Opioid Rotation: Benefits, Challenges, Hazards

There are many reasons why switching from one opioid analgesic to another may be necessary and helpful, yet safely doing so appears to involve as much clinical art as science. This can make healthcare providers and their patients justifiably nervous, and may be a prime reason why opioids are not prescribed appropriately. What can practitioners do?

In an earlier blogpost [10/23/09] we noted that many healthcare providers avoid prescribing opioid analgesics due to concerns about patient compliance with treatment, the possibility of opioid abuse, and perceived scrutiny by regulatory authorities. However, there is another reason: once having started a patient on opioids there is a well-founded fear of how to manage switching or rotating from one opioid to another if it becomes necessary. Recent APS/AAPMed guidelines on opioid-analgesic therapy have recommended opioid rotation as a strategy for patients who experience intolerable adverse effects or inadequate benefit despite increased opioid doses [Chou et al. 2009]. Patients often may respond better to a different opioid that overcomes individual genetic variations, interactions with comedications, effects of coexisting disease, or a nonresponsive pain condition. However, well-designed studies evaluating the benefits versus harms of opioid rotation are lacking, and available studies in patients with various types of pain show inconsistent results.

The APS/AAPMed opioid guidelines warn that there is insufficient evidence to guide specific recommendations for performing opioid rotation [Chou et al. 2009]. Current opioid rotation protocols generally call for using Equianalgesic Dosing Tables to mathematically convert daily dosing of the current opioid(s) to equivalent doses of morphine, then using the Tables again to convert from morphine to the new opioid and, finally, reducing the calculated equianalgesic dose of the new opioid by a safety margin to avoid overmedication. In theory, this is straightforward; however, conversions become more complex when patients are rotated to or from such drugs as methadone or fentanyl, and calculations that normally involve only basic algebra become almost mind-boggling when simultaneously changing opioid molecules, routes of administration (eg, oral vs parenteral), and/or type of formulation (eg, long- vs short-acting). The outcomes, at least short-term, can be unfavorable: patients may be undermedicated and uncomfortable, possibly experiencing opioid withdrawal syndrome; or, they may be overmedicated to the point of life-threatening overdose.

In September 2009, a pair of discussion articles [Knotkova et al. 2009; Shaheen et al. 2009] and a “best practice” guidelines document [Fine et al. 2009] addressing opioid rotation appeared in the Journal of Pain and Symptom Management. Additionally, a first-ever textbook solely dedicated to the subject was recently published [McPherson 2010]. Here are some brief highlights from those publications:

• Some authors candidly acknowledge that, “Current information in equianalgesic tables is confusing for physicians, and dangerous to the public” [Shaheen et al. 2009]. Some of the increases in opioid-related deaths reported in recent years may be due to improper dosing during rotation from one opioid and/or route of administration to another.


• Current Equianalgesic Dosing Tables, of which there are a number of variations, have been used for more than 40 years with little modification [Fine et al. 2009; Knotkova et al. 2009] Data incorporated in these tables are often anecdotal or based on average responses in single-dose studies, without regard for patient-response variables, and they also are deficient in other ways [McPherson 2010; Shaheen et al. 2009]. Comparisons of different commonly used tables show that they often provide inconsistent and variable equianalgesic ratios for calculating conversions — there is no current consensus on a standard set of ratios (for example, different recommended conversion ratios of oral oxycodone to oral morphine remarkably range from 1:1 to 1:3, a 300% variance) [Knotkova et al. 2009; Shaheen et al. 2009].


• “Best practice” recommendations are that, after calculating the equianalgesic dose of the new opioid it should be reduced by 25% to 50% [Fine et al. 2009; Shaheen et al. 2009] to account for incomplete analgesic cross-tolerance (that is, physiologic tolerance established to the first opioid does not carry over completely to the new one, so the patient is more sensitive to the new opioid). Doing this allows for a safety margin to help prevent overmedication; although, initial undermedication with the new agent is highly likely.


• Proposed new guidelines [Fine et al. 2009] recommend an immediate second assessment with an eye toward further applying either a dose increase or decrease of 15% to 30% to help ensure that the new dose will provide effective analgesia while limiting either opioid side effects or withdrawal.


• When selecting appropriate dose reduction percentages numerous factors must be taken into account, such as whether rotation is being done because of toxicity (side effects) versus uncontrolled pain; the amount and duration of current dosing; patient age and physical condition; the possibility of interactions with other drugs; and genetic variations in metabolic enzymes or opioid receptor systems [Fine et al. 2009; Shaheen et al. 2009]. While such factors are science-based, determining their relative importance would seem to require some clinical artistry since phenomena of individual variation and cross-tolerance are actually poorly understood [Knotkova et al. 2009].


• Rotations to/from fentanyl, methadone, or partial opioid agonists are more complex, requiring special conversion tables and knowledge [Shaheen et al. 2009; McPherson 2010]. Such knowledge can be acquired with extra time and effort in studying available literature.


• Rotating to a different opioid before the first opioid has reached steady state and achieved potential effectiveness is pharmacologically unsound [Shaheen et al. 2009]. After opioid rotation, patients should be monitored for therapeutic response and the new opioid titrated upward (or downward) as necessary to achieve desired analgesia [Fine et al. 2009].


