A new analysis of a high-risk clinical trial population finds that
antidepressant users were more likely to develop type 2 diabetes than were
individuals who didn't use those drugs.
The multicenter Diabetes Prevention Program tested metformin against either
placebo (plus lifestyle recommendations) or an intensive lifestyle
intervention focusing on a low-fat diet, physical activity, and weight
reduction among a population of patients at particularly high risk for
impaired glucose tolerance or type 2 diabetes. These patients included the
elderly, persons with a family history of the disease, overweight individuals,
women with a history of gestational diabetes, and minority populations.
Metformin is an antidiabetic drug that lowers blood sugar and increases
Overall, the study of 3,187 participants found that the intensive lifestyle
intervention reduced onset of diabetes by 58 percent, and metformin did so by
31 percent, compared with placebo.
These benefits caused the trial to be stopped early, and results were
published in 2002.
However, further study of the results pointed to the conclusions about
antidepressant use and diabetes, said study co-investigator Richard R. Rubin,
Ph.D., an associate professor of medicine and pediatrics at the Johns Hopkins
University School of Medicine.
Antidepressant use doubled the risk of diabetes in the placebo arm of the
study compared with people who did not use those medications and tripled the
risk among the intensive lifestyle group, Rubin said at the American Diabetes
Association's 2006 Scientific Sessions. There was no difference in the
metformin arm. Rubin is the association's incoming president and is helping to
prepare an article on this aspect of the program for future publication.
Actual depression was not the key factor, said Rubin. Higher Beck
Depression Inventory scores did not predict development of diabetes.
Antidepressant use thus may have been a marker for serious depression at some
time, even if it had been brought under control by medication, he said in an
Nor did the type of antidepressant apparently matter, said Rubin. About 76
percent of those taking antidepressants used SSRIS, but the effects were the
same as with other classes of drugs.
He noted that patients in the Diabetes Prevention Program were already at
high risk for diabetes, and he cautioned against extending these results to
"We don't know if this applies to a population not at high
risk," he said. "I would not tell a patient to stop taking
Depression and diabetes have a long and complex history together, although
which is a cause and which is a consequence is still debated.
"Depression may lead to diabetes, and abnormalities in glucose
regulation that characterize diabetes or prediabetes, including hyperglycemia
and insulin resistance, may then reinforce depression or diminish its
responsiveness to available treatments," said Patrick Lustman, Ph.D., a
professor of psychiatry at the Washington University School of Medicine in St.
Louis, in an interview.
"A lot of scientific evidence from population-based studies indicates
that depression significantly increases the risk of developing type 2
diabetes, and also that most people with depression don't seek or take
treatment for it," said Lustman. "This makes me suspect that
depression is the main force driving the association between depression and
Much research indicates that treating depression improves glycemic levels,
but while psychiatrists have learned about the metabolic side effects of some
antipsychotic drugs, they may be less familiar with the actions of
"Everyone picks on antipsychotics, but across that class there is a
wide spectrum of weight and diabetes liability," said John Newcomer,
M.D., a professor of psychiatry, psychology, and medicine at Washington
University. "You don't see that in antidepressants. There's little
evidence for a direct effect of the drug."
When treating depression in the context of diabetes or insulin sensitivity,
physicians should think about whether they want to use drugs associated with
weight gain, said Newcomer, in an interview. For instance, unipolar depression
may be treated with an antidepressant and an antipsychotic. Combining drugs
like amitriptyline and olanzapine, for instance, might well lead to weight
gain, a prime risk factor for diabetes.
"Physicians should be aware of the metabolic consequences of
psychiatric drugs beyond those of antipsychotics," said Rubin. "If
a patient is overweight and has a family history of diabetes or other risk
factors, a psychiatrist should monitor the metabolic consequences of the
The Diabetes Prevention Program was funded by several divisions of the
National Institutes of Health, including the National Institute of Diabetes
and Digestive and Kidney Diseases, National Institute of Child Health and
Human Development, National Institute on Aging, National Center on Minority
Health and Health Disparities, National Center for Research Resources, as well
as the Centers for Disease Control and Prevention and the Indian Health
Service. The American Diabetes Association and several pharmaceutical
companies provided additional funding. ▪