Want Less Pain? Rip Off Adhesive Bandage Quickly

Australian researchers, in somewhat of a holiday jesting spirit, have answered one of pain medicine’s oldest questions: Is quickly ripping off an adhesive bandage strip (aka, Band-Aid®) less painful than the slow tug method? Faster appears to be better, but there are limitations.

During a controlled research trial — conducted at James Cook University and published in the pre-holiday edition of the Medical Journal of Australia — medium-sized plastic adhesive bandage strips were applied to 65 hapless medical students who "volunteered" for the experiment. None had an actual injury covered by the strip and each was asked to rate the pain from 0-to-10 when the strip was removed (0 being “no pain,” 10 signaling “worst pain imaginable”).

According to study coauthor Carl O'Kane the average pain score for slow removal was 1.58 and for fast removal it was only 0.92 (a significant 45% decrease). As with other research in pain medicine, women seemed to have higher pain tolerance; the average pain scores for women were significantly lower than for men. Although, as O’Kane conceded, men tended to have more body hair and a high body-hair score was associated with higher pain scores, as one might expect.

For the record: A number of limitations should be noted. All subjects were healthy young adults, without allergies to adhesive dressings, chronic pain, or serious anxiety disorders. O’Kane acknowledges that “These results would not be applicable to patients with wounds, particularly chronic wounds and ulcers, that may adhere to bandaids or other simple dressings.” Presumably, anxious patients also might not react the same as study group participants, nor might children or older persons. Clinician skill in applying the removal technique might make a difference. O’Kane conceded that students who were tested by one of the two operators reported higher pain levels than those tested by the other operator; so, “This may indicate that there are skilled bandaid removers and less-skilled or unskilled bandaid removers.”

Another way of looking at the data is that slow adhesive bandage removal increases pain by 72%, which sounds menacing; at least until one considers that a brief burst of pain even at the higher 1.58 average level (on an 11-point scale) due to unhurried, careful removal is not much to worry about, especially if there is a scab (eschar) or other wound underneath at risk of being disturbed. And, yes, the study was adequately powered to confirm the differences as being statistically significant; albeit, this is a case where the findings are probably not of true clinical significance.

Reference: O’Kane C, et al. Fast bandaid removal less painful than slow bandaid removal. MJA [News Release]. 2009(Dec 13);191[11/12]).

Happy holidays, 2009, from the Pain Treatment Topics team!

Texting A Real Pain in the Neck (and Shoulders)

Telephone text messaging, or texting, is preferred over talking by many younger persons these days. However, a new study suggests that many of them are developing serious neck and/or shoulder pain as a result.

Researchers from Pennsylvania presented evidence at this year’s meeting of the American Public Health Association showing that the more young persons texted, the more pain they reported in their necks and shoulders. Lead researcher Judith Gold, ScD — assistant professor of epidemiology at Temple University’s College of Health Professions and Social Work — said in a news release that most people aged 18 to 21 prefer texting rather than email or phone calls, possibly putting the younger generation at increased risk for overuse injuries that have plagued office workers spending hours tapping away on computer keys.

Gold and colleagues examined correlations between the number of text messages sent per day and upper body pain in a sample of 138 college students; 58% female, mean 21 +/- 5 years of age. The subjects used body maps to indicate areas of discomfort and were asked how many text messages they sent per day. More than half (55%) of the participants complained of upper extremity and back pains overall, and there was an association between shoulder and neck discomfort and the number of daily text messages. Interestingly, while age did not make a difference, males were affected to a significantly greater extent than females.

Commentary: The researchers could not account for why texting would cause pain in the neck and shoulders rather than the arms, wrists, or hands, or why males are at such greater risk. Gold only observes, “What we’ve seen so far is very similar to what we see with office workers who’ve spent most of their time at a computer. The way the body is positioned for texting — stationary shoulders and back with rapidly moving fingers — is similar to the position for typing at a computer.” However, our own prior ergonomics research found that when it comes to cumulative trauma disorders associated with computer keyboards women have been more commonly at greatest risk than men. For now, the important clinical practice pointer seems to be that when diagnosing a young patient complaining of persistent neck and/or shoulder pain it could be worthwhile to inquire about their phone texting habits.

Reference: Gold JE, Kandadai V, Hanlon A. Text messaging and upper extremity symptoms in college students. Proceedings from the American Public Health Association 137th Annual Meeting & Expo; November 7-11, 2009; Philadelphia, PA. Abstract 201105 [available here].

Pain Relieving Coxibs Counter Aspirin’s Benefits

Millions of persons are prescribed COX-2 inhibitors, or coxibs, like Celebrex® for arthritis and other pain. However, coxibs may undermine the anti-clotting benefits of low-dose aspirin taken daily to reduce risk of heart attack or stroke in these patients, according to new research.

