Does tolerance to painkillers and opioids (narcotic pain medications) decrease as you take them?

From the Guidelines

No, tolerance to painkillers and opioids actually increases with continued use, not decreases. This means that over time, a person typically needs higher doses to achieve the same pain relief they initially experienced. Common opioid medications like morphine, oxycodone (OxyContin), hydrocodone (Vicodin), and fentanyl all produce this tolerance effect when taken regularly for more than a few weeks [ 1 ]. The development of tolerance occurs because the body adapts to the constant presence of these drugs through neurochemical changes. Specifically, opioid receptors become less responsive, and the brain adjusts its natural pain control systems.

Key Points to Consider

• Tolerance to opioids does not develop to the same extent or at the same rate across all physiological responses [ 1 ].
• Tolerance to analgesia and reward appears to develop faster than tolerance to respiratory depression [ 1 ].
• The dose escalation necessary to maintain analgesic efficacy can increase the risk of overdose and potentially the risk of addiction [ 1 ].
• Non-opioid pain management strategies like acetaminophen, NSAIDs, physical therapy, and cognitive behavioral approaches should be considered as alternatives or supplements to minimize opioid use when possible.

Clinical Implications

• Doctors typically try to use the lowest effective dose for the shortest duration possible when prescribing opioids for pain management.
• Patients should never increase their dose without medical supervision, as this can lead to dependence, addiction, or overdose.
• The mechanisms responsible for tolerance, physical dependence, and hyperalgesia are not completely understood but involve molecular- and circuit-level adaptations as well as counter-adaptations in opioid receptors and their intracellular signaling cascades [ 1 ].

From the FDA Drug Label

Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Both tolerance and physical dependence can develop during chronic opioid therapy.

Tolerance to painkillers and opioids actually increases as you take them, meaning that over time, you may need higher doses to achieve the same level of pain relief. This is because your body adapts to the presence of the opioid, leading to a decrease in its effectiveness. 2 3

• Key points:
  • Tolerance develops during chronic opioid therapy
  • Increased doses may be needed to maintain analgesia
  • Physical dependence can also occur with chronic opioid use

From the Research

Opioid Tolerance

• Opioid tolerance is a significant problem, as it requires increased opioid drug doses to achieve the same effect 4.
• The development of tolerance is associated with dose escalation in long-term opioid therapy, which can cause opioid-induced hyperalgesia (OIH), a state of hypersensitivity to painful stimuli 4.
• Mechanisms of opioid tolerance include drug-induced adaptations or allostatic changes at the cellular, circuitry, and system levels 4.

Factors Influencing Tolerance

• The use of opioids can lead to tolerance, physical dependence, and addiction, but the risk of these consequences can be minimized with appropriate dosing regimens and treatment strategies 5.
• Long-acting preparations, such as transdermal fentanyl, can minimize the occurrence of withdrawal symptoms and opioid-induced euphoria, reducing the risk of tolerance and physical dependence 5.
• Psychopathologic and psychosocial conditions can predict failed opioid effectiveness in noncancer pain subgroups, and long-term therapy with short-acting opioids can predispose to tolerance and addiction 6.

Strategies to Address Tolerance

• Various strategies, such as opioid rotation and multimodal analgesia, can provide extra-opioid analgesia and minimize tolerance development during opioid treatment 7.
• Drugs that block the mechanisms underlying tolerance, such as alpha2-adrenoreceptor agonists and NMDA antagonists, can be used to treat tolerance 7.
• Interventional techniques, such as intrathecal therapy with local anesthetics and sympathetic block, can decrease the pain input and allow a decrease in the opioid dose, thus reverting the mechanisms producing tolerance and OIH 4.