By Deborah J. DeWaay, MD, FACP
Associate Professor, Medical University of South Carolina, Charleston, SC
Dr. DeWaay reports no financial relationships in this field of study
SYNOPSIS: Most opioid prescriptions are continued after a patient overdoses accidentally, and these patients are at higher risk for a recurrent overdose compared to those who have their prescriptions stopped.
SOURCE: Larochelle M, Leibschutz J, Zhang F, Ross-Degnan D, Wharam J. Opioid Prescribing After a Nonfatal Overdose and Association with Repeated Overdose. Annals of Internal Medicine 2016; 164:1-9.
Opioid use to treat non-cancer pain has been on the rise for several decades. In turn, there has been a significant rise in opioid addiction, overdoses and deaths. The number of emergency room visits because of nonmedical use of opioids was over 300,000 in 2008, double the amount in 2003. Patients with opioid overdose are more likely to have an opioid use disorder or to have a high opioid dose prescribed to them. Although opioid overdose and misuse is an indication to stop long-term opioid therapy, the effects of continuation of opioids after overdose had not been characterized. This study analyzes opioid use and subsequent overdoses after patients being treated for non-cancer pain present to an emergency department (ED) or are admitted inpatient for an opioid overdose.
This retrospective study used the Optum database to select a cohort of patients that had a non-fatal opioid overdose while being treated with long-term opioids. This database included pharmacy, inpatient, and outpatient records of over 50 million patients from 50 states who have coverage through a major U.S. health insurance company. The cohort was sampled from records between May 2000 and December 2012. The patients had a median follow up of 15 months.
This study identified 14,725 patients, age 18-64, who had an opioid (index) overdose requiring an inpatient stay or an ED visit. Patients were excluded if they weren’t enrolled 90 days prior to the initial overdose so that continuous opioid use could be determined. The cohort was limited to 3379 patients who had consistent opioid use prior to the overdose as defined by: at least 3 opioid prescriptions filled at least 21 days apart, over 12 weeks duration of prescriptions and over 12 weeks supplied. Patients with cancer were excluded, unless they had non-melanoma skin cancer. In order to compare opioid use before and after the index overdose, authors calculated a morphine-equivalent dosage (MED) for each time an opioid was dispensed to a patient. The provider for each dispensing was noted. Patients were excluded if there was incomplete provider data. Benzodiazepine and buprenorphine use was also collected.
2848 patients, with an average age of 44 years and 60% female, were in the cohort and followed for a median of 10 months after the index overdose. 46% of patients had an average daily dose of 100mg MED or greater, 41% had a substance use disorder, 59% had a mental health diagnosis, and over 50% also had a benzodiazepine prescription. The average mean daily dose for the cohort increased from 152 - 164 MED 60 days prior to the index overdose to 184 MED one week prior to the overdose. Authors defined low, moderate and large dose opioids as <50, 50-<100, and >100 MED respectively. After the overdose the average daily dose decreased to 118 MED on average for the cohort. Post-overdose, 70% of patients received a subsequent prescription within 90 days and 91% of patients received at least one opioid prescription during the follow up period. Over 30% of patients received prescriptions of > 100mg MED. 30% of patients switched to a new prescriber after the overdose.
58% of patients received at least one prescription for a benzodiazepine. The patients who had an active benzodiazepine prescription were more likely to also have an active opioid prescription. 7% of patients were put on buprenorphine post-overdose, and it was very uncommon for these patients to also have an active opioid prescription at the same time.
Repeated overdose occurred in 7% of the patients. Authors used Cox model analysis to calculate the adjusted hazard ratios of repeated overdose for large, moderate and low dose opioid prescriptions post overdose. They were as follows: 2.57 (CI, 1.72 to 3.85) for large dosages, 1.89 (CI1.18-3.04) for moderate dosages, and 1.13 (CI, 0.69 to 1.85) for low dosages. The hazard ratio of repeated overdose was 1.74 (CI, 1.31 to 2.32) if there was a concomitant benzodiazepine prescription, whereas there was no association with repeated overdose and buprenorphine use.
This type of study can only demonstrate associations and cannot explain the reasons behind the post-overdose prescribing patterns. Authors hypothesize that prescribers may have not realized that the patient had overdosed. Other hypotheses are that the prescribers believed the overdose was a therapeutic error or they simply don’t have the skills to treat opioid use disorder. This study shows that there is an association, not causality, between the opioid dosage post-overdose and recurrent overdose.
The authors offer several limitations to their study. First, this database is an insurance database, so it will not capture encounters for which the patients paid cash. Second, coding data was used so it is subject to miscoding error. Third, the patients in this study were all insured and therefore this data may not be generalizable.
COMMENTARY
Patients who overdose are commonly cared for on hospitalist services. There are several dilemmas that the hospitalist faces when discharging these patients. First, are they restarted on their opioids? Guidelines combined with this study make a compelling argument that they should not be, and if they are, the opioid dose should be much lower. There is a conundrum because these patients often have chronic pain, adjuvant therapy takes weeks to start working, and many patients are already on adjuvant therapy. This study gives some evidence to the guidelines and hopefully will help the physician explain to the patient why the prescription is not being restarted or is being modified. Second, communication with primary care providers is even more crucial with these patients so that they are aware of the overdose and understand why the prescription was not continued. Third, follow-up with mental health and addiction experts is crucial since the rate of concurrent psychiatric and substance use disorders is prevalent.
REFERENCES
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Manchikanti L, et al, American Society of Interventional Pain Physicians. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2—guidance. Pain Physician 2012; 15:S67-116.
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Chou R, et al, American Pain Society-American Academy of Pain Medicine Opioids Guidelines Panel. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain 2009; 10:113-30.