In laboratory studies, University of Michigan researchers found that coxibs interfere with aspirin’s ability to discourage blood clot formation, if the aspirin is taken in low doses such as the recommended 81 mg/day. “The greatest risk,” according to William L. Smith, PhD, the study’s senior author, “is having people take Celebrex who are taking aspirin for cardiovascular problems that are known to be mitigated by aspirin, including patients with unstable angina or those at risk for a second heart attack.” Celebrex brand of celecoxib is the only coxib still on the market in the United States, and previous studies of healthy subjects found no ill effect on blood clotting when Celebrex was combined with aspirin at higher doses, specifically a daily “regular” aspirin tablet (324 mg). So, Smith notes, it may be that spreading out the time between taking low-dose aspirin and Celebrex or a higher aspirin dose will allow aspirin to be effective. Of course, at higher doses aspirin’s undesirable effects on the gastrointestinal tract must to be taken into account.

Caveats: This study was in laboratory animals and the detrimental effects need to be replicated in humans. If the problems are evident in people, it will be important to determine if a balance in dose and/or dose regimens can be found so that aspirin and Celebrex can both be effective. At present, more than half of older patients prescribed COX-2 inhibitors long-term are also taking low-dose aspirin to protect against thrombosis, and practitioners should be aware of the possibility that the aspirin might not be delivering the expected and desired anticoagulant effect.

Reference: Rimona G, Sidhua RS. Lauverc A, et al. Coxibs interfere with the action of aspirin by binding tightly to one monomer of cyclooxygenase-1. Proceedings of the National Academy of Sciences (PNAS). 2009 (Dec 1, advance online publication) [abstract here].

Racial, Ethnic Disparities in Pain Care Examined

According to a recent research review, racial and ethnic inequities persist in the treatment of all pain conditions, across all age groups, and in all treatment settings throughout the United States. Barriers to optimal pain management for minority-group patients include factors related to patients themselves, healthcare providers, and the healthcare system. What should be done?

In the most comprehensive literature review to date, the authors examined peer-reviewed articles published between 1990 and early 2009 focusing on racial and ethnic disparities in pain and its management in the U.S. [Anderson et al. 2009]. Writing in the December 2009 edition of The Journal of Pain, they observe that many inequities persist in acute, chronic, cancer, and palliative pain care settings, with minorities clearly receiving lesser quality care than non-Hispanic whites. Here are several examples:

• Multiple studies have shown that in emergency departments acute pain in minority patients is undertreated. In one study of long-bone fractures, Hispanic patients were twice as likely as non-Hispanic whites to receive no analgesics at all. Black (African American) patients were two-thirds more likely to receive no analgesics for their pain.


• Although opioid analgesic prescribing for pain-related emergency department visits has generally increased, white patients with pain are significantly more likely to receive an opioid analgesic than black, Hispanic, or Asian/other patients. This has been evident in children as well as adults.


• Postoperatively, white patients receive significantly higher total opioid doses than minority (black, Hispanic, Asian American) patients.


• In a study of childbirth labor and delivery, researchers found that black, Hispanic, and Asian women were less likely to receive epidural analgesia than white women.


• In the treatment of osteoarthritis, a nationwide study of veterans found that minority-group patients were less likely to receive adequate medication and the number of days’ supply of medication provided was less than for white patients.


• Treatment inequities for minority-group patients also have been evident in studies of cancer pain. In most cases, black and Hispanic patients did not receive appropriate or adequate analgesics for their cancer-related pain.


• In one study, minority-group patients were twice as likely as whites to be disabled 6 months after occupational back injuries.

There have been some inconsistencies across studies, with most finding egregious disparities in pain care but some finding improvements during more recent years. And, most research has examined non-Hispanic white populations in comparison with Hispanic/Latino and/or black/African American minority groups. Few studies have included Asian American, Arab American, Native Hawaiian, Pacific Islander, Native American, Alaskan Native, or other racial or ethnic groups that might be of concern.

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Canadian Study Distorts Rx-Opioid-Related Deaths

Understanding Evidence-Based Pain Management (EBPM)

Reports of increasing deaths associated with prescribed opioid analgesics are of concern, but also may portray a distorted picture of the scope and urgency of the problem. This was evident in a recent report on mortality trends in Canada, which serves as a lesson in why readers must be wary of how such data are presented in the literature and the press.

