Opioids merit consideration for treating chronic pain

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Opioids merit consideration for treating chronic pain

Rational use of opioid analgesics for patients with chronic

musculoskeletal pain can be an effective treatment option

http://www.biomech.com/current_full_article/?ArticleID=156

By P. Schneider, MD, PhD

Throughout history, various forms of morphine have been the most

effective medications in relieving pain. Opioid analgesics—the

natural, semisynthetic, and synthetic derivatives of morphine—are

used routinely in the management of acute musculoskeletal pain.

However, myths and misunderstandings about these drugs often prevent

practitioners from prescribing them for chronic pain, such as that

seen in common musculoskeletal conditions (e.g., low back pain,

osteoarthritis, rheumatoid arthritis, and osteoporosis).

Although pain is one of the most common symptoms that bring patients

to a clini­cian's office, those with chronic musculoskeletal or other

noncancer pain all too often are undertreated.

In many cases, the use of opioid analgesics for patients with chronic

musculoskeletal pain is a legitimate treatment approach and is

gaining acceptance in the medical community. Although some reports

question the efficacy of long-term use of opioid analgesics in

improving function,1 several randomized controlled trials of these

agents showed at least a 30% reduction in pain.2 Although these

medications are effective, practitioners tend to underuse them

because they lack knowledge about them, are concerned about possible

addiction, and also fear regulatory scrutiny.

Adverse effects

Opioid analgesics exert their effects by binding to µ, ê, and ä

receptors in the central nervous system (brain and spinal cord), the

GI tract and, to a lesser extent, the peripheral tissues. They

counteract pain signals ascending to the brain. Although pain relief

is the desired effect, opioid analgesics also have adverse effects

(e.g., nausea, sedation, and constipation).

Starting the patient at a low dose and progressively titrating upward

for pain relief minimizes the adverse effects while permitting

development of tolerance (the need for an increased dose to achieve

the same adverse effect or a diminished effect with the same dose) to

the nauseating and se­­dating effects. Tolerance to nausea and se­­dation

(and its extreme, respiratory de­­pression) is desirable, but not to

the con­stipating effect of opioid analgesics. Therefore, it is

important for the patient to maintain a bowel regimen (stool

softener, bowel stimulant, fluids, and activity) for as long as an

opioid analgesic is being taken.

Tolerance to the pain-relieving effects of opioids is uncommon. Once

titrated to an effective pain-relieving dose, most patients continue

taking the same or a similar dose for long periods.3 Pain specialist

Portenoy, MD,4 wrote, " Contrary to conventional thinking, the

development of analgesic tolerance appears to be a rare cause of

failure of long-term opioid therapy. "

Although some evidence indicates that long-term exposure to high

doses of opioid analgesics results in hyperalgesia (increased pain

sensitivity), this is rarely of clinical significance.5 Most often, a

request for an increased dose reflects increased physical activity, a

worsening physical problem, or deterioration in the patient's

psychological status, such as depression.

An often unappreciated adverse effect of long-term opioid analgesic

use is lowered sex hormone levels in men. In those who are taking

significant doses, long-term, subnormal testosterone levels are the

rule rather than the exception.6

Men who are taking moderate to high doses of opioids should have

their total and free testosterone levels checked. Many will need

testosterone replacement, preferably with patches or transdermal

preparations. It is wise to also monitor their prostate-specific

antigen levels. Untreated hypotestosteronism can lead to osteoporosis

in men, as well as decreased muscle strength.

Some patients taking morphine experience itching. Morphine is more

likely than other opioid analgesics to cause histamine release and

pruritus. If antihistamines do not provide enough relief, switching

to another opioid analgesic may be the answer.

There is no accepted upper limit of safety for opioid agents. Because

of genetic differences and varying pathology, there are enormous

differences among patients in the amount of opioid analgesics they

need for adequate pain relief. Historically, some patients with

cancer have required grams of morphine. For many patients, however, 5

mg of hydrocodone provides adequate pain relief.

As long as the dose is started low and increased gradually, large

doses may be taken and are limited only by adverse effects. Unlike

acetaminophen, aspirin, and many other drugs, opioid analgesics do

not have any specific organ toxicity. Therefore, the right dose is

the one that provides adequate pain relief without unacceptable

adverse effects.

