Self Care Pharmacy Blog


The Impact of NSAIDs on Depression in Osteoarthritis Patients

November 6th, 2013

By Anna Smith, Cedarville University PharmD Student

Imagine waking up every morning for the rest of your life with stiff, aching joints. This is what people with osteoarthritis have to go through.  Osteoarthritis is the result of cartilage breakdown in the joints and can result in pain, swelling, and reduced joint motion.1  It is estimated that 27 million Americans suffer from osteoarthritis, which is a chronic condition.  Although there is no cure, medications have helped to relieve pain.2  On top of the daily pain endured, osteoarthritis patients are twice as likely to struggle with depression.3

Fox News recently released an article about a study published by The American Journal of Medicine.  The study found non-steroidal anti-inflammatory drugs (NSAIDs) used to relieve pain from osteoarthritis, such as ibuprofen and naproxen, may also play a role in reducing depression related to osteoarthritis.  The study used approximately 1500 osteoarthritis patients not taking antidepressants.  Patients were either given over-the-counter (OTC) NSAIDs, Celebrex, or a placebo to observe the impact on depression.3  Depression was measured using the Patient Health Questionnaire (PHQ-9) constructed by Pfizer, using a scale of 0-27.  The total points scored in the questionnaire represent different categories of depression, 1-4 being minimal depression, 5-9 as mild depression, 10-14 as moderate depression, 15-19 as moderately severe depression, and 20-27 being severe depression.4  The median score for the patients before treatment was 3, showing scores were low and around the minimal depression range.  Results showed combined data of OTC NSAIDs and Celebrex lowered depression scores significantly more than the placebo (p<0.039).  However, OTC NSAIDs alone did not have a significant impact compared to the placebo in lowering depression symptoms (p=0.087).  With these results, researchers are suggesting NSAIDs may help reduce depression symptoms in osteoarthritis patients.5

Research on the relationship between NSAIDs and depression is lacking.  The only outside source supporting the use of NSAIDs for depression dealt with interferon-induced (IFN-induced) depression.  This article stated interferon-alpha (used for treatment in some chronic diseases and viral illnesses) can cause depression as a side effect.  NSAIDs are known to treat many IFN-induced side effects. The article suggests NSAIDs could play a role in reducing IFN-induced depression.6  Although NSAIDs could possibly reduce this type of depression, they have been found to interact negatively with antidepressants.  A study showed that NSAIDs were linked to increased depression in patients using selective serotonin reuptake inhibitors to treat depression.7  This suggests simultaneous use of NSAIDs and antidepressants may reduce effectiveness of depression treatment.

By looking through outside sources, it is clear the study on NSAIDs easing depression is limited.  First, there is not enough outside literature and research to support NSAIDs playing a role in depression.  Also, the results could have been due to pain relief.  Rather than having a direct method of action in reducing depression, the treatment could have relieved pain and put patients in a better mood.  The study also stated OTC NSAIDs, Celebrex, and placebo all reduced depression scores.  Since patients taking the placebo were also less depressed, this could mean outside factors altered their mood.  Furthermore, the median score of depression on the PHQ-9 scale before treatment was a 3.  With a score of 3, patients are thought to only have minimal depression, which is the lowest depression category on the scale.4  Without having higher scores, I feel that the data does not accurately represent patients who are truly depressed.

Taking the study and outside research into consideration, I would still recommend using NSAIDs for relieving osteoarthritis pain.  These medications can still be effective in the relief of pain.  However, I would not recommend NSAIDs for treating depression since there is currently no evidence that NSAIDs work to treat depression alone.  Since NSAIDs have been shown to interfere with antidepressant treatment, I would also advise caution when recommending NSAIDs to patients taking antidepressants.

I do not agree with the study that NSAIDs play a role in easing depression of arthritis patients.  There are too many limiting factors to the study and not enough supporting evidence.  There was no significant difference observed between OTC NSAIDs and the placebo on lowering depression symptoms.  Also, the participants did not have high depression scores to start out with.  Additional resources do not support a mechanism for NSAIDs lessening depression.

There does not appear to be a significant amount of research on NSAIDs and depression.  The study mentioned by Fox News may lead to new research studies dealing with NSAIDs and depression, which may clarify a direct or indirect correlation.  The link between pain and depression is complex, and depression may only be lessened by NSAIDs due to their influence on pain.  Until further research is conducted, we must ask – do NSAIDs truly play a significant role in reducing depression?




