CATR: I know you’ve done a lot of research around overdose deaths, both intentional and unintentional, and how this may help psychiatrists more wisely prescribe opioids for pain. Can you start by giving us a little more background on that?
Dr. Bohnert: Sure. I’ll start by talking a little about overdose deaths. The study that we did in the VA with mortality data shows there’s a relationship between the dose of opioids a patient is prescribed and the patient’s likelihood of dying by an unintentional overdose (Bohnert AS et al, JAMA 2011;305(13):1315–1321). What we found is that there’s roughly a linear dose response curve, meaning simply that the greater the dose, the higher the risk of death.
CATR: Can you tell us what you specifically learned about the risk associated with higher doses of opioids?
Dr. Bohnert: Specifically, the risk of death from an overdose with patients prescribed at least 100 mg daily morphine equivalent is about 7 times higher than a patient prescribed less than 20 mg of morphine a day. This paper, as well as additional similar research findings, led to a CDC guideline recommending against prescribing high doses of opioids (see: https://www.cdc.gov/drugoverdose/prescribing/guideline.html).
CATR: So, is there a consensus on what is a safe dose of opioids to manage chronic pain?
Dr. Bohnert: What we found when we did our analysis was that there really was no dose that is completely safe, and there are patients who die of opioid overdoses across the full spectrum of dosages (Bohnert AS et al, Med Care 2016;54(5):435–441). So, there isn’t a point at which you can say, “oh, as long as the patient’s not above 20 morphine-equivalent milligrams, that means there’s no problem.” There’s an overdose risk at every level. But in the interest of trying to encourage physicians to prescribe lower, less risky doses, we determined through the research that less than 50 morphine-equivalent mg per day should be the recommendation put forth in the new CDC guideline. Above 50 mg, the rates of overdose were considerably higher.
CATR: Is there anything else we should know about the CDC guideline?
Dr. Bohnert: Yes. We need to keep in mind that the CDC guideline overall really addresses the question, “How do we approach pain treatment going forward?” What it did not intend to answer was, “What do we do with the cohort of people who were prescribed long-term opioids before the guideline was released?” So, the guideline is more about taking a proactive approach going forward. It also left a lot of unanswered questions, which we’ll need to answer through future research. For example, when is it appropriate to have patients de-intensify or go off opioids? Until we get those answers, it might be a struggle for clinicians dealing with issues of opioid pain management treatment across all clinical settings. The CDC, though, has offered some guidance here (see: https://bit.ly/2oHXK4C).
CATR: Can you tell us more about what you’ve learned while researching deaths associated with intentional vs unintentional opioid overdose?
Dr. Bohnert: We were able to cross-match between medical records data and mortality data, and we specifically looked at the presence of mental health conditions as indicated by diagnostic codes (Bohnert AS et al, Inj Prev 2013;19(5):326–330). What we found was that the risk of intentional overdose (eg, suicide), unintentional overdose, and what we termed “undetermined intent” was associated with essentially every mental health diagnosis group in the study. Not surprisingly, people with a diagnosis of substance use disorder had a stronger association with unintentional overdose deaths and suicide. The undetermined deaths were higher across all the diagnoses, which suggests there are patients who are struggling with a lot of comorbidity—that is, their psychiatric and substance use disorder history makes it more difficult to determine whether the overdose was intentional or unintentional.
CATR: What else can we as psychiatrists and addiction treatment specialists learn from these new CDC guidelines?
Dr. Bohnert: One thing that would be particularly relevant to mental health practitioners is to avoid concurrently prescribing benzodiazepines and opioids. In our VA study, about 50% of those who died from an overdose were on both opioids and benzodiazepines. I think this makes it very important to decide, on a patient-by-patient basis, which of the treatments to prioritize. More research likely needs to be done here, but for now it’s a good idea to proceed with caution when using both medications.