Tramadol
Kevin Willmann
A study published online on October 7, 2025, in BMJ Evidence-Based Medicine found that tramadol may have a slight effect on reducing chronic pain, but the potential harms seem to outweigh any benefit.
Trials included in the analysis were related to osteoarthritis, diabetic nerve pain, and chronic lower back pain and totaled 19 randomized placebo-controlled studies published up to February 2025 with a total of 6,500 patients, mean age being 58.
Compared with placebo, statistical analysis of these trials found a doubling in the risk of harms associated with tramadol when compared with placebo. This was mainly presented in more cardiac events for patients, including chest pain, coronary artery disease, and congestive heart failure.
The analysis showed that tramadol increased the risk of several nonserious adverse events, too, such as nausea, dizziness, constipation, and somnolence.
Researchers noted that the results were at high risk for bias. However, they said this may increase likelihood that the findings overestimate the beneficial effects and underestimate the harmful effects of tramadol.
A meta-analysis of the quality of life could not be conducted due to a lack of data.
Takeaways
Tramadol is known to have limited benefits despite its widespread use.
“Tramadol is a relatively ‘weak’ opioid to begin with,” said Mark Garofoli, PharmD, from West Virginia University.
Knowing that tramadol does not reduce pain scores as much as had been originally thought, he was not surprised by the results of the study.
In its most recent guideline update, CDC increased the morphine milligram equivalent (MME) factor from 0.1 to 0.2, which may sound closer to “useless” than potent, according to Garofoli, who was not involved with the research.
“Remember that an MME factor must be multiplied by the milligram dosage to yield the MMEs/day,” Garofoli said. “Although MME factors are an almost futile attempt at comparing potency of opioids, consider a tramadol 100 mg tablet, multiplied by the tiny little 0.2 MME factor, yields 20 MMEs in one single pill, often bewildering knowledgeable and experienced clinicians as that is the equivalent of four hydrocodone/apap 5/325 mg pills.”
Garofoli noted tramadol’s one point reduction of pain indicted by the study contrasts with how clinical significance “tends to aim for two points or even a three-pointer.”
“Yet, we clinicians should amplify our respect for tramadol’s ‘baggage’ of potential mixed-action opioid side effects,” said Garofoli.
This is in direct comparison to its structural cousin tapentadol—lacking serotonergic effects—or even traditional phenanthrene prescription opioids, like morphine, hydrocodone, codeine, or oxycodone, according to Garofoli.
When it comes to tramadol, Garofoli urged pharmacists to proceed with caution, especially for older patients or patients with kidney impairment or cardiovascular concerns.
“The question then resonates as ‘who’s left?’” Garofoli said.
Background
Tramadol was patented in 1972 under the name Tramal by the West German pharmaceutical company Grünenthal GmbH. It is an opioid pain medication as well as a serotonin–norepinephrine reuptake inhibitor for the treatment of moderate to severe pain. The drug was approved by FDA in 1995. It is known under a variety of brand names such as Ultram, Ultram ER, and Conzip.
By 2023, Tramadol was listed as the 36th most commonly prescribed medication in the United States, with more than 16 million prescriptions.
Tramadol was classified by DEA as a schedule IV-controlled substance in 2014, meaning it had a lower risk of abuse and dependence than opioids like oxycodone and hydrocodone, which are listed as a schedule II-controlled substance.
Garofoli noted that because of the lower cost as a pain medication and the “lesser demand in the illicit/diversion market,” an uptick in the use of tramadol has been observed in the last decade or so.
“In fact, when traveling beyond our country, tramadol seems to have become the opioid-of-choice by clinicians in so very many other countries,” he said. “That realization has propelled me to ask countless clinicians over the last few years, ‘Perhaps less diversion/misuse concerns, but is the pain actually being mitigated?’ ” ■