March-April 2006; Issue 2

Perioperative Opioid Tapering Not Advised
Mental Disorders Prevalent in Rx Opioid Abusers
Medicaid Data Show Increased Use & Cost of Opioids
Low-Dose Morphine in Opioid-Naïve Cancer Patients
Many Chronic Pain Sufferers Silent
Acupressure Reduces Disability in Back Pain
Fibromyalgia Pain is Complex, Multidimensional
Art Therapy Beneficial in Cancer Patients
Acupuncture vs Drugs Similar for Migraine Prevention
Hyaluronan Reduces Shoulder Pain
Conversion to ER Hydromorphone HCl Examined
Fentanyl Patch: Effective Pain Control in Children
Shockwave Therapy for Plantar Fascitis

This edition of of News/Research Updates was researched/compiled by Winnie Dawson, RN, and edited by Stewart B. Leavitt, PhD; Medical reviewers were: Lee A. Kral, PharmD, BCPS; Paul w. Lofholm, PharmD, FACA; James D. Toombs, MD.  Posting Date: April 20, 2006.

Perioperative Opioid Tapering Not Advised

In Medscape Pharmacists, Gordon C. McCarter, PhD – Assistant Professor of Pharmacy, Touro University, Vallejo, California – responded to a question about the advisability of tapering opioids in an opioid-dependent patient prior to surgery.

Tolerant patients can still be given additional opioids on top of their withdrawal-preventing maintenance levels to achieve adequate postsurgical pain control. This can be accomplished by using opioids different from those in the patient's maintenance regimen, to which he or she may have less cross-tolerance, or by combining opioids with other pain-control modalities. Additionally, tolerance to the side effects of opioids, particularly respiratory depression, is usually greater than any tolerance to their pain-relieving effects; opioid analgesic dosages can be titrated carefully to prevent adverse events.

Practice Pointer: McCarter emphasizes that all practice guidelines regarding pain management require that maintenance opioids be continued in the opioid-dependent patient who is about to undergo surgery, and that a full multimodal pain-control regimen be instituted as aggressively as needed to relieve any acute postsurgical pain.

Reference:McCarter GC. Perioperative Opiate Tapering. Ask the Experts about Pharmacotherapy. Medscape Pharmacists. 2006;7(1). Available at: http://www.medscape.com/viewarticle/528839?src=mp. Access checked 4/14/06.

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Mental Disorders Prevalent in Rx Opioid Abusers

In response to ongoing concerns about the amount of opioid prescriptions that are diverted and/or abused, a study identified 109 Kentucky chemical dependency treatment facility patients who completed a structured interview regarding their prescription drug abuse before admission. While 100% reported abuse of prescription opioids, 84% stated that they had received a prescription for pain at some prior point, and 61% noted that they had chronic pain issues.

Hydrocodone- and oxycodone-containing products were the most frequently abused, at 78% and 69%, respectively. The abuse of methadone and fentanyl-based formulations occurred less frequently. More than half of the participants had taken another person’s prescription with permission, 36% had stolen a medication at least once, and 80% admitted to altering the delivery system by chewing, snorting, or injecting a prescription opioid drug.

In addition to pain reported on the Brief Pain Inventory, the results of additional assessments demonstrated high levels of anxiety disorders, depression, insomnia, fatigue, and post-traumatic stress disorder in this population. Polysubstance abuse plus a mental disorder was prevalent in 45% of participants.

Comment: In a nationwide report released by the U.S. Substance Abuse and Mental Health Services Administration (SAMHSA) in April 2006, Kentucky had the greatest percentage of nonmedical pain reliever use in persons aged 12 and older. This report, based on 2003-2004 surveys, listed Colorado, Utah, and Washington as the states with the next highest percentages. The complete report by state can be viewed at: http://www.oas.samhsa.gov/2k4State/States.htm. Access checked 4/14/06. – W. Dawson.

