Identifying and Managing Postherpetic Neuralgia: The Consultant Pharmacist’s Role

Postherpetic neuralgia (PHN) can cause intense pain well after the episode of herpes zoster with which it is associated. The elderly are at elevated risk of experiencing this complication. Assessment and management of it, as with other forms of pain, can pose special challenges in long-term care settings. At a symposium held on May 15, 2003, during the American Society of Consultant Pharmacists’ midyear meeting, experts discussed the pain of PHN as distinguished from other forms of pain, as well as assessment of pain, and pharmacologic agents available for managing it.

This program was supported by an unrestricted educational grant from Pfizer Inc.

Overview of Pain and the Pain Associated with PHN

María-Carmen B. Wilson, MD, Associate Professor and Residency Director of Neurology, and Director of the Headache and Pain Management Division of the University of South Florida College of Medicine in Tampa, discussed the definition and management of pain. She also provided an overview of pain associated with postherpetic neuralgia (PHN).

Pain is classified as acute or chronic, nociceptive or neuropathic. Chronic pain extends 3 to 6 months beyond the onset of pain, or beyond the expected period of healing. Such pain is associated with depression, social isolation and loss of friends and family support. “It serves no biological purpose. And it degrades health and functional capability,” she said.

Neuropathic pain is caused by a primary lesion or dysfunction in the nervous system, with no nociceptive stimulation required. The pain is disproportionate to the stimulation of the receptor. PHN is a classic example of neuropathic pain.

PHN can be defined as pain arising or persisting in areas affected by herpes zoster, at least 3 months after skin lesions have healed. Presenting symptoms vary, and pain may peak at any time—before, during, or after the rash. “Just because the pain is not present during the rash stage…doesn’t mean that…the patient is not going to develop the pain syndrome,” she emphasized. PHN is a complication of herpes zoster. It is caused by the varicella zoster virus infecting the dorsal root ganglion and processes, and altering the nerve tissue. Damage can occur from the spinal cord to the skin. Cause of viral reactivation is unknown. Stress, use of immunosuppressive medications such as steroids or chemotherapy, and autoimmune conditions can be associated with reactivation.

Risk of PHN rises with age, so that the elderly are at higher risk (Edmunds et al. Vaccine. 2001;19:3076-3090). “If you are in the 80- to 84-years of age group, you have almost a 40% chance to suffer with it,” she noted. Other risk factors for PHN include trigeminal (especially ophthalmic) distribution, severe acute pain, sensory loss, extensive rash, and high antibody titers. “If you’ve ever seen people suffering with postherpetic neuralgia, you realize how devastating that is,” she said, especially for elderly persons with other health problems and other sources of pain. “It really goes to your heart.”

Both peripheral and central mechanisms of pain can be involved in PHN. If central involvement occurs, Dr. Wilson said, pain “is harder to control and (is) more diffused.” Allodynia, a painful response to a non-painful stimulus, “is an indicator that the pain is getting central.”

Dr. Wilson said that her clinic uses both visual and emotional analog scales to assess pain’s intensity and its associated suffering. However, she also suggests evaluating functional changes. Rather than focusing on changes in the analog scales to determine a patient’s progress, she asks, “Were you able to do something different?”

Positive sensory symptoms of PHN include spontaneous and evoked pain. Negative sensory symptoms are loss or impairment of sensory quality, and numbness and reduced sensation. In some cases, negative symptoms may be more refractory to therapy than positive ones. “Sometimes we have to discuss with our patients in a gentle manner what realistic expectations are,” she counseled. Sensory deficit and pain frequently occur in the same individual, she said, along with a transitional zone elicited upon physical examination.

Patients describe spontaneous pain as burning or shock-like. Other spontaneous symptoms are dysesthesias (abnormal, unpleasant sensations such as shooting, lancinating, or burning), and paresthesias (abnormal, but not unpleasant sensations such as tingling or ants crawling). Stimulus-evoked symptoms include allodynia, hyperalgesia (heightened response to painful stimulus), and hyperpathia (delayed explosive pain in response to a painful stimulus).

Developing an Effective Pain Management Program for PHN

Nancy L. Losben, RPh, CCP, FASCP, Senior Vice President for Clinical Services at NeighborCare in Baltimore, reviewed drug therapies for PHN. Two medications—gabapentin and the lidocaine patch—carry an FDA indication for PHN.

Gabapentin
Gabpentin is an anticonvulsant, but its mechanism of action is unclear. It appears to affect the electrical voltage at the alpha-2 delta receptor site. It promotes the inhibition of the neurotransmitter GABA and decreases excitation at that nerve ending.

