Chronic pain not caused by cancer is among the most prevalent and debilitating medical conditions but also among the most controversial and complex to manage. The urgency of patients’ needs, the demonstrated effectiveness of opioid analgesics for the management of acute pain, and the limited therapeutic alternatives for chronic pain have combined to produce an overreliance on opioid medications in the United States, with associated alarming increases in diversion, overdose, and addiction.
The epidemic of opioid abuse is related in part to incomplete understanding of pain-relief management, opioid tolerance, and opioid addiction. Among the prevention strategies are more widespread sharing of data about opioid neuropharmacology and opioid-use patterns. A new Review Article summarizes.
Clinical Pearl
• How does opioid addiction differ from opioid tolerance and physical dependence?
There is lingering misunderstanding among some physicians about the important differences between physical dependence and addiction. The repeated administration of any opioid almost inevitably results in the development of tolerance and physical dependence. These predictable phenomena reflect counter-adaptations in opioid receptors and their intracellular signaling cascades. These short-term results of repeated opioid administration resolve rapidly after discontinuation of the opioid. In contrast, addiction will occur in only a small percentage of patients exposed to opioids. Addiction develops slowly, usually only after months of exposure, but once addition develops, it is a separate, often chronic medical illness that will typically not remit simply with opioid discontinuation and will carry a high risk of relapse for years without proper treatment.
Clinical Pearl
• Does tolerance to the different effects of opioids develop at the same rate?
Tolerance leads to a decrease in opioid potency with repeated administration. Thus, prescribing opioids long-term for their analgesic effects will typically require increasingly higher doses in order to maintain the initial level of analgesia — up to 10 times the original dose. Some opioid effects show tolerance after a single dose, whereas for others, tolerance occurs more slowly. In particular, tolerance to the analgesic and euphoric effects of opioids develops quickly, whereas tolerance to respiratory depression develops more slowly, which explains why increases in dose by the prescriber or patient to maintain analgesia (or reward) can markedly increase the risk of overdose.
Morning Report Questions
Q: What are some of the risk factors for opioid overdose?
A: The contributing factors associated with overdose can be divided into those associated with the opioid itself (type, dose, potency, and duration of action) and those associated with critical features of the patient. Although the use of any opioid can lead to overdose, research suggests that exposure to higher doses of all opioids increases the risk of overdose. Opioid doses of more than 100 morphine milligram equivalents (MME, the conversion factor used to facilitate comparison of potency among opioids) are disproportionately associated with overdose-related hospital admissions and deaths. Several identifiable characteristics among patients have been reliably associated with an elevated risk of opioid overdose. Included among these factors are a history of overdose, a history of addiction to any substance (but particularly alcohol, benzodiazepines, or opioids), and health problems associated with respiratory depression or concurrent prescription of any medication that has a depressive effect on the respiratory system, such as benzodiazepines and sedative hypnotics. The presence of renal or hepatic dysfunction also increases the risk of overdose, since in patients with either of these conditions, the clearance of many opioid drugs is impaired, which leads to higher and longer-lasting drug levels in blood. Finally, because some cases of overdose may be purposeful suicide attempts, a history of suicidal thoughts or attempts and a diagnosis of major depression are also markers for an elevated risk of overdose.
Table 1. Misconceptions Regarding Opioids and Addiction.
Table 3. Factors Associated with the Risk of Opioid Overdose or Addiction.
Q: What strategies are recommended to reduce the risk of opioid overdose?
A: Recommended mitigation strategies include an overdose risk assessment and urine drug screening before prescription or represcription of opioids (to verify absence of drugs of abuse). The identification of these risks does not automatically rule out opioids as part of effective pain management. However, these risks do indicate the need for much greater education of the patient (and the patient’s family) about overdose risks, the use of an opioid treatment agreement, increased caution in prescribing high opioid doses or long-acting opioids, more frequent clinical follow-up, and, potentially, a prescription for and instruction in the use of naloxone, an opioid antagonist that can reverse an opioid-induced overdose. Indeed, expanding access to naloxone has been shown to significantly reduce the rate of death from opioid overdoses.
Table 4. Mitigation Strategies against Opioid Diversion and Misuse.