Tiagabine

Up to one-half of community-dwelling adults over age 65 report pain severe enough to interfere with normal function, and 60% to 80% of nursing home residents have persistent pain. (1) Reasons for the frequent undertreatment of pain in older adults are myriad (Table).

The withdrawal of the COX-2 inhibitors rofecoxib (Vioxx) and valdecoxib (Bextra) and the questions being asked about the cardiac safety of other COX-2 inhibitors, naproxen (Aleve, Naprosyn), and older nonsteroidal anti-inflammatory drugs (NSAIDs), have raised concerns among clinicians and patients who use these drugs for pain management. Safety questions about these drugs have left physicians asking: What can we do now to alleviate chronic pain in older patients?

In 2002, the American Geriatrics Society published its revised position paper on the management of persistent pain in older adults. (2) Every physician who cares for older patients must read this document. It details the initial assessment that older patients with persistent pain should receive and discusses treatment options.

Evaluating chronic pain

A thorough evaluation is needed to determine the cause of the patient's pain and whether disease-modifying interventions can treat the pain. In many cases, the clinician must recognize that the disease process, even once identified, will not likely be reversed through medical intervention, and that the chronic pain should be regarded as a separate medical entity. This is often true of the most common types of chronic pain, including back pain or the neuropathic pain of peripheral diabetic neuropathy or post-herpetic neuralgia.

Some patients with osteoarthritis, another common cause of chronic pain in older adults, can be helped by joint replacement. But for those patients who are not surgical candidates, the pain itself should be treated as the primary problem.

Physicians are usually most comfortable with diagnoses that can be documented by abnormal lab results or imaging studies. But in the assessment of chronic pain, the gold standard is the patient's word, and the physician must learn to accept the gray areas that come with such a subjective evaluation. I use a pain intensity scale of zero to ten. I have found that although patients vary greatly in how they initially describe their pain (including twice the maximum-20/10!), they tend to be very consistent from visit to visit, which makes for a semi-quantitative measure with which to follow-up the results of treatment.

Chronic pain treatment has two goals: reducing pain and improving function. This means that treatment must be multimodal and include:

* medications

* physical activity

* psychological interventions

* alternative therapies

Although this article will focus on pharmacologic treatments, improving a patient's physical functioning is a critical aspect of treating chronic pain. In addition to drug treatment, physicians need to emphasize increasing the patient's physical activity and improving the patient's emotional state. Depression and pain reinforce and worsen each other, so depression must be addressed and treated. Alternative approaches, such as acupuncture, hypnosis, yoga, and herbal medications, can be useful for some chronic pain conditions.

Pharmacologic treatments

Despite increased susceptibility to adverse drug reactions, older patients can be treated safely and effectively with analgesic and pain-modulating drugs. Combinations of drugs are often more useful than a single drug, and can in fact be less toxic. The older NSAIDs, such as ibuprofen and naproxen, are widely used but have well-known side effects and risks including kidney damage, elevated blood pressure, and GI bleeding. The AGS position paper considers nonselective NSAIDs to have unacceptable risks in frail older patients with multiple-system disease. The paper's authors prefer the COX-2 inhibitors, which are becoming less available. "In the final analysis, the chronic use of opioids for persistent pain or some other analgesic strategies may have fewer life-threatening risks than does the long-term daily use of high-dose nonselective NSAIDs," according to the position paper (p. S213). (2)

Non-opioid medications

Non-opioid analgesic strategies include:

* acetaminophen and tramadol

* topical agents

* anticonvulsants for neuropathic pain

* antidepressants for neuropathic pain and for depression

* muscle relaxants

* sedatives.

Acetaminophen and tramadol. Acetaminophen is useful for mild-to-moderate pain, but because it is present in so many over-the-counter preparations, patients must read labels and be careful not to exceed the daily limit, which could increase the risk of liver toxicity. For a healthy older person using acetaminophen for a short time, the daily limit is 4,000 mg, but chronic users, especially those with liver problems, should not exceed 2 to 3 grams/d.

Tramadol (Ultram) is a non-opioid analgesic with dual action. It binds weakly to the mu opioid agonist, resulting in efficacy similar to that of codeine, 30 mg; a typical dose is 50 mg/qid, not to exceed 400 mg/d. Topical agents. Topical lidocaine patches (Lidoderm) can be very effective for pain close to the skin's surface. It is effective for neuropathic pain, such as peripheral neuropathy, and, at times, for osteoarthritis. The patch is large and can be cut into pieces. Three patches or less can be used daily without causing a significant increase in serum lidocaine levels. The patch is safe and worth trying for various types of pain.

Anticonvulsants. Anticonvulsants can be effective for neuropathic pain. Gabapentin (Neurontin) is the oldest agent available. It is a sedative and should be initiated at a very low dose (ie, 100 mg at hs), and increased only every few days to a maximum daily dose of 1,800 mg. Newer anticonvulsants that are also effective include topiramate (Topamax) and tiagabine (Gabitril). Topiramate has also been found useful in treating chronic headaches. Back pain, although generally considered somatic, often has a neuropathic component, especially when the back pain is associated with sciatica, so anticonvulsants are definitely worth trying in this patient group.