Source:Passik SD, Hays L, Eisner N, et al. Psychiatric and pain characteristics of prescription drug abusers entering drug rehabilitation. J Pain Palliat Care Pharmacother. 2006;20(2):5-13.

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Medicaid Data Show Increased Use & Cost of Opioids

Opioids are important in the management of moderate to severe pain and the Medicaid category of “analgesics-narcotic drugs” has become one of the highest reimbursement categories. Investigators analyzed trends in the use and cost of opioid medications between 1998 and 2003. During this period, the number of Medicaid enrollees increased by about 27%, while total dollars spent on opioid prescriptions increased approximately 300%.

The total number of opioid prescriptions nationally for Medicaid enrollees in 1998 was slightly more than 15 million and this nearly doubled to 27.5 million in 2003 (see Graph). The morphine derivatives clearly account for the majority of this increase, with the methadone derivatives a distant second. During the 6-year time period, prescriptions for morphine derivatives doubled from 10.5 million to nearly 21.5 million in 2003. Prescriptions for meperidine/fentanyl derivatives increased three-fold: 0.5 million prescriptions to just over 1.5 million.

The 2 classes of opioids representing the greatest opioid Medicaid dollar expenditures were morphine derivatives and meperidine/fentanyl derivatives, and per unit increases were led by morphine derivatives at more than 200%. Methadone derivatives showed only modest increases in dollar expenditures, while the only decline was reported for the agonist/antagonist/partial-agonist class. Major variations exist between states but, nationally, reimbursement for opioid units per enrollee almost doubled between1998 and 2003.

Clinical Implications: The total dollars spent in relationship to the percentage increase of Medicaid enrollees implies that the cost of many prescription opioid drugs increased significantly during the 6-year period studied. Since the cost-effectiveness of a medication – defined as the cost to achieve effective pain relief – is important to the patient, it should also be important to the clinician. Alternative pain management drugs may be equally effective and provide a lower-cost option for some patients.

Source: Brixner DI, Oderda GM, Roland CL, et al. Opioid expenditures and utilization in the Medicaid System. J Pain Palliat Care Pharmacother. 2006;20(1):5-13.

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Low-Dose Morphine in Opioid-Naïve Cancer Patients

In a multicenter study, 110 consecutive opioid-naïve patients with moderate-to-severe pain were treated and evaluated for tolerability and effectiveness of very low doses of morphine. These patients had been reported as unresponsive to nonopioid drugs in Step 1 of the WHO analgesic ladder.
Initially, patients received immediate-release oral morphine in 4 to 6 doses totaling 15 mg daily. Older patients, above age 70, received 10 mg. During opioid titration, up to an additional 1/6th of the daily dose could be administered for breakthrough pain. Patients achieved dose stabilization – judged as pain intensity less than 4 (of 10) with acceptable adverse effects – within a median timeframe of 2 days.

Practice Pointer: The results of this study reinforce the principle that individualization of pain treatment is ideal. Initiating low doses of morphine, possibly with slower titration, in opioid-naïve cancer patients appears to provide good results.

Source: Mercadante S, Porzio G, Ferrera P, et al. Low morphine doses in opioid-naïve cancer patients with pain. J Pain Sympt Manage. 2006(Mar);31(3):242-247.

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Many Chronic Pain Sufferers Silent

A cross-sectional survey investigated characteristics of patients who typically do not report their chronic pain. In a random sampling of adult patients in Olmsted County, Minnesota, 3,575 people responded. The survey included standard demographics questions and requested data on the duration, location, and severity of pain. The 2,221 patients (62%) who reported pain in excess of 3 months comprised the final sample for analysis.

More than 1 in 5 of those chronic pain respondents were silent sufferers, answering “no” to the question “Have you ever discussed your pain with a doctor of healthcare provider?” Surprisingly, approximately 70% of these patients reported moderate or severe pain and almost half had pain for 8 or more days each month. More than 40% of the silent sufferers were under age 45, and a greater proportion of males than females were silent.