• Some experts note that successful opioid rotations depend on “common sense” [McPherson 2010], while others say “clinical judgment” or “practitioner discretion” are required [Shaheen et al. 2009]. Nowhere is it described how one acquires such relevant but abstract traits when it comes to this complex subject.

Clearly, opioid rotation is not for prescribers uneducated or inexperienced in its use, and the above highlights should not be viewed as a complete protocol. Perhaps the most comprehensible and comprehensive tutorial at present is McPherson’s textbook [2009]; although, it would be good to also have a companion “quick guide” that one can carry in a lab coat pocket for point-of-care reference. Experts advise that whichever Equianalgesic Dose Table is used it should serve only as a general guide for estimating equivalent opioid doses [Shaheen et al. 2009]; using the same Table consistently, however deficient, will allow the prescriber to learn how to adjust its values for achieving maximum effectiveness and safety. There also are available a number of computerized equianalgesic-conversion calculators for desktop personal computers or handheld PC devices that automate math functions. All of them have their shortcomings and quirks, and some are not recommended [for a review of these, see Quinn 2007]; however, using the same automated program over time, taking its flaws into account, might incur satisfactory results.

A final caveat — all of the papers and discussions on opioid rotation that we have examined overlooked what may be the most critical part of the equation: patient education. There has been a strongly lopsided emphasis in the literature in recent years on minimizing risks of opioid misuse, diversion, or abuse, with relatively little attention paid to educating patients (along with their family or other caregivers who will monitor them) on recognizing opioid dose-related problems (eg, overmedication, side effects) and what to do about them (including responding to overdose crises). While there are currently few patient-education resources addressing these issues for healthcare providers to utilize, this vital aspect of opioid rotation should not be neglected — for safety’s sake.

References:
> Chou R, Fanciullo GJ, Fine PG, et al. APS/AAPM clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009(Feb);10(2):113-130 [available here].
> Fine PG, Portenoy RH, Ad Hoc Expert Panel on Evidence Review and Guidelines for Opioid Rotation. Establishing “best practices” for opioid rotation: conclusions of an expert panel. J Pain Symptom Manage. 2009;38(3):418-425.
> Knotkova H, Fine PG, Portenoy RK. Opioid rotation: the science and the limitations of the equianalgesic dose table. J Pain Symptom Manage. 2009;38(3):426-439.
> McPherson ML. Demystifying Opioid Conversion Calculations: A Guide to Effective Dosing. Bethesda, MD: American Society of Health-System Pharmacists; 2010 (softbound, 200 pages, ISBN: 9781585281985 [click here for info]).
> Quinn TE. Converting opioid analgesics, part II: review of equianalgesic conversion calculators; 3rd revised version. Pain Topics. 2007(Feb) [PDF available here].
> Shaheen PE, Walsh D, Lasheen W, et al. Opioid equianalgesic tables: are they all equally dangerous? J Pain Symptom Manage. 2009;38(3):409-417.

Fatigue a Good Indicator of RA Treatment Success

Newly reported research has demonstrated that a simple assessment of fatigue in patients with rheumatoid arthritis (RA) can be a reliable and sensitive measure of treatment success. Although, it does not necessarily replace other essential outcome assessments, such as pain and tender joint count.

Researchers at two medical centers in Ireland assessed 49 successive patients referred to their rheumatology clinics at baseline and 3 months after commencing TNF-blockade therapy for RA. Fatigue was measured using an 11-point numeric rating scale (0 to 10) and statistically compared with other core measures of therapeutic response. At baseline, the mean (+/- standard deviation) fatigue scores were 6.7 +/- 2.1 on the 11-point scale, and at 3 months these declined significantly to 4.3 +/- 2.6 (p < 0.001). Repeated testing showed that this simple approach for assessing fatigue was highly reliable. Overall, fatigue was ranked 3rd in terms of sensitivity to changes in therapeutic response as compared with a number of standard measurements of RA severity (in rank order): pain, tender joint count, fatigue, swollen joint count, health assessment questionnaire, C-Reactive Protein, and patient global health. However, compared with the other measures, fatigue accounted for the greatest share of independent variance; that is, it was a strong indicator of therapeutic response relatively uninfluenced by scores on other measures.

The researchers conclude that this simple and practical assessment of fatigue is reliable and sensitive to changes in response to therapy for RA; therefore, it should be routinely considered for inclusion as an outcome measure. However, this was an observational study in a relatively small sampling of patients, so further clinical experience in assessing fatigue as an important indicator of RA treatment response and success will help to establish its validity.

Reference: Minnock P, Kirwan J, Bresnihan B. Fatigue is a reliable, sensitive and unique outcome measure in rheumatoid arthritis. Rheumatology. 2009;48(12):1533-1536 [abstract here].

Depressed Patients Receive More Opioids for Pain

Patients with chronic noncancer pain and a history of depression are 3 times more likely to receive long-term prescriptions for opioid medications than similar patients who do not suffer from depression, according to new research. However, the association of depression with chronic pain and the proper role of opioid therapy in these patients need further consideration.

