Antidepressant Failure May Be Due to NSAID Use

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Clinical depression is one of the most commonly treated medical conditions, affecting nearly 19 million American adults. Selective Serotonin Reuptake Inhibitors (SSRIs) such as Prozac and Paxil are among the most frequently prescribed medications to treat depression, but as many as one-third of patients report that the drugs are not adequately relieving their symptoms. Researchers from The Rockefeller University have found a potential reason why – anti-inflammatory drugs may reduce the effectiveness of the antidepressant medication.

Researchers Paul Greengard PhD and Jennifer Warner Schmidt PhD of the Fisher Center for Alzheimer’s Disease Research at Rockefeller first tested the interaction of SSRI antidepressant medications and non-steroidal anti-inflammatory drugs (NSAIDs) in mice. The mice given the pain relievers responded less well to the antidepressants. They were also found to have less P11in their brains. Because this protein is involved with serotonin receptor function, mice deficient in P11 display depression-like symptoms.

Read: More than Half of Patients Give Up Early on Anti-Depression Treatment

To test the theory in humans, the researchers used data from the STAR*D study, which followed more than 4,000 people over seven years. Only 40% of depressed individuals who reported anti-inflammatory use responded to antidepressant treatment, compared to 54% of those not taking the drugs.

"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," notes Dr. Warner-Schmidt.

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NSAID’s block the function of two prostaglandins that promote inflammation, pain and fever. As a consequence, these symptoms are reduced. Popular brand names of over-the-counter products include Advil (ibuprofen) and Aleve (naproxen). Aspirin is also an anti-inflammatory medication.

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SSRI’s work by blocking the re-absorption of serotonin in the brain, which helps boost mood. They also help brain cells send and receive chemical messages. Over the past decade, antidepressants have become the most commonly prescribed drugs in the US, more than high blood pressure and cholesterol drugs according to the Centers for Disease Control and Prevention (CDC).

The study findings especially impact the elderly, as those suffering from depression often also have arthritic or related diseases and are taking both types of drugs, notes Dr. Greengard. Untreated depression is also a risk factor for developing Alzheimer’s disease.

Patients and doctors should be aware of the problem because they have other options. Tricyclic antidepressants, for example, probably do not interact the same way, Greengard says, and in fact, previous studies have found that NSAIDs may actually boost the potency of tricyclic or noradrenergic antidepressants.

Journal Reference:
Jennifer L. Warner-Schmidt, Kimberly E. Vanover, Emily Y. Chen, John J. Marshall, and Paul Greengard
Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans
PNAS 2011 ; published ahead of print April 25, 2011, doi:10.1073/pnas.1104836108

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