A new systematic review of published studies suggests when prescribing antidepressant medication, clinicians should be extra aware that they are linked to raised risk for type 2 diabetes, although the study does not suggest the drugs are the direct cause.

Reporting their findings in the latest issue of Diabetes Care, researchers from the University of Southampton say use of antidepressants has risen sharply over recent years, and there are concerns they may have an adverse effect on glucose metabolism.

They note 46.7 million prescriptions for antidepressants were issued in 2011 in the UK.

Antidepressant use has also soared in the US, where a 2011 study found they are now the third most widely prescribed group of drugs.

Several studies have shown that antidepressant use is linked to diabetes, but the results have been varied, depending on the methods and numbers involved and also on the types of drugs themselves.

For instance, one study that found a link between antidepressants and risk for type 2 diabetes discovered the risk almost doubled in patients using two types of drugs at the same time: tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs).

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Researchers found a link between people who take antidepressants and type 2 diabetes, although it does not mean there is a direct causal effect.

For their systematic review, Southampton health psychologist Dr. Katharine Barnard and colleagues assessed 22 studies and three previous reviews that looked at the link between antidepressant use and risk for type 2 diabetes.

They found that overall, people on antidepressants were more likely to have type 2 diabetes.

Within that, however, the picture is somewhat “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.”

They note that although study quality was variable, the more recent, larger studies suggest a modest effect.

The researchers also propose that different types of antidepressants may be linked to different amounts of risk and call for long-term randomized, controlled trials to examine the effects of individual drugs.

While their review was not designed to investigate causes, the team says there could be several plausible explanations for the link. For instance, some antidepressants cause patients to put on weight, which in itself increases risk for type 2 diabetes.

But they also point out that some of the studies they reviewed found the raised risk for type 2 diabetes persisted when they took out the effect of weight gain, suggesting other factors could be involved.

Dr. Barnard says:

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.”

She says that in light of rising prescriptions, “this potential increased risk is worrying,” and:

“Heightened alertness to the possibility of diabetes in people taking antidepressants is necessary until further research is conducted.”

Co-author Richard Holt, professor in Diabetes and Endocrinology at Southampton, adds:

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.”

He says doctors prescribing antidepressants should be aware of this raised risk for diabetes and ensure they monitor patients for the condition, as well as take steps to reduce the risk by encouraging changes to lifestyle.