Chronic use of tramadol after acute pain episode: cohort study
BMJ 2019; 365 doi: https://doi.org/10.1136/bmj.l1849 (Published 14 May 2019) Cite this as: BMJ 2019;365:l1849
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Dear Editor
Unfortunately the design of this study precludes the conclusions the authors come to. It is unfortunate that this may be used for policy decisions.
1) Their population base is Medicare patients.
2) This population suffers disproportionately from chronic pain from arthritis and other chronic conditions.
3) There is no data regarding overdose or abuse in this study therefore their conclusions that this is a drug of abuse cannot be substantiated.
4) Their ongoing use most probably has zero to do with their surgery except that they found a medication that enables them to function that doesn’t cause GI bleeds, cardiac disease, renal failure etc that NSAIDS do.
5) Considering the population, 7% continued use is not a huge percentage.
6) To schedule this drug would not in the least decrease the opiate epidemic. It would greatly reduce the quality of life of many chronic pain patients.
7) I now see chronic pain patients whose physicians have reduced their pain meds or discontinued them. They have changed from functioning members of society to alcoholics and seeking drugs on the street which are far more lethal.
8) Addiction is a psycho-social problem. It cannot be solved by depriving chronic pain patients of medical treatment. They are not drug abusers.
9) Drug addiction cannot be solved by reducing access to prescription narcotics. This has been shown as the number of opiate deaths continues to rise as addicts have turned from known dosage narcotics to street drugs of far more potency and unknown dosage.
10) Considering that we are dealing with a finite population and people can only die once , rising death tolls are highly problematic and symbolic of the fact that the current strategy is highly flawed. It will not be improved by scheduling Tramadol.
Competing interests: No competing interests
Dear Editor
It is not surprising that patients are taking Tramadol for long periods. It is intended to treat chronic pain which by its very definition is longstanding pain. Its use in a post op setting is somewhat surprising. Much as we like to think otherwise, some patients will have chronic, untreatable pain and need medication to function with a decent quality of life. NSAIDS have their own problems, not being suitable for those with renal disease and increasing the risk of hypertension and cardiac disease. Drugs like Gabapentin are loaded with side effects and often not well tolerated. Changing the schedule of Tramadol would be a grave disservice to chronic pain patients and might possibly force them to look for illegal and dangerous street drugs. Not all pain can be overcome by thinking positive thoughts.
Competing interests: No competing interests
I couldn't agree with Dr. Hochman more. A study such as this should never elicit policy recommendations. The discussion/conclusions should be used to highlight the limitations of the study, not to extrapolate findings.
In addition, there is little evidence that limiting opioid prescriptions has translated into less consumption by the populace of the US. Up-scheduling tramadol would likely share those same unintended consequences.
Sincerely,
Brian Poore, MD
Competing interests: No competing interests
Dear Editor,
Our country is in the midst of an opioid crisis, and I fear that well-intentioned authors have made a misguided recommendation that will further harm the public. The conclusion that tramadol presents a similar or greater risk of opioid dependence is neither supported by the study design nor clinical practice. In fact, the findings of the study may support the opposite conclusion to the one made.
While I welcome the advancement of epidemiologic data around opioid use, the suggestion that tramadol confers greater risk to patients struck me in particular since it is inconsistent with clinical experience among fellow psychiatrists involved in the spectrum of addiction care.
I suggest critical thinking around the following two study limitations:
1. The groups were not matched. The data presented for the groups at baseline does not allow meaningful interpretation except that there were more women receiving tramadol, and that the prescriptions for tramadol vs other short-acting or long-acting opioids varied widely by type of surgery. It is highly likely that the patient groups differed in significant and relevant ways. Authors attempted to use logistic regression to account for potential confounders but this is recognized to be inferior to other methods.1
Critical thinking: It remains entirely plausible that tramadol was prescribed preferentially for patients with histories of opioid dependence or substance use disorder since it is considered less addictive than standard opiates.
2. Persistent treatment for pain may be appropriate and should not be considered synonymous with abuse or addiction. The reason for continuing the medication is not provided, and the study did not evaluate whether persistent pain was the driver for continued treatment. The study would have benefited from inclusion of a non-addictive control group such as an NSAID. Without that, it is not appropriate to assume that addiction or abuse is responsible for the findings with tramadol.
Critical thinking: It remains entirely plausible that tramadol was prescribed preferentially for patients (with or without substance use disorder concerns) who require ongoing pain management since it is considered less addictive than standard opiates.
My field’s experience is more consistent with the existing body of evidence that has shown tramadol to be of lesser risk for abuse and dependence than other opiods.2,3,4 We must pay attention to the very population this study aims to protect and take note: among opiates, tramadol has the lowest street value and is seldom a “drug of choice.” Said another way: addictive drugs always have high street value/demand, and tramadol does not.
