Anti-inflammatory drugs reduce effectiveness of SSRI antidepressants

Scientists at Rockefeller University have shown that anti-inflammatory drugs, which include ibuprofen, aspirin and naproxen, reduce the effectiveness of the most widely used class of antidepressant medications, the selective serotonin reuptake inhibitors, or SSRIs, often prescribed for depression and obsessive-compulsive and anxiety disorders. The discovery, published online this week in the Proceedings of the National Academy of Sciences, may explain why many depressed patients taking SSRIs do not respond to antidepressant treatment and suggests that this lack of effectiveness may be preventable. The findings were made in mice and confirmed in humans.

In the recent study, investigators in Rockefeller’s Fisher Center for Alzheimer’s Disease Research treated mice with antidepressants in the presence or absence of anti-inflammatory drugs. They then examined how the mice behaved in tasks that are sensitive to antidepressant treatment. The behavioral responses to antidepressants were inhibited by anti-inflammatory and analgesic treatments. They then confirmed these effects in a human population, finding that depressed individuals who reported anti-inflammatory drug use were much less likely to have their symptoms relieved by an antidepressant than depressed patients who reported no anti-inflammatory drug use. The effect was dramatic: in the absence of any anti-inflammatory or analgesic use, 54 percent of patients responded to the antidepressant, whereas success rates dropped to approximately 40 percent for those who reported using anti-inflammatory agents.

“The mechanism underlying these effects is not yet clear. Nevertheless, our results may have profound implications for patients, given the very high treatment resistance rates for depressed individuals taking SSRIs,” says Jennifer Warner-Schmidt, a research associate in Paul Greengard’s Laboratory of Molecular and Cellular Neuroscience at Rockefeller.

“Many elderly individuals suffering from depression also have arthritic or related diseases and as a consequence are taking both antidepressant and anti-inflammatory medications. Our results suggest that physicians should carefully balance the advantages and disadvantages of continuing anti-inflammatory therapy in patients being treated with antidepressant medications,” says Greengard, who is Vincent Astor Professor and director of the Fisher Center for Alzheimer’s Disease Research at Rockefeller.

The study may be especially significant in the case of Alzheimer’s disease. Such patients commonly suffer from depression and unless this can be treated successfully, the course of the illness is likely to be more severe. Depression in the elderly is also a risk factor for developing Alzheimer’s disease and researchers have suggested that treating depression in the elderly might reduce the risk of developing the disease.

This research was supported in part by grants from the National Institute of Mental Health and the National Institute on Aging at the NIH and The Fisher Center for Alzheimer’s Research Foundation.

Proceedings of the National Academy of Sciences online: April 25, 2011
Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans
Jennifer L. Warner-Schmidt, Kimberly E. Vanover, Emily Y. Chen, John J. Marshall and Paul Greengard


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