Antidepressants May Be Linked to Diabetes Risk

Depressed patients have increased risk for diabetes

Antidepressants appeared to be associated with an increased risk for diabetes, according to a systematic review published online ahead of print in Diabetes Care. However, it is unclear whether this is a causal relationship and the magnitude of the effect may be small.

"While depression is an important clinical problem and antidepressants are effective treatments for this debilitating condition, clinicians need to be aware of the potential risk of diabetes, particularly when using antidepressants in higher doses or for longer duration,” said coauthor Richard Holt, MD, Professor in Diabetes and Endocrinology at the University of Southampton, United Kingdom. “When prescribing antidepressants, doctors should be aware of this risk and take steps to monitor for diabetes and reduce that risk of diabetes through lifestyle modification,” Dr. Holt said.

“What this review by Dr. Barnard and colleagues points out is that the question about whether antidepressants make diabetes worse or increase the risk for diabetes remains unresolved and needs further research,” commented Alan J. Gelenberg, MD, Shively/Tan Professor and Chair of the Department of Psychiatry at Penn State College of Medicine, in Hershey, PA.

“We have known for a number of years that patients with diabetes are more likely to be depressed, and when they are depressed their diabetes is less likely to be in good control,” Dr. Gelenberg said. However, “it is also well known that depression has adverse consequences on glucose regulation; thus, there is an obvious confound when we talk about antidepressants and diabetes because you are not sure which [factor] is causative,” he explained.

Conflicting Findings

The researchers assessed 22 studies and three previous systematic reviews on this topic. Overall, the evidence suggests that some antidepressants affect glucose metabolism and that antidepressant use may be an independent risk factor for diabetes.

“Causality is not established, but rather, the picture is confused, with some antidepressants linked to worsening glucose control, particularly with higher doses and longer duration, others linked with improved control, and yet more with mixed results,” the researchers noted.

For example, case reports in the analysis suggest that some antidepressants have been linked to development of diabetes, with return to normal glycemic control following treatment discontinuation. Cross-sectional studies, on the other hand, do not suggest an increase in diabetes prevalence with antidepressant use that is independent from depressive symptoms, but do show that patients taking antidepressants are more likely to have metabolic changes associated with diabetes. Furthermore, while some cohort studies have shown an increase in diabetes incidence among patients taking antidepressants, recent larger studies including the Nurses’ Health Initiative suggest that this risk is relatively small.

“What Barnard’s review points out is that we don’t really have good prospective, systematic, blinded controlled studies [on this topic],” Dr. Gelenberg said. Mostly, the evidence is based on case reports and cross sectional studies, he noted. Based on the currently available evidence included in this review, “one might assume that antidepressants may have a possibly small effect on diabetes control,” he said adding that “clearly, we don’t know enough.”

Clinical Implications

“Our research shows that when you take away all the classic risk factors of type 2 diabetes; weight gain, lifestyle, etc, there is something about antidepressants that appears to be an independent risk factor…. Heightened alertness to the possibility of diabetes in people taking antidepressants is necessary until further research is conducted,” said coauthor Katharine Barnard, PhD, a Health Psychologist from the University of Southampton.

Dr. Gelenberg said that without knowing whether antidepressants increase the risk for diabetes, the best approach when treating a depressed patient with a history or risk factors for diabetes is to prescribe antidepressants (in addition to psychotherapy) when necessary and to inform patients of the possibility that antidepressants could have a negative impact on glucose levels.

“Not knowing what the truth is, the best thing I can do as a practicing doctor is to just keep checking. If a patient is depressed, you want to monitor the patient more closely anyway. If the depression gets better but glucose regulation gets worse, then I’d worry that maybe the antidepressant is the culprit. If the depression isn’t getting better, I would probably pursue a [different] treatment to improve the depression,” Dr. Gelenberg said.

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