While I am open to questioning old notions, this study is neither designed to refute current notions, nor is it supported in clinical practice. Using these potentially confounded results to group tramadol with conventional opiates may be misleading, and may wrongly influence prescribers to ignore a reasonable alternative to these highly addictive drugs.
Prior to my submission of this response, I spoke with several patients about the study. Some laughed because of how shocked they were. Anecdotally, they shared three agreed upon facts about their experience:
1. Tramadol has little to no “nod” effect (a high).
2. Tramadol is most commonly used as a matter of convenience, or as a last option.
3. It is common to drug seek tramadol first briefly in order to appear to be a genuine patient, prior to stepping up requests for any other opiate.
Ultimately my patients voiced genuine concern: “What if physicians who read the study are led away from prescribing safer opiates and towards risker ones?” We need to be careful.
Daniel Hochman, MD
President, selfrecovery.org
Supervisor, University of Texas Dell Medical School, Department of Psychiatry
REFERENCES
1Stürmer T, T, Wyss R, Glynn RJ, Brookhart MA. Propensity scores for confounder adjustment when assessing the effects of medical interventions using nonexperimental study designs. J Internal Med 2014; 275: 570-580
2Dart RC, Cicero TJ, Surratt HL, Rosenblum A, Bartelson BB, Adams EH. Assessment of the abuse of tapentadol immediate release: the first 24 months. J Opioid Manag. 2012 Nov-Dec;8(6):395-402.
3Mojtabai R, Amin-Esmaeili M, Nejat E, Olfson M. Misuse of prescribed opioids in the United States. Pharmacoepidemiol Drug Saf. 2019 Mar;28(3):345-353
4World Health Organization (WHO). Critical Review Report: Tramadol. 2018. Available at: https://www.who.int/medicines/access/controlled-substances/Tramadol.pdf?....
Competing interests: No competing interests
The present and recent issues of the BMJ have highlighted some of the stock crazies of the medical-pharmacological-corporate world. For example, the marketing of opiates including Tramadol. If you promote opiates like Sackler and Purdue Pharma did in the United States you get 130 opiate deaths a day - marketing works.1 If you give female hormones (contraceptive pill, HRT) to widespread populations you get three things: 1. An epidemic of breast cancer, 2. Plummeting birth rates, 3. Pollution of the water tables with feminization of fish and aquatic life (all documented in national databases with correlations).2 If you promote a TV series detailing teenage suicide like "Thirteen Reasons Why", you get teen suicides and mental health issues in teens. If you legalise cannabis (despite its unproven efficacy in any medical condition save intractable epilepsy in childhood) you fill psychiatric units with psychosis (33% of acute units in London were occupied by skunk users) and do untold harm to developing brains of young people who need to be motivated to achieve their potential (amotivational effect of cannabis). You also make money for manufacturers. Finally if you release Ketamine on the market as the new panacea for depression and let marketing take over you will probably get an epidemic of addiction and side effects. All these interventions are backed by corporate interest. The medical authorities and government were and are no match for vested interest and corporate greed and muscle.
There is urgent need for another voice for the people, an advocate that will protect them from pseudo medicine and the corporate machine. This advocate should be similar to NICE or Cochrane with independence, resources and most of all a guarantee that its primary aim is for the benefit of the health of the community. It needs to have teeth to block expensive industry driven interventions that are unnecessary of doubtful efficacy and are even harmful. This is not happening based on the above debacles and upcoming possible debacles. Complicity, money and absolute silence on behalf of those responsible for safe and intelligent healthcare has allowed health budgets to soar (20% of GDP in USA, averages of 10-12% in Europe), creating the medicalization of many aspects of life and a spawning industry serving the share holders. Medicine is big business and has gone from being a service to the state to being serviced by the state at the expense of ordinary taxpayers. The realistic position for health is in education, prevention, healthy lifestyle and behaviours, good housing and green spaces and employment. Expensive corporate medicine should be way down somewhere like 10th position after a host of other societal needs have been satisfied - instead it is in pole position dictating what health is.
1. Preying on Prescribers (and Their Patients) — Pharmaceutical Marketing, Iatrogenic Epidemics, and the Sackler Legacy. Scott H. Podolsky, M.D., David Herzberg, Ph.D., and Jeremy A. Greene, M.D., Ph.D. NEJM 2019;380: 1785-1787.
2. Breen EG. The Screech Owls of Breast Cancer. AuthorHouse 2013.
Competing interests: No competing interests
Re: Chronic use of tramadol after acute pain episode: cohort study
Dear Editor
We thank the respondents for their responses to our work and would like to address some of their concerns and further engage in this important conversation.
