As an addiction advances, the person's life becomes progressively more constricted. The addiction becomes the addict's number one priority, and relationships with family and friends suffer. The addict's mental interior becomes filled with preoccupation about the drug. Other activities are given up. Life revolves around obtaining and using the drug. This constriction is an important characteristic which distinguishes use of a drug by an addict from its appropriate use by a patient with chronic pain.

Another common characteristic of addiction is tolerance, meaning that with time, more of the drug is needed to obtain the same mood-altering effect. The alcoholic finds himself/herself gradually consuming more and more alcohol in order to "feel good." Cigarette smokers tend to increase the number of cigarettes they smoke.

In the medical setting, a patient who is addicted to drugs will show some of the following signs:

Clinicians who are uncomfortable prescribing opioids often have patients who keep requesting more medication and seem preoccupied with the quantity being prescribed. This type of patient is often stigmatized with the label of "drug seeker," whereas in fact the real problem may be that the pain is being inadequately treated. Once a sufficient dose of opioid is prescribed, this phenomenon, termed "pseudoaddiction," vanishes.

Patients can become (psychologically) addicted to a variety of drugs. Some of these drugs have intrinsic properties which result in physical dependence if the drug is repeatedly taken into the body. Months of heavy use are required to produce physical dependence on alcohol or nicotine, whereas only weeks of using opioids can induce physical dependence. Some drugs of abuse -- for example marijuana, cocaine, and hallucinogens --do not produce physical dependence.

Physical dependence has nothing to do with addiction. It simply means that a habituated user will experience certain symptoms if the drug is stopped abruptly. For opioids these withdrawal symptoms include: anxiety, irritability, goose bumps, salivation, lacrimation, rhinorrhea, diaphoresis, nausea and vomiting, abdominal cramps, and insomnia. Withdrawal from morphine starts at 6-12 hours and peaks at 1-3 days. Longer-acting opioids such as methadone have a slower onset of these symptoms, and they are less severe than with shorter-acting drugs such as morphine and hydromorphone. Withdrawal symptoms can be avoided simply by tapering the drug over days.

According to the recent position paper of the American Society of Addiction Medicine3 , "Physical dependence on an opioid is a physiologic state in which abrupt cessation of the opioid, or administration of an opioid antagonist, results in a withdrawal syndrome. Physical dependency on opioids is an expected ocurrence in all individuals in the presence of continuous use of opioids for therapeutic or for non-therapeutic purposes. It does not, in and of itself, imply addiction."

Physical dependence is also associated with tolerance to some of the physical effects of the drug. For example, a person who regularly drinks can remain awake and alert at a blood alcohol level that would put an alcohol-naive person to sleep. It is important to recognize, however, that not all the physical effects of a drug are subject to tolerance. With opioids, for example, tolerance develops to the respiratory depression, sedation, and nausea that opioids induce, but not to constipation. In practice, this means that if the dose of opioid is gradually increased, respiratory depression can be avoided and sedation and nausea will abate, whereas constipation will remain a problem to be dealt with. Most importantly, tolerance does not develop to the pain-relieving effects of opioids.

Does prescribing opioids for pain lead to addiction?

The fear that prescribing opioids for chronic pain will engender iatrogenic addiction is not supported by experience. Zenz et al 4 report on 100 patients who were chronically treated with opioids for nonmalignant pain; none developed addiction to opioids. Portenoy4 reviewed this and other studies, as well as his own experience, and concluded that addiction to opioids in patients without an addiction history rarely results from long-term opioid treatment for pain.

Even patients with a prior addiction history need not automatically be excluded from opioid treatment for chronic pain. According to the AAPM/APS position paper1 "experience has shown that known addicts can benefit from the carefully supervised judicious use of opioids for the treatment of pain due to cancer, surgery, or recurrent painful illnesses. . ." Careful supervision is the key in such cases. A contract (to be described below) is crucial, with provisions made for random urine screens as indicated. Patients with prior drug abuse histories in whom opioid prescription is being considered should be strongly encouraged to strengthen their chemical dependency recovery programs by increasing attendance at 12-step self-help meetings, obtaining a sponsor in Alcoholics Anonymous or other 12-step program, and arranging for accountability to others. My experience and that of other clinicians is that recovering alcoholics are less likely to relapse than are patients who formerly were addicted to opioids; prescribing opioids to the latter group should be considered only as a last resort if every other approach has failed.

