Combination of Antidepressants Linked to Risk of Diabetes 3-27-08

The use of two types of antidepressants at the same time was associated with an increased risk for type 2 diabetes, a nested case-control study showed.

Patients taking both a tricyclic antidepressant and a selective serotonin reuptake inhibitor (SSRI) were nearly twice as likely to develop type 2 diabetes as those taking a tricyclic antidepressant alone, Jeffrey Johnson, Ph.D., of the University of Alberta, and colleagues reported in the January issue of Diabetes Research and Clinical Practice.

"If our findings are confirmed by others," they concluded, "it could be that antidepressant therapy will need to be tailored to depressed individuals' risk of developing diabetes, and that patients on combination therapy will require vigilance regarding the development of glucose intolerance."

The increased risk of diabetes in depressed patients is well-documented, the researchers said, but the mechanisms are unknown.

Possible theories relate to the biochemical and behavioral changes associated with depression, as well as to the side effects of antidepressants.

To explore the issue further, the researchers examined information in health databases from the province of Saskatchewan on 2,391 patients age 20 and older who had been treated for depression.

The average age of all patients was 53.6 (SD 16.4), 68% were female, and the average follow-up was 4.07 years (SD 2.76).

Overall, 41.9% were taking a tricyclic antidepressant only, 38.7% were taking an SSRI only, 7.7% were taking one of each, and 11.8% were taking at least three medications, at least one of which was not a tricyclic antidepressant or SSRI.

After adjusting for age, sex, number of physician visits, and use of augmentation therapy, only use of one each of a tricyclic antidepressant and an SSRI was associated with an increased risk for type 2 diabetes compared with use of a tricyclic antidepressant alone (adjusted OR 1.89, 95% CI 1.35 to 2.65, P<0.001).

Being male was also correlated with an increased risk (adjusted OR 1.35, 95% CI 1.13 to 1.63, P<0.001).

To explain the association between taking a tricyclic antidepressant and an SSRI and type 2 diabetes, the researchers proposed that it could be a consequence of the additive side effects of taking more than one medication or of depression severity, although a significant association was not found in the patients taking at least three drugs.

"It is likely that an increased risk of type 2 diabetes was not seen in this group due to heterogeneity," they said.

As strengths of the study, the researchers noted that it was population-based, had detailed data on medication use, and was the largest study to look at the association between specific antidepressant therapies and risk of type 2 diabetes.

They also acknowledged some limitations, including the fact that patients may be less likely to seek treatment for mild cases of diabetes or depression that would, therefore, not be captured in a database study.

Additionally, the researchers did not have access to detailed clinical data on the patients.

And finally, they used augmentation therapy as a measure of depression severity, but some of these patients may have had another mental illness such as bipolar disorder.