Fisher Center Scientists Show That Anti-Inflammatory Drugs...

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April 25, 2011

Fisher Center Scientists Show That Anti-Inflammatory Drugs Reduce Effectiveness of SSRI Antidepressants

Scientists at the Fisher Center for Alzheimer's 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, 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 Scientist in Dr. Greengard’s lab. 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."

The Fisher Center for Alzheimer’s Research Foundation is a leading source of funding for Alzheimer’s research and education. They serve Alzheimer’s patients and their families by seeking to understand the causes of, discover a cure for, and improve the lives of people with Alzheimer’s disease. Nobel laureate Dr. Paul Greengard directs the Foundation’s team of internationally renowned scientists. Of the money raised by the Foundation, only 9 cents out of every dollar is used for overhead and administrative purposes. For more information about the Fisher Center for Alzheimer’s Research Foundation, click here.

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5 Responses to Fisher Center Scientists Show That Anti-Inflammatory Drugs Reduce Effectiveness of SSRI Antidepressants

  1. Gisela Turner says:

    It may be of interst to you: My husband, 88 yrs, a former muclear scintist has lost all or nearly all memory of former events and friends. More recent events are are also forgotten within sometimes only 24 hours. Yet, he can mentally still solve slightly complicated arithmetic problems in a very short time! My question is, have you observed a similarity between patients of former higher education? Thank you for sending me your scientific news reports.

  2. Sharon Close says:

    My mother, an ex bookkeeper and was an avid crossword puzzler, she 75 years old and in the mid to later stages of Alzheimer’s. Her memory span is about 3 minutes. Although she cannot remember how to work her computer or mobile phone or do crossword puzzles and has problems remembering names, dates and where she is, she can spell any word you give her without hesitation. I have realized that although her memory is dimming she is still very intelligent and for those 3 precious minutes at a time can make perfect sense and is still very wise.

  3. Tammy Taylor says:

    this may be of interest to you. My mom was diagnosed with vascular dementia and alzheimer’s in aug 2009, stage 4-5. she was under chiropractic care for 1 year until she could no longer go physically. when she was her adl’s got better and she moved from the alz unit to the rehab unit…when she stoppped she got worse…he md also worked with us for her to be on natural supplements instead of rx drugs.
    something to consider…treat the person, the cause of the disease rather than the symptoms they have. also here is a concept, to teach the caretakers in the nursing homes how to work with the symptoms rather than treat them with another pill. my Mom has not been on a dementia medication in a year, and is a lot better off for it.

  4. Michelle Woodruff says:

    I wonder if acetominophen (Tylenol) is also on the list of problematic analgesics to use in conjunction with anti-depressants?

  5. Paula Schuck says:

    I was also curious about Tylenol. I appreciate the research here and the excellent social media work. I wonder why more workers are not trained to effectively manage and work with patients having Alzheimer’s and dementia.


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