Tolerance, dependence and addiction are three separate conditions that may occur with prolonged use of some medications. Patients who use certain over-the-counter or prescription drugs, including painkillers, may be affected. Some people mistakenly believe the three terms are different names for the same condition. In reality, they are distinct physiological or psychological states.

In 2001, three organizations – the American Academy of Pain Medicine, the American Pain Society and the American Society of Addiction Medicine – issued a paper defining tolerance, physical dependence and addiction as three separate conditions that require different diagnoses and treatment approaches.

Tolerance may occur in patients who use certain medications over a long period of time. When this occurs, increasingly higher amounts of the drug are required before the user obtains the same effect that was achieved at the initial dosage. Patients may develop tolerance more quickly to some of a drug’s effects than to others.

Tolerance is a natural reaction to almost any substance to which the body is exposed. It does not indicate dependence or addiction. In some cases, tolerance can have positive effects. For example, patients who experience side effects (e.g., sedation or respiratory depression) when using a drug to relieve pain may find that the incidence of these negative effects decreases as their tolerance increases.

Tolerance should not generally limit long-term use of opioids and there usually does not seem to be an arbitrary cap on the dose as was once thought, according to the AAPM and the APS.

Physical dependence may occur in patients whose bodies become accustomed to using a drug. It can be triggered by suddenly ceasing all use of the drug, suddenly and significantly reducing the dosage level of a drug, suddenly experiencing lower levels of the drug in the bloodstream, or using another drug that counteracts the effects of the original drug.

When any of these circumstances arise in a person who is physically dependent upon the drug, the body requires a certain amount of the substance to avoid going into withdrawal. Symptoms of withdrawal may include:

• Restlessness
• Muscle pain and bone pain
• Insomnia
• Diarrhea
• Vomiting
• Cold flashes (including “goose bumps”)
• Involuntary leg movements and tremors
• Seizures

Physical dependence to certain drugs such as opioids, sedatives, antidepressants or beta blockers (blood pressure drugs that are sometimes used as headache medications) is likely in patients who use a drug for a long period of time. Patients who display symptoms of withdrawal often can be successfully treated by reinstituting doses of the original medication at lower levels, such as 25 percent or 40 percent of the patient’s previous regular dosage level. Withdrawal can be avoided by gradually tapering the patient off the drug rather than quitting it “cold turkey.”

In some cases, physicians may prescribe a rotation of medications for the same condition. In this way, a patient can use one drug for a period of time and then shift to another. This helps to prevent physical dependence upon any one medication.  

Addiction, sometimes called psychological and physical dependence, is a disease characterized by harmful and compulsive use of a drug that results in repeated and significant negative consequences. The psychological dependence is marked by the compulsive use of a substance of abuse because of its reinforcing qualities.  People who are addicted to a substance may have one or more of the following symptoms:

• Impaired ability to control their use of the substance
• Compulsive use of a substance
• Craving of a substance
• Use of a substance despite harm
• Feelings of euphoria when using the substance

Some experts identify addiction by the presence of the three “Cs” – craving or compulsive use, loss of control and use despite adverse consequences.

When physicians treat someone with chronic pain by prescribing a drug that has the potential for addiction, the goal is to improve the patient’s function and quality of life. Pain results from the interaction between three components of the nervous system: the peripheral nerves, spinal cord and brain. Nociceptive pain occurs when nerve receptors that sense tissue damage (nociceptors) are stimulated by an unpleasant sensation or damage. 

However, sometimes addiction does occur. Addiction to prescription drugs may occur in patients who use some types of drugs, including: opioids, central nervous system (CNS) depressants or stimulants. Of these three drugs, opioids are the group chiefly used for pain relief from various disorders.

Opioids block pain receptors in the brain and affect the part of the brain that mediates feelings of pleasure. As a result, people who do not require the drugs for pain relief often experience feelings of euphoria that in some users can lead to the psychological and behavioral syndrome known as addiction. It is important to note, however, that medications prescribed for pain relief rarely cause addiction when used correctly under a physician’s close supervision, even when used over long periods.

Opioid medications rarely cause addiction when used correctly under a physician’s close supervision for acute pain or cancer pain. However, there is a greater risk of addiction when opioids are used to treat non-cancer chronic pain.

In 2005, more than 6 million Americans reported nonmedical use of prescription drugs within the previous month, according to the National Survey on Drug Use and Health. That figure is more than the total number of people who used cocaine, heroin, hallucinogens or inhalants.

As the number of opioid prescriptions has risen in recent years, so have fatal overdoses. Between 1999 and 2002, prescription opioids caused more overdose deaths than cocaine or heroin, the U.S. Centers for Disease Control and Prevention (CDC) reported in 2006. Still, the agency cautioned that the findings should not cause physicians or patients to have unwarranted fear about using opioids to control pain.

Organizations such as the American Medical Association warn that undertreatment of pain is a major social problem fueled by fear of using opioids. Misperceptions about tolerance and addiction contribute to unwarranted withholding of these strong analgesics, according to the AAPM and the APS.

Some cases of suspected addiction to prescription medications are actually examples of poor pain management that may lead to pseudoaddiction. This occurs when patients who are undertreated for pain behave like addicts, resorting to behaviors such as lying just to obtain a drug. However, unlike actual addiction, this behavior ceases once a patient’s pain is properly treated.

Though tolerance, dependence and addiction are three separate conditions, they can be related in the addicted person. For example, people who are addicted to narcotics may also have developed a physical dependence upon them. In addition, the longer people are addicted to some types of drugs, the greater their tolerance to the drug is likely to grow.