Quick, simple test developed to identify patients who will not respond to the painkiller tramadol

June 10, 2012

French researchers have found a way to identify quickly the 5-10% of patients in whom the commonly used painkiller, tramadol, does not work effectively. A simple blood test can produce a result within a few hours, enabling doctors to switch a non-responding patient on to another painkiller, such as morphine, which will be able to work in these patients.

Dr Laurent Varin, an anaesthesiologist at the Caen (Caen, France), presented the findings to the European Anaesthesiology Congress in Paris today (Sunday).

Tramadol is a synthetic opioid that is metabolised in the liver via an enzyme called cytochrome P450 2D6 (CYP2D6) to produce a small molecule (or "") called O-demethyltramadol (ODT). ODT is between two and four times better at inducing than tramadol that is not metabolised successfully. This is because ODT has a 200-fold higher affinity to the opioid receptors in humans than un-metabolised tramadol, meaning that it binds to the receptors more successfully, blocking out the signals for pain.

Dr Varin said: "In our hospital we frequently use tramadol after surgery – about 50-60% of are treated with it, while the rest are treated with nefopam, which is a non-opioid painkiller. However, in about 5-10% of Caucasian patients the CYP2D6 enzyme is inefficient and does not produce enough ODT to bind effectively to the ; these patients are known as 'poor metabolisers' and will have poorly controlled pain unless the problem is identified quickly and they are switched to or nefopam."

In order to identify the "poor metabolisers", Dr Varin and his colleagues decided to investigate the ratio between tramadol and ODT in patients' blood to see if this would give an indication of how efficiently CYP2D6 was working. They recruited 294 Caucasian patients who were receiving tramadol after surgery for a number of digestive conditions such as stomach, bowel and cancer, or for surgery on the spleen, gall bladder or pancreas. They collected blood samples after 24 and 48 hours post-surgery, and tested them for concentrations of tramadol and ODT using "high performance liquid chromatography tandem mass spectrometry", which separates out the different components in the blood.

The researchers also used genotyping to analyse and identify the DNA make-up of the patients to discover which of them had inefficient CYP2D6. This revealed that eight per cent (23) of the patients were "poor metabolisers". Then the researchers assessed the ratio of tramadol to ODT in the blood samples of the "poor metabolisers" and the other patients.

"We found that, after 24 hours, an ODT/tramadol ratio of less than 0.1 indicated a deficient CYP2D6 activity with an accuracy of 87% sensitivity – the test's ability to correctly identify positive results – and 85% specificity – the test's ability to correctly identify negative results," said Dr Varin [1]. "This means that this ratio is highly accurate at detecting 'poor metabolisers' who need to be switched to another painkiller."

Dr Varin and his colleagues believe that the ODT/tramadol ratio gives doctors a new tool to identify 'poor metabolisers' in the clinic. "This test is simple and cheap, costing only about 30 Euros. It can be performed quickly in just a few hours, instead of many days when the genotyping method is used, and will enable clinicians to make the best treatment choices for their patients. If a patient is suffering unrelieved postoperative pain and the reveals an ODT/tramadol ratio of less than 0.1, then the clinicians can switch quickly to morphine, rather than trying to increase the dose of tramadol and risk adverse drug effects by overdosing.

"Furthermore, once a patient has been identified as a 'poor metaboliser', this means that other drugs that are also metabolised via CYP2D6 will be less effective, such as codeine and, to a lesser extent, oxycodone, and so this knowledge will help clinicians to decide on alternative treatment strategies for their patients," concluded Dr Varin.

The researchers are continuing to investigate the ODT/tramadol ratio in more patients. The study was carried out in a number of hospitals and so Dr Varin and his colleagues believe their results are independent of the way different hospitals and doctors might prescribe tramadol. They also believe that use of the ODT/tramadol ratio tool could be extended to patients prescribed tramadol in circumstances other than for post-operative pain relief.

Explore further: Studies show that CYP2D6 genotype does not predict tamoxifen benefit

More information: Abstract no: ESAPC1-5

Related Stories

Studies show that CYP2D6 genotype does not predict tamoxifen benefit

March 6, 2012
Two studies published March 6 in the Journal of the National Cancer Institute provide insights about the CYP2D6 genotype in postmenopausal breast cancer patients and represent a major step forward in understanding the usefulness ...

Recommended for you

Drug for spinal muscular atrophy prompts ethical dilemmas, bioethicists say

December 11, 2017
When the Food and Drug Administration approved the first drug for people with spinal muscular atrophy a year ago, clinicians finally had hope for improving the lives of patients with the rare debilitating muscular disease. ...

FDA's program to speed up drug approval shaved nearly a year off the process

December 7, 2017
Speeding the pace at which potentially lifesaving drugs are brought to market was a rallying cry for Donald Trump as a candidate, and is a stated priority of his Food and Drug Administration commissioner, Dr. Scott Gottlieb. ...

Dangers of commonly prescribed painkillers highlighted in study

December 6, 2017
Commonly prescribed painkillers need to be given for shorter periods of time to reduce the risk of obesity and sleep deprivation, a new study has revealed.

Viagra goes generic: Pfizer to launch own little white pill

December 6, 2017
The little blue pill that's helped millions of men in the bedroom is turning white. Drugmaker Pfizer is launching its own cheaper generic version of Viagra rather than lose most sales when the impotence pill gets its first ...

Surgery-related opioid doses can drop dramatically without affecting patients' pain

December 6, 2017
Some surgeons might be able to prescribe a third of opioid painkiller pills that they currently give patients, and not affect their level of post-surgery pain control, a new study suggests.

Four-fold jump in deaths in opioid-driven hospitalizations

December 4, 2017
People who end up in the hospital due to an opioid-related condition are four times more likely to die now than they were in 2000, according to research led by Harvard Medical School and published in the December issue of ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.