Common painkillers decrease effectiveness of antidepressants: Study

According to a latest study, antidepressants like Prozac and Aspirin do not mix. Researchers found that painkillers such as aspirin and ibuprofen appear to decrease the effectiveness of a popular class of antidepressants that includes Prozac, Paxil, Lexapro and Zoloft and Celexa.

These findings, published Monday in the journal Proceedings of the National Academy of Sciences explain why even the most effective antidepressants don't work for everyone. At best only about two-thirds of patients respond effectively to Celexa and other selective serotonin reuptake inhibitors, or SSRIs. Non-steroidal anti-inflammatory drugs, or NSAIDs, are a widely used class of pain medicines and include aspirin and ibuprofen but not acetominephen.

Jennifer Warner-Schmidt, first author of the study and a researcher at Rockefeller University in New York said, “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.”

However researchers add that it is not clear yet whether taking ibuprofen for an occasional headache is enough to blunt the effect of an antidepressant or whether it takes long-term use for a condition such as arthritis for there to be an inhibitory effect.

Major depression is estimated to affect 16.5% of U.S. adults over their lifetime, according to the National Institute of Mental Health. And it is to be noted that antidepressants, mainly SSRIs, were the second most popular drug class prescribed in the U.S. last year, netting $11.6 billion in sales, according to IMS Health, which tracks pharmaceutical sales. There were 253 million prescriptions for antidepressants in the U.S. in 2010.

For this study the research team initially looked at changes of a biochemical marker of depression in mice when the animals were consistently given an SSRI, an anti-inflammatory or both medicines. They noted if there was any effect from combining the two, it would have been to improve depressive symptoms since inflammation, an immune system response to infection, it thought to worsen or even cause depression in some people, Dr. Warner-Schmidt said. But they found that mice given a combination regimen had a dampened response—and sometimes no response—to the antidepressant compared to the group that got the SSRI alone. Mice who received just the anti-inflammatory didn't show any change in the protein marker, called p11.

This was followed up by studying humans. By examining data from an already-completed 4,000-patient large clinical trial of depressed patients known as STAR*D, they found that there was indeed a significant difference. Depressive symptoms—such as feeling down, crying more frequently than usual or having decreased appetite—in patients who took Celexa went away 55% of the time, but that rate dropped to 45% in individuals who reported they also had taken an anti-inflammatory.

Steve Wengel, a depression researcher and chair of the University of Nebraska Medical Center psychiatry department who wasn't involved with the current study said, “If it's substantiated in further studies, it would certainly imply we would have to use a different treatment for patients who are chronically taking NSAIDs.” But Dr. Wengel said that physical pain can make depression worse so patients taking both types of medicines may have harder-to-treat depressions. The Rockefeller researchers plan to carry out a study that follows human SSRI users over time—some taking NSAIDS and some not—to better investigate the issue.

According to Madhukar Trivedi, a psychiatry professor at the University of Texas Southwestern Medical Center, Dallas, who co-led the STAR*D trial and wasn't involved in the new study, called the mouse data “clearly compelling” and the STAR*D analysis “very fascinating” but in need of follow-up. He added that he would not routinely urge depressed patients to stop taking an NSAID based on the findings, but if they weren't responding well to the SSRI, he would evaluate whether they needed the painkiller. Patients who are taking these medicines shouldn't stop them on their own, experts said, and should talk to their doctor if they have concerns.

“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,” said Paul Greengard, senior author on the paper and head of the molecular and cellular neuroscience lab at Rockefeller. Previous studies have suggested that anti-inflammatories may actually boost the potency of two other but less common types of anti-depressants, known as tricyclic or noradrenergic anti-depressants.

Dr. Ananya Mandal

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.


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