  1. U.S. National Library of Medicine. Osteoarthritis. MedlinePlus. Updated September 27, 2013.  Accessed October 27, 2013.
  2. Arthritis Foundation. Osteoarthritis. Arthritis Foundation. Accessed October 27, 2013.
  3. Ibuprofen may ease arthritis patients’ depression. Fox News Published September 26, 2013. Accessed October 27, 2013.
  4. Pfizer Inc.  Patient Health Questionnaire (PHQ-9).  SAMHSA-HRSA Center for Integrated Health Solutions.  Accessed November 1, 2013.
  5. Iyengar, RL, Gandhi S, Aneja A, Thorpe K, Razzouk L, Greenberg J, Mosovich S, Farkouh M. NSAIDs Are Associated with Lower Depression Scores in Patients with Osteoarthritis. The American Journal of Medicine. 2013;126(11):1017.e11-1017.e18. Accessed November 1, 2013.
  6. Asnis GM, De la Garza II R, Kohn SR, Reinus JF, Henderson M, Shah J. IFN-induced depression: a role for NSAIDs. Psychopharmacol Bull. 2003;37(3):29-50. Accessed October 27, 2013.
  7. Gallagher PJ, Castro V, Fava M, Weilburg JB, Murphy SN, Gainer VS, Churchill SE, Kohane IS, Iosifescu DV, Smoller JW, Perlis RH. Antidepressant Response in Patients with Major Depression Exposed to NSAIDs: A Pharmacovigilance Study. Am J Psychiatry.  2012;169(10):1065-1072. doi:10.1176/appi.ajp.2012.11091325.


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5 Responses to “The Impact of NSAIDs on Depression in Osteoarthritis Patients”

  1. Tirhas Mekonnen Says:

    Anna your article is very interesting. I would love to read more studies with good evidences. I also think that treating depression with NSAIDs may alleviate the symptoms of depression. For instance someone who is depressed may have headache and other in general pain and achy symptoms. NSADs might alleviate some of those symptoms and so NSAIDs may seem to help treat the depression itself. It is very interesting to me to know from the study how they measure their findings.
    As you have mentioned there are studies about NSAIDs helping people with osteoarthritis. It kind of makes sense since NSAIDs are not selective and work by their effect on COX1 and COX2. I believe they may help reduce that inflammation and help the patient alleviate the pain. However the relationship between NSAIDs and depression and the mechanism by which NSAIDs treat depression is not clear to me.
    Overall the article is very interesting and what you wrote makes sense. I agree on your decision to recommend NSADs for osteoarthritis and not to recommend for depression (especially not for primary treatment of depression).

  2. Maria Miller Says:

    Anna this is such an interesting post!! I’ve never heard of NSAIDs being used as possible treatment for depression especially in the case of patients with osteoarthritis (OA). I’ve also never thought of the fact that those with OA might also suffer depression because of their loss of function in their joints and the pain they bear on a daily basis. It makes sense that they would feel depressed and may also feel better while using NSAIDS. I agree that they could be experiencing almost a placebo effect on their depression with the use of NSAIDs due to their pain relief and therefore they are happier. I would be interested to see if more studies are done on this topic and to see what they find. I believe that the prescription medications available for depression are probably better for treating it, but in the case of an OA patient, if they take both then they’re just going to feel worse. How interesting that those products counteract each other in that way.
    This was such an enlightening article and shows what future treatments could come into practice with more research.

  3. Elizabeth Ledbetter Says:

    Anna, I think you made some great points in this post. I think it is bold to say that NSAIDs may, in fact, cause a decrease in depression in OA patients. I’m sure that there is a correlation between NSAID use and lower depression because of the pain relief, but i’m not sure you can assume there is a causal relationship. As you mentioned, I don’t think this “conclusion” can be extrapolated to the general population. There is not enough evidence other than this one study to support the idea that NSAIDs lower depression in OA patients.

    I agree with you that I would still recommend NSAIDs for OA. I am curious to see if there is an increase in NSAID purchase after this article has been published.

  4. Olumami Amaye Says:

    The article is very interesting, but I would like to see the future direction for researches in the area of treating depression with OTC NSAIDs. First I totally disagree with the research of treating depression with OTC NSAIDs, but will have to admit that NSAIDs are very good medications for the management of osteoarthritis. As a future pharmacist, I would recommend OTC NSAIDs to my patients for treatment of osteoarthritis. According to the article NSAIDs doesn’t truly play a significant role in reducing depression? The best are prescription medication for depression. Although the average changes in depression symptoms seen in the study would not be enough for patients to notice in their everyday lives, the research lack correlation between depression and OA. This is a very good article, but the evidence does not support the research.

  5. Yevgeniy A Solokha Says:

    I don’t think that we can say for sure whether NSAIDs play a significant role in depression treatment for osteoarthritis patients until more research is done. However, I do believe that, based on the study results, that they may have an important role. You mentioned that the pooled data of both NSAIDs and Celebrex did indicate a statistically significant result. I would argue that even a small placebo effect due to the patient’s belief that additional NSAID therapy would help with their pain and depression is significant if it makes their day go a little bit smoother.

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