Opioids remain the strongest and most effective analgesics available. The downside is that they are addictive and potentially dangerous. Throughout history, although recognizing the value of opioids in treating serious pain, especially acute pain and pain at the end of life, there has been caution about using opioids to treat chronic pain. This article presents how opioids should be used to treat chronic pain considering recent concerns about their efficacy and safety.
Key points
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Not all patients with pain are suitable candidates for chronic opioid therapy (COT).
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Short-term opioid therapy has different goals and purposes and should not progress to COT without reconsideration of goals and purposes.
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Opioid dependence develops in all patients receiving COT, may have a strong psychological component, and is not always easily reversible.
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COT should be goal oriented and discontinued if goals are not met.
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There are significant safety issues that need consideration during COT.
Introduction
Opioids have a long history of use for the treatment of pain, and despite efforts to find alternatives, they remain the strongest and most effective analgesics available. The downside is that they are addictive and potentially dangerous, especially when used not as prescribed, and there are many complex reasons why opioids used to treat pain in outpatients, who control their own use, may not be taken strictly as prescribed. Throughout history, although recognizing the value of opioids in treating serious pain, especially acute pain and pain at the end of life, there has been caution about using opioids to treat chronic pain. This caution existed because of the perceived increased risk of addiction when opioids are used long term and at home. There has been a surge in prescribing of opioids for chronic pain, especially in the United States, and this surge has been produced by a combination of increased availability, production of new opioids and new formulations that have been aggressively marketed, and changed beliefs about whether the risk of addiction for some should preclude use when it might help the many who do not become addicted. The surge in prescribing for chronic pain has produced a parallel increase in cases of opioid abuse and related deaths, and despite what is now more than 2 decades of experience, it is still unclear whether, and under what conditions, opioids can be used to treat chronic pain safely and effectively. Many questions remain, but what this article presents is how opioids should be used to treat chronic pain considering recent concerns about their efficacy and safety.
Introduction
Opioids have a long history of use for the treatment of pain, and despite efforts to find alternatives, they remain the strongest and most effective analgesics available. The downside is that they are addictive and potentially dangerous, especially when used not as prescribed, and there are many complex reasons why opioids used to treat pain in outpatients, who control their own use, may not be taken strictly as prescribed. Throughout history, although recognizing the value of opioids in treating serious pain, especially acute pain and pain at the end of life, there has been caution about using opioids to treat chronic pain. This caution existed because of the perceived increased risk of addiction when opioids are used long term and at home. There has been a surge in prescribing of opioids for chronic pain, especially in the United States, and this surge has been produced by a combination of increased availability, production of new opioids and new formulations that have been aggressively marketed, and changed beliefs about whether the risk of addiction for some should preclude use when it might help the many who do not become addicted. The surge in prescribing for chronic pain has produced a parallel increase in cases of opioid abuse and related deaths, and despite what is now more than 2 decades of experience, it is still unclear whether, and under what conditions, opioids can be used to treat chronic pain safely and effectively. Many questions remain, but what this article presents is how opioids should be used to treat chronic pain considering recent concerns about their efficacy and safety.
Patient selection
Not all patients are suitable candidates for opioids. In fact, proper selection of candidates for the treatment can do more to improve efficacy and safety than any other aspect of managing the treatment. It is tempting to think that a patient’s complaint of severe pain is enough to warrant use of strong pain medications. Recent teaching has been that a report of severe pain warrants treatment with opioids if all efforts to use alternative treatments have failed. But recent evidence shows that for some pain conditions, opioids not only may not work well but also may hinder the progress toward recovery that can be achieved by other means. It is becoming clear that this is true for several pain conditions and is particularly true for musculoskeletal pain. Opioids allow people to rest comfortably and are useful for providing comfort. They are also useful during acute onset or acute exacerbations of pain when they can reduce pain enough to start the process of active rehabilitation. With long-term usage, however, they may have a different role. Analgesia is not always maintained long term, and the numbing effect of opioids tends to make people less inclined to move even when exercise, or at least maintained activity, is the intervention most likely to achieve recovery. There are many musculoskeletal conditions and so-called centralized pain states such as nonstructural low back pain or fibromyalgia, where the numbing effects of opioids can actually lessen the likelihood of recovery. At the same time, when there is significant damage due to disease, trauma, or surgery, and normal activity is not a realistic goal, the numbing effect of opioids can be helpful and may even improve function in patients with serious functional incapacity. Opioids at low doses can also be helpful in low-risk patients who are intolerant of alternative treatments and cannot realistically be active, for example, the elderly. Choosing candidates for opioid therapy based on their disease state and not on their reported pain severity has several advantages. It allows one to exclude cases that are more likely to recover without opioids. It allows one to target opioids only toward cases that can be improved. It removes the need to make judgments about pain severity and what a report of pain suggests. Past teaching was that because pain is a subjective experience, “pain is what the reporting person says it is.” Although this is indisputable, severe pain that would be better managed without opioids should not be treated with opioids simply because of a report of severe pain. Decisions about the suitability of opioid treatment must always be made on an individual patient basis, but Table 1 attempts to summarize some of the broad categories of suitability for long-term opioid treatment.
