David Juurlink is the head of the Division of Clinical Pharmacology and Toxicology, Department of Medicine, at the University of Toronto.
The patient was a man in his early 60s. A year and a half before we met, he was in a surgeon's office seeking treatment for a painful shoulder. "We could try some Percocet," the surgeon said. Wary of opioids, the patient demurred. The surgeon understood his reservations and instead prescribed tramadol, a drug the patient had never heard of. It seemed to help.
The first sign of trouble arose three months later. His shoulder pain gone, the patient assumed he no longer needed tramadol. He was wrong. Shortly after stopping it, he developed debilitating insomnia, shakes and back pain – something he'd never experienced before. Irritable, exhausted and functioning poorly at work, he soon found the solution: All he needed to do was keep taking tramadol, and these problems went away.
In hindsight, what happened to my patient is clear. His body became accustomed to the presence of tramadol. Without it, he became sick; with it, he felt well again. Put bluntly, he no longer needed tramadol for pain; he needed it simply because he'd been taking it. This phenomenon is known as physical dependence and it's distinct from addiction, which includes behavioural elements and harm despite continued drug use.
In some ways, this man's story is unexceptional. Millions of North Americans are physically dependent on drugs prescribed for pain, anxiety and depression. When the drugs are tapered too quickly, withdrawal symptoms ensue, but they resolve with continued treatment. It's not hard to see how this can sometimes fuel the perception that a drug is effective or even essential, even when it's not really helping.
What led the surgeon to view tramadol as a safer option isn't clear, but there's a good chance that a decade-old misstep by Health Canada helped influence his thinking. To appreciate the misstep, it's necessary to first understand the drug.
Tramadol is a synthetic painkiller developed in the 1960s. In the body, it increases serotonin levels in much the same way antidepressants do. This contributes to its analgesic effect. In the liver, tramadol is converted to a different compound called M1, an opioid that relieves pain the same way morphine does. In a sense, tramadol is two drugs in one, and this "dual mechanism of action" has helped companies promote it to doctors wanting to help patients in pain.
But there's a catch: The conversion of tramadol (the antidepressant) to M1 (the opioid) varies tremendously from person to person. About 6 per cent to 7 per cent of Caucasians lack the enzyme completely, deriving none of the opioid effects, while in other patients the conversion is highly efficient. Roughly a third of people of East African or Middle Eastern descent, for example, convert tramadol to M1 readily.
The practical implication of this variability is that when a doctor prescribes tramadol, he or she rolls the dice, not knowing whether the patient will get a bit of opioid, a lot of opioid or none at all. In the patient-level experiment that is pain management, a key goal is to find a medication that works and is well-tolerated. Tramadol adds needless uncertainty to this experiment.
Fully aware of tramadol's pharmacology, in 2007 Health Canada announced it was considering "scheduling" tramadol as a controlled drug, like codeine, morphine and every other opioid in clinical use. It then sought input from stakeholders and, in doing so, was quickly lobbied by tramadol manufacturers and at least one patient advocacy group supported financially by these same companies. The lobbying seems to have worked: Ten years later, tramadol is nowhere to be found in the Controlled Drugs and Substances Act; in Canada, it enjoys more or less the same legal status as drugs for hypertension.
It's not hard to see why tramadol's preferential classification might lead a doctor to perceive it as safer than, say, Percocet.
To its credit, Health Canada is now revisiting its 2007 decision. Placing tramadol where it belongs – in Schedule 1 of the Controlled Drugs and Substances Act – won't solve the opioid crisis. What the larger crisis demands is a massive federal and provincial investment in addiction treatment, more cautious opioid prescribing by doctors and a frank governmental rethink of whether it makes sense to put people in jail for something that is fundamentally a health issue. (It doesn't.) But classifying tramadol as its pharmacology demands will help dispel the perception that it's somehow safer than other opioids. This is Health Canada's opportunity to correct an old mistake and put the health of Canadians ahead of commercial interests.
My patient, I am pleased to report, is doing well. With the help of his pharmacy, we've tapered his daily tramadol dose from 150 milligrams down to 60, dropping by five milligrams every week. Going slowly has meant no insomnia, no back pain and no irritability. He'll take his last dose of tramadol some time in 2018.