Concerns with the safety and adverse effects of opioids have grown with increases in prescribing and dose, and higher doses have been associated with worse patient-reported outcomes in a study by researchers at Veterans Affairs (VA) and Kaiser Permanente health systems.
Benjamin Morasco, PhD, and his colleagues at the VA Portland Health Care System and the Kaiser Permanente Northwest Center for Health Research, in Portland, Ore., administered a battery of self-report measures to over 500 patients with chronic musculoskeletal pain treated with long-term opioid therapy. Their findings were published online on Dec. 17, 2016, in the Journal of Pain.
Most assessments of clinical outcomes in patients treated with opioid analgesics have been drawn from medical record reviews, Dr. Morasco and his colleagues noted, rather than associating patient-reported outcomes with the prescribed opioid dose.
“One of the things that makes this current study unique is [it] is the first to identify more impairment, and higher pain based on opioid dose, when using question and answer survey instruments,” Dr. Morasco said in an interview.
Patients in the current study, receiving a stable dose of opioid therapy for at least 90 consecutive days, were grouped by dose level for study analysis: “low dose,” with a daily morphine equivalent dose (MED) of 5 to 20 mg; “moderate dose,” with an MED of 20.1 to 50 mg; and “higher dose,” with an MED of 50.1 to 120 mg. Although the 120-mg ceiling is lower than the highest doses in some dose-effect studies, it was established by the institutional review board for a larger study on opioid dose escalation from which this cohort was drawn.
The three dose-level groups had similar demographic characteristics with the exception of working status, with the low-dose group significantly more likely to be working or retired and the moderate- and higher-dose groups more likely to be receiving disability benefits.
The patient self-report measures on pain perception and response included the Chronic Pain Grade Scale of pain intensity and pain-related function, the Pain Medication Questionnaire to assess beliefs and behaviors related to the misuse of pain medications, and the Pain Catastrophizing Scale.
The Patient Health Questionnaire was applied to screen for depressive symptoms, and the Generalized Anxiety Disorder-7 Scale was used to assess severity of anxiety symptoms. Quality of life was reflected in responses to the 36-Item Short-Form Health Survey. Potential alcohol use disorder and use of illicit substances were screened with, respectively, the Alcohol Use Disorders Identification Test and the Drug Abuse Screening Test-10.
More Pain, More Dysfunction at Higher Opioid Doses
Dr. Morasco and his colleagues found patients in the higher-dose group reported greater pain intensity, more impairments in functioning and quality of life, poorer self-efficacy for managing pain, greater fear avoidance, and more health care utilization.
The researchers interpreted the low self-efficacy for managing pain in those on the highest opioid doses as reflecting lower expectations and less confidence in the ability to perform tasks as a result of pain. This was supported by the group also expressing more fear avoidance of physical activity. Contrary to the researchers’ expectations, however, this group did not demonstrate higher levels of pain catastrophizing.
Of note, the low-dose group reported the highest rates of problematic alcohol use but had the lowest measures of potential substance use disorder. The reverse was found in patients in the higher-dose group, whose self-reports suggested a high rate of potential substance use disorder and low rate of problematic alcohol use. This lack of consistency suggested to the researchers that their method of assessment may not have accurately associated alcohol and substance use disorder with opioid doses.
The question of whether high opioid doses are contributing to or reflecting the requirements of more pain and dysfunction was considered by Dr. Morasco. “Are people that are trying high doses finding those lead to more impairment, and more problems, and more adverse effects, or do people that have more pain and lower quality of life—are they more likely to get higher doses of opioids?” he posed.
“The answer is, unfortunately, that we don’t know, and the results of the study don’t inform that question,” Dr. Morasco told Pain Medicine News.
To better address that question, however, the group is embarking on a larger study on a cohort from the VA and Kaiser that will prospectively examine circumstances involved in the decision to increase opioid dose.
“One of the questions in our larger research study is, ‘What are the factors that predict who gets an increase in their prescription opioid dose?’” Dr. Morasco said. “We’re studying, certainly, pain-related factors, but also mental health factors, and psychological factors about strategies people use for coping with pain. We’re also studying institutional factors and characteristics associated with who is prescribing the medication.”
The results of the current study and objectives for the larger investigation were of particular interest to Brett Stacey, MD, medical director for the Center for Pain Relief, in Seattle, who previously served as medical director of the Comprehensive Pain Center at Oregon Health & Science University, in Portland.
“This study emphasizes that higher doses don’t necessarily give better pain relief,” Dr. Stacey said. “It is not just the pain score that is driving it. People with high pain levels do not require higher opioid doses independent from the other factors. It is anxiety, its depression, its other things that tend to push the higher dose other than just pain relief.”
Dr. Stacey underscored how difficult it can be to treat patients with high distress and high pain levels. “When they’re hard to treat, opioids, certainly by themselves, only complicate the picture,” he said. “Especially at higher doses, they don’t make it easier.”