Article: Concerns on Tramadol Overprescription

in Pharmaceutical Articles

It is known that theory and practise sometimes differ, not always for better. In the University lectures tramadol hardly deserved more than brief remark at the end of the pain management chapter. Maybe it should not have been so, seeing how frequently it is prescribed. This is, at least, the impression I have got from my first time in a Hospital, where I am doing my training placement. Unfortunately I have no quantitative data on the tramadol use, but I think it follows strong opioids prescription increase1,2,3. The United Kingdom has a highest percentage of prescription of strong opioids for chronic pain in Europe, but it is not least with weak opioids: it shares the first place with Norway4. And the data from the United Stated should act as a warning: when opioid prescription rises, so does their misuse and the problems associated with them5.

 Pain

The question of the correct use or not of tramadol cannot be considered in the abstract, but has to be seen in the whole vision of pain treatment. And this, in turn, requires refreshing some important features of pain. First of all, its importance: it has a great prevalence2,4 and it is the most common reason for seeking medical care6.  Second, something that is often forgotten: pain is not a disease, but a symptom7. However, drug treatments are only focused on their relief, and they have important side effects. Finally, the definition8 of pain is very subjective: “An unpleasant sensory and/or emotional experience,
associated with actual or potential tissue damage, or
described in terms of such damage.”

Although they share medicines, the different types of pain have different treatments. Neuropathic pain is usually difficult to treat, and normaly, different medicines have to be tested until the one that best suits the patient is found. Tramadol is licensed for this use, and thus, should be used when necessary. This, according to the National Institute for Health and Clinical Excellence  guideline9, is as third line treatment.  The recommendations from International Association for the Study of Pain are similar10.

However, the recommendations for acute pain are not so well defined, so important differences are found between guidelines:  Tramadol’s recommended use (in combination with paracetamol) varies from first11 to third12 line treatment. This  lack of consensus increases the risk of doctor´s preferences to prevail over evidence based treatment. Moreover, the WHO pain relief ladder13, initially developed for cancer pain but now widely used, opens the door to the use of tramadol both as a weak opioid in step 2 or as adjuvant in any11.

Tramadol’s mechanism of action 

TramadolThe pharmaceutical industry, with last years’ aggressive marketing and highly promotion of opidoids14 is behind the overdiagnosis and thus, overprescription of opioids, which has been mainly reported in the United States5. In tramadol’s case, pharmaceutical companies took advantage of tramadol’s “special” mechanism of action, and contributed to spread the idea of a drug with opioids’ effectiveness but with little of their side effects.

It is indeed true that tramadol is different from other opioids:  Apart from its weak opioid agonist action it releases serotonin and inhibits the reuptake of noradrenaline15. Incidentally, point out the confusion created since not everybody describes this drug as a weak opioid. Opioids in persistent non-cancer pain2 and British Pain Society’s Opioids for persistent pain: good practice 16, place the tramadol, incorrectly, among the strong opioids.

Being weak agonist does not mean that it will not have the adverse effects of the opioids, and, since it is known, these are not trivial. In addition, it is worth remembering that the 80% of patients taking opioids will experience at least one adverse effect16.  Tramadol’s release of serotonine and the inhibition of reuptake of noradrenalin contribute to the relief of pain, but they are, in turn, source of additional interactions, as it will be later seen.

Effectiveness comparison

Drug’s first acid test is the efficacy they show. A good tool for that is the table 1, taken from the Oxford league table of analgesics17. This table is based on randomised, double-blind, single-dose studies in patients with moderate to severe acute pain and shows the number of patients that need to be given the active drug (NNT) to achieve at least 50% pain relief in one patient compared with a placebo over a 4 to 6 hour treatment period.

Although, fortunately, tramadol hardly ever is prescribed instead of paracetamol, it is never bad to remember why this should continue to be like that: it is just less effective (and has more side effects). It has also to be noted that ibuprofen is one of the most effective in the whole table, but its side effects18 make it.

More tricky is to decide which combination is better:  paracetamol + tramadol or  paracetamol + codeine. Table’s data have the drawback that the paracetamol dose in the combination is different, this is, there is not paracetamol 1000 + tramadol 100 to check against the paracetamol 1000 + codeine 60.  With the available data what can be said is that there seem to be no big differences in effectiveness. Other sources support this idea:  paracetamol 325mg + tramadol 37.5mg can be as effective as parecetamol 300 + codeine3019.

