Ibuprofen and Acetaminophen Combo As Effective as Opioid Analgesia for Acute Pain

Close up of hand with pills, glass of water, and prescription bottles.

By Martina McGrath, MD
November 9, 2017

The opioid epidemic is the preeminent public health crisis facing the US today. In recent days, the CDC has reported that opioid overdose deaths rose by 17% in 2016, and the annual rate of fatal overdose deaths now stands at 20 per 100,000 people.1

While multiple factors have been implicated in driving the epidemic, prescription of short-term opioids for acute pain is an important risk factor for long-term opioid use.2 Opioid prescribing has grown dramatically, and over 30% of ED visits are estimated to lead to some prescription of opioid analgesia.3 Several recent studies have indicated a link between more intensive opioid prescribing practices among emergency physicians and increased risk of subsequent opioid dependence.4 Given these data, more judicious prescription of opioids is an obvious strategy to try to prevent the development of opioid dependence. Furthermore, increased use of non-opioid analgesia, particularly for short-term pain, should be emphasized.

The Study

In this context, Chang et al. conducted an ED-based randomized, double-blinded study, comparing the efficacy of a single dose of opioid- and non-opioid-based analgesia in patients presenting with moderate to severe acute extremity pain.5 Four hundred and sixteen patients were enrolled and were randomized to one of four treatment arms: 400 mg of ibuprofen and 1000 mg of acetaminophen; 5 mg of oxycodone and 325 mg of acetaminophen; 5 mg of hydrocodone and 300 mg of acetaminophen; or 30 mg of codeine and 300 mg of acetaminophen. All patients received identical capsules containing the study-drug combinations, and had pain scored at baseline, 1 and 2 hours after receiving analgesia. The primary outcome was pain score (rated at 0 to 10; where 0 is no pain and 10 is the worst pain imaginable) at 2 hours after receiving the study medication.

The Results

Enrolled patients were in moderate to severe pain, with a baseline pain score of 8.7. Pain declined in all groups over time and at 2 hours, there was a 4.3 point decline in pain score in the ibuprofen and acetaminophen treated group, with similar declines seen across the opioid arms. Mean pain scores at 2 hours were no different between any of the treatment groups, indicating the combination of acetaminophen and ibuprofen was as effective as any of the opioid combinations in this setting.5


In terms of limitations, this was a relatively small, ED-based study with very short follow-up. More data on the efficacy of this combination versus opioids over 1-2 days of pain would be informative. No data on adverse effects was collected, but the authors quote prior data suggesting that these would have been more common in opioid-treated patients.

As physicians, one of our primary instincts is to relieve pain and suffering. However, the opioid epidemic necessitates a rethink in our approach to pain management. This study suggests that pain, at least in the acute setting, can be similarly well-controlled with non-opioid alternatives,5 potentially reducing the exposure of large groups of patients to opioids, and their attendant risks.

Harvard Medical School is offering free, accredited, online CME courses in opioid education to physicians, physician assistants, nurses, nurse practitioners, and other healthcare professionals collaborating to treat patients with substance use disorder.

Learn more about the HMS Opioid Use Disorder Education Program.


  1. D.C. Reports a Record Jump in Drug Overdose Deaths Last Year. https://www.nytimes.com/2017/11/03/health/deaths-drug-overdose-cdc.html. Accessed: November 8th 2017
  2. New Persistent Opioid Use After Minor and Major Surgical Procedures in US Adults. Chad M. Brummett, Jennifer F. Waljee et al. JAMA Surg. 2017;152(6):e170504
  3. Rising opioid prescribing in adult U.S. emergency department visits: 2001-2010. Mazer-Amirshahi M, Mullins PM, et al. Acad Emerg Med. 2014
  4. Opioid-Prescribing Patterns of Emergency Physicians and Risk of Long-Term Use. Michael L. Barnett, M.D., Andrew R. Olenski, B.S., and Anupam B. Jena, M.D., Ph.D. N Engl J Med 2017; 376:663-673
  5. Effect of a Single Dose of Oral Opioid and Nonopioid Analgesics on Acute Extremity Pain in the Emergency Department. A Randomized Clinical Trial. Andrew K. Chang, MD, MS; Polly E. Bijur, PhD, et al. JAMA. 2017;318(17):1661-1667

Headshot of Dr. McGrathDr. Martina McGrath is an Instructor in Medicine at Harvard Medical School, and a member of the Renal Division, Department of Medicine, at Brigham and Women’s Hospital, both in Boston. Dr. McGrath is the Medical Editor for the Trends in Medicine blog.

2 thoughts on “Ibuprofen and Acetaminophen Combo As Effective as Opioid Analgesia for Acute Pain

  1. I have always been told not to mix ibuprofen and acetaminophen as it can damage the liver. So understand using this to deter initial introduction to highly addictive drugs makes sense. However for patients with chronic pain from arthritis and failed surgeries this wouldn’t benefit them. Really wish patients were more responsible in securing their pain medications as I feel if it weren’t for them getting into the wrong hands, patients that would benefit from increased opioid treatment wouldn’t be limited to minimal regulated treatment and in some cases completely denied continued treatment. Seems the elderly and chronic pain patients are being disciplined for the wrong doing of drug addicts that steal and deal what is supposed to be a “controlled “ substance. There is no way the amount of opioids on the street are coming from little billy stealing grand moms medicine as implied by FDA and drug enforcement agencies.


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