Evolving Therapeutic Strategies to Improve Nonsteroidal Anti-inflammatory Drug Safety

The question of how to treat chronic pain is one that seems to be drawing more and more attention. As people are living longer, more will eventually come to face chronic pain caused by osteoarthritis, diabetes neuropathy, or other chronic conditions. Additionally, increasing misuse of opioid pain medications and the dangerous side effects associated with medications like NSAIDs has pressed for development of alternative forms of pain management. This retrospective analysis of 2177 patient charts looked at the comparative effectiveness of three topical options for chronic pain management: two compounded creams and one NSAID based gel.

Cream I creams contained 20% Flurbiprofen, 5% Tramadol, 0.2% Clonidine, 4% Cyclobenzaprine, and 3% Bupivacaine. Cream II contained 20% Flurbiprofen, 2% Baclofen, 0.2% Clonidine, 10% Gabapentin, and 5% Lidocaine. The NSAID based gel, Voltaren, contains 1% diclofenac sodium. 1141 patients were given Cream I, 527 received Cream II, and 509 patients received Voltaren gel.  Voltaren gel caused a decrease in pain intensity score of 19%, which is statistically significant to be less than the pain intensity decrease caused by both Cream I (37% ) and Cream II (35%). It is hypothesized in the journal article that this increase in efficacy of the two compounded creams stems from the inclusion of multiple active ingredients with different mechanisms of action.

Use of a cream for chronic pain treatment is beneficial in many areas. It can be topically administered at the site of the pain and will have lower systemic bioavailability.  This will lead to less of the dose-limiting adverse effects commonly seen with oral medications such as NSAIDs and opioids. Do you think topical pain medication should always be an option for patients with chronic pain? Can you think of an example of when it may not be as effective as an oral medication?


Somberg JC, Molnar J. Retrospective Evaluation on the Analgesic Activities of 2 Compounded Topical Creams and Voltaren Gel in Chronic Noncancer Pain. Am J Ther. 2015;22:342-349.


Pain Intensity Related to Smoking Dependency

It has been proven through previous studies that there is a positive correlation between smoking dependency and pain. It is hard, however, to determine which comes first.  Is it that pain patients turn to smoking or the smoking creates higher levels of pain?  Previous studies identified the correlation between the two, but left out some important parameters we needed to get a closer look at this correlation.  A problem with previous studies is that they specifically looked at patients that were being seen for pain.   If a patient is seeking treatment for pain then it is probably on the more moderate to severe end of the pain scale.  This particular study that I looked into wanted to see how strong this correlation was when comparing smoking dependency in patients that had little to no pain against patients that had moderate to severe pain.

In this study, they wanted to look at how strong the correlation was between patient’s pain and their smoking habits. The best way to measure these two categories was with surveys.  Participants in this study were given multiple surveys to fill out to determine their pain level and smoking dependency.  These surveys include  the “Smoking History Questionnaire” (SHQ) to understand the patients smoking history, the “Fagerstrom Test for Nicotine Dependence” (FTND) that helps determine how depend a patient is to smoking, “The Short –Form Health Survey” which was used to determine the bodily pain in the patient, and the “Positive and Negative Affect Scale” (PANAS) which assessed a patients emotions.  The DSM-IV was also used during the assessment process.

The results of the study showed that there was an increase in smoking dependency in individuals that have a higher intensity of pain.  That being said, the study did have many limitations including diversity issues and relying heavily on self-reporting.  This study was a good step towards trying to figure out whether smoking dependency was associated with increased levels of pain.   This study is helpful because we can use this information to help patients that are trying to quit.  We can try to treat their pain so that we can reduce their dependency.  Further studies would help better understand this correlation and improve treatment of this disease.

http://Psychiatry Res. 2016 Mar 30;237:67-71. doi: 10.1016/j.psychres.2016.01.073. Epub 2016 Feb 3.

Pain Affects Clinical Patterns and Treatment Outcomes for Patients With Major Depressive Disorder Taking Fluoxetine

Although pain is not listed in the Diagnostic and Statistical Manual of Mental Disorders (DSM) as a symptom of major depressive disorder (MDD), previous studies have shown that a large proportion of patients with depressive report symptoms of pain. In addition, research has shown that pain and depression may share common pathways in the body. They may be connected through stress and the hypothalamic-pituitary-adrenal axis.

This study aimed to see how baseline levels of pain affect outcomes in patients treated for MDD with fluoxetine. Specifically, the study hypothesized that severity of baseline would be associated with poorer outcomes and a distinct clinical profile. For 6 weeks in an in-patient hospital, 119 MDD patients were given 20 mg fluoxetine daily doses and monitored for various outcomes. Outcomes included adherence, pain severity and pain interference (measured by the body pain index of the Medical Outcomes Study Short-Form), symptom severity (measured by the Hamilton Rating Scale for Depression), social functioning (measured by the Work and Social Adjustment Scale), and adverse event severity (Utvalg for Kliniske Undersogelser Side Effect Rating Scale).

Results from this study showed that pain and multiple aspects of MDD were associated and that patients with higher baseline levels of pain experienced more severe depressive symptoms. Specifically, subjects with higher levels of pain had greater risk of suicide and stressful life events. They also had less improvement in depressive symptoms despite receiving the same fluoxetine treatment as well as more functional impairment.

This study reminds me of the pain lecture from Dr. Pruskowski as she also explained the connection between depression and pain. Being cognizant of this connection can help us better understand our patients as pharmacists. Perhaps we can inquire about MDD patients’ pain levels during medication therapy management. I would be curious to see if there is evidence supporting the use of pain treatments to help improve depressive symptoms in those with both severe pain and depression. If so, many patients may have a drug therapy problem of needing additional therapy.

Lin H, Wang F, Lin C. Pain affects clinical patterns and treatment outcomes for patients with major depressive disorder taking fluoxetine. J Clin Psychopharmacol. 2015; 35(6):661-6