Types of chronic non-cancer pain which can be alleviated by opioids

Pain has been classified into three types:

Although it was earlier believed that neuropathic pain was poorly responsive to opioids, experience has proven that all types of pain can be effectively treated with these drugs.5 In my chronic pain practice, patients with each of the above types of chronic pain have obtained benefit from opioids.

Assessment for appropriateness of opioid use.

Opioids are not first-line therapy for chronic pain; nor are they recommended as the only treatment. Opioids should be used as part of a comprehensive treatment plan involving other medications as well as other modalities. Optimal treatment of chronic pain involves a team effort. In addition to the primary physician, other possible team members are: a physiatrist, physical therapist, anesthesiologist (for administering local injections), biofeedback specialist, hypnotist, acupuncturist, orthopedic surgeon, neurologist, neurosurgeon, addictionist, and psychologist.

Before a patient is begun on opioid treatment for chronic pain, a comprehensive assessment is indicated. The first step is to assess the goal of treatment -- is it to diagnose and eliminate the pain by removing the source? or is it to allow the patient to live more comfortably with the pain? Has the patient had a workup to determine the cause of the pain and the treatment options? For example, a patient with severe hip pain due to osteoarthritis might best be served by undergoing a hip replacement, which might result in no pain and improved function. Consideration of opioid management is appropriate only if the goal of treatment is palliation and not cure.

Once the clinician is comfortable that palliation is an appropriate goal, pain assessment is undertaken. Acute pain is associated with observable physical and autonomic changes such as rapid pulse, hypertension, rapid breathing, sweating, pupils dilate. These changes are not usually observed in chronic pain patients. It is not possible to assess chronic pain objectively. Pain is an experience, not an objective finding, so the patient's subjective experience is the gold standard of assessing pain severity. Direct questioning is therefore indicated: "On a scale of 1 to 10, how severe is your pain now? How severe is it usually? What kinds of medications, and how much, does it take to relieve your pain?"

History of the pain. Chronic pain becomes independent of the original injury, but it is nonetheless helpful to have a history of the pain. For example, a patient may have fallen down several stories in an elevator, with resultant back pain, or may have had multiple failed back surgeries, or had osteomyelitis.

The patient's quality of life. It is crucial to learn how the pain has impacted the patient's life, and what his or her life was like before the pain began. The constriction of the patient's life helps assess the severity of the pain. It's also important to document the quality of life, because one of the important facts differentiating addiction from appropriate dependency is that addiction constricts one's life, whereas appropriate opioid use enhances it. It is important to be able to compare what happens to the patient's life once opioid use begins.

The next part of assessment is obtaining a history of treatments already tried. Opioids are generally a last resort. Has the patient been tried on:

If the patient has not seen a physiatrist or an anesthesiologist who specializes in pain management, such a consultation can be extremely helpful. Both specialists can evaluate the role of local injections, physical therapy, TENS units, and other physical modalities. The physiatrist can recommend improved assistive devices such as wheelchairs or braces. The anesthesiologist might consider placement of a spinal cord stimulator for some types of pain.

If a patient with neuropathic pain has not been treated with anticonvulsants, a trial of gabapentine (Neurontin) or carbamazepine (Tegretol), might decrease the need for opioid treatment.

Most patients with chronic pain can benefit from counseling to help them cope better with the pain and to learn strategies for distracting themselves from focusing on the pain.

A crucial part of the assessment is the patient's addiction history.

The Diagnostic and Statistical Manual of Mental Disorders (DSMIV)5 lists seven criteria for diagnosis of addiction; the presence of any three is needed to make the diagnosis of addiction. Only two criteria are physical: development of tolerance and presence of withdrawal symptoms. The other five are all behavioral: Three involve loss of control, two continuation despite negative consequences, for example, "continued use despite a persistent or recurrent social, psychological, or physical problem that is caused or exacerbated by use of the substance."

A patient on opioids for chronic pain, by definition fits most of the criteria (drug taken for longer time than intended, inability to cut down, development of tolerance, withdrawal symptoms, drug taken to avoid withdrawal symptoms), so these are not useful for diagnosis. In addition, the patient may be very concerned with obtaining the medication, so he may be labeled a "drug seeker". Since we can't use these criteria, we must rely on the patient's level of functioning. Addiction causes a person's life to be constricted; pain relief allows him to expand his life. The clinician need to see what happens to the patient once he gets the pain relief he claims he seeks. In questionable cases, a useful strategy is to give patients the benefit of the doubt. If they are using the drug for other than pain relief, their loss of control will become apparent soon enough. Use of an opioid contract (described below) gives the clinician the ability I to immediately cease prescribing the medication should there be any problems.