Antidepressants. Depression is common among chronic pain patients, who are persistently uncomfortable and limited in their activities. Extensive medical literature supports the finding that depression worsens pain, pain worsens depression, and that both must be treated. (3-6) Some antidepressants appear to directly alleviate pain in addition to treating depression. Tricyclics in low doses have traditionally been used for this purpose. Because drugs such as desipramine and amitriptyline are also sedative, they are often used at bedtime, with the goal of improving pain relief and improving sleep. Selective serotonin reuptake inhibitors (SSRIs) are excellent antidepressants, but don't seem to have a pain-relieving effect. Venlafaxine (Effexor) has been found to improve various types of pain when used at high doses (225 mg or higher), doses at which this drug is both a serotonin and a norepinephrine-reuptake inhibitor. Recently, the antidepressant duloxetine (Cymbalta), which is both a serotonin and norepinephrine-reuptake inhibitor, was approved for managing depression and the pain of diabetic peripheral neuropathy.

Muscle relaxers. Muscle relaxers are helpful for acute muscle spasm, but in chronic pain they mostly relax the brain and cause sedation. Many patients swear by them, but for older patients who are already on other sedative drugs, it is best to minimize the doses of muscle relaxers.

Sedatives. Most chronic pain patients have trouble sleeping. In some cases, this problem will resolve with effective pain management, but many patients require sleep medications as well.

Opioids

Despite endorsement by several professional medical organizations, myths about opioid use have made most primary care physicians leery of using opioids for chronic non-cancer pain, in contrast to their relative comfort in using opioids for cancer pain. Three misperceptions about opioids include:

* They are dangerous.

* They are likely to turn patients into addicts.

* Their chronic use entails ever-increasing doses because of patient tolerance.

Safety of opioids. When used as directed, opioids are safe. Unlike NSAIDs, they are not associated with organ toxicity. Many patients have taken high doses for decades without experiencing organ damage and no medical literature describes organ damage as a result of opioid use. The initial side effects of nausea and sedation dissipate rapidly as the body develops tolerance to these effects.

Constipation caused by opioid use is a problem, but can be managed with a regular bowel regimen that includes a stool softener, bowel stimulant such as senna or bisacodyl, and a back-up prescription for an osmotic laxative such as lactulose syrup or Miralax powder. (See Patient Handout, Does constipation ruin your day?, page 19.)

Long-term high-dose opioid use frequently causes a significant decrease in testosterone levels in men. Even if male patients don't complain about decreased sexual function, check their total and free testosterone levels and replace their testosterone if it is low. Untreated hypotestosteronism can cause osteoporosis and decreased muscle strength and energy.

Addiction versus physical dependence

Addiction is characterized by the presence of ALL three of the following:

* loss of control (compulsive use)

* continuation despite adverse consequences

* obsession or preoccupation with obtaining and using the substance. (7)

As addiction progresses, the person's life becomes increasingly constricted. Life revolves around obtaining and using the drug, while activities and relationships suffer. This constriction is an important characteristic that distinguishes drug abuse by an addict from its appropriate use by a patient with chronic pain. In contrast, patients who are appropriately treated with opioids find their lives expanding and improving. Studies confirm that patients without an addiction history are unlikely to become addicts. (8)

On the other hand, most patients who use opioids chronically in more than minimal doses become physically dependent, meaning that if they stop the drug abruptly, they will develop a defined set of withdrawal symptoms. Withdrawal symptoms for opioids can include diarrhea, rhinitis, salivation, diaphoresis, nausea and vomiting, abdominal cramps, anxiety, and insomnia. Physical dependence is avoidable simply by tapering the dose of the drug. Physical dependence is also a property of other commonly used medications, such as steroids.

Behaviors that are "red flags" for opioid addiction include:

* injecting oral or topical opioids (in order to experience euphoria)

* selling prescription drugs

* using illicit street drugs

* repeatedly running out of the medication early after being given a dose that the patient agreed was effective

* repeatedly "losing" prescriptions or having them stolen.

Pain patients given inadequate doses of pain medication can resemble addicts if they take higher doses than prescribed and run out early. This phenomenon, termed pseudoaddiction, is an understandable response to undertreated pain. It will resolve with adequate pain treatment.

Tolerance

Tolerance is the need for a higher dose of a medication in order to get the same effect, or a reduced effect with the same dose. Tolerance to the sedative and nauseating side effects of opioids is common, but tolerance to the pain-relieving effect of opioids is rare. Most patients who initially obtain good pain relief with opioids can be maintained for months or years on the same or slightly higher doses. The clinician will usually need to increase the dose initially as the patient's activity level increases. Once a stable dose is reached, a renewed complaint of lack of efficacy months or years later requires re-evaluation of possible progression in the patient's disease or of a new pain problem.

