"The Reality of Tramadol: 'Effects That Go Unnoticed' and 'Side Effects That Cannot Be Ignored'"

The "Safety Myth" of Painkillers is Shaken—Is Tramadol's "Effectiveness" Outweighed by Its "Cost"?

"Tramadol seems 'safer' than other opioids." This sentiment has long lingered in the field of chronic pain management. However, at the end of 2025, a large-scale review published in a BMJ-affiliated journal and covered by ScienceDaily quietly overturned this assumption. The conclusion is provocative—while pain may decrease "slightly," dangerous side effects might "clearly" increase.ScienceDaily

What Exactly is Tramadol?

Tramadol is one of the opioid analgesics, known for its pain-relieving effects. In the United States, it is classified as a controlled substance (Schedule IV) due to concerns about abuse and dependence. Its mechanism of action involves not only central opioid receptors but also elements related to metabolism and neurotransmission (it is converted into active metabolites by CYP2D6, which is known to cause individual variability).NCBI

The perception that it is "milder than other strong opioids" and "relatively less addictive" has undeniably lowered the threshold for its prescription. However, "seems safe" is not synonymous with "safe." The recent study highlighted this obvious fact.

What Did the Study Investigate and Conclude?

The investigation involved a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing "tramadol vs. placebo" in adults with chronic pain. The search covered major databases up to February 6, 2025, and ultimately 19 trials involving 6,506 participants were included in the analysis.PubMed

The chronic pain conditions studied included neuropathic pain, osteoarthritis, chronic low back pain, and fibromyalgia. The treatment duration ranged from 2 to 16 weeks, with relatively short-term follow-up being a common feature.ScienceDaily

"Statistically Significant" but "Inconsequential in Daily Life"—Pain Improvement of 0.93 Points

The most attention-grabbing result was the difference in pain intensity (0-10 NRS). The meta-analysis showed that the tramadol group experienced a mean reduction of 0.93 points in pain compared to the placebo group. At first glance, this number seems to indicate effectiveness. However, the researchers had pre-specified the minimum difference (MID) that patients would easily notice as 1.0 point, and 0.93 points does not meet this criterion. This suggests that "while there is a statistical difference, it may be 'hardly noticeable' in daily life."PubMed

ScienceDaily also summarized that "the improvement is small and falls below the level considered clinically significant."ScienceDaily

The Most Serious Issue: Serious Adverse Events "About Twice as Likely"

On the other hand, the risk side was clearly elevated. The analysis suggested an increase in serious adverse events with an odds ratio of 2.13 (about twice as likely), mainly attributed to cardiovascular events (such as chest pain, coronary artery disease, and congestive heart failure) and reports of neoplasms.PubMed

Regarding neoplasms, the short follow-up period makes it difficult to determine causality (there is a tone of caution, acknowledging the possibility but urging careful consideration)—this is a point where readers should remain calm.ScienceDaily

Common Side Effects Also Increase at "Realistic Frequencies" (Indicated by NNH)

Furthermore, side effects that "do not threaten life but diminish quality of life" also increased. Nausea, dizziness, constipation, and drowsiness were representative, with the study estimating NNH (number needed to harm) as 7 for nausea, 8 for dizziness, 9 for constipation, and 13 for drowsiness.PubMed

For people with chronic pain, the pain itself erodes the center of their lives. Adding "nausea, dizziness, and drowsiness" can lead to a chain reaction that affects commuting, household chores, childcare, and work concentration."Reducing pain by less than one point, at the cost of other discomforts"—this cost-benefit analysis is at the heart of the current debate.

However, the study also has weaknesses: Bias and Short-Term Follow-Up

The authors clearly stated that many of the included trials have a high risk of bias. This is important because it can lead to "overestimation of effectiveness and underestimation of harm." In other words, if the bias is strong, the reality could be "even less favorable."ScienceDaily

Additionally, the fact that many of the studies are short-term, under 16 weeks, is also a limitation. What happens with long-term use, or whether certain patient groups benefit more relatively, remains a challenge for the future.

Clinical Reception: "No Surprise, but Still Concerning"

Reactions from the medical community have also emerged. Australia's GP-targeted media RACGP newsGP described the results as "concerning," while emphasizing that chronic pain is linked not only to "tissue damage" but also to nerve sensitization and changes in pain processing, highlighting the importance of a comprehensive approach that does not rely solely on medication.RACGP

This is a point easily misunderstood on social media. Many chronic pain conditions cannot be explained by **"pain = inflammation or damage = controlled by painkillers"** alone. This is why the approach of "restructuring the whole" rather than "adding more medication" can be effective, as clinicians have consistently stated.

Social Media Reactions: Polarized "Voices from the Field" and "Voices from Data"

When news like this emerges, reactions on social media (X, Reddit, article comment sections, etc.) tend to be divided. The same pattern is evident this time.

1) The "Show Me the Paper First" Group: Primary Information Over Spread

In the Reddit fibromyalgia community, there is a noticeable trend of requesting "data (paper link)" rather than relying on TikTok introductions. For example, demands for "a link to the data itself?" have led to the eventual sharing of the BMJ paper link.Reddit

"can we have a link to the data itself…?"Reddit

In the age of social media, even if the entry point is a short video, the strong message is to "return to primary information" in the end.

2) The "It's Working, So I Want to Continue Despite the Risks" Group: Lived Experience Takes Priority

Within the same thread, there are more earnest voices. A tramadol user posted that "reducing pain is more important than side effects," reflecting the reality that there is "no alternative" for chronic pain.Reddit

In the article comment section of New Atlas, a person suffering from long-term leg pain (related to RLS) argues that "it's not 100%, but it's better than dangerous narcotics, and it keeps life manageable." This encapsulates the gap between the "average" shown by the meta-analysis and the "individual" reality lived by those affected.New Atlas

3) The "Didn't You Say It Was a 'Safe Drug'?" Group: Anger at Lack of Explanation

Conversely, the theme is prone to ignite distrust, with sentiments like "I was told it was safe" and "Doctors and media conveniently change their narrative." The study suggests "not an immediate ban" but "minimization due to limited benefits and potential harm," yet in the context of social media, it tends to be translated into 'black and white.'

4) The "Isn't It Different Due to Genetics or Constitution?" Group: Discussion on Personalization

Tramadol is a drug whose effectiveness can vary due to metabolism (CYP2D6), leading to individual differences. New Atlas, in an addendum, touches on the point that, considering genetic metabolic differences and the "small number of cardiovascular events," decisions should be made cautiously on an individual basis.New Atlas

So What Should We Do? (Important)

This is likely the part that readers of the article most want to know. However, as a major premise, sudden discontinuation or dosage changes based on self-judgment are dangerous. Withdrawal symptoms or worsening pain may occur. Always consult with your doctor or pharmacist.

With that in mind, if you want to translate the news into "practicality," there are three points to consider.

1. Re-evaluate "How Much the Pain Has Decreased" in Numerical Terms
   If you are continuing without much thought, it is worthwhile to reassess the effects using NRS or life functions (sleep, activity level, impact on work). The figure of an average 0.93-point reduction indicates both "there are people for whom it works" and "for many, it is not dramatic."PubMed

2. Inventory Side Effects with "The Same Weight as Pain"
   Drowsiness, dizziness, constipation, and nausea are often underestimated but can be fatal to the life of someone with chronic pain. The NNH figures suggest that these are not rare occurrences.PubMed##HTML