People who use antidepressants for the long term may be more likely to develop type 2 diabetes than non-users, including other individuals with severe depression, two new studies suggest.
The findings, reported in the journal Diabetes Care, add to evidence linking antidepressant use to a modest elevation in type 2 diabetes risk.
They do not, however, prove that the medications are the cause, researchers say.
It's possible that antidepressant users have other characteristics that raise their odds of developing diabetes, according to Dr Mika Kivimaki of the University College London in the UK, the lead researcher on one of the studies.
In addition, he said that antidepressant users may see doctors more often than non-users do - which, in turn, could increase their likelihood of being diagnosed with diabetes or other medical conditions.
"I would interpret these findings cautiously and not draw firm conclusions yet," Kivimaki said.
For their study, he and his colleagues used data on more than 150,000 Finnish adults followed for an average of five years. During that time, 851 were newly diagnosed with type 2 diabetes.
At the outset, there were 9,197 individuals who were considered longer term users of antidepressants - having been on the medications for more than six months. Overall, the researchers found, these men and women were more likely to develop diabetes during the study period, with the odds climbing in tandem with the length of use.
Among study participants who had not used the medications, 1.1% were diagnosed with diabetes over five years. That compared with 1.7% among individuals who had taken between 200 and 400 daily doses of an antidepressant, and 2.3% among those who had taken 400 or more daily doses.
One question about the association between antidepressants and diabetes has been whether the medications are just serving as a marker for more-severe depression: severe depression, or the generally poorer health and lifestyle that may come with it, could help explain the connection to diabetes risk.
But when Kivimaki's team looked only at participants considered to have severe depression, antidepressant users were two to three times more likely than non-users to be diagnosed with diabetes. That was with rates of chronic physical health conditions, like high blood pressure, heart disease and cancer, taken into account.
Of 159 people who had severe depression and had taken at least 200 doses of an antidepressant, 58 developed diabetes. That compared with 12 of 69 men and women who had severe depression but had taken fewer doses, or no medication at all.
In the second study, researchers led by Dr Richard R. Rubin of Johns Hopkins University in Baltimore looked at data on more than 3,200 US adults who were enrolled in a clinical trial on type 2 diabetes prevention.
All of the study participants were at high risk of diabetes because they were overweight and had elevated blood sugar. They were randomly assigned to either lifestyle changes, the blood-sugar-lowering medication metformin, or a placebo. At the study's start, almost 6% were using an antidepressant regularly.
Rubin's team found that in the lifestyle and placebo groups, study participants who were consistently on antidepressants during the study period were about twice as likely as non-users to develop diabetes over 10 years.
There was no such pattern seen in the metformin group, however. The reason for that finding, Rubin's team writes, is unclear for now.
More research required
Kivimaki said that more research is needed to understand why antidepressant use is related to diabetes.
In their study, he noted, he and his colleagues were limited to data from Finland's national medical registers. So they lacked information on lifestyle habits and other factors that might affect a person's diabetes risk.
If antidepressants themselves do contribute to diabetes, one mechanism may be via weight gain, according to Kivimaki. Weight gain is a known side effect of antidepressants, and excess weight is a prime risk factor for type 2 diabetes.
In their study, Kivimaki and his colleagues found that longer term users of antidepressants reported an average weight gain of 5.5 pounds over five years. That compared with 3 pounds among non-users.
However, Kivimaki noted that there are other potential mechanisms as well, including direct effects of the medications on blood sugar levels.
He said that further research on the relationship between antidepressant use and long-term changes in people's blood sugar levels could help show whether the drugs themselves contribute to diabetes development." (Reuters Health/ September 2010)
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