The Centers for Disease and Control and Prevention published an important article in their Morbidity and Mortality Weekly Report on March 17, 2017, titled, “Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use – U.S., 2006-2015.”
You can read the article here: https://www.cdc.gov/mmwr/volumes/66/wr/mm6610a1.htm
To summarize for my readers, this article describes a study from a very large pool of patients. This study, felt to represent the U.S. population with commercial health insurance, was done on patients with records in IMS Lfelink+database. With nearly 1.3 million subjects, this was a large study, giving it power to detect even small differences.
The study included patients over age 18 who received at least one opioid prescription during the time frame of June 1, 2006 through September 1, 2015. To be included, the patient had to have been free of opioid prescriptions for at least six months prior to receiving an initial opioid prescription. This patient pool was followed over time, to see what risk factors were associated with continued opioid prescriptions. The patient left the study if they de-enrolled from their insurance, or when the patient went for more than 180 days without any opioid prescriptions, or when the study ended.
Patients with cancer were excluded, as were patients with a substance abuse disorder, and patients who were prescribed buprenorphine for the treatment of substance use disorder, since those patients could be expected to have opioid prescriptions lasting longer than patients without those diagnoses.
The duration and dose of the first prescriptions were examined to see which patient or treatment factors were associated with longer opioid use and ongoing opioid prescriptions.
Out of all of the 1.3 million patients, 2.6% continued on opioids for more than one year. These patients were more likely to be female, have a pain diagnosis prior to the first opioid prescription, be older, and have public insurance such as Medicaid or Medicare. They also tended to be started on higher doses of opioids compared to the patients who used opioids for less than one year.
Of all of the patients who were prescribed opioids, 70% were prescribed opioids for seven or fewer days. Only around 7% were prescribed opioids for more than a month. The rest of the patients were prescribed opioids for one to four weeks.
Of the people initially prescribed seven or fewer days of opioids, only around 6% were still on opioids a year later. But 13% of the patients with an initial opioid prescription for eight or more days were still on opioids a year later. Actually, at around the fifth day, the study showed the biggest spike in likelihood of chronic opioid use. For patients with an initial opioid use episode of more than a month, around 30% were still prescribed opioids a year later.
The amount of opioid prescribed influenced risk of continued opioid use. Authors of the study found that a cumulative dose of more than 700 morphine-milligram equivalents were several times more likely to become chronic opioid prescription users than those patients prescribed less than this amount.
The study looked at regional differences too. Of the patients who continued prescription opioid use for more than three years, 38% lived in the South. Only 19% lived in the East, and Midwestern patient accounted for 31% of users of opioids for more three years. Western patients accounted for around 9% of these patients, and the rest couldn’t be classified as to area of the country for some reason.
I doubt this regional variation is from differences in medical issues of the patients. I suspect these differences are due to physician prescribing practices. I could be wrong. The study authors didn’t elaborate on this data. Maybe doctors in the South are getting it right, and doctors in other areas are undertreating pain. However, many southern states have high opioid use disorder rates, and high opioid overdose death rates. And relative to the entire world, the U.S. takes more than its share of opioid medications, as shown in the graph at the beginning of this blog.
Of course, this study doesn’t show cause and effect, just an association. Longer initial opioid prescriptions are associated with continuation of opioid prescriptions for more than a year; however, perhaps the conditions being treated in that group of patients were more severe.
This study looked to see if there was an association between which opioid was prescribed and the risk of long-term opioid use. Patients given prescriptions of long-acting opioids were more likely to have long-term use. That’s no unexpected, but the second most likely medication to be associated with long term use was tramadol.
Tramadol is still mistaken thought by many physicians to be a benign pain medication, unlikely to cause physical dependence or substance use disorder. But in this study, more than 64% of patients who were started on tramadol were still taking some sort of opioid one year later.
As an aside, I’ve seen a fair number of patients present for treatment of their opioid use disorder who used tramadol, usually with other opioids. And some of the worst withdrawals I’ve seen have been with tramadol, with high fevers along with other more typical opioid withdrawal symptoms.
This study’s authors recommended limiting the initial opioid prescription to less than seven days when possible, to reduce the risk of continued opioid prescription and use. Since their data found that a second opioid prescription roughly doubled the patient’s risk of being on opioids for more than a year, the authors also recommended serious consideration of the second prescription.
This study makes intuitive sense. It showed that the longer the number of days of the initial prescription, the greater than risk of the patient still being on opioids one year later.
But what surprised me was the degree of increased risk, even with only a second prescription, and even with only more than seven days prescribed.
Readers may ask, what’s the big deal about being on opioids for more than one year? That doesn’t necessarily mean the patient has opioid use disorder. That is correct, and this study isn’t saying these patients who became chronic users of opioid pain medication developed opioid use disorder.
However, as the authors say in their summary, previous research does show an increased risk for harm in patients on long-term opioid therapy.
In view of our current opioid overdose death problem, it would seem prudent to limit risk to patients. We can use this information, and be cautious about prescribing more than seven days of opioids. We (physicians) should carefully consider whether to give second opioid prescriptions, and be more cautious about prescribing tramadol and long-acting opioids.