Tolerance, dependence and addiction are three separate conditions that can be linked to the use of certain over-the-counter and prescription drugs. Although they often are mistakenly confused with one other, each condition has distinct characteristics, including:

• Tolerance. Occurs in patients who use certain medications over a long period of time and find that larger amounts of the drug are required to obtain the same effect achieved at the initial dosage.
  
  
• Physical dependence. Occurs in patients whose bodies adapt to using a drug. Patients who become physically dependent upon a drug will suffer symptoms of withdrawal if their bodies are suddenly deprived of the medication.
  
  
• Addiction. A primary physical and psychological disease. It is characterized by harmful and compulsive use of a drug that results in repeated and significant adverse consequences. Addiction to painkillers such as opioids is uncommon when they are used correctly under close supervision of a physician  to control pain such a migraine attack.

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.

Addiction is the result of a complex web of genetic, psychological and environmental factors. Patients with a history of psychological disorders (e.g., psychosis, anxiety, personality disorders) or prior substance abuse are at greater risk for addiction when using certain prescription medications.

For this reason, physicians must exercise special care when using medications to manage acute or chronic pain in people with a history of substance abuse. It is recommended that, before starting any opioid medication, patients discuss with their physician in detail if they have had addiction to any drug or alcohol in the past.

When possible, physicians are likely to look for alternative approaches to treating pain that do not involve the use of potentially addicting medications such as opioids. For example, treatments such as exercise therapy, physical therapy or thermotherapy may ease conditions such as herniated discs or whiplash. Also, other medications such as ibuprofen or acetaminophen are tried before prescribing opioids.

However, in some situations, opioids are the best treatment option available and are prescribed to patients even if they have a history of substance abuse. In such situations, physicians may work with psychiatrists or experts in addiction medicine to reduce the risk of addiction. Physicians may also prescribe different medications and rotate them in a patient’s treatment regimen to help lower the risk of addiction to any one substance. Also, methadone clinics are available, where patients can be switched and maintained on methadone to deal with addiction.

The U.S. National Institute on Drug Abuse is launching the first large-scale national study to evaluate treatment of addiction to prescription painkillers. The 11-site Prescription Opiate Addiction Treatment Study will examine the effectiveness of buprenorphine/naloxone tablets (Suboxone), along with different kinds of drug counseling, in patients addicted to prescription opioids.

Preparing questions in advance can help patients to have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about tolerance, dependence and addiction:

1. How do tolerance, dependence and addiction differ?
   
   
2. Do my medications put me at risk of tolerance, dependence or addiction?
   
   
3. Should lower dosages or alternate treatments be tried to reduce my risk?
   
   
4. Is drug tolerance necessarily undesirable, or can it be a positive thing for me?
   
   
5. Are tolerance and dependence early signs of addiction?
   
   
6. What symptoms might I show if I’m going through withdrawal?
   
   
7. How can I avoid withdrawal?
   
   
8. If I become addicted, what treatments can help me?
   
   
9. Is addiction not a concern if I am severely ill and in great pain?
   
   
10. What is pseudoaddiction? Am I likely to experience it?
    
    
11. If have a history of substance abuse, are drugs such as opioids still a treatment option for me?