An extensive retrospective study, published in the November-December issue of the journal General Hospital Psychiatry, analyzed the medical records between 1997 and 2005 of tens of thousands of patients enrolled in two large Northern California health plans; together, the plans cover about 1% of the U.S. population. Long-term opioid use was defined as a patient with chronic noncancer pain receiving a prescription for 90 days or longer. The incidence rates of long-term opioid use were 3 times higher in patients with a history of depression than in those without diagnosed depression. During the 9-year study period, the overall prevalence of long-term opioid prescriptions for noncancer pain in patients with depression increased from roughly 70 to 126 per 1000 patients at Group Health and from 84 to 118 per 1000 at Kaiser Permanente. Furthermore, those with a history of depression were more likely to receive higher average daily opioid doses, greater amounts (more days supply), and more Schedule II opioids than nondepressed persons.

Clinical Comments: The researchers conclude that persons with a history of depression appear more likely to receive long-term opioid therapy for chronic noncancer pain than those without depression. According to Mark Sullivan, MD, a study coauthor and professor of psychiatry at the University of Washington, depression is a common finding in patients with chronic noncancer pain: 46% of patients seeing primary care doctors for ongoing pain have a history of depression and the vast majority of those seeing pain specialists have suffered both disorders. Previously, we noted research indicating that patients with depression are highly prone to “somatoform pain” — pain without medical explanation — which might account for up to 80% of pain symptoms reported in general medical practices [see blogpost of 7/30/09]. Other research found that the prevalence of chronic pain due to any cause in typical samples of persons in the U.S. may be 22%, with more than a third (35%) of those persons also suffering depression [see blogpost 7/19/09].

Sullivan expresses concern that patients with depression are generally excluded from controlled clinical trials testing the efficacy of opioids for noncancer pain. So, whether or not opioids are adequate and/or appropriate therapy for these patients has not been evaluated by the research. “If you study depressed people, they tend to have lot of pain complaints that are poorly responsive to a lot of things so it’s not surprising that they end up on opioids,” he says. Pain perception and depression are mediated in significant ways by the same limbic structures and opioid receptor systems in the brain. Therefore, it can be difficult to assess whether pain is causing or exacerbating the depression — or vice versa. Sullivan and colleagues recommend that opioid treatment for chronic noncancer pain should not replace or distract from screening for and treating concurrent mental disorders like depression.

Reference: Braden JB, Sullivan MD, Ray GT, et al. Trends in long-term opioid therapy for noncancer pain among persons with a history of depression. Gen Hosp Psychiatry. 2009(Nov);31(6):564-570 [see abstract].

Presence or Thoughts of Loved One Relieves Pain

Can the presence, or even mere thought, of a loved one help to reduce pain? It can, according to a new study by UCLA psychologists; however, there are some limitations to consider.

The study, appearing in the November 2009 issue of Psychological Science [Master et al. 2009], involved a group of women who received moderately painful heat stimuli to their forearms while they went through two different conditions. In one situation, each woman alternately held the hand of a boyfriend (with whom she had been in a good relationship for at least 6 months), the hand of a male stranger, and a squeeze ball. Researchers found that when holding their boyfriends' hands the women reported less physical pain than when holding a stranger's hand or a ball.

In a second situation, during the painful procedure the women viewed photographs of their boyfriends, a stranger, and a chair. "When the women were just looking at pictures of their partners, they actually reported less pain to the heat stimuli than when they were looking at pictures of an object or pictures of a stranger," said study coauthor Naomi Eisenberger, assistant professor of psychology and director of UCLA's Social and Affective Neuroscience Laboratory. "Thus, the mere reminder of one's partner through a simple photograph was capable of reducing pain.”

Commentary: The study authors suggest their findings demonstrate the importance of the social support provided by loved ones, particularly during stressful or painful experiences, and that this works even by proxy via photographs. However, it is important to note that, despite all the attention in the press devoted to this study, it involved merely 25 university coeds; so, while the outcomes appear to make good sense, the external validity of this research is questionable. Also, we wonder if a reverse effect might be encountered if the relationship with the loved one is strained — would the pain be worsened rather than relieved?

Furthermore, it is interesting to consider that this study may actually demonstrate the power of placebo effects; which some have defined as “positive clinical outcomes caused by a treatment [in this case, the physical or pictorial presence of a loved one] that is not attributable to its known physiological properties or mechanism of action” [Tilburt et al. 2008]. However, another viewpoint might be that inherently “psychological therapies” such as this — invoking mind-body mechanisms that relieve pain and suffering — have a legitimate place in pain management and are not merely inert placebos. In either case, the study authors suggest that the presence of a loved one, or even a photograph of the person, can help patients to cope with acute pain, at least to some extent.

References:
> Master SL, Eisenberger NI, Taylor SE, Naliboff BD, et al. A picture's worth: partner photographs reduce experimentally induced pain. Psych Sci. 2009(Nov);20(11):1316-1318 (no abstract).
> Tilburt JC, Emanuel EJ, Kaptchuk TJ, Curlin FA, Miller FG. Prescribing “placebo treatments”: results of national survey of US internists and rheumatologists. BMJ. 2008(Oct 23);337:a1938(online) [see abstract].

AMA Agrees Marijuana May Have Analgesic Benefits

The American Medical Association (AMA) has reversed its long-held position that marijuana should remain as a DEA Schedule I substance having no medical value. Rescheduling of the drug could open the door to more and better scientific exploration of its benefits in helping persons with various pain conditions.