Canadian investigators supported by the Institute for Clinical Evaluative Sciences (ICES) and Ontario Ministry of Health and Long Term Care reviewed opioid prescribing trends and all deaths involving alcohol, drugs, or both in Ontario during 1991 to 2004 [Dhalla et al. 2009]. Their report, published in the December 8, 2009, edition of the Canadian Medical Association Journal (CMAJ) concluded that increases in opioid analgesic prescribing have directly contributed to an alarming rise in associated mortality, and they pay particular attention to concerns about oxycodone formulations. Sensational national news headlines proclaimed, “Canada’s pain reliever deaths double”; however, a close look at the data and their presentation suggests some alternative perspectives worth considering:

• During the 14-year time period of the study there were a total of 7,099 deaths involving alcohol, drugs, or both; of those, less than half (3,406 or 48%) implicated opioids in the cause of death. Fatalities associated with opioids increased from 13.7 deaths per million residents to 27.2 deaths per million. In perspective, however, while there indeed was nearly a doubling, the population incidence rate rose from merely 0.0014% to 0.003%, making such events a rare occurrence even at the higher extreme in 2004. (From another viewpoint, the lifetime odds of being struck by lightning, at least in the U.S., is more than 5-times greater or 0.016% [data here].)


• Curiously, the 3,693 deaths (52%) involving alcohol (possibly also including nonopioid drugs) were not mentioned by the authors as being of concern. And, further complicating the picture, more than a third (38%) of opioid-associated deaths involved multiple drugs, including possibly heroin (which confounds the focus on prescription opioids) and nonopioids (benzodiazepines, antidepressants, and/or alcohol).


• Most of the victims (84%) had visited their physicians or the emergency room within 2 weeks prior to death, and analysis of records revealed anxiety, depression, or drug dependence were common diagnoses in addition to pain-related complaints. And, death was attributed to suicide in nearly a quarter of all cases (24%) involving opioids. So, while the availability of opioids was a factor, mental health problems may have been a more critical precipitating factor in a significant portion of all deaths. In some cases, the undertreatment of pain could have been a contributing factor in either suicide or in opioid over-use leading to unintentional death; however, the study does not address these vital issues of concern.


• The study authors note that the introduction of long-acting oxycodone formulations in 2000 resulted in multifold increases in prescribing and associated deaths with that drug by 2004 (at one point in the text the authors state a 416% increase in deaths, in other places they indicate it as “5-fold”). However, according to the data, the 234 oxycodone-related deaths were ranked 4th in frequency, coming after morphine or heroin (or both), codeine, and methadone; also, in 92% of the oxycodone cases one or more additional drugs were implicated. The authors concede that there is no evidence of oxycodone itself being more intrinsically dangerous than other opioids; and, we might speculate that it was found to be a particularly effective analgesic, which contributed to increased prescribing and a natural occurrence of associated fatalities as part of the overall trend. Therefore, it is peculiar that oxycodone was targeted for such attention in this study, other than the long-acting formulation being a newly introduced agent during the data gathering period.


• The authors provide two trend graphs — one for oxycodone-related deaths and a second for opioid-related deaths — which each show declines in fatalities between 2003 and 2004. It could be important and enlightening to know if this decreasing mortality trend continued in subsequent years. For example, we had previously shown a leveling-off of opioid-related problems in the U.S. during 2005 to 2008 [see blogpost 9/16/2009].


• There is no indication in the study data of what proportion of decedents were patients for whom the opioids were prescribed, versus being diverted to other persons, and whether death was associated with accidental misuse or intentional abuse. Such factors could make significant differences in how the purported hazards of opioids are interpreted and portrayed.


• Although the authors actually examined prescribing trends from 1991 to 2007, they made no attempt to assess the probability risk of prescribed-opioid fatalities; for example, one way this could be calculated is the number of deaths divided by the total number prescribed doses during the time period. We have previously shown that such risks are extremely low in the U.S. [see blogpost 9/12/2009] and would likely be similar or even lower in Canada.

All of this is not to belittle legitimate concerns about the misuse or abuse of opioids and the tragedy of analgesic-related deaths. There is no question about opioids being strong medications that can be fatally toxic if improperly prescribed and/or used. However, data manipulations that exaggerate opioid problems can be a misrepresentation of reality, and it is important to recognize that there is almost always more than one way to view, analyze, and present data as evidence depending on how one wishes to slant the perspective. In a commentary accompanying the study report in CMAJ, Fischer and Rehm [2009] note that “prescription-opioid-rich” environments throughout North America have created major public health challenges. Yet, they concede that these analgesics are essential therapeutic tools and caution regarding the possible “chilling effects” of tightened regulatory controls that could result in practitioners’ unwillingness to prescribe the medications. Such mixed messages are confusing and, when combined with a “data-rich” study report that obscures rather than clarifies the problems at hand, can lead to misguided conclusions by the unwary reader and in the mass media.

Note: In fairness we must acknowledge that alternative analyses of evidence, such as presented above, are only possible when article authors are intellectually honest in reporting sufficient data from their research, as was the case in this Canadian study.

References:
> Dhalla IA, Mamdani MM, Sivilotti MLA, et al. Prescribing of opioid analgesics and related mortality before and after the introduction of long-acting oxycodone. CMAJ (Canadian Med. Assn.). 2009(Dec 8);181(12):891-896 [article available here].
> Fischer B, Rehm J. Deaths related to the use of prescription opioids [commentary]. CMAJ (Canadian Med. Assn.). 2009(Dec 8);181(12):881-882 [article here].

