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11 Articles in Volume 13, Issue #6
Ask the Expert: Cash Patient on High-Dose Oxycodone With Negative Urine Screens
Cluster Headache: Providing Relief for a Debilitating Disorder
Editor's Memo: Keeping the Trust in Difficult Times
Gout: New Guidelines for Managing An Ancient Disease
History of Pain: A Brief Overview of the 17th and 18th Centuries
Letters to The Editor: Guidelines for Opioid Prescribing, Drug Legislation
Long-term Opioids, Sickle Cell Disease, and Pain Patches
Lumbar Spinal Stenosis: A Review of the Treatment Options and Modalities
Malabsorption of Opioid Medications
Non-Opioid Pharmaceutical Treatment of Cancer Pain
Treatment of Postherpetic Neuralgia With Low Level Laser Therapy

Long-term Opioids, Sickle Cell Disease, and Pain Patches

The American Pain Society annual meeting was held in May in New Orleans, Louisiana. Forest Tennant, MD, Editor in Chief of Practical Pain Management, was in attendance. Below are his impressions of the meeting, as well as news highlights.

Evidence of Benefits of Long-term Opioid Use

As almost everyone knows by now, a small group of physicians known as PROP (Physicians for Responsible Opioid Prescribing) have petitioned the FDA to restrict opioid labeling to 120 mg of morphine equivalents per day for only a 90-day duration. One of their major claims is that there is no “evidence” long-term opioid use is beneficial. To my surprise, one highlight of the meeting was a series of posters on the benefits of long-term opioid therapy.1-3 Purdue Pharma, LP, who admittedly has a vested interest in the topic, sponsored the studies, which reviewed the world’s literature to find out if there is reported evidence that long-term opioid use is effective. Here is a review of their research:

In the first study, the research team, headed by Rayna Matsuno, reviewed published studies using Medline, EMBASE, BIOSIS Previews, and PubMed through October 2012.1 Studies included all randomized controlled trials (RCTs) and open-label extension studies ≥6 months. To further elucidate data, the researchers compared within-patient versus between-patient designs.

The researchers found 55 reports of long-term opioid therapy among non-cancer chronic pain patients of greater than 6 months duration.* Ninety percent (90%) of the studies showed analgesia efficacy, and 88% of patients reduced their pain score by more than 25%. Analgesia effectiveness remained steady over the time course of the studies (majority of open-label studies [>75%] demonstrated a reduction in pain scores).

The investigators also reported that mental health of patients was universally unchanged or improved.2 Of the original 55 long-term opioid studies, 38 were within-patient studies and 17 were between-patient studies. Of the 38 within-patient studies, 86.8% demonstrated a reduction or maintenance of pain scores with long-term opioid therapy. Of the 17 between-patient studies, 9 demonstrated positive effects of long-term opioid therapy, 3 demonstrated negative effects, and 5 were neutral. Most studies also showed improvements in function and quality of life. Physical health improvement was more varied, with most studies showing a modest improvement. Side effects were relatively common and consisted of nausea, vomiting, constipation, and somnolence. Detrimental aspects of long-term opioid therapy were the utilization of more health and mental health services, endocrine abnormalities, and more depression and physical discomfort when compared to published norms. The researchers could not tell from the reports, however, whether the detrimental aspects were from opioids or the underlying pain condition.

In a related study, a research team led by Angela DeVeaugh-Geiss, also of Purdue, reviewed 43,519 patients started on extended-release (ER) oxycodone and 22,414 patients started on ER morphine for cancer (10%) and non-cancer pain. Eighty percent (80%) of patients on ER oxycodone and 86% on ER morphine discontinued their opioids within 3 months of their initiation. By 6 months, 72% of patients on ER oxycodone and 81% on ER morphine had discontinued their opioid. Interestingly, if the patient remained on their opioid for more than 6 months, they likely continued for 18 months.

This information indicates that opioids are not used long term by most patients and that they must promote or allow some natural healing and resolution of a patient’s pain problem. During a poster presentation, the researchers pointed out the significant value of these 55 reports. Most phase III RCTs of opioid analgesia for chronic non-cancer pain only last, at most, 3 months, the investigators noted. This has limited researchers from studying the long-term efficacy of these agents. Moreover, conducting longer placebo-controlled, double-blind RCTs presents an unacceptable ethical challenge because suffering pain patients would receive a placebo. Consequently, there is great value in open-label studies, particularly those that reflect patient experience over a time period greater than 6 months.

Sickle Cell Anemia: New Treatment Approaches

A symposium on the treatment of chronic pain in adults with sickle cell disease (SCD) illustrated the need to consider multiple different underlying pain mechanisms when treating individuals with chronic pain. As noted by the moderator, Carlton Dampier, MD, SCD is one of the most difficult management problems for hematologists and primary care physicians.