In its recently-announced decision, the AMA adopted a report drafted by its Council on Science and Public Health (CSAPH) entitled, "Use of Cannabis for Medicinal Purposes," which affirmed the potential therapeutic benefits of marijuana and called for further research. The CSAPH report concluded that, "short term controlled trials indicate that smoked cannabis reduces neuropathic pain, improves appetite and caloric intake especially in patients with reduced muscle mass, and may relieve spasticity and pain in patients with multiple sclerosis." Furthermore, the report urges that "the Schedule I status of marijuana be reviewed with the goal of facilitating clinical research and development of cannabinoid-based medicines, and alternate delivery methods."

This change of position by the largest physician-based group in the country overturns their viewpoint adopted 8 years ago calling for maintaining marijuana as a Schedule I substance. Such substances are considered to have a high potential for abuse, no accepted medical use, and a lack of accepted safety; other drugs in the category include heroin, LSD, and PCP. The AMA's decision follows an announcement by the Obama Administration in October discouraging U.S. Attorneys from taking enforcement actions in states that have supported medical marijuana. Much earlier, in February 2008, a resolution was adopted by the American College of Physicians (ACP), the country's second largest physician group, calling for an evidence-based review of marijuana's status as a Schedule I controlled substance to determine whether it should be reclassified to a different level permitting medicinal use.

It should be noted that these initiatives are NOT advocating universal legalization of marijuana; rather, the AMA and ACP appear to emphasize the need for placing patients above politics by examining the drug’s scientific validity as an effective medication. The recent CSAPH report has not been officially released to the public; however, according to AMA documentation, it notes that the cannabis sativa plant (marijuana) contains more than 60 unique structurally-related chemicals. Despite much public interest, fewer than 20 small randomized controlled trials of smoked marijuana, involving about 300 patients total, have been conducted during the past 35 years (this excludes trials of the chemical THC and synthetic analogs). The limited findings suggest that smoked marijuana has analgesic effects for certain conditions, but more research examining both its long-term benefits and potential health risks is needed; it is believed that rescheduling marijuana from Schedule I status would help to facilitate this effort.

Although 13 states have enacted laws to remove criminal penalties for marijuana possession by qualified patients, the federal government still does not recognize medical benefits of the cannabis plant. And, it is believed that the patchwork of state-based systems for medical marijuana is inadequate for establishing safeguards that normally accompany the appropriate clinical use of a psychoactive substance. For example, the FDA has claimed that the marijuana plants used in these programs do not meet standards of uniform potency, quality, and purity required of federally-approved medicines. Furthermore, there are currently no well-established clinical guidelines for the appropriate and safe prescribing of smoked marijuana.

For more information see: Summary – report 3 of the (AMA) Council on Science and Public Health. Use of Cannabis for Medicinal Purposes [PDF available here].

American Pain Foundation Absorbs Natl Pain Foundn

The American Pain Foundation (APF) will be taking over key assets of the National Pain Foundation (NPF), including Web content, program and membership materials, a pain healthcare-provider directory, and the John C. Oakley Memorial Fund. The transfer will occur during the next 6 months with an anticipated completion date of May 2010, at which point the NPF will cease operations.

The NPF was established in 1998 to improve the quality of life for those living with pain, through information, education, and support that connects persons with pain to each other and to those who can help them. The APF, founded in 1997, is the largest consumer pain advocacy organization in the United States, and the combined membership of the two organizations will be an estimated 100,000 people.

“We are honored to be the repository of important program materials and resources that have been designed to serve people with pain and their loved ones. The National Pain Foundation’s efforts and hard work will live on at the American Pain Foundation. These materials will complement existing American Pain Foundation materials without being redundant, and we look forward to featuring them on our website over the coming months,” said Will Rowe, CEO, American Pain Foundation.

For more information, visit http://painfoundation.org. The American Pain Foundation has been a Pain Treatment Topics affiliate organization since 2007.

How Much Relief from Chronic Pain is “Enough”?

Healthcare providers often advise their patients with chronic pain that complete relief is an unrealistic goal of therapy. However, what is a reasonable expectation for pain relief? And, is that the only clinical outcome of importance to patients? Research on these questions suggests some answers.

Since 2002, a multidisciplinary group of international experts — called the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) — has been meeting and developing consensus reviews and recommendations for improving the design, execution, and interpretation of clinical trials of treatments for pain. An important focus has been on chronic pain and how effective treatment outcomes can be defined and measured in clinical trials, as well as how research results translate to clinically meaningful outcomes.

The latest publication from the IMMPACT group [Dworkin et al. in press] notes that change in pain intensity typically serves as a primary efficacy endpoint in clinical trials and is an important measure of treatment effectiveness in everyday clinical practice. Various approaches to quantifying changes in pain intensity have been developed, with measures of patient-reported differences from baseline on either a numerical rating scale (NRS) or visual analog scale (VAS) being widely accepted assessment tools. The NRS has patients rank their pain by number, from 0 (none) to 10 (worst pain imaginable); the VAS has patients mark their pain intensity along a line (usually 100 mm long, from 0 [no pain] to 100 [worst imaginable]). Multiple analyses have confirmed that patients view clinically relevant reductions in pain intensity as follows: [Dworkin et al. 2008]

• substantial improvement = 4 or more points reduction on NRS, or 50% or more reduction on VAS;


• moderately meaningful = 2 points reduction (NRS), or 30-36% reduction (VAS);


• minimally important = 1 point reduction (NRS), or 10-20% reduction (VAS).