REMS: When Elephants Prance, Ants Take a Pounding

At a meeting last Friday, December 4, 2009, the U.S. Food and Drug Administration (FDA) called upon pharmaceutical company representatives to report on their progress in developing a REMS (Risk Evaluation and Mitigation Strategy) for extended-release or long-acting opioid analgesic products containing oxycodone, morphine, methadone, and other agents. Concerned about what are perceived as high rates of misuse, abuse, addiction, and overdose with these powerful pain relievers, this is the first time the FDA has demanded a REMS program for an entire class of drugs.

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Powers of Placebo in Pain Management Revisited

Understanding Evidence-Based Pain Management (EBPM)

Placebo effects in pain management can exert very real and powerful influences either for good or harm. The question is, how can positive powers of placebo be harnessed to improve patient outcomes? The answer depends on the clinical skills of healthcare providers.

An article in USA Today last month [November 13, 2009], entitled “Placebo effect behind many 'natural' cures,” asserts that “People looking for natural cures will be happy to know there is one. Two words explain how it works: ‘I believe.’" The article goes on to note that the placebo effect — the ability of a fake pill or presumably ineffective treatment to make people feel better just because they think that it will — “looms large in alternative medicine, which has many therapies and herbal remedies based on beliefs versus science.” While acknowledging that this statement has pejorative implications, the author quotes Robert Ader — a psychologist and placebo researcher at the University of Rochester in New York — as saying, “placebos can have real and beneficial effects. Much of the results of certain alternative procedures are largely placebo effects."

The nature of placebos and their effects are actually quite complex and still poorly understood, but a closer look at placebo powers suggests interesting possibilities for better pain management research and practice. In a classic paper, more than 50 years ago Harvard researcher Henry Beecher [1955] discussed placebos as having a double meaning: (1) a “pure placebo” intended or expected to have no therapeutic effect (eg, a “dummy drug” used in research), or (2) something known or intended to act through psychological rather than physiological mechanisms. Whether a “pure placebo”— a completely inert agent or a therapy exerting absolutely no mental or physical response — actually exists in medical science is debatable.

After examining the limited clinical research of the time, Beecher found that placebos were consistently effective in more than 30% of patients treated for pain conditions, providing clinically significant reductions in pain of 50% or greater. A further important observation was that placebos were most effective when the pain state was greatest. Beecher also makes distinctions between two phases of pain suffering: (a) the original pain sensation, and then (b) the reaction to it, or its processing by the brain. As might be expected, placebos exert their most profound effects during the second phase, which is psychological and subjective in nature, by altering the reaction to or perception of pain. In certain circumstances, placebos also can incur toxic effects (adverse reactions) that are both objective (signs) and subjective (symptoms).

Today, there is an emphasis on randomized, double-blind, placebo-controlled trials as the “gold standard” for clinical research. This approach allows researchers to filter out the influence of confounding factors, such as psychological placebo effects, that could make it difficult to know if the active treatment in question is truly worthwhile or not. However, placebos in pain medicine research often exert surprising benefits. In previous UPDATES blogposts we reported on a number of pain therapy trials that demonstrated robust placebo effects: for example, sham procedures — during acupuncture, vertebroplasty, and surgery for migraine — a placebo analgesic cream, and a dummy pill for abdominal pain were all noted to produce considerably beneficial outcomes. In some cases, whether or not the placebo interventions were actually physiologically inert must be questioned and, in other cases, the role of patients’ positive expectations, beliefs, or hopes must be taken into account [Tilburt et al. 2008].

Brain imaging studies show that positive expectations or beliefs ("I know these pills will help") can incur neurobiological changes (largely in limbic regions of the brain) and affect levels of chemical messengers that modulate pain [Tracy 2008]. Conversely, anticipation of pain or harm can influence brain activity in opposite ways to produce adverse reactions. For example, a current literature review found that the specific adverse event profiles associated with antimigraine medications (either triptans, NSAIDS, or anticonvulsants) were matched by negative effects reported in placebo groups. In other words, research subjects knowing of possible adverse events associated with a particular active drug that they might be taking as part of a clinical trial actually developed those effects to a certain extent even when administered a placebo — subjects anticipated certain harms and they happened, which is called a “nocebo” effect [Amanzio et al. 2009].

While the potential for nocebo effects might advocate for not informing patients of possible adverse reactions associated with a therapy, there are ethical and medicolegal concerns associated with such practice. Another questionable practice is the prescribing of agents expected to have little or no pharmacologic benefit for the particular condition in hopes of inducing a positive placebo effect. A fairly recent survey of 679 internists and rheumatologists in the U.S. found that up to 58% prescribed placebo treatments on a regular basis [Tilburt et al. 2008]. Most prescribers (62%) believed the practice was ethically permissible; however, the most frequently prescribed “placebos” included over-the-counter analgesics (41%) and vitamins (38%), and to a lesser extent sedatives (13%). Actually, however, these were not truly inert agents, and nearly 7 out of 10 practitioners described the agents to patients as potentially beneficial treatments not typically used for their condition; curiously, roughly 5% of respondents said that they honestly described the agents to patients as placebos.