Prescribing opioid medications

Short-acting opioid combinations [such as hydrocodone/acetaminophen (Vicodin) or oxycodone/acetaminophen (Percocet)] are appropriate for acute or intermittent pain, but their usefulness is limited by their short duration of action and by the presence of acetaminophen or aspirin, which limit the maximum number of doses that can be safely taken per day. Sustained-release opioids are most effective for relieving round-the-clock pain.

In an opioid-naive patient, begin low and titrate upwards as needed, so as to avoid nausea, sedation, or respiratory depression. Available long-acting opioids include sustained-release morphine (MS Contin, Oramorph, Avinza, Kadian), sustained-release oxycodone (OxyContin), and transdermal fentanyl (Duragesic patch applied once every 3 days). Methadone, the opioid with a long half-life, prevents withdrawal in once-daily dosing but requires 3 to 4 doses per day for pain relief. Methadone requires slower upward titration than other opioids. An extended-release hydromorphone, Palladone, was recently approved by the FDA. Because hydromorphone is about 4 times as potent as morphine, Palladone is most useful in patients who require high doses of opioids for pain reliefs.

Because chronic pain varies in intensity, it is often necessary to provide the patient with a short-acting opioid for break-through pain. Some useful short-acting opioids include immediate-release morphine and oxycodone, fentanyl lozenges (Actiq), and combinations of acetaminophen and oxycodone (eg, Percocet) or acetaminophen and hydrocodone (eg, Vicodin, Lorcet).

4 A's of assessment

When treating chronic pain with opioids, it is important to schedule regular follow-up visits. At each visit the following "4 A's" should be assessed and documented:

1. Analgesia: "On a scale of zero to ten, how much pain are you having today?"

2. Activities of daily living: Be specific in asking how far and how long the patient walks, etc.

3. Adverse effects: Ask about constipation, and review the bowel regimen.

4. Aberrant behaviors: Is the patient on schedule with the medications? Document any losses, need for early refills, etc.

Other opioid treatment issues

Treating patients who have an addiction history. An addiction history does not automatically rule out opioid treatment, (9) but patients cannot be current drug users and must have careful structure and rules for their opioid use. Prior opioid addiction is a higher relapse risk than a history of alcohol dependence. (10) Consultation with an addiction specialist can be helpful.

Supervening acute pain problems. Patients using chronic opioids who experience trauma or surgery still need pain medication for their acute pain problem, and usually require 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 with the patient's other physician during the acute problem, because general surgeons, for example, 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 physically dependent. Patients should be cautioned not to stop the opioid suddenly, or withdrawal symptoms will appear. The medication should be tapered even if the patient's pain is completely gone. Opioid withdrawal is not dangerous, but can be very uncomfortable.

Summary

Safety issues involving COX-2 inhibitors and NSAIDs have raised concerns among clinicians about how to treat chronic pain in older adults. Non-opioid analgesics can be used for mild-to-moderate pain, neuropathic pain, and more. Opioids should be considered for long-term chronic pain. With appropriate dosing, vigilant management, and careful tapering, opioids are a safe and effective choice for pain management in older adults.

References

(1.) Ferrell BA. Pain evaluation and management in the nursing home. Ann Intern Med 1995; 123(9):681-7.

(2.) AGS Panel on Persistent Pain in Older Persons. The management of persistent pain in older persons. J Am Geriatr Soc 2002; 50(6 Suppl):S205-24.

(3.) Mossey JM, Gallagher RM, Tirumalasetti F. The effects of pain and depression on physical functioning in elderly residents of a continuing care retirement community. Pain Med 2000; 1(4):340-50.

(4.) Verma S, Gallagher RM. Evaluating and treating co-morbid pain and depression. International Review of Psychiatry 2000; 12(2):103-14.

(5.) Lin EH, Katon W, Von Korff M, et al. Effect of improving depression care on pain and functional outcomes among older adults with arthritis: A randomized controlled trial. JAMA 2003; 290(18):2428-9.

(6.) Bair MJ, Robinson RL, Katon W, Kroenke K. Depression and pain comorbidity: A literature review. Arch Intern Med 2003; 163(20):2433-45.

(7.) American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders DSM-IV, 4th edition. Washington DC: American Psychiatric Publishing, 1994.

(8.) 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: 247-87.

(9.) American Academy of Pain Medicine and American Pain Society. The use of opioids for the treatment of chronic pain: A consensus statement from American Academy of Pain Medicine and American Pain Society. http://www.ampainsoc.org/advocacy/opioids.htm

(10.) Zenz M, Strumpf M, Tryba M. Long-term oral opioid therapy in patients with chronic nonmalignant pain. J Pain Symptom Manage 1992; 7(2):69-77.

Jennifer P. Schneider, MD, PhD

Dr. Schneider is certified in internal medicine, addiction medicine, and pain management, and is in private practice in Tucson, Arizona. She is author of the book, Living with chronic pain (2004).

Disclosure: The author has no real or apparent conflict of interest with the subject under discussion.

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