Typically, it takes three to seven days for the body to overcome

sedation produced by opioid agents. Thus, it is wise for patients to

avoid driving when they begin to take these drugs and when the dose

is increased. Once patients are taking a stable dose and feel alert,

it is generally safe to drive because they have adequate psychomotor

functioning.7-9 Of course, it is wise to avoid using alcohol and

benzodiazepines before driving, because they are likely to increase

any sedative effects of opioid analgesics.

Opioid analgesics are significantly safer than nonsteroidal anti-

inflammatory drugs; they are not associated with upper

gastrointestinal bleeding or renal toxicity. This may be particularly

important in older patients who are put at risk by the GI and renal

toxi­city of NSAIDs.

Many practitioners believe that anyone who is taking opioid

analgesics long-term becomes addicted. This misunderstanding results

when the concepts of physical dependency and addiction are confused.

Physical dependency

This is a form of physiologic adaptation to the continuous presence

of certain drugs in the body. Abrupt discontinuation of the drug

after the body has become accustomed to it results in a predictable

withdrawal syndrome. For opioid analgesics, this may include anxiety,

irritability, goose bumps, salivation, lacrimation, rhinorrhea, dia­

phoresis, nausea and vomiting, abdominal cramps, and insomnia.

Withdrawal from morphine begins at six to 12 hours after last use and

peaks at one to three days. The symptoms associated with longer-

acting opioids, such as methadone, have a slower onset and are less

severe than those with shorter-acting drugs, such as morphine and

hydromorphone. Withdraw­al symptoms may be avoided by tapering the

drug over days.

Patients who take opioid analgesics for more than a few days should

be considered physically dependent. The patient should be cautioned

to avoid stopping the opioid suddenly because withdrawal symptoms may

appear. Even if pain stops totally, the medication should be tapered.

Opioid withdrawal is not dangerous, but it can be very uncomfortable.

A patient's physical dependence on an opioid agent is a physiologic

state in which abrupt cessation of it or administration of an opioid

antagonist results in a withdrawal syndrome, according to the

American Society of Addiction Medicine.10 It is expected in all

persons in the presence of continuous use of opioids for therapeutic

or nontherapeutic purposes and does not, in and of itself, imply

addiction.

Corticosteroids are another class of drugs that produce physical

dependency. The corollary, known by all physicians, is that when

corticosteroids are stopped after ongoing use, they should be tapered

rather than stopped abruptly. The same is true of opioid analgesics.

Addiction

This is a psychological and behavioral disorder characterized by the

presence of all three of the following: loss of control (compulsive

use); continuation despite adverse consequences; and obsession or

preoccupation with obtaining and using the drug or other substance.As

an addiction advances, the person's life becomes progressively more

constricted. The addiction becomes the top priority and relationships

with family and friends suffer. The addict's mental state grows

preoccupied with the drug. Life revolves around obtaining and using

the drug. This constriction distinguishes use of a drug by an addict

from its appropriate use by a patient who has chronic pain.

Clinicians who are uncomfortable prescribing opioid analgesics

probably have patients who keep requesting more me­­­di­cation and seem

preoccupied with the quantity being prescribed. These patients often

are stigmatized with the label of " drug seeker. " The real problem may

be that the pain management is inadequate. Once a sufficient dose of

an opioid agent is prescribed, this pseudoaddiction vani­shes.

Does prescribing opioid analgesics for pain lead to addiction? The

fear that prescribing them for chronic pain will engender iatrogenic

addiction is not supported by experience. Addiction to opioid

analgesics from long-term treatment for pain rarely occurs in

patients who do not have a history of addiction.3,11

Even patients who have a previous history of addiction need not

automatically be excluded from opioid analgesic treatment for chronic

pain. Known addicts may benefit from the carefully supervised,

judicious use of opioid analgesics for pain resulting from cancer,

surgery, or recurrent painful illnesses.12 When contemplating a

prescription for opioid analgesics for a patient with an addiction

history, however, practitioners are advised to consult with a pain or

addiction medicine specialist.

For such patients, careful supervision is the key. This includes a

contract outlining the practitioner's expectations of the patient,

provisions made for random urine screens, and increased attendance at

12-step self-help meetings.