The first of 2 landmark studies of gabapentin was a placebo-controlled trial conducted among 229 persons whose average age was 73 to 74 years old (Rowbotham et al. JAMA. 1998;280: 1837-1842). In this respect, “it was perfect for our population” of nursing home residents, Ms. Losben noted. Gabapentin relieved pain (33% improvement in pain score at 8 weeks, [P < .001]), while also enhancing sleep, mood, and quality of life (Figure 1). Improvement in pain scores began as early as 1 week into therapy. Side effects included somnolence (as often as 27%), dizziness (24%), edema (about 10% in persons of “advanced age”). Another noteworthy, placebo-controlled study of gabapentin (N = 344; patients “well into their 70s”), found that doses of 1800 or 2400 mg daily produced similar effect (Rice et al. Pain. 2001;94:215-224). “There really isn’t any significant benefit to treating beyond 1800 milligrams,” she said.

The starting dose for gabapentin is 300 mg once daily for a day, then 300 mg twice daily for a day, then 300 mg three times daily, increasing dosage to about 1800 mg daily. Older adults may need much less than this dosage, she said. The 1800 mg should be given in 3 divided doses, for administration every 8 hours. “A lot of times the q8h is an awful schedule in the nursing home. You don’t know whether to give it at 12 midnight or somewhere mid-morning,” Ms. Losben noted. However, equal hourly intervals are needed for around-the-clock coverage. Dosage cannot exceed 1200 mg daily (divided into 3 daily doses, given ever 8 hours) in persons with creatinine clearance less than 60 mL/min.

Gabapentin does not interact with protein-binding medications or with other anti-epileptic medications. Coadmin-istration of naproxen raises gabapentin levels by as much as 12% to 15% (Gabapentin package insert. New York, NY. Pfizer, Inc. 2002). “If you’re looking at someone who’s got some kidney failure or who has some creatinine clearance problems, you need to adjust the dose” when using both medications, she said. Coadministration of long-acting morphine sulfate increases gabapentin levels by 44%. “You need to titrate the dose effectively, monitor the efficacious results and watch for side effects of somnolence and dizziness,” she said.

When gabapentin (125 to 500 mg) is administered concomitantly with 10 mg hydrocodone, levels of gabapentin rise by 14% and levels of hydrocodone fall by at least 4%. (Gabapentin package insert. New York, NY. Pfizer, Inc. 2002). As the dose of gabapentin rises, the absorption of hydrocodone decreases. Gabapentin is relatively safe, she said, as long as doses are adjusted for kidney function.

Lidocaine patch 5%
Lidocaine blocks sodium channels, thereby preventing generation and spread of nerve impulses. The patch has demonstrated moderate or greater pain relief in PHN in controlled clinical trials. One study reported significant improvement in pain scores with the lidocaine patch 5% compared to placebo (P = .023) (Alper and Lewis. J Fam Pract. 2002; 51:121-128). Efficacy of the lidocaine patch 5% is “controversial” because FDA approval was based on a 32-patient randomized, controlled “enriched enrollment” study rather than on a 150-patient trial submitted earlier. Still, she said, “This offers some significant relief, especially to our (nursing home) population.”

Advantages of the patch include that it can be cut and placed over the most intense areas of pain. Patches are 10 x 14 cm. Dosing is no more than the equivalent of 3 full patches per day, with 12 hours on and 12 hours off the patch during any 24-hour period. “You’re going to have to educate the nursing staff on exactly how they should be using it,” she said. Patches usually are applied at bedtime rather than during the day, Ms. Losben said.

There are no systemic side effects because it is a topical product, and no drug interactions, she said. It should not be used in residents with severe hepatic disease, as “they would have a very difficult time metabolizing and eliminating it.” There is some irritation of the application site, especially in the elderly.

Non-FDA-approved Medications Used for PHN
These are the tricyclic antidepressant nortriptyline, and the opioid agonist oxycodone. Although nortriptyline is on the Beers list of drugs that are potentially inappropriate in older patients, she said, “We can justify this use for sure.” Nortriptyline usually is used in mild to moderate pain, and can be a valuable adjunctive therapy. Dosing is variable—usually 10 to 20 mg at bedtime, titrated to acceptable pain relief or unacceptable side effects. A trial demonstrated that nortriptyline and amitryptyline have equivalent efficacy in PHN (nearly 60% of patients responding to each drug) (Watson et al. Neurology. 1998;511: 1166-1171). However, “you really want to choose nortriptyline because it has a far better side effect profile than the amitriptyline,” she said. Both agents are associated with side effects such as sedation, dry mouth, and postural hypotension, but these occur less often
and less severely with nortriptyline (Goodman and Gilman. The Pharmaco-logical Basis of Therapeutics. 9th ed. 1996).

