Monday, July 6, 2009

Drug Tolerance, Drug Dependence, Drug Addiction

"Why is the prescribed medication no longer working like it used to?"
"Could I have become addicted?"

This post covers the popularly misconceived notions of Drug Tolerance, Drug Dependence (habit forming) and Drug Addiction (getting hooked on) as they relate to narcotic analgesics. The similar concepts of physiological dependence and psychological dependence are also discussed. These misconceptions occur commonly within the general public as well as the medical profession at large. The result has been needless misunderstanding, unfounded fears and, most importantly, the denial of adequate pain relief to deserving patients in the U.S. and around the world. Hopefully, the information that follows will help clarify these issues so that the patient and clinician will adopt a healthier respect and greater understanding for these agents and benefit from their use in the treatment of persistent pain.

Drug tolerance or tolerance is the simplest concept of the three to understand. Tolerance to a drug (narcotic analgesic) is said to exist when greater and greater doses and/or strengths of the medication are needed to achieve the same desired effect (i.e., pain relief). This commonly occurs after the patient has been regularly taking the prescribed dose of medication over a period of time. The key words here are: "regularly", "prescribed dose" and "period of time."

"REGULARLY" means that the patient is taking the medication on a fairly constant basis (daily or weekly). However, tolerance will be less likely if the patient is taking the medication on an as needed basis versus around-the-clock (i.e., regularly).

"PRESCRIBED DOSE" means that the dose actually taken by the patient must be a fairly constant amount and not deviate downward or upward significantly from the dose prescribed by the physician. This is important because, should the patient take a smaller dose of the medication than was ordered, the appearance of tolerance may be significantly delayed or aborted all together. Unfortunately, the patient will also likely experience inadequate pain relief. If a larger dose is taken, the likelihood of tolerance will increase - appearing much sooner than expected.

"PERIOD OF TIME" refers to the length of time that the patient has been taking the medication such that drug tolerance has now occurred (see below).

Drug tolerance may first appear as early as three to six weeks in some patients. But there are cases where it does not appear, even after several years of treatment. However, this is definitely the exception, as most patients (60%-80%) will go on to develop drug tolerance after a 12-16 week period of continued use. What is actually happening is that the narcotic analgesic is being metabolized or broken down (detoxification) by the liver. Due to the liver's constant exposure to and processing of the narcotic drug, over time, it will enhance its metabolic and detoxification efficiency. This results in the substance being eliminated from the bloodstream earlier than occurs in a patient who has not taken the drug regularly. The patient then notes that after taking their usual dose, the expected degree of relief or duration of relief is no longer the same. If the dose is increased or the dosing interval (time between doses) is decreased, the patient will again experience the drug's original effects. However, dosing will now become a practical problem in terms of the number of dosing units (pills, capsules, tablets, etc.) required and/or an unrealistically short interval between doses (one to two hours).

Because of the above, regular users of tobacco (nicotine, cigarettes, chewing tobacco) and alcohol (beer, liquor, wine) may develop drug tolerance earlier than nonusers since nicotine and alcohol having similar effects of the liver's metabolic and detoxification efficiency. To overcome this problem, a patient must be "detoxed" from the particular medication over a period of time (two to six weeks) and another analgesic, preferably from the same class/schedule, is substituted. The prior drug tolerance, or "immunity" as many patients call it, will eventually be lost and the original drug can then usually be reinstated at its starting dose. The period of time required for the loss of drug tolerance (after detoxification is complete) varies from patient to patient. Experience reveals an average of 12-24 weeks. At that time, the original drug can usually be restarted successfully with an immediate discontinuation of the substituted narcotic analgesic. In this way, two to three effective narcotic analgesics may be rotated fairly uneventfully over several years, if necessary.