Clinical Implications: In their survey report, Tilburt and colleagues [2008] reasoned that most physicians probably felt that doing something was better than doing nothing; for example, nearly 6 out of 10 respondents said they would recommend a sugar pill for patients with chronic pain if it had been shown to be more effective than no treatment at all. Unfortunately, the survey did not inquire about outcomes: Did the “placebo treatments” actually help the patients?

Intentionally recommending or prescribing otherwise ineffective treatments solely to invoke positive placebo effects seems to involve an element of deception that is contrary to the principle of informed patient consent. Yet, there are several principles of placebos that might be helpful to practitioners:

• As Beecher [1995] suggested long ago, for any analgesic or other pain therapy, the total benefit may be equal to its “active” effect plus its placebo effect. For example, a clinical trial may show a 50% response rate in the placebo group and a 70% response in the treated group; the 20% difference is the “active” effect of the treatment itself. Could the success rate be improved by enhancing the placebo effect?


• The reactive or suffering component of pain is affected by neurobiological processes that may be altered by a patient’s expectations, beliefs, or hopes. In such cases, the placebo power of any therapy might be bolstered by the healthcare provider’s own positive attitudes and beliefs communicated to the patient. If the practitioner reinforces a positive and optimistic mindset in the patient regarding the effectiveness of a therapy it lends added potency.


• The more severe the pain or suffering, the greater latitude there is for invoking favorable placebo effects, at least to some extent.


• While discussing potential adverse effects associated with any pain therapy could be a prudent component of informed patient consent, the possibility of invoking negative expectations and nocebo effects must be considered. The ways in which possibly negative aspects of treatment are presented by the healthcare provider can make a critical difference in the outcomes.

In sum, placebo effects can play vital roles in pain management that are often overlooked, whether considering pharmacotherapies, interventional procedures, or complementary and alternative approaches. While some healthcare providers have found it appropriate to prescribe or recommend what they consider as “pure placebos” in hopes of invoking favorable responses, such practices are questionable. Of greater value could be the potential for healthcare providers to capitalize on placebo effects for relieving pain and suffering by creating positive expectations in patients regarding active therapies. However, this is a clinical skill that must be learned.

References:
> Amanzio M, Corazzini LL, Vase L, Benedetti F. A systematic review of adverse events in placebo groups of anti-migraine clinical trials. Pain. 2009(Dec);146(3):261-269 [abstract here].
> Beecher HK. The powerful placebo. JAMA. 1955;159(17):1602-1606.
> 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].
> Tracey I. Imaging pain. Br J Anaesth. 2008;101(1):32-39 [article PDF here].

Intranasal Naloxone: Overcoming Opioid Overdose

Naloxone has been approved and used since 1971 as an antidote to respiratory failure during opioid overdose, primarily by emergency medical services. Research is accumulating to suggest that this agent administered intranasally by caregivers at home may have even far-greater lifesaving potential.

Naloxone, which is an opioid antagonist, is FDA-approved for administration parenterally via either intravenous (IV), intramuscular (IM), or subcutaneous (SC) injection. However, intranasal naloxone (IN) administration (an off-label application) can reduce the risk of needlestick injury or air-bubble embolism — and, it has the potential to be prescribed for at-home emergency use by patients prescribed opioid analgesics or their caregivers. Administration of IN naloxone simply entails attaching an atomizer device to a prefilled syringe for delivering a mist of the drug to nasal mucus membranes; but would this be as effective as IV or IM naloxone administration?

In a very recent report, researchers in Australia conducted a randomized trial comparing IN with intramuscular (IM) naloxone administered in prehospital settings during 172 episodes of opioid overdose [Kerr et al. 2009]. Emergency services personnel arriving on the scene administered 1 mL (2 mg/mL) of either IN (n=83) or IM (n=89) naloxone to the subjects. Rates of favorable response within 10 minutes were statistically equivalent (73.3% IN vs 77.5% IM), and there were no differences in mean times for adequate response (IN=8 minutes vs IM=7.9 min.); although, a significantly greater number of patients receiving IN naloxone did need a supplemental dose. Overall, opioid overdose was reversed successfully in 82% of IN naloxone-treated patients (NOTE: In some cases, before outside help arrives with naloxone, victims may deteriorate to a point beyond rescue, so any failure to revive the persons is not due to ineffectiveness of naloxone).

