NSAIDs Reduce Effectiveness of Antidepressants

Patient Expert

Researchers at the Fisher Center for Alzheimer's Disease Research at The Rockefeller University have published the results of their recent study, which showed that non-steroidal anti-inflammatory drugs (NSAIDs) reduced the effectiveness of selective serotonin reuptake inhibitor (SSRI) antidepressants.

NSAIDs include over-the-counter medications like ibuprofen, aspirin and naproxen as well as prescriptions drugs such as Celebrex, Daypro, diclofenac, etodolac, ketoprofen, meloxicam, Mobic, Naprosyn, Relafen, Toradol, Voltaren, etc.

You may be wondering what this study has to do with chronic pain.   Antidepressants are sometimes prescribed as a treatment for chronic pain because they help increase serotonin, which is important for pain modulation.   If NSAIDs prevent antidepressants from being effective for depression, they may also interfere with the ability of antidepressants to reduce pain.

Study Design and Results

Scientists first tested their theory on mice, then humans.   In the animal model, mice were given SSRI antidepressants.   Part of the mice were also given an NSAID.   Not only did the mice who received both the anti-inflammatory and the antidepressant score worse on tests measuring their stress and depression than those who received only the antidepressant, there was also less of the SSRI found in their blood.

In the human portion of the study, researchers examined data gathered in separate clinical trial of 4,000 depressed patients.   They found that the people who had reported taking NSAIDS were much less likely to experience improvement in their symptoms when they took an antidepressant than those who used no NSAIDS.   Of patients taking only the SSRI, 54% reported symptom improvement after 12 weeks.   But only 45% of those taking both an SSRI and an NSAID showed improvement.   Interestingly, the results were the same whether individuals took NSAIDs on a regular basis or only once or twice during the 12 weeks.

The scientists are not yet clear on exactly how NSAIDs interfere with the effectiveness of SSRIs, but they felt the results were significant enough to suggest that physicians should carefully balance the advantages and disadvantages of continuing anti-inflammatory therapy in patients being treated with antidepressant medications.

My Thoughts...

While more research needs to be done, I think there is enough evidence to warrant talking with your doctor if you are taking both an antidepressant and an anti-inflammatory medication and are finding that the antidepressant is not helping your depression or your chronic pain.

Although SSRI was the only type of antidepressant studied, if you are taking a serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressant (like Cymbalta or Savella) and it is not reducing your symptoms, it might be a good idea to discuss this study with your doctor.   Since both SSRIs and SNRIs affect serotonin levels, it's worth considering the possibility that NSAIDs could have similar effects on both.

Warner-Schmidt JL, et al. Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans. Proc Natl Acad Sci U S A. 2011 Apr 25.

Fisher Center Scientists Show That Anti-Inflammatory Drugs Reduce Effectiveness of SSRI Antidepressants. Fisher Center for Alzheimer's Research Foundation. April 25, 2011.

Painkillers and antidepressants might make a bad mix. CTV News. April 26, 2011.

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