Anti-inflammatory drugs reduce effectiveness of widely used antidepressant medications

Scientists at the Fisher Center for Alzheimer's Disease Research at The Rockefeller University, led by Paul Greengard, Ph.D., and Jennifer Warner-Schmidt, Ph.D., 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, taken for depression and obsessive-compulsive disorder and anxiety disorders. This surprising discovery, published online this week in the Proceedings of the National Academy of Sciences, may explain why so many depressed patients taking SSRIs do not respond to antidepressant treatment and suggests that this lack of effectiveness may be preventable. 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.

In the recent study, investigators treated animal models with antidepressants in the presence or absence of anti-inflammatory drugs. They then examined how the models behaved in tasks that are sensitive to antidepressant treatment. The behavioral responses to antidepressants were inhibited by anti-inflammatory/analgesic treatments. They then confirmed these effects in a human population.  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 rather dramatic since, in the absence of any anti-inflammatory or analgesic use, 54% of patients responded to the antidepressant, whereas, success rates dropped to approximately 40% 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," noted Dr. Warner-Schmidt.  Dr. Greengard added, "Many elderly individuals suffering from Alzheimer's disease 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."

This is the third significant finding in nine months by Fisher scientists. Previously, Fisher Center researchers headed by Nobel laureate Dr. Paul Greengard in the Fisher laboratory at The Rockefeller University found two new ways to control beta-amyloid.  In September of 2010 published in Nature, they discovered a previously unknown function for a protein in the brain that stimulates the production of beta-amyloid which is known to contribute to the cause of Alzheimer's. Controlling this protein, called GSAP, is a key and also has the advantage of not interfering with other life functions which caused the failure of many earlier drug trials. In another finding published in the FASEB Journal in March 2011, they also succeeded in accelerating the breakdown of accumulated beta-amyloid. They discovered that a process called autophagocytosis reduces the buildup of beta-amyloid in isolated cells and might be utilized to eliminate the buildup of beta-amyloid in the brains of Alzheimer's patients. They discovered that a compound called SMER28 lowers the level of beta-amyloid found in nerve cells. According to Dr. Greengard, "the combination of inhibition of formation and acceleration of breakdown of beta-amyloid represents a new and powerful strategy for treating Alzheimer's disease."

"This is the third major finding by the Fisher Center scientists at the Greengard lab in only nine months," says Kent L. Karosen, President of the Fisher Center for Alzheimer's Research Foundation. "It's quite amazing that their novel techniques are proving to be so prolific. This latest finding shows their success in not only one day ending Alzheimer's, but in also having even broader implications for society."