On Friday, February 21, Dr. Kelly Dunn of Johns Hopkins School of Medicine gave a lecture entitled “The Promise of Tramadol as a Medication to Treat Opioid Use Disorder.” Dr. Gina Fernandez of the St. Mary’s College of Maryland (SMCM) Psychology department introduced Dunn as the first speaker of the semester in the SMCM opioid lecture series. Dunn began with an overview of the ongoing opioid epidemic, as well as an explanation of how it became the epidemic it is today before moving into the treatment strategies she is involved in at Johns Hopkins.
Dunn explained that heroin, a natural derivative of the poppy plant, started out as a treatment for morphine addiction, which was effective in small doses, but became addictive in larger doses and when abused. From this, a desire to develop synthetic opioids arose as pain became a target for doctors to alleviate. Dunn states that this is what has contributed to the longevity and persistence of opioids, and that now, pain is a billion dollar industry. “It is not likely that the medicines [opioids] will go away because it has this huge market behind it,” Dunn noted. Narcotics are the fifth most prescribed form of drug in the United States and “when a medication is widely available, it is widely abused.” Often prescribed for chronic pain, there has been no concrete evidence that opioids and opiates are helpful, but paradoxically can even increase a patient’s sensitivity to pain.
Looking at how the opioid epidemic has gotten to this level involves considering a multitude of factors. As pain became considered the “fifth vital sign” and doctors placed more stock in pain with the goal of no pain for a patient, patients began receiving more prescription pain medication and opioids more and more frequently. When given more medication than necessary, patients would use more than necessary, and leftover pills had the potential to be abused. These leftover pills are often difficult to get rid of in a safe manner. When flushed down the toilet, there have been fish found with high opioid levels because there is not a system in place to filter the opioids out of the water. As exposure to opioids increases, so does the likelihood of developing an opioid problem.
According to Dunn, there are three identifiable stages of the opioid epidemic. When heroin became more accessible and pain became considered the fifth vital sign, abuse of prescription opioids increased. As a result of this abuse increase, the producers of OxyContin changed the formula of the drug so that it could not be injected or snorted. Those who were addicted to OxyContin could not get what they needed to suppress withdrawal from it, so many switched to heroin. Because heroin is naturally derived and the poppy plant requires specific climates to grow, heroin was in short supply. Then came the development of fentanyl, a synthesized opioid more potent than heroin that met the opioid demand, but can quickly lead to overdose if tolerance is not high enough. This development gives us the opioid crisis of today, and fentanyl has spread widely and rapidly. Dunn says that most patients she works with have only fentanyl in their bloodstream. “For many of these patients we have no evidence that they even consumed heroin, their tolerance is very high.”
Dunn states that fentanyl overdoses happen very fast and have “changed everything we know about treating abuse.” Today in the United States, drug poisoning and opioid-involved poisoning are the highest decrement to life expectancy. Fentanyl, as a short-acting opioid, has a protracted withdrawal, with withdrawal beginning four to six hours after the last does and lasting five to seven days.
To combat this, researchers have begun using long-acting opioids to help patients manage withdrawal and focus on other aspects of rehabilitation. However, there is a treatment gap, with not enough medication available and restrictions placed on prescriptions making it so not everyone who needs it can access these treatments. Tramadol, or ultram, a long-acting opioid, is promising to combat the treatment gap because it has been a pain medication since the 1960s, doctors and pharmacists are familiar with it, and when the dose is increased, patients begin to feel bad effects instead of feeling better. It effectively suppresses withdrawal, there is low risk of abuse and the ease of prescription is higher than other long-acting opioids.
Dunn conducted a series of studies to determine the effectiveness of tramadol, and in a double-blind, double dummy study, the effects of tramadol on withdrawal suppression were clinically significant as compared to two other long-acting opioids. When tapered off tramadol, the majority of withdrawal occurred while a patient in a treatment facility would be cared for by a provider, rather than after discharge. However, because there are still limits to prescription access to tramadol, Dunn also conducted a study to determine how to optimize treatment for patients most in need. To do this, Dunn assessed the level of dependency on opioids during withdrawal before administering the different long-acting opioids. She found that withdrawal symptoms were worse for those with high dependency, and that for patients with lower ratings of withdrawal effects, there was no difference in withdrawal between the medications. For patients with high ratings of withdrawal symptoms, there was a better response with tramadol as compared to the other two. Based on this, Dunn is looking to ascertain whether health care providers can predict which medication would work best for patients.
Dunn concluded, saying “If people have meaningful differences with withdrawal, we can prescribe them the optimal drug, with the difficult-to-prescribe drugs going to those who most need it.” She goes on to note that withdrawal differences need to be further explored to best target treatments. Tramadol is still difficult to prescribe, as all prescription opioids become more restricted with the rise of the opioid epidemic, however it is still easier to prescribe than many, and in these preliminary studies, shows a lot of promise.