The Impact of NSAIDs on Depression in Osteoarthritis Patients

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November 6, 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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Posted in: Pain/Arthritis