Side effects and interactions comparison

If similar in effectiveness, the next step is to look at the side effects of the different drugs. Since both codeine and tramadol are opioids, they share this kind of drug’s side effects2,16,20,21: sedation, dizziness, nausea, vomiting, constipation, respiratory depression, tolerance and physical dependence. However, tramadol has fewer of the opioids’ typical side effects15,22,23: less respiratory depression, less constipation and less addition potential24. This has lead to postulate its use for chronic pain15,24, but as for the rest of opioids data demonstrating sustained analgesic efficacy in the long term are lacking16. Anyhow, there are other reasons for not recommending it as first line treatment for chronic pain.

Opioids interact with quite a lot of drugs, and in this point tramadol and codeine are similar. However, tramadol has its own particular interactions22,23, numerous and important:

  • enhances antiocoagulant effect of coumarins
  • increases serotonergic effects when given with duloxetine, mirtazapine or venlafaxine. This may lead to serotonergic syndrome10.
  • increases risk of CNS toxicity when given with SSRIs or triciclics.
  • increases risk of convulsions when  given with antipsychotics.
  • possibly increases risk of convulsions when given with atomoxetine.
  • its effects are reduced by carbamacepine
  • its effects are possibly antagonized by ondansetron

Moreover, withdrawal problemsmay occur even after short period of doses and with modified release formulations16. All this drawbacks may explain why a French study25 on the reporting rate of adverse drug reactions(ADR) of  dextropropoxyphene, tramadol and codeine (combined with paracetamol)  it was found that although the rate of deaths due to ADRs did not differ among the three combinations, “the rate and ‘seriousness’ of reported ADRs were the highest with tramadol+paracetamol and the lowest with codein+paracetamol”.

Definitely, the interaction point tips the balance to in favour of using codeine (with paracetamol) as first option.

What pharmacist can do?

The idea of writing an article came from what I said in the first paragraph: my surprise at how frequently is tramadol prescribed in the hospital where I am.  More astonishing even is that hospital’s joint phormulary26 states it only for patients that do not tolerate the adverse effects of other opioids or paracetamol. Unfortunately, this is seldom the cause of its prescription.

Therefore, there is need of not only good guideline; this information has to reach the doctors. Pharmacists should remind them the evidence and to query when recommendations are not followed. We have an important role to play in this chapter of the evidence based medicine, and we may have to do even more, since we might have double dose of tramadol in the near future27.

Table 1

Analgesic and dose       (mg, oral)

Percent with at least 50% pain relief

NNT

Ibuprofen 400

55

2.5

Tramadol 100

30

4.8

Paracetamol 1000

46

3.8

Paracetamol 1000 + Codeine 60

57

2.2

Paracetamol 600/650 + Codeine 60

42

4.2

Paracetamol 650 + tramadol 75

43

2.6

Paracetamol 650 + tramadol 112

60

2.8

 

About Author

 Pablo Ortiz, Grantee, Pre-Registration, Southport & Ormskirk Hospital NHS Trust, England.

References

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2. Coupe MH,  Stannard C. Opioids in persistent non-cancer pain. Contin Educ Anaesth Crit Care Pain [Online]   2007; 7 (3): 100-103. Available from: http://ceaccp.oxfordjournals.org/content/7/3/100.full. [Accessed 29th march 2012]

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8. International Association for the Study of Pain(IASP). Pain Terms[Online] Available from: http://www.iasppain.org/Content/NavigationMenu/ GeneralResourceLinks/PainDefinitions/default.htm [Accessed 29th march 2012]

9. National Institute for Health and Clinical Excellence (NICE). Neuropathic pain: The pharmacological management of neuropathic pain in adults in non-specialist settings [Online] 2010. Available from: http://publications.nice.org.uk/neuropathic-pain-cg96 [Accessed 29th  march 2012]

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12. Ayad AE, Ghaly N, Ragab R, Majeed S, Nassar H, Al Jalabi A et al. Expert Panel Consensus Recommendation for the Pharmacological Treatment of Acute Pain in the Middle East Region. J Iint Med Res [Online] 2011; 39:1123-1141. Available from: http://www.iasp-pain.org/PainSummit/MiddleEastAcutePainGuidelines.pdf [Accessed 29th  march 2012]

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27. MIMS. Could tramadol treat premature ejaculation? [Online] Available from: http://www.mims.co.uk/mims_specialist/article/1090254/tramadol-treat-premature-ejaculation/?DCMP=ILC-SEARCH [Accessed 30th March 2012]

How to Cite

Ortiz, P. (2012) Concerns on Tramadol Overprescription . [Online] Available from: http://pharmamirror.com/pharmaceutical-articles/concerns-on-tramadol-overprescription/ [Accessed …Date…]

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