From this it can be surmised that a 10% to 20% reduction in pain attributed to a therapy is the minimally acceptable threshold as being of clinical significance to patients; whereas, a 50% or more reduction in pain is generally considered by patients as satisfactory improvement, which some may describe as “treatment success” [Dworkin et al. 2008]. It should be acknowledged, however, that patients' expectations and responses to any therapy can vary, and in the case of chronic pain the situation may be complicated over time: eg, what was satisfactory pain relief a month ago when therapy was started may not be acceptable today as a patient seeks further reductions in persisting pain levels.

Further research has demonstrated that there are additional dimensions of chronic pain and its treatment beyond pain relief that are of clinical importance to patients and worthy of consideration. In cooperation with the American Chronic Pain Association, the IMMPACT group conducted a survey to identify important outcome domains [Turk et al. 2008]. The first part of this investigation identified 19 aspects of life that patients believe are significantly and negatively impacted by chronic pain syndromes. In the second part, 959 respondents with chronic pain selected the following out of the 19 as being most problematic and, therefore, essential targets for improvement: (1) common physical activities (eg, walking, climbing stairs), (2) weakness, (3) fatigue (feeling tired), (4) difficulty concentrating, (5) staying asleep at night, (6) emotional well-being (eg, feeling sad, depressed, unmotivated), and (7) overall enjoyment of life. The high rankings of these areas in importance were remarkably consistent across all chronic pain conditions represented, including arthritis (OA and RA), migraine, low back pain, neck or shoulder pain, neuropathy, and fibromyalgia.

Turk and colleagues [2008] note that it may be unrealistic to expect that a treatment targeting reductions in pain intensity (analgesic effects) should also have beneficial effects on other dimensions, such as fatigue, weakness, depression, etc. “Just because patients desire change in various pain-related aspects of their functioning does not mean that the efficacy or effectiveness of a pain treatment should be measured by its effects on these other outcomes,” they write. However, it seems reasonable that knowledge of the pain-related domains that patients themselves regard as important, and the degree of change considered as clinically meaningful to them, can help in developing treatment plans and assessing therapeutic success. In the final analysis, armed with an appreciation of what is most important to individual patients, healthcare providers are better able to tailor therapies that best meet patient expectations — with the understanding that, as statistician Darrell Huff suggested in 1954, “…a difference is a difference only if it makes a difference.” We would welcome comments from practitioners sharing their opinions or perspectives.

References: documents are available for free access at http://immpact.org/publications.html.
> Dworkin RH, Turk DC, McDermott MP, et al. Interpreting the clinical importance of group differences in chronic pain clinical trials: IMMPACT recommendations. Pain. 2009 (in press).
> Dworkin RH, Turk DC, Wyrwich KW, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain. 2008;9:105-121.
> Turk DC, Dworkin RH, Revicki D, et al. Identifying important outcome domains for chronic pain clinical trials: an IMMPACT survey of people with pain. Pain. 2008;137:276-285.
For Additional Information See...
> Tubach F, Ravaud P, Baron G, et al. Evaluation of clinically relevant changes in patient reported outcomes in knee and hip osteoarthritis: the minimally clinically important improvement. Ann Rheum Dis. 2005;64:29-33 [PDF available here].
> Farrar JT, Young Jr JP, LaMoreaux L, et al. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001;94(2):149-158 [abstract here].
> Salaffi F, Stancati A, Silvestri CA, et al. Minimal clinically important changes in chronic musculoskeletal pain intensity measured on a numerical rating scale. Eur J Pain. 2004;8(4):283-291 [abstract here].

Biofield Therapies for Pain: Help or Hype?

Biofield therapies — such as therapeutic touch or healing touch, Reiki, and others — claim to use subtle natural energy for stimulating the body's healing processes and relieving pain. A surprising amount of clinical research has examined the efficacy of these complementary interventions, yet medical practitioners still may be skeptical of their validity.

Concepts of biofield therapies — administered largely by a "laying on of hands" for manipulating an unseen “life force energy” to invoke stress reduction and relaxation that promotes natural healing — are unfamiliar to most Western healthcare providers; some may believe these approaches are frankly outlandish from scientific perspectives. With this in mind, Shamini Jain, from the UCLA Division of Cancer Prevention and Control Research, and Paul J. Mills, from the Department of Psychiatry at the University of California, San Diego, conducted a rigorous systematic review of research into biofield therapies that was recently reported in the International Journal of Behavioral Medicine.

The reviewers identified 15 pain-related clinical trials, most of which examined chronic pain disorders and were randomized placebo-controlled trials (RCTs) of good quality. Overall, the studies suggested a strong level of evidence favoring positive effects of biofield therapies to reduce pain intensity as measured on visual analog scales. Three studies, all high-quality RCTs, examined health-related quality of life (QOL) and found strong evidence of improvements in energy/vitality and physical functioning as a result of therapy. However, 5 studies that incorporated comprehensive pain assessments (eg, the McGill or Multidimensional Pain Inventory) demonstrated inconsistent evidence of biofield therapies benefitting cognitive and functional aspects of pain reduction, and 8 trials examining mood variables (eg, depression, anxiety) reported mixed outcomes for improvements in anxiety and negative mood.