A second recently published study compared IN versus intravenous (IV) naloxone administration in the prehospital opioid overdose setting [Robertson et al. 2009]. In a retrospective review of emergency services records spanning 17 months, investigators in California uncovered 50 victims treated with IN naloxone and 104 treated with IV naloxone. Favorable clinical response was noted in 33 (66%) and 58 (56%) of the IN and IV groups, respectively (p = 0.3). The mean time between naloxone administration and clinical response was longer for the IN group (12.9 vs 8.1 min, p = 0.02); however, when taking into account the added time required for IV naloxone administration (eg, preparing the syringe, attaining venous access, etc.) the mean times from patient contact to clinical response were equivalent (IN=20.3 vs IV=20.7 min, p = 0.9). As in the above study, more patients in the IN group received an extra dose of naloxone (34% vs 18%, p = 0.05).

On another subject related to emergency naloxone, a very interesting and current report suggests that the agent may be of some benefit for opioid-overdose-related cardiac distress [Saybolt et al. 2009]. Researchers at the Robert Wood Johnson Medical School in New Jersey conducted a retrospective chart review of 32,544 advanced life support (ALS) emergency medical dispatches between January 2003 and December 2007 and identified 36 patients in non-traumatic cardiac arrest who received naloxone for suspected opioid overdose. Fifteen (42%; 95% confidence interval: 26-58%) had improvements in electrocardiogram rhythm, and in nearly half (47%) of those who responded the ECG rhythm changes occurred immediately following naloxone administration. The authors do note that, while naloxone's benefits for aiding cardiac distress have been of recent interest, due to both human case reports and animal studies demonstrating antiarrhythmic and positive inotropic (heart contraction strengthening) effects, some results have been conflicting (particularly when higher-dose naloxone is infused too rapidly [see, van Dorp et al. 2007]). Nonetheless, naloxone administration during cardiac distress associated with opioid overdose can be especially important because rates of return to spontaneous circulation and survival in such cases are quite low; therefore, any intervention leading to rhythm improvement could be important.

Clinical Concepts: Naloxone has been used effectively in emergency departments and by emergency responders to reverse opioid overdoses for more than 35 years. Yet, to this day, the increasing incidences of opioid analgesic overdose fatalities are garnering public attention and outrage. As noted by the current research above, as well as by evidence from prior investigations, intranasal naloxone is easy and quick to administer and generally equivalent in all respects to more invasive IM, IV, or SC modalities. In certain cases, properly administered naloxone also may be of benefit in averting or ameliorating cardiac complications of overdose.

Also important, IN naloxone administration is a feasible approach for opioid overdose rescue at home that can be easily delivered by caregivers (relatives, friends, or others who monitor a patient’s response to opioids). According to some experts, there is growing support for regularly pairing naloxone with all new prescriptions of long-term opioids, or in association with opioid rotation or dose increases, and in other circumstances. Under this scenario, practitioners would routinely prescribe intranasal naloxone (along with providing necessary instruction for its use) to accompany the respective opioid prescription whenever there is concern about possible overmedication or overdose; under current law, this is permissible in every state in the U.S. Such an approach would have the dual benefits of safeguarding the life of the patient and also potentially serving as a lifesaving measure for family members or others who inadvertently or intentionally consume the patient’s medication and experience an opioid intoxication or poisoning crisis.

As Jill Harris, Managing Director of Public Policy at the Drug Policy Alliance, has noted, “Tens of thousands of lives could be saved if naloxone were more widely available and more people (including doctors, pharmacists and other healthcare professionals, as well as law enforcement professionals many of whom are currently unfamiliar with naloxone), were trained in its use. Providing take-home naloxone to opioid users, along with instructions for its use, could significantly reduce the number of accidental overdose deaths” [Harris 2009]. What do you think? Add a comment.

References:
> Harris J. No one deserves to die by overdose. AlterNet [online]. 2009(Jun) [article available here].
> Kerr D, Kelly AM, Dietze P, Jolley D, Barger B. Randomized controlled trial comparing the effectiveness and safety of intranasal and intramuscular naloxone for the treatment of suspected heroin overdose. Addiction. 2009(Dec);104(12):2067-2074 [abstract here].
> Robertson TM, Hendey GW, Stroh G, Shalit M. Intranasal naloxone is a viable alternative to intravenous naloxone for prehospital narcotic overdose. Prehosp Emerg Care. 2009(Oct-Dec);13(4):512-515 [abstract here].
> Saybolt MD, Alter SM, Dos Santos F, et al. Naloxone in cardiac arrest with suspected opioid overdoses. Resuscitation. 2009 (Nov 12, Epub ahead of print) [see abstract].
> van Dorp EL, Yassen A, Dahan A. Naloxone treatment in opioid addiction: the risks and benefits. Expert Opin Drug Saf. 2007;6(2):125-132 [open-access article here].

Migraine Relief: Looking Beyond Medications

A troublesome impediment to effective and continuing control of chronic migraines is medication overuse headache (MOH). In a recent article, the authors describe MOH as a biobehavioral disorder that can be addressed by nonpharmacological approaches for achieving greater long-term pain relief.