DRUG DEPENDENCE (Physiological Dependence)
Drug dependence or "dependence" on a narcotic analgesic is said to exist when an withdrawal/abstinence syndrome appears in the patient after the medication has been discontinued, the dose (strength) decreased or the dosing interval increased. Conversely, the withdrawal/abstinence syndrome resolves if the medication, dose or dosing interval is reinstated. Drug dependence is more properly referred to as physiological dependence. Its presence alone does not mean that a person is addicted (see below) to or "hooked on" the particular medication. It is also not synonymous with drug tolerance (see above). The terms "habituation" and "habit forming" also commonly refer to drug dependence. The key words here are: "Withdrawal/abstinence Syndrome." This refers to a collection of objective bodily signs (physical, bodily changes) and subjective symptoms (what or how the person is feeling) that occur when a narcotic analgesic has been withdrawn, its dose decreased or another medication interferes with the action of the narcotic. One person's set of signs and symptoms may differ from another's but remains fairly constant in the same person.

COMMON SYMPTOMS ARE: restlessness, anxiety, nausea and the reappearance or increase in pain.

COMMON SIGNS INCLUDE: dilated pupils, sweating, diarrhea, vomiting, increased pulse, increased heart rate, increased breathing rate, tearing, goose pimples and a fine muscle tremor, especially in the hands.

What is actually happening is that the narcotic analgesic's molecules have inserted themselves in cellular receptors of the corresponding body systems that control these various functions eye, skin, gastrointestinal tract and cardiovascular. When the drug is withdrawn or decreased, there is a corresponding decrease in its blood level. This results in a "rebound" effect as the narcotic drug molecules are no longer present in sufficient amounts to keep the various systems stable and the signs and symptoms appear. This is why "physiological dependence" is a more descriptive and correct term as it reflects the dependence of bodily functions on the presence of the drug's molecules in adequate amounts to prevent the appearance of a withdrawal syndrome - thus, the return of system stability once the drug (narcotic analgesic) is reinstated as mentioned above. Of course, a person's drug or physiological dependence can be readily overcome or eliminated by successfully undergoing a drug detoxification program (Drug Tolerance, above).

DRUG ADDICTION (Psychological Dependence; Getting Hooked)
Drug addiction or "addiction" to a narcotic analgesic is said to exist when the person's mind-set or mental state is fixated on obtaining the next dose of the medication to re-experience the associated pleasurable sensation (euphoria) or "high" feeling. Unfortunately, this is usually to the exclusion of all else with subsequent deterioration in the person's social sphere - adversely affecting one's attention to self, family, job, marriage and educational responsibilities. Given the overwhelming need to experience the euphoria, a person may resort to deception and even criminal behavior in order to secure the "next dose." Broken families, divorce, loss of employment and/or educational failures may all be consequences of the "craving" and "slaving" that occurs in drug addiction. The key words here are: "mind-set" and "fixated." It is the fixated mind-set of one's obsession with the drug and the associated pleasure it provides that is the hallmark of drug addiction. Because of this, drug addiction is more properly termed psychological dependence. When comparing drug addiction to tolerance and physiological dependence, the latter two are missing the key psychological elements: a mind-set fixated on obtaining the next dose and the absence of any positive, pleasurable reinforcing experience ("high" feeling or euphoria).

Drug addiction may possess features of tolerance and physical dependence, but the converse is not true. Hence, the three concepts, at times, may be unintentionally misinterpreted by the unwary, leading to the unnecessary denial or withholding of treatment for the persistent pain patient and/or the application of the inappropriate and undeserved social stigma - drug addict.

Treatment of true drug addiction or psychological dependence is a difficult and lifelong task. Symptoms of anxiety and hopelessness are pervasive and should be treated in order to decrease addiction behavior, especially in those patients who initially believe their addiction to be untreatable. With the patient at its center, a multidisciplinary treatment team must be utilized to effect long lasting change and abstinence. Indeed, the emerging medical specialty of Addiction Medicine (Addictionologist) is dedicated to this problem exclusively. In concert with allied specialists from the fields of Psychiatry, Psychology, Nursing, Physical and Occupational Medicine, Social Services, Family Counseling, Law Enforcement, Peer Support Groups and Spiritual Counselors, enduring remissions are being achieved and the outlook is hopeful.

by John A. Campa III, MD
Neurology and Pain Diagnosis