Physicians may be reluctant to prescribe opioids such as oxycodone, she said. However, “you cannot dismiss the use of opioids as we have in the past when it comes to treating neuropathic pain.” Oxycodone use is associated with significant relief of pain in PHN, as well as reduced allodynia and improved functioning (Attal. Clin J Pain. 2000;16: S118-S130; Kanazi et al. Drugs. 2000; 59:1113-1126). Few studies evaluate long-term use of opioids in PHN.

When writing a care plan, remember that “the goal shouldn’t just be pain relief...but what do we expect because the pain is relieved” in terms of
functional improvement, Ms. Losben counseled.

Assessment of Pain in Long-Term Care: Quality Measures and MDS Elements

Sheryl B. Rosenfield, RN, C, Director of Clinical Services for Zimmet Healthcare Services Group, LLC, in Morganville, New Jersey, discussed how to assess pain. Because of staff shortages and “the change in the dynamics of the staff who are taking care of the residents, we’re not spending the time to evaluate pain,” she said. “So pain unfortunately goes unrecognized.”

Role of care team members
Physicians are responsible to assess, monitor and evaluate patients. However, she said, “Many of them do not know the residents.” Additionally, when facilities treat residents for short-term care or rehabilitation, physicians are reluctant to order new medications “because that person’s only going to be there for a short time,” she said.

Nurses also should assess patients upon admission, then follow up with monitoring and evaluation. The uniform assessment tool is the Minimum Data Set (MDS). She characterized it as “absolutely inadequate.” Therefore, pain is not being assessed well in long-term care, she said. Staffing issues, reimbursement, and lack of access to pharmacists “create a difficult environment (in which) to treat appropriately,” Ms. Rosenfield asserted. Additionally, “nurses receive very little education in pain management.”

Of consultant pharmacists, she said, “You need to come in and teach.” Pharmacists can teach nurses, who then make recommendations to physicians. “Nurses love the opportunity to sit and learn and discuss and watch you do your drug reviews,” she said, acknowledging that pharmacists also are pressed for time. Pain medications should be given around the clock to provide continuous pain relief. However, the relatively small night staff and absence of registered nurses on night shifts in most facilities create obstacles to around-the-clock administration of pain medications.

Quality Measures—MDS
Ms. Rosenfield expressed concerns about use of the MDS as a quality indicator. “The quality measures are being filled out inaccurately, in a rush, and the way the questions are asked on the assessment and how they get reported are meaningless right now, especially in pain,” she said. Measures are not being answered accurately “for fear that the public is accessing the quality measures.” Quality indicators are available to consumers on the Web. One problem is that quality indicators assess pain at a given time. However, pain fluctuates for many residents. “To focus on 1 week at 1 time…means nothing,” she said.

The MDS is a screening tool containing more than 720 items. It examines function using 18 Resident Assessment Protocols (RAPs). The pain protocol, she said, has never been released but is “wonderful.” Readers who would like a copy of the protocol can e-mail Ms. Rosenfield at SHERYL@ zhealthcare.com. The MDS “does not consider the high-cost resident…(or) the high-cost medications,” she said. Yet it is used as a tool for reimbursement. The MDS now in use was written in the early 1990s. Since then, nursing home residents have become older and sicker, with shorter lengths of stay. Additionally, less funding is available. When the MDS was designed, “pain was absolutely not a focus at all,” she said.

The MDS asks whether pain intensity is mild, moderate or excruciating, and if frequency is daily or less than daily. Facilities are scored based on the percentage of all residents with moderate pain at least daily or horrible excruciating pain at any frequency. The sum of these two parameters is divided by the number of all residents with valid target assessments. Admission assessments are excluded. Recorded answers can vary depending upon how a nurse or other evaluator asks the questions, she said. A staffer who knows how to ask questions in a way that generates a low (favorable) score can do so. Evaluators are to code objective presence of pain regardless of pain management efforts. Residents who have no pain during the observation period due to effective pain management score a zero, which will be viewed as a positive mark for the facility. “The current parameters of the MDS do not meet the need for accurate assessment” of pain, she said. The proposed MDS 3.0 will include a revised section to identify residents who experience pain, and also residents who are well managed with pain relief.

Facilities, she said, “need help in developing policies and procedures.

They need tools to identify pain.” Consultant pharmacists can assist with this, she said.

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