In a separate area of concern, 10 trials looked at biofield therapies for helping patients with cancer and reported moderate evidence for positive effects in relieving acute cancer pain, but conflicting evidence for longer-term benefits of biofield therapies. Similarly, there was a lack of strong evidence favoring these therapies for improving fatigue or quality of life, or in producing relaxation responses in patients with cancer. Looking at investigations of biofield therapies applied in hospitalized patients, 6 trials showed moderate-quality evidence for reductions in acute pain and favorable effects in lowering anxiety, but conflicting evidence for reductions in pain medication consumption.

Commentary: Overall, Jain and Mills conclude that there is strong, good-quality evidence for effects of biofield therapies in decreasing pain intensity in noncancer pain, and moderate evidence to support their short-term analgesic efficacy among patients with cancer or those hospitalized. In some patients, vitality/energy and physical functioning may be improved; however, the evidence is less convincing regarding therapeutic benefits for improving mood or reductions in pain medication consumption.

While the research literature on biofield therapies is not vast, the number of good or high quality clinical trials is surprising when considering the scarcity of research funding for this field. Many of the favorable responses to these therapies might be merely attributed to placebo effects were it not for the fact that most studies were randomized placebo-controlled trials — that is, effects of therapy were significantly better compared with actual placebo. Still, there is much to learn about biofield therapies since there is a lack of large-scale RCTs examining different patient populations having a range of pain conditions, and the research to date has widely varied in methodology. For example, in the many studies examined by Jain and Mills for their review, subjects underwent 1 to 15 healing sessions (mean 4) that ranged from 3 to 90 minutes (mean 23). And, the particular skill or experience of the biofield therapist, as well as the particular technique(s) employed, would seem to be factors that could make significant differences.

Although many traditionally-trained practitioners may remain skeptical, significant numbers of patients apparently seek biofield therapies, often without telling their healthcare providers, and the techniques have been used over millennia in various cultures to allegedly heal physical and mental disorders. In general, complementary and alternative therapies are used by 38% of adults and 12% of children in America, and it is a $34 billion per year business; so, these approaches cannot be easily ignored. The customary caveat — more research is necessary to arrive at definitive conclusions — would seem very appropriate regarding biofield-based therapies for pain. However, as the 16th Century Swiss physician Philipus Aureolus Paracelsus advised, “The art of healing comes from nature, not from the physician. Therefore the physician must start from nature, with an open mind.”

Reference: Jain S, Mills PJ. Biofield therapies: helpful or full of hype? A best-evidence synthesis. Int J Behav Med. 2009(October 24); online ahead of print [access full article here].

Mayday Panel Report Urges Revolution in Pain Care

Warning that patients should not assume their doctors have enough knowledge to treat their pain, a national panel of experts called for better education on pain care in medical and nursing schools, reforms of America’s reimbursement system, and addressing pain as a public health crisis. Otherwise, people with untreated pain may face a lifetime of pain as a chronic illness, leading to job loss, depression and, in some cases, even suicide.

The report — released November 4, 2009 by the New York City-based Mayday Fund — is titled “A Call to Revolutionize Chronic Pain Care in America: An Opportunity in Health Care Reform” [access report here]. It says that an “epidemic” of undertreatment affects more than 70 million Americans suffering from persistent back pain, headaches, and joint pain, and that minorities and low income persons are disproportionately affected. In addition to calling for medical school reforms and expanded funding for pain management training programs, the 22-member report panel offers recommendations for government agencies, Congress, and the medical community to address, including:

• Healthcare providers, insurers and government agencies should eliminate disparities in access to pain care related to race, gender, age and socioeconomic status. All Americans in pain, including low-income Americans, should be offered timely and effective treatment for their pain.


• The Department of Health and Human Services should reform payment to eliminate the current incentives that drive pain care toward procedures or unproven treatments. Primary care doctors should be reimbursed for the time it takes to provide comprehensive pain care to patients who are disabled by chronic pain.


• The Surgeon General should mount an education campaign to inform the public about the risks associated with undertreated pain. Consumers should understand that if they wait too long to treat acute pain they run the risk of developing a chronic syndrome, one that is costly to treat and potentially disabling.


• Government, healthcare payors, and providers should develop coordinated health information technology (IT) systems to track pain disorders and treatments. Computerized IT systems can boost physicians’ knowledge about effective treatments for pain by providing them with best practice information quickly.

Additionally, the panel recommends that the National Institutes of Health should increase funding for pain research to a level commensurate with the scope of the problem. Incredibly, less than 1% of the NIH budget in 2008 was devoted to pain. Along with that, more research is needed to establish a set of best practices for treating specific types of chronic pain. And, there is a need for federal, state, and local agencies to adopt a balanced approach to the regulation of controlled prescription drugs, particularly opioid analgesics; practitioners’ prescribing decisions should not be inappropriately influenced by fear of regulatory scrutiny.

According to Lonnie Zeltzer, MD, co-chair of the panel, and director of the Pediatric Pain Program at the University of California, Los Angeles, otherwise compassionate and skilled physicians “often offer only limited treatments to patients disabled by chronic pain. With little or no specific training in pain management, and working in systems that make it much easier to treat common conditions like high blood pressure than a complex problem like pain, doctors may intend to help but leave most patients under-assessed and undertreated.”

