"'Opioid' is a generic term for natural or synthetic substances that bind to specific opioid receptors in the central nervous system (CNS), producing an agonist action. Opioids are also called narcotics—a term originally used to refer to any psychoactive substance that induces sleep. Opioids have both analgesic and sleep-inducing effects, but the two effects are distinct from each other.

"Some opioids used for analgesia have both agonist and antagonist actions. Potential for abuse among those with a known history of abuse or addiction may be lower with agonist-antagonists than with pure agonists, but agonist-antagonist drugs have a ceiling effect for analgesia and induce a withdrawal syndrome in patients already physically dependent on opioids.

"In general, acute pain is best treated with short-acting (immediate-release) pure agonist drugs at the lowest effective dosage possible and for a short time; Centers for Disease Control and Prevention (CDC) guidelines recommend 3 to 7 days (1 ). Clinicians should reevaluate patients before re-prescribing opioids for acute pain syndromes. For acute pain, using opioids at higher doses and/or for a longer time increases the risk of needing long-term opioid therapy and of having opioid adverse effects.

"Chronic pain, when treated with opioids, may be treated with long-acting formulations (see tables Opioid Analgesics and Equianalgesic Doses of Opioid Analgesics ). Because of the higher doses in many long-acting formulations, these drugs have a higher risk of serious adverse effects (eg, death due to respiratory depression) in opioid-naive patients.

"Opioid analgesics have proven efficacy in the treatment of acute pain, cancer pain , and pain at the end of life and as part of palliative care . They are sometimes underused in patients with severe acute pain or in patients with pain and a terminal disorder such as cancer, resulting in needless pain and suffering. Reasons for undertreatment include
"Underestimation of the effective dose
"Overestimation of the risk of adverse effects

"Generally, opioids should not be withheld when treating acute, severe pain; however, simultaneous treatment of the condition causing the pain usually limits the duration of severe pain and the need for opioids to a few days or less. Also, opioids should generally not be withheld when treating cancer pain; in such cases, adverse effects can be prevented or managed, and addiction is less of a concern.

"Duration of opioid trials for chronic pain due to disorders other than terminal disorders (eg, cancer) has been short. Thus, there is little evidence to support opioid therapy for long-term management of chronic pain due to nonterminal disorders. Also, serious adverse effects of long-term opioid therapy (eg, opioid use disorder [addiction], overdose, respiratory depression, death) are being increasingly recognized. Thus, in patients with chronic pain due to nonterminal disorders, lower-risk nonopioid therapies should be tried before opioids; these therapies include
"Nonopioid drugs
"Complementary (integrative) medicine techniques (eg, acupuncture, massage, superficial electrical stimulation)
"Cognitive-behavioral techniques
"Interventional therapies (epidural injections, joint injections, nerve blocks, nerve ablation, spinal or peripheral nerve stimulation)

"In patients with chronic pain due to nonterminal disorders, opioid therapy may be considered, but usually only if nonopioid therapy has been unsuccessful. In such cases, opioids are used (often in combination with nonopioid therapies) only when the benefit of pain reduction and functional improvement outweighs the risks of opioid adverse effects and misuse. Obtaining informed consent may help clarify the goals, expectations, and risks of treatment and facilitate education and counseling about misuse.

"Patients receiving long-term (> 3 months) opioid therapy should be regularly assessed for pain control, functional improvement, adverse effects, and signs of misuse. Opioid therapy should be considered a failed treatment and should be tapered and stopped if the following occur:
"Patients have persistent severe pain despite increasing opioid doses.
"Patients do not adhere to the terms of treatment.
"Physical or mental function do not improve.

"Physical dependence (development of withdrawal symptoms when a drug is stopped) should be assumed to exist in all patients treated with opioids for more than a few days. Thus, opioids should be used as briefly as possible, and in dependent patients, the dose should be tapered to control withdrawal symptoms when opioids are no longer necessary. Patients with pain due to an acute, transient disorder (eg, fracture, burn, surgical procedure) should be switched to a nonopioid drug as soon as possible. Dependence is distinct from opioid use disorder (addiction), which, although it does not have a universally accepted definition, typically involves compulsive use and overwhelming involvement with the drug, including craving, loss of control over use, and use despite harm."


James C. Watson, MD, Treatment of Pain, Merck Manual Professional Version, last accessed August 31, 2021.