Recovering alcoholics are less likely to relapse than patients who

once were addicted to opioid analgesics.13 Prescribing them to former

addicts should be considered only as a last resort—if every other

approach has failed—and with the participation of an addiction

medicine specialist. Patients who are current drug addicts cannot be

trusted to manage their opioid pain medications reliably. These

patients are not candidates for opioid therapy unless they are in a

supervised setting with someone else dispensing the medication.

Comprehensive treatment plan

Opioid analgesics are not first-line therapy for chronic pain and are

not recommended as the only treatment. They should be used as part of

a comprehensive treatment plan that involves other medications and

modali­ties. Other medications to consider may include the following:

• Nonopioid analgesics (for example, acetaminophen);• Aspirin and

other NSAIDs;

• Muscle relaxants;• Antidepressants (because patients with chronic

pain often are depressed). Low-dose tricyclic agents may have some

utility in managing some chronic pain conditions, such as

fibromyalgia and neuropathic pain;

• Anticonvulsants for neuropathic pain, including gabapentin,

pregabalin, and di­valproex sodium;• Topical preparations (e.g., a

lidocaine patch);

• Drugs used to counteract residual opioid sedation, including

modafinil and methylphenidate; and• Sleeping pills (because patients

who have chronic pain often have insomnia).

Optimal management of chronic pain involves a team effort. In

addition to the primary care physician, possible team members include

a rheumatologist, orthopedic surgeon, physiatrist, physical

therapist, anesthesiologist, pain specialist (who can perform

invasive procedures, such as epi­dural corticosteroid injections or

nerve ablation), biofeedback specialist, hypnotist, acupuncturist,

neurologist, neurosurgeon, addictionist, and psychologist.

P. Schneider, MD, PhD, is a physician certified in internal

medicine, addiction medicine, and pain management. She is the author

of eight books and numerous articles in professional journals. She

has been a member of speakers bureaus for pharmaceutical companies

that have an interest in the topic covered in this article.

This is part I of a two-part article. Next month, part II will

discuss patient assessment and management of opioid use. A version of

this article originally appeared in our sister publication, the

Journal of Musculoskeletal Medicine, in March 2006.

References

1. Chou R, E, Helfand M. Com­parative efficacy and safety of

long-acting oral opioids for chronic non-cancer pain: a systematic

review. J Pain Symptom Manage 2003;26(5):1026-1048.2. Kalso E,

JE, RA, McQuay HJ. Opioids in chronic non-cancer pain:

systematic review of efficacy and safety. Pain 2004;112(3):372-380.

3. Zenz MK, Strump M, Tryba M. Long-term oral opioid therapy in

patients with chronic nonmalignant pain. J Pain Symp­tom Manage

1992;7:69-77.4. Portenoy RK. Using opioids for chronic nonmalignant

pain: current thinking. Intern Med 1996;17(suppl):S25-S31.

5. Mercadante S, Ferrera P, Villari P. Hyper­algesia: an emerging

iatrogenic syndrome. J Pain Symptom Manage 2003;26(2):769-775. 6.

Rajagopal A, Vassilopoulou-Sellin R, Palmer JL, et al. Hypogonadism

and sexual dysfunction in male cancer survivors receiving chronic

opioid therapy. J Pain Symptom Manage 2003;26(5):1055-1061.

7. Jamison RN, Schein JR, Vallow S, et al. Neuropsychological effects

of long-term opioid use in chronic pain patients. J Pain Symptom

Manage 2003;26(4):913-921.8. Sabatowski R, Schwalen S, Rettig K, et

al. Driving ability under long-term treatment with transdermal

fentanyl. J Pain Symptom Manage 2003;25(1):38-47.

9. Fishbain DA, Cutler RG, Rosomoff HL, Rosomoff RJ. Are opioid-

dependent/tolerant patients impaired in driving-related skills? A

structured evidence-based interview. J Pain Palliat Care Pharmacother

2002;16(1):9-28.10. 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. J

Addict Dis 1998;17:129-133.

11. 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, 1994:247-287.12.

American Academy of Pain Medicine and American Pain Society. The use

of opioids for the treatment of chronic pain. Chicago; 1994. Position

paper.

13. Dunbar SA, Katz NP. Chronic opioid therapy for nonmalignant pain

in patients with a history of substance abuse: report of 20 cases. J

Pain Symptom Manage 1996;11:163-171.