Chronic pain costs the nation more than $100 billion a year in lost productivity and direct medical costs, the report says. “This is a wasteful system,” observes Russell K. Portenoy, MD, panel co-chair and chairman of Pain Medicine and Palliative Care at the Beth Israel Medical Center in New York, “major reforms in the healthcare system are needed if we want to improve the quality and cost effectiveness of care for chronic illnesses, and pain is as much a chronic illness as diabetes and heart disease.”

Commentary: The report and recommendations have been endorsed by more than 30 organizations, including Pain Treatment Topics. However, this is not the first document to make recommendations such as these, which seem like a “no-brainer” in terms of their commonsense necessity and urgency. Yet, as the panel observes, even though the impact of pain on individuals and American society is among the most serious of public health concerns, chronic pain has been largely left out of the current national debate on healthcare reform. One would think that members of Congress, themselves, as well as their families, are not immune to pain disorders, so they would be clamoring to institute the recommendations of reports like this. At the least, Congress should realize that the 70 million pain sufferers in America, along with their loved ones, represent an enormously powerful voting block that could some day rise up to demand the pain care revolution promulgated in this report — even if it means replacing congressional representatives who do not vigorously support such measures.

AAPMedicine Offers Plan for Better Pain Care

According to a new Pain Medicine Position Paper from the American Academy of Pain Medicine (AAPMedicine), pain care in America is severely inadequate and costly. Leaders from the organization are now recommending a new, "population-based" stepped approach to delivering care with the goal of alleviating pain so patients can get on with their lives. However, it could be many years, possibly decades, before the quality of pain care delivery reaches acceptable levels in the U.S.

Each year $100 billion is spent on care for the 75 million persons in the U.S. with acute or chronic pain; yet, businesses still lose $60 billion annually from lost productivity due to ineffective and suboptimal pain care delivery, mainly for chronic pain conditions. AAPMedicine President, Rollin M. Gallagher, MD MPH, says the population-based approach in their new plan includes four steps designed to deliver timely access to levels of care that are needed to prevent chronic pain from beginning, or when pain persists, minimizing morbidity through effective care:

• Step One: Prevention of disease or injury with the use of evidence-based self-care, such as diet, exercise, ergonomics (alteration of work activities), or cessation of smoking and other drug abuse to reduce the risk of injury or disease.


• Step Two: If self-care is not working, the patient will then visit their primary care physicians for evaluation and management using evidence-based algorithms.


• Step Three: If disabling pain persists, the patient will be referred to a pain medicine specialist [called “algiatrist”] who will collaborate with a team of providers, including, nurse case managers, psychologists, and physical therapists.


• Step Four: If the patient remains in disabling pain [called “maldynia” at this point], he/she will be referred to a pain medicine specialist within a subspecialty of care.

The AAPMedicine concedes that there currently is no unified organizational model of pain medicine in America, which has led to ineffective and fragmented pain care with poor outcomes and higher costs than necessary. This fragmentation threatens patient safety and causes the passing of a patient from doctor to doctor for a diagnosis and pain treatment, even though those physicians may have had minimal or even no specific training in chronic pain management. The Academy believes one of the solutions to this complex problem is the establishment of pain medicine as a recognized primary medical specialty [“algiatry”]. This recognition would allow pain medicine's specialized knowledge, education, training, and multidisciplinary approach to provide standardized training for all physicians, along with integrated and comprehensive pain care to millions of Americans suffering with acute, cancer, and chronic pain.

Commentary: The Academy’s Position Paper offers an excellent review of the state of pain medicine today; so, it is recommended reading for everyone in the field [PDF available here]. However, the Paper also is somewhat disturbing and it is disheartening, to say the least, that when it comes to managing a condition so ubiquitous in our society as pain the healthcare delivery system appears to be in a state of such disarray and deficiency. As things stand today, the AAPMedicine’s four-step plan outlined above breaks down at Step Three; they acknowledge that, “Currently there are not enough pain medicine specialists to treat back pain and other pain conditions, and the system for training physicians in the discipline of pain medicine remains insufficient”; and, the number of pain specialists is actually declining. The Academy's solution calls for better residency training programs in pain medicine, which will lead to better and more cost-effective pain care. They further believe that recognizing pain medicine as a primary medical specialty also would increase federal funding for pain research and improve healthcare coverage for pain care by insurance companies (which often refuse to cover many pain-relieving treatments today).

However, according to conditions described in this Position Paper, it appears that it could take years, possibly decades, before pain care achieves an acceptable level of performance in America. Furthermore, it should be understood that the so-called “Healthcare Reform Program” still being debated in the U.S. Congress is actually an “access to healthcare insurance reform program.” The outcome may well be that more Americans will have insurance coverage to receive healthcare that, in the case of pain management, is still in limited supply and inadequate. If you have opinions, add a comment.

Reference: Dubois MY, Gallagher RM, Lippe PH, eds. Pain Medicine Position Paper. Pain Med. 2009;10(6):972-1000 [Click here to view the document PDF].