Medication overuse headache (sometimes called “rebound headache”) occurs when usually effective pain-relieving agents are used inappropriately and excessively, leading to decreased headache relief. Once this rebound phenomenon occurs, preventive, abortive, or analgesic agents may paradoxically increase the frequency and severity of head pain. Writing in the journal Neurological Sciences, clinicians from the U.S. and Italy note that MOH is now recognized as a condition wherein emotion and pain become intermingled, rather than its being a painful condition associated solely with neurobiological physiology.

Considering the behavioral or psychological aspects of MOH, there are some basic issues that can be key contributors to the disorder:
> A belief that medication is the only or the best treatment option.
> Panic due to anticipatory fear of headache pain (‘‘cephalagiaphobia’’).
> Intolerance to or difficulty dealing with pain.
> Seeking sedation (“soporophilia”).
> The need to be functional despite pressures that may provoke headache.
> The presence of psychiatric comorbidities, primarily depression and anxiety.

In a typical scenario, the authors describe how patients become conditioned to taking antimigraine medications at the first sign of a headache attack in anticipation of debilitating pain. Eventually, the medications, which often have sedating and/or anxiolytic effects, are taken in a preemptive or prophylactic manner during times of anticipated stress or events that might trigger a migraine. Eventually, medication overuse headache “rears its ugly head,” they write. However, these and other behavioral risk factors can be modified to avert MOH.

The general consensus seems to be that patients need to be withdrawn from all medications involved in overuse. Then, a first step involves educating patients about MOH and the pathways to headache chronicity. The second step concerns working with patients to identify risk factors and current behaviors that are contributing to the problem. The final step involves behavioral interventions, such as cognitive behavioral therapies to cope with stress, biofeedback, and/or various relaxation techniques. While these and other behavioral treatments rarely provide the rapid relief that can occur with medications, patients learn to restructure their perspectives on pain, essentially learning how to tolerate discomfort, reduce pain-related emotional distress, stop their pharmacological preemptive treatment of anticipated headache, and reduce debilitating aspects of the headache experience. If the nonpharmacologic approaches are reinforced and maintained over time, the learned behaviors help reduce the likelihood of overusing pain medication and MOH relapse in the future. The authors note that, in their own clinical experience, migraineurs receiving both behavioral and appropriate medication therapies had long-term (3-year) success rates in headache control without relapse to MOH.

Clinical Comment: Patients with frequent headaches frequently progress to overuse of their medications. The diagnosis of chronic migraine with MOH is clinically important because patients rarely respond to preventive medications while overusing acute medications. Treatment of MOH can be difficult because there is no clear consensus about the best strategies, so further research is needed to confirm the most effective approaches. The application of behavioral modification therapies in conjunction with the judicious reintroduction of antimigraine medications makes sense; however, the entire process would require much time and effort by both practitioners and patients. This may be the purview of headache specialists and their clinics; whether it also can be addressed adequately in other clinical settings is of some concern since there are many locales where headache specialists are few and far between.

Reference: Andrasik F, Grazzi L, Usai S, Buse DC, Bussone G. Non-pharmacological approaches to treating chronic migraine with medication overuse. Neurol Sci (2009) 30 (Suppl 1):S89–S93 [abstract here].
Also see:
> Weeks RE. Practical strategies for treating chronic migraine with medication overuse: case examples and role play demonstrations. Neurol Sci. 2009;30(Suppl 1):S95–S99 [abstract here].
> Grazzi L, Andrasik F, Usai S, Bussone G. Treatment of chronic migraine with medication overuse: is drug withdrawal crucial? Neurol Sci. 2009;30(Suppl 1):S85–S88 [abstract here].

Addendum: The journal publisher, Springer, originally made these important articles available in full at no charge; then, changed their mind. While we strongly support an open access policy, others believe differently. —SBL

Aches, Pains in Elderly Increase Hazardous Falls

Chronic pain to some extent is experienced by as many as 2 of every 3 older adults. Now, a new study reports that such pain may be more hazardous than previously thought, contributing to an increased risk of falls in persons 70 years of age and older.

Writing in the Journal of the American Medical Association (JAMA), Suzanne G. Leveille and coauthors write, “Falls rank among the 10 leading causes of death in older adults in the United States, resulting in more than $19 billion in health care costs annually. Despite a growing body of scientific evidence supporting associations between a number of risk factors and falls, efforts to translate these findings into effective fall prevention strategies have been limited. …. Pain contributes to functional decline and muscle weakness and is associated with mobility limitations that could predispose to falls.”