To examine the scope of the pain problem, Wally R. Smith, MD, Professor and Vice Chair for Research, Division of General Internal Medicine at VCU Medical Center, reported on the results of PiSCES (Pain in Sickle Cell Epidemiology Study). Of the 29,839 pain diaries collected from 308 SCD patients, “55% of patients had pain on more than half of their diary days, and 30% had pain essentially every day,” he noted. When looking at crisis days and when patients sought out care, Dr. Smith said most clinicians are seeing “just the tip of the iceberg.” In the PiSCES study, there were 4,429 crisis days (14.8%), “but patients reported only 1,057 utilization days [3.5%].”

Dr. Dampier, Professor of Hematology/Oncology at Emory University School of Medicine, Atlanta, Georgia, reported that daily opioid usage becomes increasingly prevalent starting in late adolescence—reaching more than 50% in mid-aged adults—yet less than 10% to 15% of SCD patients receive anticonvulsants or antidepressants, which are commonly used to manage pain in other chronic musculoskeletal disorders. “At present, chronic pain in SCD is managed as if it was acute pain that simply lasted longer, with a heavy reliance on opioids and non-steroidal anti-inflammatory agents—reflecting the thought that the pain is caused primarily by inflammation. However, just as in the broader pain field, it is important to consider multiple different underlying mechanisms of pain [peripheral vaso-occlusive pain and central sensitization] and their potential antecedents in childhood, and to treat individuals accordingly,” he noted.

Postmastectomy Pain Can Last Years

Approximately 50% of breast cancer patients reported having chronic neuropathic pain 3 years after their mastectomy, noted researchers from the State University of New York at Buffalo.4 This percentage decreases with time; however, a small percentage (19.5%) still had pain up to 10 years after surgery.

The investigators conducted a literature review and examined 27 studies, which included 5,646 women who underwent mastectomies for breast cancer. In addition to short- and long-term follow-up, approximately 33% of women who had mastectomies reported pain at 4 years, 5 years, and 9 years after undergoing the surgery. “With greater than 200,000 new breast cancers diagnosed annually in the United States alone and mean survival at 15 years post-diagnosis approaching 90%, the national burden of morbidity from this often unrecognized but commonly occurring condition is staggering,” noted the lead author Ognjen Visnjevac, MD. Medication cost, patient morbidity, and work and productivity loss also contribute significantly, culminating in an annual national financial burden approaching $1 billion, they concluded.

Low Overdose Potential With 7-Day Patch

The new buprenorphine patch (Butrans) appears to have greater resistance to overdose than either the fentanyl patch or oral morphine, according to a poster study. The FDA approved Butrans, a partial opioid agonist, in June 2010 for the management of moderate to severe chronic pain in patients requiring continuous around-the-clock opioid therapy. It is schedule III medication.

In a British study where buprenorphine patches have been on the market since 2005, 20,560 patients have been prescribed the patch.5 Overdose rates with the patch were less than in patients prescribed fentanyl patches or oral ER morphine, which had the highest rate, reported the authors, led by Paul Coplan. The relative risk of overdose among patients prescribed ER morphine versus the buprenorphine patch was 1.82 (95% CI: 1.35-2.46) and for fentanyl versus the buprenorphine patch was 1.42 (95% CI: 1.01-2.00). All in all, the buprenorphine patch may be a therapeutic advance that appears to have a superior safety profile. The poster was supported by a grant from Purdue Pharma.

Ceftriaxone Useful for Surgical Prophylaxis

A single dose of the antibiotic ceftriaxone prior to carpel tunnel surgery “enhanced patient pain threshold after surgery,” according to Italian researchers.6 Previous studies have shown that the drug, which activates the GLT-1 gene and enhances glutamate clearance, reduced both visceral and neuropathic pain in animals.

For this study, 45 patients were randomized into three treatment groups: IV doses of saline, saline with ceftriaxone, and saline with cefazolin. Injections were administered 1 hour prior to surgery, and mechanical pain thresholds were measured 10 minutes before the injections and 4 to 6 hours following surgery. No analgesic drugs were allowed in the first 6 hours after surgery, noted the researchers from University Sapienza in Rome.

Study results found that patients treated with saline and cefazolin showed no change in mechanical pain thresholds 6 to 7 hours after surgery, but pain thresholds in patients given a single preoperative does of ceftriaxone increased significantly. The authors concluded that ceftriaxone should be the drug of choice for surgical prophylaxis in situations when pain does not rapidly resolve following surgery or when strong pain is expected to occur after surgery.

—Reported by Forest Tennant, MD, DrPH
Editor in Chief

*Practical Pain Management asked for and has the list of these 55 reports.

Last updated on: October 28, 2014
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