Nov2009 – Pain Product Announcements & Warnings

Featured Items: unapproved codeine sulfate tablet warning, fentanyl buccal film (Onsolis), colchicine (Colcrys) for gout, certolizumab pegol (Cimzia) approved for RA.
— All brand names are trademarks of their respective manufacturers. Compiled by Winnie Dawson, MA, RN, BSN.

Unapproved Codeine Sulfate Tablets — FDA Says “Stop”
In October 2009, the FDA sent warning letters to 4 companies making or distributing unapproved codeine sulfate tablets and required a 15-day response time. The manufacturers were given 90 days to cease production and distributors have 180 days to discontinue shipment of existing drugs. The FDA reminds consumers and healthcare providers that there is no evidence that these opioid analgesic tablets are safe or effective and states that the approved codeine sulfate tablet from Roxane Laboratories is available to meet product demand. See the FDA news release for unapproved product information and company names.

Fentanyl Buccal Film (Onsolis®) for Cancer Pain — Now Available
Following FDA approval in July 2009, the makers of Onsolis — BioDelivery Sciences International and Meda Pharmaceuticals — have finalized the details of the required restricted distribution program (REMS) and the product is now commercially available. Onsolis, a new fentanyl formulation delivered through a dissolvable film that adheres to the inside of the user's cheek, was developed for opioid-tolerant adult patients with cancer. It was designed to treat breakthrough pain and offers an alternative to oral or injectable drugs by rapidly delivering a dose of pain therapy across mucous membranes. The distribution program called FOCUS™ will restrict access of Onsolis to patients, prescribers, and pharmacies registered with the program. As part of the program, education and counseling will be provided to patients and healthcare professionals. Further information is available at the FDA website "Questions and Answers About Onsolis" and the FOCUS program website. Also see prior Pain-Topics webpost [7/17/09].

Colchicine (Colcrys™) — FDA-Approved for Prevention of Gout Flares
URL Pharma announced an October 2009 FDA approval of Colcrys as prophylaxis for acute flares of gout. Two randomized trials showed a decrease in the frequency of gout flares with 0.6 mg twice-daily Colcrys dosing in patients initiating treatment with uric-acid lowering therapy. The drug — an oral form of colchicine — was first approved in July 2009 for the treatment of painful acute gout flares and has been formulated for optimal efficacy and tolerability when taken at the first sign of a flare. Because the product has a long-term history of use before approval, it is important to become familiar with new dosing recommendations; see the CenterWatch Drug Information fact sheet and the patient Medication Guide for full details. There have been reports of fatal toxicity reported in patients taking medications that interact with colchicine. For further information, please read the FDA safety information notice.

Certolizumab Pegol (Cimzia®) — Approval in Europe and the U.S.
UCB Group of Belgium has announced an October 2009 European Commission approval — following the summer U.S. FDA approval — of Cimzia for the treatment of rheumatoid arthritis in adult patients. The drug is administered as a subcutaneous injection and can be given in combination with methotrexate or as monotherapy (in cases of methotrexate intolerance) to treat the symptoms of severe active rheumatoid arthritis when DMARDS have been inadequate. It is also available in a prefilled syringe. For complete information, see the prescribing information and patient Medication Guide.

Tough Times Amplify Aches & Pains, APF Survey

A new survey from the American Pain Foundation (APF) found that economic strain from the recession is resulting in an epidemic of back pain or other muscle strains and sprains among Americans. Yet, a majority do not seek medical care, and then many do not follow through with prescribed or recommended treatments.

According to the APF survey — supported by King Pharmaceuticals and conducted by Greenfield Online — nearly 70% of all adults interviewed experienced acute back pain or other minor muscle strains and sprains during the past year; 1 in 3 suffered back pain. They said that the recession caused or increased their pain, often because of greater stress and working harder at home and on the job. For many of the sufferers the economy’s effect was pronounced, with more than a third (37%) reporting that some aspect of the recession had a big impact on their pain. Furthermore, 1 in 5 said that health problems related to the recession — like sleeplessness, bad eating habits, or cutting back on healthcare — exacerbated their pain.

Acute back pain sufferers were especially likely to report that the recession had affected their pain, particularly those with children. Nearly 7 of 10 parents with back pain (68%) said the recession increased or negatively affected their pain, compared with 55% of non-parents with back pain. And, the pain had an effect on their quality of life, impacting everything from their work lives to their ability to take care of other health issues to their sexual desire. Despite this, many sufferers of acute back pain or other muscle strains or sprains took treatment matters into their own hands: only about 4 in 10 reported seeing a healthcare professional for their pain, and 90% had tried some type of other remedy, most commonly over-the-counter treatments, before consulting a healthcare professional. Interestingly, only 71% of those who consulted a healthcare professional followed through with prescribed or recommended treatments.

“These findings demonstrate the unexpected impact that mental and physical stress can have on our bodies,” said Will Rowe, chief executive officer of the American Pain Foundation. “In addition to stress and other health effects of the recession, this survey indicates there is an actual physical effect that translates into pain and injuries for Americans working harder to keep up with the tasks of daily life.” The survey was conducted online between July 27 and 30, 2009, and the overall margin of error for the total sample of 2,192 online Americans was +/- 2%.

Reference: American Pain Foundation. Acute Pain and the Recession Omnibus Survey. 2009 [Executive Summary available here].