| Suitable Candidates | Rationale |
|---|---|
| Arthritis or other pain in the elderly | Low dose can be helpful. Not tolerant of alternative treatment. Frailty may preclude maintenance of activity or rehabilitative exercise |
| Provision of comfort in cases of serious disease or existential suffering or when persistent attempts to treat without opioids have failed | Reasonable to abandon ideas of functional restoration. Different risk/benefit balance |
| Acute exacerbations of chronic musculoskeletal pain, including back pain | Short course of opioids may help in initiating rehabilitation |
| Not Suitable Candidates | Rationale |
|---|---|
| Chronic musculoskeletal pain, including low back pain without a pathoanatomic diagnosis (nonstructural back pain) | Restoration of normal activity, normal social and work functions, and healthy habits (such as diet and exercise) likely to be more effective than opioids. Opioids are deactivating when activity is beneficial |
| Centralized pain states such as fibromyalgia, irritable bowel disease, and pelvic pain | There are hyperalgesic pain states that can be made worse by opioids. The factors listed under chronic musculoskeletal pain also apply |
| Headache | Well established that long-term opioid therapy does not help headache and can cause headache in some cases, especially rebound |
Basic principles of chronic opioid management
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Decisions about opioid treatment always take place after a full history and physical examination and after reaching and documenting a pain diagnosis.
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Continuous treatment with an opioid for 90 days or longer is COT.
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At 90 days, or preferably sooner, a process of shared decision making needs to occur concerning whether COT is a good choice.
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Before offering COT
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Patient completes a screening instrument for addiction risk.
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Baseline urine drug toxicology screen is done.
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If available, active or prior usage is checked in prescription monitoring system.
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Decision to treat is made based on benefit versus risk.
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If COT is chosen, the following safeguards are necessary:
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Patient studies and signs a treatment agreement that includes a statement of agreed goals.
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Patient receives prescriptions in person on a monthly basis or more frequently if high risk.
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Once effective dose is established, dose escalation is avoided.
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Either long-acting opioid or short-acting opioid is used but not both.
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Concomitant sedatives should not be used, especially benzodiazepines or alcohol.
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Goals are reassessed regularly (at least 3 monthly).
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Urine drug test (UDT) is repeated according to clinic standards.
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Opioid is weaned if goals are not met or for noncompliance.
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The lowest effective dose should always be used and should not exceed 100 mg morphine equivalent daily dose (MEDD) (see the “Opioid Medication Choices” section for definition of MEDD).
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Safe-keeping practices and disposal of unused opioid should be encouraged.
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Starting Chronic Opioid Therapy
Most COT begins with short-term opioid therapy. For example, the opioid is used to treat an acute exacerbation of chronic back pain or pain after surgery or trauma. Occasionally, administration of opioids is started in the absence of an acute exacerbation. Short-term opioid therapy should not be allowed to become COT without a formal decision that COT is indicated. When using opioids to treat acute pain, the likely duration of pain should be kept in mind and only the amount and duration that is necessary should be prescribed. Most routine surgery and trauma do not require opioids after 3 days. Sometimes longer is needed, but prescribing for acute pain should never be open-ended. Susceptible individuals may rapidly progress to dependence or addiction.