The addiction history assessment should also include questions about the patient's present and past use of alcohol and other legal and illegal drugs, including nicotine, and particularly, any prior experience with opioids. Was there evidence of loss of control (prescriptions lost, getting medications from several doctors, demanding refills early)? Some patients state that they drink alcohol in order to dull their pain. If the patient is using mood-altering substances, ask about his or her willingness to forego using these drugs in exchange for adequate pain relief with opioids.

Because chemical dependency often is often found in several generations within a family, it is very useful to ask about a family history of alcoholism and other addictions. A personal or family history of addictions constitutes a red flag. In such cases, the decision to dispense opioids must be made reluctantly and with great caution.

The history obtained from the patient should be corroborated by records obtained from other treating clinicians. Records of prior surgeries, accident reports, physical therapy and other assessments and treatments will not only assist in the current evaluation, but will also protect the clinician in case of questions by licensing bodies.

After the comprehensive history, a physical examination is carried out, with particular attention to the problem areas of the body. Deformities, surgical scars, and other relevant features should be documented in the chart. In particular I look for physical signs that support the history provided by the patient. In addition, if the patient has not had an evaluation by a physiatrist, rheumatologist, or other specialist knowledgeable in the area of the patient's problems, I refer the patient for such consultation.

The contract

Once a decision has been made to proceed with opioid treatment, the first step is to discuss a contract with the patient and obtain his or her signature. The intent of the contract is to make it clear to the patient what are the clinician's expectations and the patient's responsibilities; it assists the patient to be accountable. It is understood that if the patient breaks the contract, prescription of opioids will cease. Occasionally, even the most knowledgeable clinician will be fooled by a drug-seeker who is experienced in deception. The contract makes it easier for the clinician to identify what Portenoy4 has termed "aberrant behaviors." In the contract, the patient agrees:

Prescribing Opioid Medication

The patient may have had some prior experience with a trial of an opioid. Because pain is a subjective experience, it is helpful to establish the dosage range which the patient has found effective, and begin by prescribing the upper range. The clinician's goal is not to minimize the dose of opioid, but rather to get to a steady-state level which provides adequate pain relief with a minimum of side effects. Initially there must be frequent contact between clinician and patient so that dosage adjustments can be made. If the patient is opioid-naive, the initial dose should be low, with gradual increments, to avoid the side effects of sedation, nausea, and respiratory depression.

With regard to the choice of opioids, long-acting drugs providing 8-12 hours of pain relief such as methadone (Dolophine, which must be given 2-3 times a day for pain control), sustained-release morphine (MS Contin, Oramorph, Kadian) and sustained-release oxycodone (OxyContin) are preferable to the short acting combinations of oxycodone, hydrocodone, or codeine with acetaminophen and aspirin (e.g. Tylenol with codeine, Vicodin, Percocet or Percodan) for two reasons. One, a long-acting formulation requires less frequent dosing and provides a smoother blood level so that there is more consistent pain relief and less euphoric effect. Second, whereas there is no upper limit to the quantity of opioid that can be safely prescribed, more than 4 grams a day of acetaminophen, (equivalent to 12 regular Tylenol) risks liver toxicity. Similarly, excessive aspirin use can have adverse effects on the GI tract. It is best to separate the opioid from the aspirin or acetaminophen, then titrate each individually.

For patients who cannot take opioids orally, a transdermal fentanyl patch (Duragesic), applied once every 3 days, provides high-dose opioids and a steady blood level.

For patients on a tight budget, methadone is by far the most cost-effective long-acting opioid. Its primary drawback is the negative associations it carries for many people because of its use in treating opioid addicts. Methadone metabolism is enhanced by commonly used drugs such as anticonvulsants, so that patients who simultaneously receive these drugs may require very large doses of methadone. Transdermal fentanyl patches are the most expensive, but may be the best option if severe nausea prevents oral intake. Long-acting morphine and oxycodone preparations are equally cost-effective, but some patients develop pruritis with morphine and do better with oxycodone.