While a significant number of silent sufferer respondents reported that pain interfered with their quality of life, this survey did not provide answers as to why these chronic pain sufferers did not seek medical attention. The survey reached primarily a white population and does compare to other similar surveys; however, comparable assumptions cannot be made for other cultural and ethnic populations.

Clinical Implications: It is important to educate pain patients on two facts that could improve their quality of life: 1) it is not necessary to live silently with chronic pain that interferes with quality of life, and 2) there are acceptable drug choices that provide effective pain relief with relatively few side effects.

Source:Watkins EW, Wollan PC, Melton LJ III, et al. Silent Pain Sufferers. Mayo Clin Proc. 2006(Feb);81(2):167-171.

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Acupressure Reduces Disability in Back Pain

Low back pain is a common cause of disability and chronic pain. This study randomly allocated 129 patients with chronic low back pain to a conventional physical therapy treatment group or to an alternative and complementary therapy group that utilized acupressure. (Acupressure is a non-invasive, traditional Chinese medicine therapy that uses the therapist’s finger pressure to stimulate the same acupressure points as acupuncture, called acupoints. This technique is thought to unblock energy pathways and stimulate the body’s own natural curative abilities.)

Participants in each group received 6 treatment sessions within a month. The same acupressure therapist administered all treatments to ensure consistency. The physical therapy group was given routine physical therapy that could include traction, spinal manipulation, thermotherapy, infrared light therapy, electrical stimulation, and exercise therapy as deemed appropriate by the therapist.

Comment:Acupressure is a non-invasive therapy that is usually offered by massage therapists who are specially trained in pressure therapy techniques. One popular form is Shiatsu, a Japanese practice based on the principles of Chinese medicine. Treatment varies widely from one practitioner to another and, while most states regulate massage school requirements, many states do not have licensing practices for massage therapists. The American Massage Therapy Association does provide certification, but without regulation many therapists do not take certification exams. It is important that healthcare providers investigate a therapist’s credentials before recommending this treatment. – W. Dawson, SB Leavitt.

Source: Hsieh LL, Kuo CH, Lee LH, et al. Treatment of low back pain by acupressure and physical therapy: randomized controlled trial. BMJ, 2006(Mar);332(7543):696-700.

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Fibromyalgia Pain is Complex, Multidimensional

This study examined the relationship between the physical and psychological variables of fibromyalgia pain using sensory, affective, and pain intensity measurements. Each of 107 female participants, with a mean of 72 months since diagnosis, completed 2 pain surveys, a self-reported activity profile, and 3 actual measures of physical fitness. In addition, a demographics survey, a 16-item fatigue self-report, and a 20-item depression questionnaire were completed.

Clinical Implications:This study emphasizes that fibromyalgia pain is complex and multidimensional, so it is important to assess all 3 components of pain: sensory, affective, and intensity. Treating the depression and fatigue, as well as gradually increasing activity, may help to lessen overall pain for fibromyalgia patients.

Source:Hughes L. Physical and psychological variables that influence pain in patients with fibromyalgia. Orthop Nurs. 2006(Mar/Apr);25(2):112-119.

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Art Therapy Beneficial in Cancer Patients

A quasi-experimental study was done in 50 adult cancer inpatients to determine the effect of art therapy on pain and other symptoms. The objective was for each patient to use creativity to increase awareness and expression of deeper emotions about their illness and hospitalization, as well as to attempt to reduce pain and other symptoms.

An art therapist assisted patients in choosing their subject matter and media; stressing that it is the art process that can be therapeutic and not the end product. Each patient participated in the required 1-hour art therapy session and, subsequently, completed a modified Edmonton Symptom Assessment Scale (ESAS) and the state portion of the Spielberger State-Trait Anxiety Index (STAI-S). In addition, 3 qualitative questions were asked of all participants to capture additional impressions after the therapy session.

