CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016

Deborah Dowell, MD, MPH; Tamara M. Haegerich, PhD; Roger Chou, MD

ABSTRACT

Importance Primary care clinicians find managing chronic pain challenging. Evidence of long-term efficacy of opioids for chronic pain is limited. Opioid use is associated with serious risks, including opioid use disorder and overdose.

Objective To provide recommendations about opioid prescribing for primary care clinicians treating adult patients with chronic pain outside of active cancer treatment, palliative care, and end-of-life care.

Process The Centers for Disease Control and Prevention (CDC) updated a 2014 systematic review on effectiveness and risks of opioids and conducted a supplemental review on benefits and harms, values and preferences, and costs. CDC used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to assess evidence type and determine the recommendation category.

Evidence Synthesis Evidence consisted of observational studies or randomized clinical trials with notable limitations, characterized as low quality using GRADE methodology. Meta-analysis was not attempted due to the limited number of studies, variability in study designs and clinical heterogeneity, and methodological shortcomings of studies. No study evaluated long-term (≥1 year) benefit of opioids for chronic pain. Opioids were associated with increased risks, including opioid use disorder, overdose, and death, with dose-dependent effects.

Recommendations There are 12 recommendations. Of primary importance, nonopioid therapy is preferred for treatment of chronic pain. Opioids should be used only when benefits for pain and function are expected to outweigh risks. Before starting opioids, clinicians should establish treatment goals with patients and consider how opioids will be discontinued if benefits do not outweigh risks. When opioids are used, clinicians should prescribe the lowest effective dosage, carefully reassess benefits and risks when considering increasing dosage to 50 morphine milligram equivalents or more per day, and avoid concurrent opioids and benzodiazepines whenever possible. Clinicians should evaluate benefits and harms of continued opioid therapy with patients every 3 months or more frequently and review prescription drug monitoring program data, when available, for high-risk combinations or dosages. For patients with opioid use disorder, clinicians should offer or arrange evidence-based treatment, such as medication-assisted treatment with buprenorphine or methadone.

Conclusions and Relevance The guideline is intended to improve communication about benefits and risks of opioids for chronic pain, improve safety and effectiveness of pain treatment, and reduce risks associated with long-term opioid therapy.

Key Questions for the Clinical Evidence Review

Key Question 1. Effectiveness and Comparative Effectiveness

In patients with chronic pain, what is the effectiveness of long-term opioid therapy vs placebo or no opioid therapy for long-term (≥1 year) outcomes related to pain, function, and quality of life?
How does effectiveness vary depending on: (1) the specific type or cause of pain (eg, neuropathic, musculoskeletal [including low back pain], fibromyalgia, sickle cell disease, inflammatory pain, and headache disorders); (2) patient demographics (eg, age, race, ethnicity, gender); and (3) patient comorbidities (including past or current alcohol or substance use disorders, mental health disorders, medical comorbidities, and high risk for addiction)?
In patients with chronic pain, what is the comparative effectiveness of opioids vs nonopioid therapies (pharmacologic or nonpharmacologic) on outcomes related to pain, function, and quality of life?
In patients with chronic pain, what is the comparative effectiveness of opioids plus nonopioid interventions (pharmacologic or nonpharmacologic) vs opioids or nonopioid interventions alone on outcomes related to pain, function, quality of life, and doses of opioids used?

Key Question 2. Harms and Adverse Events

In patients with chronic pain, what are the risks of opioids vs placebo or no opioid on (1) opioid abuse, addiction, and related outcomes; (2) overdose; and (3) other harms, including gastrointestinal-related harms, falls, fractures, motor vehicle crashes, endocrinologic harms, infections, cardiovascular events, cognitive harms, and psychological harms (eg, depression)?
How do harms vary depending on (1) the specific type or cause of pain (eg, neuropathic, musculoskeletal [including back pain], fibromyalgia, sickle cell disease, inflammatory pain, headache disorders); (2) patient demographics; (3) patient comorbidities (including past or current substance use disorder or at high risk for addiction); and (4) the dose of opioids used?

Key Question 3. Dosing Strategies

In patients with chronic pain, what is the comparative effectiveness of different methods for initiating and titrating opioids on outcomes related to pain, function, and quality of life; risk of overdose, addiction, abuse, or misuse; and doses of opioids used?
In patients with chronic pain, what is the comparative effectiveness of immediate-release vs extended-release/long-acting (ER/LA) opioids on outcomes related to pain, function, and quality of life; risk of overdose, addiction, abuse, or misuse; and doses of opioids used?
In patients with chronic pain, what is the comparative effectiveness of different ER/LA opioids on outcomes related to pain, function, and quality of life and risk of overdose, addiction, abuse, or misuse?
In patients with chronic pain, what is the comparative effectiveness of immediate-release plus ER/LA opioids vs ER/LA opioids alone on outcomes related to pain, function, and quality of life; risk of overdose, addiction, abuse, or misuse; and doses of opioids used?
In patients with chronic pain, what is the comparative effectiveness of scheduled, continuous vs as-needed dosing of opioids on outcomes related to pain, function, and quality of life; risk of overdose, addiction, abuse, or misuse; and doses of opioids used?
In patients with chronic pain on long-term opioid therapy, what is the comparative effectiveness of dose escalation vs dose maintenance or use of dose thresholds on outcomes related to pain, function, and quality of life?
In patients on long-term opioid therapy, what is the comparative effectiveness of opioid rotation vs maintenance of current opioid therapy on outcomes related to pain, function, and quality of life; and doses of opioids used?
In patients on long-term opioid therapy, what is the comparative effectiveness of different strategies for treating acute exacerbations of chronic pain on outcomes related to pain, function, and quality of life?
In patients on long-term opioid therapy, what are the effects of decreasing opioid doses or of tapering off opioids vs continuation of opioids on outcomes related to pain, function, quality of life, and withdrawal?
In patients on long-term opioid therapy, what is the comparative effectiveness of different tapering protocols and strategies on measures related to pain, function, quality of life, withdrawal symptoms, and likelihood of opioid cessation?

Key Question 4. Risk Assessment and Risk Mitigation Strategies

In patients with chronic pain being considered for long-term opioid therapy, what is the accuracy of instruments for predicting risk of opioid overdose, addiction, abuse, or misuse?
In patients with chronic pain, what is the effectiveness of use of risk prediction instruments on outcomes related to overdose, addiction, abuse, or misuse?
In patients with chronic pain prescribed long-term opioid therapy, what is the effectiveness of risk mitigation strategies, including (1) opioid management plans, (2) patient education, (3) urine drug screening, (4) use of prescription drug monitoring program data, (5) use of monitoring instruments, (6) more frequent monitoring intervals, (7) pill counts, and (8) use of abuse-deterrent formulations on outcomes related to overdose, addiction, abuse, or misuse?
What is the comparative effectiveness of treatment strategies for managing patients with addiction to prescription opioids on outcomes related to overdose, abuse, misuse, pain, function, and quality of life?

Key Question 5. Effect of Opioid Therapy for Acute Pain on Long-term Use

In patients with acute pain, what are the effects of prescribing opioid therapy vs not prescribing opioid therapy for acute pain on long-term opioid use?

Key questions 1-4 were developed for the Agency for Healthcare Research and Quality review.