Opioids are not used in isolation. Most patients are also receiving combinations of acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), low-dose tricyclic antidepressants, full-dose SSRI antidepressants, anticonvulsants, and muscle relaxants. Patients are seen initially weekly, then monthly or every two months. At each visit the following areas are assessed and documented in the chart5:

1. Efficacy -- extent of analgesia.

2. Emergent side effects: impaired thinking, somnolence, constipation, nausea.

3. Functional status. Is the person able to do more on the drug than off of it? It is helpful to document specific activities they are now able to do, such as walking, shopping for food, traveling to visit family, working in the garden, attending movies, or resuming employment.

4. "Aberrant drug-related behaviors." Whenever there is aberrant drug-related behavior, its cause must be assessed, and a decision made whether or not to discontinue the medication. If it appears that the patient indeed has an addiction problem, referral to an addiction medicine specialist for further evaluation is appropriate.

It often happens that the increased activity which opioid use permits the patient will initially result in a need for a larger dose. The patient may need 40 mg of methadone a day in order to sit in a chair all day, but he may need 60 or 80 mg a day in order to take a daily walk or travel. So when the patient requests an increased dose, the physician must carefully assess the reason why rather than jumping to the conclusion that this is "drug seeking" behavior.

To avoid problems with medical licensing boards, documentation is crucial. Initially this includes why the clinician is putting the patient on the drug, the extensive initial evaluation, prior records, and the opioid contract.

At each visit each of the four factors ( pain relief, functioning ,side effects, and "aberrant drug-related behaviors") should be assessed and documented. Every prescription should be documented on a data sheet, and every single deviation from the expected date or amount should be fully explained in the chart. For example, if a prescription is dated 2 days early because of a holiday, I document this on the data sheet.

Case Histories:

Case 1 --Pain that can be relieved by other means:

Joan A., aged 45, was a new patient who had recently moved to my city. At age 30 she had had osteomyelitis of her right leg, resulting in significant chronic pain. Scars on her leg from her prior surgery, and old records, confirmed her history. She had been taking 2 acetaminophen with codeine (Tylenol #3) 4 times a day for many years, and felt that this regimen was adequately controlling her pain. On this medication, she rated her pain as 3-4 out of 10. She was also using a TENS unit, with some relief. Because Joan had not had a trial of other modalities in many years, I referred her to an anesthesiologist pain specialist, while continuing her on her current pain medication. The specialist recommended implantation of an intrathecal spinal stimulator. After the procedure, the patient returned to my office, entirely pain free. Over the next week she tapered off the acetaminophen with codeine, and has expressed no need for opioids since.

Case 2: -- Pain in the context of alcohol abuse:

David B, aged 64, was referred to me by a local physiatrist, who felt she had exhausted all her means of relieving David's severe low back pain. David was a physician who had been forced to retire early because of incapacitating back pain that had persisted despite surgery for a herniated disk years back. David, who rated his pain as an 8 or 9 out of 10, spent his days lying on a sofa in the living room. He had recently been through alcohol rehabilitation, instigated by his wife, who stated that their relationship was suffering because her husband was nearly comatose most evenings. David explained that he had gradually taken to drinking more and more in the evenings as a means of getting enough pain relief to get some sleep. He insisted that he was using alcohol only for pain relief, and was prepared to cease drinking entirely if he could get relief some other way. Although ascribing drinking to some other problem is typical of alcoholics, David clearly deserved treatment for his significant pain, so I decided to work with him.

As he was on a limited income, I began David on methadone, gradually titrating upward to a dose of 10 mg 4 times a day, which he felt gave him adequate pain relief. A major early problem was persuading David -- who had the traditional physician's bias against using opioids on a chronic basis, as well as the belief that methadone use meant that the user is a "drug addict" -- that this was a legitimate treatment approach.

Five years later, David is still on the same dose of methadone. He has consumed no alcohol in the past 5 years. He is now able to take trips out of town to visit his grandchildren, to go out to dinner with his wife, and to do some gardening. His life has considerably expanded, and marriage relationship has significantly improved.

Case 3 -- The Value of a Case Manager in Complex Cases.

Betty C is a 38-year old woman who suffered a stroke resulting from a ruptured intracerebral aneurysm. Consequences of the stroke included right-sided hemiplegia requiring wheelchair use, chronic pain and spasm in the affected limbs, severe speech and affect impairment, and a seizure disorder. She was living with her brother, who provided a significant amount of daily care.