Clinical Implications: The results of this study appear to suggest that art therapy can play an important role in reducing symptoms. This therapy also provides a creative task that allows patients to express their feelings and exert control over one aspect of their life in spite of health concerns. The authors suggest that future research might be beneficial in identifying the number of sessions needed to produce long-term effects and the type of patients who could realize the greatest benefits.

Source: TNainis N, Paice JA, Ratner J, et al. Relieving symptoms in cancer: innovative use of art therapy. J Pain Sympt Manage. 2006(Feb);31(2):162-169.

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Acupuncture vs Drugs Similar for Migraine Prevention

While effective drug treatment to help prevent migraine headache attacks is available worldwide, acupuncture is the most frequently used preventive therapy in Germany. Using a multicenter population, 835 patients who had 2 to 6 migraine attacks per month were randomly assigned to a ‘true’ (verum) or sham acupuncture group for 10 sessions of acupuncture treatment within 6 weeks, or to a continuous drug therapy group. True acupuncture was done using traditional Chinese medicine acupuncture points, while sham acupuncture was done using a similar procedure on areas of the skin where no acupuncture points are known to exist.

Acupuncture patients who experienced partially successful results at the end of treatment could apply to receive 5 additional interventions. Patients in the drug therapy arm received beta blockers, flunarizine, or valproic acid according to guidelines of the German Migraine and Headache Society.

Clinical Observations: It is interesting to note that all 3 treatments were effective in terms of a reduction in migraine days as well as global patient assessment scores. The effectiveness of the sham acupuncture was a surprise to the researchers, who proposed the possibility that needling at non-acupuncture points could exert biological effects similar to true acupuncture. However, this would challenge the basic principles of Chinese medicine and, minimally, require further investigation. In addition, the authors stated that a high dropout rate of 34% in the drug treatment group occurred due to disappointment at not being randomized to the acupuncture group. A resulting imbalance in the ratio of drug-treatment participants to acupuncture participants may have affected the validity of comparative results.

Reference: Diener HC, Kronfeld K, Boewing G, et al. Efficacy of acupuncture for the prophylaxis of migraine: a multicentre randomised controlled clinical trial. Lancet Neurol. 2006(Apr);5(4):310-316.

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Hyaluronan Reduces Shoulder Pain

A double-blind, randomized trial evaluated the efficacy of the treatment of chronic shoulder pain syndrome in 602 patients who failed to respond to physical therapy, steroids, and oral pain medications. The primary diagnosis in this patient population was osteoarthritis, rotator cuff tear, and/or adhesive capsulitis.

Two treatment arms included intraarticular administration (IA) of Hyalgan®, (sodium hyaluronate; Sonofi Aventis) 5 times weekly (HYL-5) and Hyalgan 3 times weekly plus IA saline 2 times weekly (HYL-3), as well as a control group that received saline 5 times per week. Hyaluronan is a natural chemical found in many tissues throughout the body and present in particularly high amounts in joint tissues and fluid.

Comment: In a news interview, the lead investigator in this study stated that the results were additionally impressive because this particular patient population was identified as difficult-to-manage due to age, concomitant medications, and concurrent disease conditions. – W. Dawson.

Reference: Blaine TA, Skyhar MJ, Collins PC, et al. Double-blind, randomized trial of IA sodium hyaluronate (HYALGAN) for chronic shoulder pain. Proceedings Book: American Academy of Orthopaedic Surgeons Annual Meeting; 2006 Mar 22-26; Chicago, IL. 2006. Abstract #426.

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Conversion to ER Hydromorphone HCI Examined

Extended-release hydromorphone hydrochloride (ER hydromorphone HCl) is a capsule formulation designed for administration every 24 hours. A total of 343 adult patients receiving opioids for persistent moderate to severe pain were admitted to the conversion phase of a prospective evaluation of ER hydromorphone, and a ratio of 8:1 mg of oral morphine to oral hydromorphone was used to establish the initial dosage. Breakthrough pain was treated with 2 mg tablets of immediate-release hydromorphone HCl at dosages of 1/8 to 1/6 of the daily ER hydromorphone HCl administered every 4-6 hours as needed.