Evidence suggests that patients treated with opioids for 90 days or longer are likely to continue treatment for life. Ninety days is also the point at which persistent pain is termed chronic. If opioids have been provided continuously for 90 days, this would be a reasonable stopping place, or a time to define the treatment as COT if the decision is to continue the opioid.
Before starting COT, there must always be a fully documented history and physical examination (repeated if the patient is inherited), culminating in a pain diagnosis. Screening for addiction risk should ideally take place before starting an opioid (ie, before short-term treatment is started), but failing that, screening should take place before starting COT. Table 2 lists some commonly available screening tools. The simplest and most commonly used is the Opioid Risk Tool ( Fig. 1 ). A baseline UDT should also be performed before starting COT (see the “Urine Toxicology” section for more details on urine drug toxicology). COT may be contraindicated in patients with high risk of addiction or with illicit drugs in the urine.
| Butler et al, 2004 | Screener and Opioid Assessment for Patients with Pain (SOAPP) 5-, 14-, or 24-item questionnaire. Completed by patients |
| Webster & Webster, 2005 | Opioid Risk Tool (ORT) 5-item questionnaire. Completed by patients |
| Passik et al, 2005 | Pain Assessment and Documentation Tool (PADT) Assesses 4 domains. Completed by physicians |
| Belgrade et al, 2006 | Scoring system to predict outcome (DIRE) Assesses 4 domains (diagnosis, intractability, risk, efficacy). Completed by physicians |
| Butler et al, 2007 | Current Opioid Misuse Measure (COMM) 17-item questionnaire. Complete by patients |
Decision to Treat
The decision to use COT should never be considered trivial. COT has huge implications for patients’ lives, including the likelihood that they will not return to work, they will be infertile and lose libido, they risk becoming dependent, they may become cognitively impaired, and pain relief will be partial at best. Ideally, family members should be included in the decision. COT also has huge implications for the prescriber, because neither is COT simple nor are the patients who receive this treatment simple: the treatment can be draining of both resources and time. For the right indications, COT can be tremendously valuable, and worth the effort, but COT should never be undertaken lightly.
Reducing the Risks of Chronic Opioid Therapy
Written agreements
The best way to reduce the risk of COT is to ensure that the patient is well informed about the limitations and risks of COT, as well as the safe keeping of the medications. Written agreements can be useful as educational tools, as well as for documenting patients’ acceptance of the terms of treatment and their stated goals. Many other educational tools are available, including more comprehensive written materials, videos, and Web sites, and patients should be encouraged to pursue these. However, a simple and short written agreement in lay language is probably preferable as a starting point. Box 1 lists the principles that should be present in a written agreement. Fig. 2 is an example of a written agreement.
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Pain medications cannot be refilled early.
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Refills require a clinic visit by appointment.
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No urgent requests for refills. Call to make appointments in advance.
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Lost or stolen pain medications or prescriptions cannot be refilled. They must be safeguarded.
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Never get pain medication for chronic pain from other clinics or emergency rooms.
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If you get any pain medications from another provider for any other reason, you must tell your provider here immediately.
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Do not share, sell, or trade your pain medications with anyone.
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You must allow your urine to be tested for drugs at any time.
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Failure to follow these rules may result in discontinuation of your pain medications.
Urine toxicology
Urine toxicologic tests are imperfect and complex but have become a standard of care during COT. Simple dipsticks that can be used in the clinic are notoriously inaccurate; there is a high rate of both false-positive and false-negative results. Nevertheless, they are much cheaper than the laboratory-based tests, and it is reasonable to use a simple test before progressing to a laboratory test, particularly as a means of familiarizing patients on COT with the process of giving urine and the need to give urine as a routine part of COT. The least likely compounds to give false-positive results are cocaine and amphetamines, so if these are found at initial simple in-house screening, that may be a reason to postpone starting COT until confirmatory tests can be completed and further history sought if necessary. Opioids are the most likely to show false-positive and false-negative results. No action should be taken on dipstick testing, and even after confirmatory laboratory testing, no action should be taken without discussing the result with the laboratory because there are many reasons that an unexpected test result may be due to factors other than taking a nonprescribed substance or not taking the prescribed opioid.