Betty was on multiple medications, was seeing several specialists, and had already been assigned a case manager by a local supervisory agency. The case manager had suggested that Betty see me.

Betty's pain was a major issue when she first became my patient. I initiated treatment with sustained-release morphine, which I gradually increased to a dose that provided significant pain relief. Betty, who had previously been a respiratory therapist, was clinically depressed by her situation, so I initiated an SSRI antidepressant and referred her for counseling. Valium was begun for her spasms. Meanwhile, Betty's neurologist recommended injections of botulinum toxin (Botox) to relieve the contractures and spasms in her right hand, followed by physical therapy. The case manager was able to facilitate Betty's multiple treatments, arrange for her appointments, keep her physicians informed of Betty's various appointments, arrange her physical therapy, and provide an overview of her current status.

Other issues:

Tolerance: Patients don't usually develop tolerance to the pain-relieving effects of opioids. Most often a request for increased dose reflects increased physical activity, a worsening physical problem, or deterioration in psychological status (e.g depression). Patients also don't develop a tolerance to the constipating effect of opioids, but they do to sedation and respiratory depression. Some may continue to complain of nausea and sedation. Most can drive safely. Several published studies confirm that patients on chronic opioids have no significant impairment in their ability to drive.

Supervening acute pain problems: Patients on chronic opioids who experience trauma, surgery, etc. still need pain medication for their acute pain problem, and usually need larger amounts of opioids for the acute problem. They should be maintained on their usual dose of opioid plus medication for acute pain. Plan on consulting during the acute problem, as general surgeons, etc. may be uncomfortable prescribing the relatively high doses of opioids required.

Withdrawal: Patients who take opioids for more than a few days should be considered to be physically dependent. The patient should be cautioned not to stop the opioid suddenly, or withdrawal symptoms will appear. Even if pain stops totally, the medication should be tapered. Opioid withdrawal is not dangerous, but can be very uncomfortable.

Getting duped: In its recent Public Policy Statement on the Rights and Responsibilities of Physicians in the Use of Opioids for the Treatment of Pain3 , the American Society of Addiction Medicine wrote, " Despite appropriate medical practice, physicians who prescribe opioids for pain may occasionally be misled by skillful patients who wish to obtain medications for purposes other than pain treatment, such as diversion for profit, recreational abuse, or maintenance of an addicted state. The physician who is never duped by such patients may be denying appropriate relief to patients with significant pain all too often. . . Physicians who are practicing medicine in good faith and who use reasonable medical judgment regarding the prescription of opioids for the treatment of pain should not be held responsible for the willful and deceptive behavior of patients who successfully obtain opioids for non-medical purposes."

Conclusions

The use of opioid medications in the treatment of chronic non-cancer pain is in many cases a legitimate treatment approach which is increasingly gaining acceptance in the medical community. Physicians tend to underuse this modality because of myths related to lack of education. Case managers who become knowledgeable about the appropriate use of opioids in chronic pain can identify physicians in their community who are knowledgeable in this treatment and facilitate referral to such physicians for patients with chronic pain who might benefit from this approach.

References

1.American Academy of Pain Medicine and American Pain Society. The use of opioids for the treatment of chronic pain. Chicago, 1994.

2. American Pain Society: Principles of Analgesic Use in the Treatment of Acute Pain and Chronic Cancer Pain. Skokie, IL. 1989.

3. American Society of Addiction Medicine. Public Policy Statement on definitions related to the use of opioids in pain management/public policy statement on the rights and responsibilities of physicians in the use of opioids for the treatment of pain, Journal of Addictive Diseases , 1998, 17:129-133.

4. Zenz, MK, Strump M, and Tryba M. Long-term oral opioid therapy in patients with chronic nonmalignant pain. J Pain & Symptom Management . 1992;7:69-77.

5. Portenoy, RK. Opioid therapy for chronic nonmalignant pain: Current status. In: Fields HL, Liebeskind JC, eds.Pharmacologic Approaches to the Treatment of Chronic Pain: New Concepts and Critical Issues . Seattle: IASP Publications; 1994: 247-287.

6. American Psychiatric Assn.Diagnostic and Statistical Manual of Mental Disorders, Fourth Revision , Washington DC. American Psychiatric Assn, 1994.