At 48 hours, 83% of subjects did not require a dosage change, while nearly 16% were titrated up and 2% were titrated down. The mean number of rescue doses per day was 2.8 and the average pain intensity (API) score decreased from 5.3 at baseline to 4.7.

Practice Pointer: A conversion ratio of 8:1 mg of pre-study opioid to ER hydromorphone HCl was identified as clinically useful in this evaluation of the conversion and titration phases, and it did not significantly underestimate the initial dosage required for stabilization. The investigators emphasize that conversion ratios are an approximation for initial treatment and do not eliminate the need to assess each patient for individual issues that could influence the initial dose. NOTE: This product is not yet available in the United States.

Source: Weinstein SM, Minggao S, Buckley BJ, et al. Multicenter, open-label, prospective evaluation of the conversion from previous opioid analgesics to extended-release hydromorphone hydrochloride administered every 24 hours to patients with persistent moderate to severe pain. Clin Ther. 2006(Jan);28(1):86-98.

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Fentanyl Patch: Effective Pain Control in Children

Analgesic delivery can be a challenge in children with chronic pain. This study evaluated the safety and tolerability of transdermal fentanyl in 173 pediatric patients (ages 2 to 16) from 66 sites in 10 countries. Dosage conversion from oral or parenteral opioids on Day 1 was done by using an equianalgesic potency conversion table. Titration commenced on Day 2 and was increased until a steady-state analgesic effect with transdermal fentanyl alone was achieved.

The primary treatment period lasted 15 days and 130 patients entered a 3-month extension period. While slightly more than 90% of patients reported at least 1 adverse event, only 10% required a change in dosage due to this. About 60% of the patients did not require increased titration during the initial 15 days, and adequate analgesia was achieved by most patients within 6 days.

Clinical Implications: Studies have shown that chronic pain in children may be undertreated and the transdermal delivery approach may be optimal for a seriously ill pediatric patient when oral or injectable routes of drug administration are difficult.

Caution: Safety of the DURAGESIC® (Ortho-McNeil) fentanyl patch has not been established in children under 2 years of age, and should be administered to children only if they are opioid-tolerant and 2 years of age or older. See the Package Insert for dosage conversion guidelines. (Source: Janssen Pharmaceutical Products, Titusville, NJ, February 2005.)

Reference: Finkel JC, Finley A, Greco C, et al. Transdermal fentanyl in the management of children with chronic severe pain. Cancer. 2005(Dec);104(12):2847-2857.

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Shockwave Therapy for Plantar Fascitis

Plantar fasciitis, a common disorder of the heel, causes pain and impairs functionality. This prospective study examined the long-term results of extracorporeal shockwave treatment in a randomized comparison against a conservatively-treated control group. Of the total of 149 patients (168 heels), 79 patients (85 heels) received a 1-time shockwave treatment while 70 patients (83 heels) received NSAIDs, orthotics, physical therapy, an exercise regimen, or a localized cortisone injection.

Patients in the control group were treated with one initial modality and additional treatments were prescribed if initial therapy was unsatisfactory or symptoms recurred. A cortisone injection was only administered in cases of severe heel pain. Shockwave patients with an inadequate response in 30 to 45 days were advised to receive additional treatments. More than 70% of patient heels received one treatment, while 22% received 2 treatments, and less than 1% received a total of three treatments.

Clinical Implications: Extracorporeal shockwave treatment is a non-invasive treatment involving the delivery of high energy sound waves, or acoustical energy, to affected areas of the body. These purportedly trigger natural repair mechanisms and stimulate healing. Some previous studies have reported good results in plantar fasciitis treatment with extracorporeal shockwave, and this particular study demonstrated good long-term results without reported complications or device-related problems.

Reference: Wang CJ, Wang FS, Yang KD, et al. Long-term results of extracorporeal shockwave treatment for plantar fasciitis. Am J Sports Med. 2006(Apr);34(4):592-596.

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