For medical purposes, giving urine is usually done unobserved. Urine specimens can easily be adulterated or swapped. Tampering or swapping can be detected to some extent by shaking the urine to test for frothiness (possible soap contamination), assessing its color, and measuring its temperature and pH immediately after collection.
The appearance of opioid metabolites can be confusing. For example, codeine is metabolized to morphine, hydrocodone may be metabolized to hydromorphone, and oxycodone may be metabolized to oxymorphone. Tests for oxycodone may not have the sensitivity to pick up low levels.
Weaning
It is easy to say if the treatment does not work, stop it. Or if aberrant behaviors arise, stop the treatment. It is not always easy to wean opioids, and in fact, it may not always be appropriate even in the face of poor efficacy or aberrancy. Patients who are given opioids for a long time become dependent on them (see Section “Dependence and Addiction”). Not all dependence is addiction, but dependence is often hardwired and difficult to reverse, especially when it accompanies prolonged treatment, which makes it important (1) not to use COT other than for the most refractory of cases in which the treatment can provide comfort and risks are acceptable and (2) to stop COT early or as soon as it becomes evident that it is not meeting goals of treatment.
Principles of weaning are as follows:
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Patient must agree.
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Structure a weaning protocol (eg, 10% reduction in dose per visit).
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Be prepared to plateau (most patients tolerate a few dose reductions and then stall; it is reasonable to allow a break and then restart the wean later).
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Be prepared to fail (if a wean is not tolerated, be prepared to continue opioid for life).
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If a wean is not tolerated, patient is likely to have complex and persistent dependence ; treat this much like addiction, with opioid maintenance and counseling.
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Always consider the possibility of addiction and need for addiction treatment.
Dependence and addiction
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There are special considerations when using COT in patients with known risk of substance abuse.
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Dependence or addiction may arise during COT in any patient.
Using Chronic Opioid Therapy in Patients with Risk of or Current Substance Abuse
Neither risk of nor current substance abuse precludes the use of COT. However, in both cases there is a high risk of development or worsening of addiction; this means that COT should not be used without the full understanding of risks by both patients and their families. Full precautions should be taken (eg, only use long-acting opioids, pick up prescriptions weekly or even daily if indicated, use frequent UDTs and random pill counts, involve family in giving medications, involve family in safe keeping of medications, and reevaluate frequently).
Dependence or Addiction Arising During Chronic Opioid Therapy
Dependence on opioids is completely expected during COT, particularly extended COT. Dependence essentially means that there are symptoms of withdrawal if the drug is withdrawn or the dose reduced, when circumstances change and the dose requirement changes, or if tolerance develops and is not satisfied by a dose escalation. For a few patients, withdrawal consists simply of classic withdrawal symptoms such as pupillary dilatation, goose flesh, nausea and vomiting, abdominal pain, tachycardia, worsening pain, and agitation. These physical symptoms of withdrawal usually subside within weeks of discontinuing opioid altogether, although they may recur as circumstances change for a patient receiving COT. But for many patients, there is also a psychological component to withdrawal, which does not reverse easily and may be a strong factor in difficulty weaning patients from opioids, especially when they have been receiving COT for a long time. The combination of physical and psychological dependence can seem much like addiction because the dependence is a strong driver of opioid-seeking behavior, behavior that may even seem compulsive. Some patients on COT exhibit clear signs of true addiction, and if they do, they should be referred for specialty treatment. Many fit into a gray zone between clearly not addicted and clearly addicted ( Fig. 3 ). These patients are dependent and warrant treatment much like addiction treatment. They may do better if their opioid pain treatment is maintained. As mentioned in “Weaning” section, it is always worth trying to wean if the treatment does not seem to be working well, but if the wean is not tolerated, then it may be better to continue the opioid. The other important aspect of treatment of these patients is counseling. In the United States at least, because of the past 2 decades of gross overprescribing of opioids for chronic pain, there are not enough specialty centers that can handle patients at the intersection of chronic pain and opioid dependence, and there are not enough trained counselors to help busy medical practitioners with counseling. This is another reason to be circumspect about the decision to embark on COT.