The researchers — at Beth Israel Deaconess Medical Center and the University of Massachusetts-Boston — prospectively studied 749 adults, age 70 and older from September 2005 through January 2008. Pain was assessed via questionnaires, and participants recorded falls on monthly basis during an 18-month period. At the beginning of the study, 40% of participants reported chronic pain in more than one joint area and 24% reported chronic pain in only one joint area. A total of 1,029 falls were reported by participants during the study. Compared with participants who reported no pain or those in the lowest groups of pain scores, significantly increased rates of falls were found in participants with 2 or more sites of pain, in those reporting the highest levels of pain severity, and in subjects whose pain interfered with daily activities. Persons reporting even very mild pain also had a somewhat elevated odds of falling in any given month.

The authors suggest there may be several possible mechanisms for the relationship between pain and falls, including neuromuscular effects of pain leading to leg muscle weakness or slowed responses to an impending fall. “Another factor may be gait alterations or adaptations to chronic pain that lead to instability and subsequent balance impairments. Chronic pain may serve as a distractor or, in some way, interfere with cognitive activity needed to prevent a fall,” they write.

Practice Pointers: This study provides evidence suggesting that the common aches and pains of old age can be a greater hazard than previously thought. “Daily discomfort may accompany not only difficulties in performing daily activities but equally as important may be a risk for falls and possibly fall-related injuries in the older population,” the authors note. Sedating effects of analgesics, particularly opioids, might be thought of as contributing to falls, but this was not found in this study. In fact, the authors note that underuse of analgesics could contribute to falls due to unrelieved pain effects. A randomized controlled trial would help assess the extent to which improved pain control might reduce falls in this population; meanwhile, this study implies that, beyond compassionate reasons for relieving pain in older patients, there could be serious consequences of falls associated with ignoring or inadequately treating common pain complaints.

Reference: Leveille SG, Jones RN, Kiely DK, et al. Chronic Musculoskeletal Pain and the Occurrence of Falls in an Older Population. JAMA. 2009(Nov);302(20):2214-2221 [see abstract].

Dec2009 – Pain Product Announcements & Warnings

Featured Items: generic fentanyl citrate approval, capsaicin skin patch (Qutenza) approval, diclofenac sodium topical (Pennsaid) approved for knee OA, generic tramadol hydrochloride approval.
— All brand names are trademarks of their respective manufacturers. Compiled by Winnie Dawson, MA, RN, BSN.

Generic Oral Transmucosal Fentanyl Citrate (OTFC) — Receives FDA Approval
Mallinckrodt (subsidiary of Covidien) and Barr Laboratories each reported a November 2009 approval of fentanyl citrate, a generic version of Actiq, the pain-relieving lollipop made by Cephalon. This oral transmucosal fentanyl formulation — indicated for the management of breakthrough cancer pain in opioid-tolerant patients 16 years of age and older — is an opioid analgesic Class II controlled substance. The product will be produced by both companies in 6 dosing strengths and is expected to be launched in early 2010. Since oral transmucosal fentanyl citrate can be abused in a manner similar to other opioid agonists, it is important to read the Risk Minimization Plan and the patient Medication Guide for complete safety information.

Capsaicin Skin Patch (Qutenza™ 8%) — Receives FDA Approval for Postherpetic Neuralgia Pain
In November 2009, the FDA approved Qutenza — a novel medicated skin patch that delivers a synthetic form of capsaicin, a compound found in chili peppers that provides heat sensation — to treat pain due to postherpetic neuralgia (PHN). Unlike systemic analgesics, Qutenza targets the regional nerve pain of PHN (a condition that sometimes occurs following shingles) which can be excruciating and affect quality of life. Clinical trials reported up to 12 weeks of pain reduction following a single one-hour dermal application. Patches are applied by a healthcare professional and can be cut or combined (up to 4 patches) to cover any pain-affected skin area. The most common adverse effects were transient and included application site redness, itching, skin pain, and a moderate increase in blood pressure. Episodes of drowsiness or drug-drug interaction are reported to be unlikely. To learn more, see the full prescribing information.

Diclofenac Sodium Topical Solution (Pennsaid®) — FDA-Approved to Treat Symptoms of OA
Covidien and Nuvo Research announced the November 2009 FDA approval of Pennsaid — a topical, transdermal non-steroidal anti-inflammatory drug (NSAID) — developed to treat the symptoms of knee osteoarthritis (OA). The product was developed using innovative, combination drug-delivery technology to provide site-specific analgesia via the skin, thereby limiting potential systemic complications. Clinical trials enrolling more than 2,500 patients showed results comparable to oral diclofenac for effective symptom-relief of pain and stiffness. For more information on administration and safety, see the Pennsaid prescribing information and the medication guide for NSAIDs.

Generic Tramadol Hydrochloride — FDA Approved
In November 2009, the FDA approved Par Pharmaceutical Industries’ application for a generic version of Johnson & Johnson’s chronic pain drug, Ultram® ER. The extended-release pain reliever is approved to manage moderate to moderately severe chronic pain in adults who require continuous treatment for an extended period of time. Par plans to begin shipping the product immediately and will offer 100 mg and 200 mg strengths.