Dr. Newman was concerned that our population base is Medicare patients, who are more medically complex and more likely to experience chronic pain than the general population. We would like to clarify that our population included both Medicare and commercially insured enrollees and that we saw no indication that our population had unusually high rates of chronic pain compared to the general population receiving medical care. In fact, our population likely included fewer people with chronic pain because we excluded anyone with any opioid fills in the prior 6 months.
Dr. Newman notes that without data on overdose or abuse, we are unable to conclude that tramadol is a drug of abuse. We agree. We do not make any claims in this study that tramadol is a drug of abuse.
Regarding the comment on whether 7% continued use is important: we would note that our study included only people who were not previously taking opioids, who had received a curative/therapeutic procedure performed on an elective basis, with no other procedures on the same day, short pre- and post-operative stays, discharged to home, and with no other surgical procedures in the follow-up period. Readers must make up their own minds on whether this is a high rate of continued use. We consider the absolute rate of continued use to be higher than expected for this cohort.
Dr. Newman also writes of her concern for people with chronic pain who have difficulty receiving treatment. We share her concerns and agree that all patients who are suffering deserve patient-centered, responsive, and humane treatment, including access to scheduled drugs where that is appropriate and effective. We neither believe nor argue that all people on long-term opioid therapy are “drug abusers” or that they are addicted to their medication. Opioid use disorder is a disease that is characterized by maladaptive behaviors that negatively affect a person’s social, emotional, and physical functioning. People taking opioids as directed by their health care provider and whose functioning is improved by their medication should certainly be able to continue this treatment.
Finally, Dr. Newman notes that scheduling tramadol will not stop people from dying. We would like to clarify that tramadol is already a scheduled substance in the United States—it falls in schedule IV. Our conclusion encourages policymakers to consider reclassifying tramadol from schedule IV to a higher schedule, as was done for hydrocodone combination products in 2014, for example.
Dr. Mastroianni notes that tramadol is intended to treat chronic pain and is surprised that it is being used in a post-op setting. She is concerned that rescheduling tramadol will force people to use street drugs. As noted above in response to Dr. Newman, our population was limited to patients without any opioid fills in the 6 months prior to surgery, which excluded all patients taking tramadol in the pre-operative period for chronic pain. Further, in our manuscript we note that tramadol is included in the post-surgery prescribing guidelines at many institutions, including our own. As was noted in the accompanying editorial, there is a sense among many providers that tramadol is an “opioid-lite”—and therefore better for patients than hydrocodone or oxycodone. This has been a perception from the first introduction of tramadol in the US in 1995. This may be because before being metabolized, tramadol is indeed only a very weak opioid. However, as Dr. Mastroianni no doubt knows, once it passes through the liver, tramadol’s main metabolite has 700 times the affinity for the mu-receptor as the parent drug. Regardless of the reasoning, there is a persistent sense among many prescribers that tramadol is not a real opioid, and that is reinforced by the fact that until 2014, it was not a scheduled substance in the US. It remains unscheduled in many countries.
Dr. Hochman has two concerns about the study design and a conclusion that tramadol presents a similar or greater risk of opioid dependence.
1. Groups were not matched and there may be preferential use of tramadol for patients whom physicians fear are at greater risk for OUD.
We did not see evidence that people with substance use disorders were more likely to receive tramadol vs. other short-acting opioids. In fact, in each of the three insurance coverage groups (commercial, Medicare Advantage aged 65+, and Medicare Advantage disabled/<65 years), the Elixhauser drug abuse diagnosis codes were equally prevalent among those receiving tramadol alone and those receiving tramadol plus another short-acting opioid. (Additional analysis after publication) In the Medicare populations, the prevalence of the drug abuse diagnosis codes were also similar (not statistically distinguishable) between the tramadol groups and the group receiving no opioid fill. Commercial beneficiaries with drug abuse diagnosis codes were more likely to receive tramadol than no opioid fill. These data are certainly not conclusive evidence of prescribers’ medical reasoning, but they suggest that an individual patient’s risk of future abuse is not the major driver of tramadol prescribing.
2. Persistent treatment for pain is not the same as abuse or addiction. Without a non-addictive control group, the study cannot conclude addiction or abuse is responsible for continued use.
We do not at any point in this study conclude addiction or abuse is responsible for continued use. We completely agree that our study cannot and does not address this question.
We would, however, encourage Dr. Hochman to review Tables 2 and 3, which report the later opioid use of people who did not receive an opioid at discharge (19.5% of the total study population) for some limited evidence on the experience of people who received over-the-counter or non-opioid pain medications after surgery. This group experienced a lower, but non-negligible risk of all three definitions of prolonged opioid use compared to those receiving an opioid.
Finally, a drug needn’t be the preferred street drug in order to be problematic, to have the risk for dependence, or to cause harm.
Competing interests: No competing interests