14 May Declines and regional variation in use of the atypical opioid tapentadol in the US

MedicalResearch.com Interview with:

Brian J. Piper, PhD
Department of Medical Education
Center for Pharmacy Innovation & Outcomes
Geisinger College of Health Sciences
Scranton, PA 18509

 

MedicalResearch.com: What is the background for this study?

Dr. Piper: Tapentadol has an unusual mechanism of action. This opioid is similar to morphine in that it activates mu, the main opiate receptor which is important for pain. This drug also acts similar to an antidepressant like duloxetine (Cymbalta) with equal ability to block both the norepinephrine and the serotonin transporters (Figure 1). The combination of opioid and monoaminergic activity may influence both therapeutic and side effect profiles.

Tapentadol is approved in the US for moderate to severe acute pain, moderate to severe chronic pain, and neuropathic pain associated with diabetic peripheral neuropathy. However, tapentadol is not generally considered first-line for any of these indications. Although this agent has a high potential for abuse and is classified as a Schedule II substance, a manufacturer of extended release tapentadol (Grunenthal) has conducted a misinformation campaign claiming tapentadol has a “minimum potential of abuse”, does not cause respiratory depression (a well-known opioid effect), does not cause any euphoric feelings, has no street value, and is not an opioid [2]. Prior pharmacoepidemiological studies have examined the use patterns of other prescription opioids that can be misused like oxycodone [3], fentanyl [4], meperidine [5] and methadone [6] but there is limited national information about the use of tapentadol.

MedicalResearch.com: What were the key points of your research?

Dr. Piper: We examined the use of tapentadol in the US using three databases, the comprehensive Automated Reports and Consolidated Orders System by the Drug Enforcement Administration, Medicaid, and  Medicare. Tapentadol use decreased nationally between 2012 and 2020 by over fifty percent. However, distribution was over twice as high in southern states versus west-coast or New England states. States with a higher prevalence of diabetes also had higher tapentadol use. Tapentadol prescribing to Medicaid patients also decreased by over fifty percent from 2011 to 2020.

MedicalResearch.com: Was the outcome compatible with your premise or were the results surprising?

Dr. Piper: These findings were generally consistent and extend upon past research [3-6] in that most prescription opioids used for pain are decreasing but there are substantial state-level differences. If the rates of a condition like acute pain are similar across the US, then the use of a particular drug therapy should be homogenous. However, if the rates of a condition like diabetes differ, then so should use of a treatment for that condition. We identified only a moderate (r = .44) correlation between diabetes prevalence and tapentadol use. This indicates that there is appreciable variance in tapentadol use that is due to other, currently unknown, factors.

MedicalResearch.com: What further questions remain to be answered? What further research is indicated?

Dr. Piper: This study is limited to the US. We hope that other developed and developing countries conduct similar research and have vigorous opioid stewardship programs to avoid the mistakes and excesses in prescription opioid prescribing in the US.

The biological effects of tapentadol for non-opioid receptor targets may be important for both therapeutic and adverse effects. The maximum daily dose is 600 mg for the immediate release formulation. The median street value from a 2016 study was 18 cents per mg [7]. Therefore, diversion of a one-year supply of tapentadol could result in an appreciable ($39,447) compensation. Large retrospective studies of misuse, the serotonin syndrome, and interactions between tapentadol and other drugs that block the serotonin transporter [1] may be beneficial.

New Publication:

Low CL, McCall KL, Piper BJ. Declines in tapentadol use in the US but pronounced regional variation.
Pharmacy 2025; 13(3):67. https://www.mdpi.com/2226-4787/13/3/67.

Citations

1. Rickli A, et Opioid-induced inhibition of the human 5-HT and noradrenaline transporters in vitro: Link to clinical reports of serotonin syndrome. British Journal of Pharmacology 2018; 175(3):532–43.
2. Davies M, et Misleading marketing claims fuel tapentadol prescriptions. Lancet 2025; 405:964-965.
3. Solgama JP, et al. State-level variation in distribution of oxycodone and opioid-related deaths from 2000 to 2021: An ecological study of ARCOS and CDC WONDER data in the BMJ Open 2024; 14(3): e073765.
4. Stemrich RA, et Pronounced declines in dispensed licit fentanyl, but not fentanyl derivatives.

Research in Social and Administrative Pharmacy 2022; 18(6):3046-51.

5. Harrison LR, et Pronounced declines in meperidine in the US: Is the end imminent? Pharmacy 2022; 10(6):154.
6. Kennalley AL, et al. Dynamic changes in methadone utilisation for opioid use disorder treatment: a retrospective observational study during the COVID-19 pandemic. BMJ Open. 2023;13(11):e074845
7. Dart RC, et al. Diversion and illicit sale of extended release tapentadol in the United States. Pain Med. 2016;17(8):1490–6.
8. Furst JA, et Pronounced regional disparities in United States methadone distribution. Annals of Pharmacotherapy 2022; 56(3):271-279.
9. Dart RC, et Diversion and illicit sale of extended release tapentadol in the United States. Pain Medicine 2016; 17(8):1490-6.

 

 

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Last Updated on May 14, 2025 by Marie Benz MD FAAD