihood for concurrent coprescription with an antidepressant.

Dr. Øivind Hundal

"In treatment of depression, to stabilize blood sugar might be favorably affecting the outcome of therapy (also in nondiabetics)," study presenter Øivind Hundal, MPharm, PhD, of Haukeland University Hospital in Bergen, Norway, told Medscape Medical News.

In 2007, Dr. Hundal proposed a new hypothesis for the pathophysiology of depressive disorder, namely, that it might be a "diabetes of the brain" — an attenuated cerebral glucose metabolism in astroglia.

Insulin-Diabetes Link

In the study, Dr. Hundal and colleagues used data from the Norwegian Prescription Database for 2006 to determine whether the odds ratio (OR) for concurrent use of antidepressants when receiving oral antidiabetic agents varies according to the type of hypoglycemic agent used.

The research team analyzed data on more than 3.4 million persons 20 years and older. They looked at concurrent prescriptions for oral antidiabetics (ie, biguanides, sulphonylureas, and thiazolidinediones) and antidepressants.

"The main finding," Dr. Hundal said, is that sulphonylureas, "the only group of oral antidiabetic drugs directly stimulating insulin release (probably also in the brain as the drug has access to cerebral tissues), are associated with a significantly lower concurrent antidepressant use."

Use of a sulphonylurea only had the lowest OR for coprescription with an antidepressant (OR, 1.27; 95% confidence interval [CI], 1.21 – 1.34), followed by use of a sulphonylurea and biguanide (OR, 1.31; 95% CI, 1.26 – 1.37) and use of a sulphonylurea, biguanide, and glitazone (OR, 1.49; 95% CI, 1.34 – 1.67).

Sulphonylurea alone or in combination had a significantly lower OR for concurrent antidepressant use compared with that for a biguanide alone (OR, 1.59; 95% CI, 1.54 – 1.64), which was the most common regimen, and a glitazone alone (OR, 2.08; 95% CI, 1.47 – 2.94).

Study Supports 'Emerging' Diabetes-Depression Link

Dr. Hundal said these data, coupled with more recent research by his group, "support the idea that there is a compensatory increased activity of brain insulin in depression.

"In this context it is important to realize that the glucose absorption of astroglia is influenced by insulin, whereas in neurons insulin does not have this effect."

Reached for comment, Noah S. Philip, MD, who studies the biology of depression, said this study indeed supports "emerging evidence linking together depression and diabetes." Dr. Philip is with the Mood Disorders Research Program at Butler Hospital and the Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, both in Providence, Rhode Island.

"Large epidemiologic studies," he noted, "have shown a relationship between diabetes and depression, although the precise nature of this relationship is still unclear. Interestingly, there is also literature showing that patients with depression may have deficiencies in brain metabolism, which is linked to glucose."

The association between diabetes and depression implies that there is more to be learned about the relationship, Dr. Philip told Medscape Medical News. A better understanding of "any potential causative factors could help researchers design better and more efficacious treatment for depression," he noted.

Correlation Not Causation

However, Dr. Philip also noted that, "as with any large, retrospective, epidemiological studies, one has to remember that correlation does not necessarily indicate causation. There are a myriad of reasons why 2 variables can be linked together statistically."

He also cautioned against "premature" use of these medications for depression, noting that sulfonylureas are associated with hypoglycemia that can cause significant medical problems.

However, based on the findings, "prospective studies carefully investigating a possible role of this medication class for depression may be indicated," Dr. Philip concludes.

The study authors and Dr. Philip have disclosed no relevant financial relationships.

American Psychiatric Association (APA) 2011 Annual Meeting: Abstract NR04-25. Presented May 15, 2011.

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