The Rise of NSAIDs as Opioid Alternatives: a Case for Cautious Optimism

When it comes to pain management, you might find it surprising to learn that relatively few medication choices exist for the practitioner. For severe pain, the first class of drugs prescribed is usually opioid analgesics. But with the national opioid crisis, prescribers are increasingly searching for viable alternatives – which, by itself, is a good thing. Aside from opioids, anticonvulsants (like gabapentin), corticosteroids (such as prednisone and methylprednisolone), muscle relaxants (cyclobenzaprine, tizanidine, methocarbamol), and non-steroidal anti-inflammatories, known as NSAIDs (ibuprofen, meloxicam, naproxen, diclofenac, celecoxib) all have the potential to treat certain types of pain – but each comes with its own risks, as shown in the following table:


Analgesic Drug Adverse Effects Pain Indication
NSAIDs Cardiovascular (heart attack, stroke), Gastrointestinal (ulcers, bleeding), Renal system (kidney failure) Inflammation
Opioids CNS Depression (anxiety, confusion, depression, insomnia, respiratory failure), Gastrointestinal (constipation, nausea), Abuse potential Severe pain
Muscle Relaxants Cardiovascular (hypotension), CNS (confusion, drowsiness, dizziness, fatigue, irritability) Muscle spasms or spasticity
Corticosteroids Cardiovascular (hypertension), CNS (psychiatric disturbance, emotional lability, seizure), Endocrine (diabetes, fluid retention), Gastrointestinal (pancreatitis, peptic ulcer, ulcerative esophagitis), Infection, Osteoporosis, Wound Healing Impairment Inflammation
Anticonvulsants CNS (dizziness, drowsiness, fatigue, vertigo), Cardiovascular (peripheral edema), Endocrine (weight gain, hyperglycemia), Gastrointestinal (diarrhea, nausea/vomiting), Ophthalmic (blurred vision, double vision) Neuropathic (nerve) pain


Any of these drug classes in various combinations may be appropriate for pain management – with their use determined by the prescriber based on the patient’s unique physiological, biological and mental characteristics and accompanying drug regimen, weighed against any side or unintended effects. For example, an injured worker with diabetes and hypertension should avoid prednisone and NSAIDs, but when inflammation is present and such drugs are indicated, the strictest precautions must be taken to avoid adverse effects.


The choice to use opioids is not an easy one, as their misuse can lead to respiratory depression, overdose, and death. And while NSAIDs are increasingly being prescribed as an alternative, they can have their own adverse effects, including stomach bleeding, heart attack and stroke, all of which can be equally disastrous. Still, when an injured worker is at risk of misuse/abuse or overdose with opioids, alternatives should be considered.


Pain management is not an “absolute” practice and can be complicated. It is difficult to anticipate what treatment an individual will respond to and how various medication regimens will affect outcomes. For example, individuals taking over-the-counter cold remedies containing acetaminophen, aspirin or ibuprofen seldom consider how those drugs will affect prescription pain medications or other drugs they are taking. Such risks should be anticipated by the prescriber and discussed with the individual to prevent negative, even tragic outcomes. The recent downward trend in opioid utilization is a step in the right direction, but that step must be taken while considering that alternative drugs carry their own risks – and are not necessarily more effective or “automatically” safer.


Have questions regarding the use of opioids in workers’ compensation claims administration? KeyScripts can help. Call 866.446.2848 and ask to speak to a clinical pharmacist, or email schitwood@keyscriptsllc.com.


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Rise of Buprenorphine May Signal Move Toward More Responsible Prescribing

Typically, the increased utilization of a brand drug – particularly an opioid – is cause for heightened awareness by workers’ compensation claims payors/adjusters. The brand opioids Belbuca® and Butrans® have been making a steady climb up the rankings on top opioid reports of late (with Butrans® cracking the top 10 among some of our customers’ top opioids in 2017), but that rise may in fact signal a shift in the prescribing environment toward more responsible, less addictive entities.


The active chemical in both Belbuca® and Butrans® is buprenorphine, a high-affinity opioid with mixed agonist-antagonist efficacy at standard opioid sub-receptors. Buprenorphine partially activates mu opioid sub-receptors and partially inactivates kappa opioid sub-receptors – meaning that increasing doses of buprenorphine appear to produce a subdued or bridled effect compared to opioid full agonists (i.e. morphine, oxycodone, and fentanyl) which elicit a correlating, complete response. (See Figure 1, following.)


Inverse agonist 2

Image Credit: Wikimedia Commons

Buprenorphine’s increasing appeal to prescribers may also be the result of recent studies suggesting that, with respect to analgesia, it acts more like a full agonist (increasing pain relief with increased dosage). At the same time, the drug appears to have a dose ceiling effect on respiratory depression exhibiting partial agonist activity in relation to this potentially lethal adverse effect, which is normally the dose-limiting factor in opioid prescribing.1,2

Buprenorphine, moreover, has such affinity for opioid receptors that when it binds, it effectively acts as an antagonist to full agonist opioids when administered together rather than induce an additive dose response. This protective antagonist effect is another appealing benefit, since blocking effects of unknown illicit or misused (alternate source, etc.) opioids may prevent injured workers from the serious adverse effects of respiratory depression and overdose.


Where opioids are indicated for the treatment of injured workers, appropriate formulations containing buprenorphine offer unique benefits. As with all opioids, while the risk of abuse and/or misuse must still be weighed, the consideration of a buprenorphine medication with an FDA-approved indication for the management of pain may be warranted for a growing number of injured worker populations.


Have questions or comments regarding this topic? Call 866.446.2848 and ask to speak to a KeyScripts pharmacist, or email schitwood@keyscriptsllc.com.



  1. Dahan A, Yassen A, Romberg R et al (2006) Buprenorphine induces ceiling in respiratory depression but not in analgesia. Br J Anaesth 96:627–632
  2. Lutfy K, Cowan A. Buprenorphine: a unique drug with complex pharmacology. Curr Neuropharmacol. 2004 Oct;2(4):395-402. doi: 10.2174/1570159043359477.

FDA Aims to Educate Prescribers on Immediate-Release Opioids

July 11, 2017

The FDA will begin requiring drug makers to provide and pay for training for clinicians prescribing immediate-release (IR) opioids – mirroring existing mandates for extended-release (ER) opioids.

Noting that “America is simply awash in immediate release opioid products,” FDA Commissioner Scott Gottlieb, MD, announced new FDA initiatives targeting the opioid epidemic. At a recent FDA meeting on abuse-deterrent drug formulations, Dr. Gottlieb said that 90% of all U.S. opioid prescriptions are for IR formulations, translating to 200 million prescriptions a year.

The FDA will notify manufacturers of the new requirements over the next few weeks. All IR formulations will be subject to the same Risk Evaluation and Mitigation Strategy (REMS) program as ER opioids, with drug makers being required to cover the cost of prescriber training.

While drug makers must provide and pay for the training, the training is voluntary for clinicians.