Opioids as MedicationsPage 7 of 17

5. Tolerance, Dependence, Addiction, and Risk of Opioid Use Disorder

Regular opioid use leads to ever increasing doses required to get the same effect, which is referred to as tolerance.

Tolerance is the body’s physical adaptation to a drug (in this case to opioids) so that greater amounts of the drug are required over time to achieve the initial effect as the body gets used to and adapts to the intake. One way to delay tolerance is to use low doses of opioids in combination with non-opioid pain relievers such as acetaminophen (common products include Vicodin, Percocet). Many opiates are marketed in at least one form with acetaminophen included (A to Z Drug Facts, 2008). Fortuitously, tolerance to the CNS-depressing side effects seems to develop as fast as tolerance to pain relief, so the dose can be escalated. There is often cross tolerance to other opioid agonists, but it is not usually equivalent, so switching drugs and using about a 50% equivalent dose can work to some degree.

Dependence is a term that has been used in the past to include both a physical and psychological need for a drug, but more recently is confined to the physical need. Dependence is a state of adaptation that is manifested by a drug class specific (in this case opioid) withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of a drug, and/or administration of an antagonist. As opioids are used over time, physical dependence will develop and the user will experience withdrawal symptoms if the drug is stopped suddenly. Tolerance is increased at approximately the same rate for analgesia, euphoria, and respiratory depression, while pupillary constriction and constipation show little tolerance and become greater symptoms with increased dose.

In general, patients using an opioid for acute pain management will taper their dosage as the pain decreases thereby avoiding withdrawal symptoms. Classic opioid withdrawal symptoms are described as severe flu-like symptoms and in general are not life threatening, but the user feels like dying if no medical assistance is available. Initial symptoms may begin 6 to 14 hours after the last dose and include anxiety, irritability, perspiration, restlessness, muscle aches, rhinorrhea, frequent yawning and insomnia. As time goes on the user experiences piloerection (goose bumps), diarrhea, abdominal cramping, nausea and vomiting, dilated pupils, tachycardia and high blood pressure. Withdrawal symptoms usually begin to taper after 3 days and should be minimal within a week, however some users may have an extended withdrawal experience.

Addiction is a primary, chronic, neurobiologic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Pseudo addiction is a term which has been used to describe patient behaviors that may occur when pain is undertreated. Patients with unrelieved pain may become focused on obtaining medications, may “clock watch,” and may otherwise seem inappropriately “drug seeking.” Even such behaviors as illicit drug use and deception can occur in the patient’s efforts to obtain relief. Pseudo-addiction can be distinguished from true addiction in that the behaviors resolve when pain is effectively treated.

Opioid Use Disorder

Due to confusion about the terms drug dependence and addiction, the new Diagnostic and Statistical Manual of Mental Disorders (DSM5) uses the diagnosis of Substance Use Disorders.

The new terminology for a diagnosis of an opioid addiction is Opioid Use Disorder and it can be categorized as mild, moderate, or severe depending upon the number of diagnostic criteria. It lists eleven diagnostic criteria of which at least two must be met within a 12-month period to make the diagnosis:

  1. Opioids are taken in larger amounts or over a longer period than was intended
  2. There is a persistent desire or unsuccessful efforts to cut down or control opioid use.
  3. A great deal of time is spent in activities necessary to obtain the opioid , use the opioid, or recover from its effects.
  4. Craving, or a strong desire or urge to use opioids.
  5. Recurrent opioid use resulting in a failure to fulfill major role obligations at work, school, or home.
  6. Continued opioid use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids.
  7. Important social, occupational, or recreational activities are given up or reduced because of opioid use.
  8. Recurrent opioid use in situations in which it is physically hazardous.
  9. Continued opioid use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance.
  10. Tolerance*
  11. Withdrawal*

*This criterion is not considered to be met if the opioid is taken under appropriate medical supervision.
Source: DSM5, 2013.