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.

http://ovidsp.tx.ovid.com/sp-3.18.0b/ovidweb.cgi?&S=BLBGFPDBADDDKCBDNCJKKDDCAJPEAA00&Link+Set=S.sh.13512_1456860318_56.13512_1456860318_68.13512_1456860318_76.13512_1456860318_78.13512_1456860318_82.13512_1456860318_106%7c3%7csl_10

A Mind-Body Program for Older Adults With Chronic Low Back Pain

Approximately 100 million individuals in the United States suffer from chronic pain. Pain is prevalent in 52.9% of the older adult population ages 65 and older. Of the 52.9% experiencing pain, 30.3% were experiencing chronic back pain. Analgesics commonly cause severe adverse effects in older adults. Because of this prevalent drug therapy problem, nonpharmacologic treatments must often be utilized for effective management of chronic low back pain.

An experimental study was conducted among 282 patients with low chronic back pain 65 years or older. The goal of this study was to assess the effectiveness of a mind-body program at increasing function and reducing pain. The patients received an 8-week group program followed by 6 monthly sessions. The program was modeled on the Mindfulness-Based Stress Reduction program. This program took regular activities such as sitting, walking, and lying down and transformed then into meditation through breathing exercises and mindful awareness of thoughts and sensations. Compared with the control group, those receiving this mind-body treatment improved short-term function and long-term current and most severe pain.

The trial did not yield sustained results in treatment of lower chronic back pain, suggesting that future development of this intervention should focus on durability. This article was particularly of interest to me because it combined two of my interest in medicine with my interest in meditation. I often use meditation as a form of stress relief, and it is intriguing to see that meditation could also be used in pain management. Prescription pain medication is not the answer  for every patient and it is very often over-prescribed. I believe that is important for pharmacists to be aware of other pain management methods and share these methods with their patients. Although I do not believe that meditation alone is the answer, I think that a combination of medication therapy and meditation could be a very effective treatment for a lot of patients suffering from chronic pain.

JAMA Intern Med. Published online February 22, 2016.

Link to article

The Need for More Education on Prescribing Opioids

When hearing the term “opioids” several ideas come to mind: addiction, abuse, under-treatment, overtreatment, severe pain, and suspicion are just a few. Opioids are undoubtedly an extremely successful route of treatment for severe pain and play a huge role in daily pain management cases. However, there is always a discussion of the risks associated with prescribing this medication.

There is often an air of distrust between physician and patient when a patient insists on opioid therapy. Unfortunately, pain cannot be measured, and there needs to be trust when prescribing this drug class. The prescriber will not know if the patient really needs the opioid for pain management or if they have developed a dependence on it. The physician is put in a position where they could under-treat the patient by refusing therapy because of the risk of abuse, or they could over-treat the patient by believing their plea for a medication they were addicted to.

There are several guidelines already in place regarding opioid prescribing, but still, much of it is up to the physician’s discretion. Right now, there is a big push for more prescriber education on the topic. For example, in 2012, the FDA encouraged a single shared Risk Evaluation and Mitigation Strategy (REMS) which required manufacturers of extended release or long acting opioids to fund accredited education on safe opioid prescribing. Currently, this program has not reached its goal number of prescribers. However, I believe with the advancement of this program, physicians will be able to make more educated and thorough decisions when it comes to prescribing opioids.

Managing pain is extremely complex, yet education on the topic is lacking. The ultimate goal would be to maintain a patient-centered approach and treat the patient in a manner in which they are comfortable and compliant with. Perhaps with more education on the topic, the physician and pharmacist can work together to make a confident decision in how to proceed with drug therapy, and hopefully avoid the mistakes that have been occurring concerning opioid therapy.

I personally see this as an opportunity for pharmacists to get more involved in the prescribing process, as they have a stronger background education on the topic. Do you think this could play a role in pharmacists eventually gaining prescribing rights?

 

Read the full article here.

Alford, Daniel P.  Opioid Prescribing for Chronic Pain — Achieving the Right Balance through Education. N Engl J Med. 2016;374:301-3

 

Opioid-induced hyperalgesia in chronic pain patients and the mitigating effects of gabapentin

Ever since the discovery of opioid medication it has been a staple in the treatment of acute and chronic pain.  However, patients who are experiencing chronic pain can experience Opioid-induced hyperalgesia (OIH).  This leads to a paradoxical chronic pain state for the patient.  The challenge is to find a way to nullify the effect of opioid medication on the patient without removing the analgesic effect.  Gabapentin, which is used to treat neuropathic pain, has been shown to limit OIH in animals receiving fentanyl and has been shown in chronic pain patients to limit their opioid consumption.  There have not been studies in the recent years on this topic.

The mechanism of OIH and the anti-hyperalgesia effects of gabapentin are not well understood but there are many studies, according to this review article, that prove its efficacy.  However, it is believed that gabapentin binds to the dorsal horn VCGGs diminishing the pain regulation pathways.  Despite this, there have not been a wide-range of standardized patient studies to definitely prove this.

This review is important because pain control is one the biggest responsibilities of a healthcare provider.  Chronic pain management will continue to be an issue in the future and opioids will be one of the ways physicians and pharmacists to treat it.  Because of this, OIH will continue to be a problem.  More research should be put into gabapentin’s effect on OIH to create a definitive therapy strategy to be used by healthcare professionals.

Stoicea N, Russell D, Weidner G, et al. Opioid-induced hyperalgesia in chronic pain patients and the mitigating effects of gabapentin. Frontiers in Pharmacology. 2015;6:104. doi:10.3389/fphar.2015.00104.