Why do antidepressants work effectively for some and not others? There are a number of reasons which may explain the phenomenon. One of the most common is misdiagnoses of the problem, such as a milder or situational form of anxiety being read as depression. The other is being prescribed the wrong class of anti-depressants; different classes block or produce different chemicals in the brain, meaning that a patient given the wrong class may not have the correct imbalance targeted. Or, their ineffectiveness could be as simple as a drug interaction, suggests a new study from The Rockefeller University in New York City.
Researchers found that mice consistently given a combination of a common painkiller and an SSRI (the largest class of antidepressants) had a reduced response—and in some cases no response—to the antidepressant compared to mice given an SSRI alone.
The research team then scoured data from a previously completed seven-year clinical trial of depressed patients known as the Sequenced Treatment Alternatives to Relieve Depression (STAR*D), which involved over 4,000 patients aged 18 to 75, looking for the same effect in humans. They found that SSRIs relieved depressive symptoms in 54 percent of patients not taking NSAIDs, compared with 40 percent of those who reported taking both antidepressants and anti-inflammatory painkillers.
The findings were surprising since the researchers had theorized that combining an anti-inflammatory with an antidepressant would improve, not reduce, depressive symptoms since inflammation is thought to worsen or cause depression in some people, said researcher and co-author of the study Dr. Jennifer Warner-Schmidt. “It appears there’s a very strong antagonistic relationship between NSAIDs and SSRIs. This may be one reason why the response rate (in patients of SSRIs) is so low.”
Dr. Warner-Schmidt says until a “double-blind real clinical trial is done,” they aren’t sure what dosage of anti-inflammatory is required or over what period of time the painkiller would have to be taken to produce the negative effect. “We may only be looking at people who are taking NSAIDs over a long period of time, but it’s not clear,” she said.
Paul Greengard, the study’s senior author and Vincent Astor Professor of the Laboratory of Molecular and Cellular Neuroscience at Rockefeller University, said “physicians should consider the advantages and disadvantages of giving an anti-inflammatory with the antidepressant depending on how severe the pain is and how depressed they are.”
Experts urge that patients currently taking these medications should NOT discontinue their use on their own, but should talk to their doctor if they have concerns. “If people out there are having trouble with SSRI efficacy and they happen to be taking anti-inflammatory drugs, they may want to speak with their clinician to evaluate whether they need to continue on the anti-inflammatory drugs, and if so, they may consider changing their antidepressant to a different class of antidepressant,” said Dr. Warner-Schmidt.
According to the National Institute of Mental Health, major depression is estimated to affect 16.5 percent U.S. adults over their lifetime. In 2010 there were 253 million prescriptions for antidepressants, the bulk of which were SSRIs, in the U.S. alone.
The study findings were published in the April 25 online edition of the Proceedings of the National Academy of Sciences.
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