Treatment Efficacy, Clinical Utility, and Cost-Effectiveness of Multidisciplinary Biopsychosocial Rehabilitation Treatments for Persistent Low Back Pain: A Systematic Review

Study Design: Systematic review. Objectives: To review the current literature on the treatment efficacy, clinical utility, and cost-effectiveness of multidisciplinary biopsychosocial rehabilitation (MBR) for patients suffering from persistent (nonspecific) lower back pain (LBP) in relation to pain intensity, disability, health-related quality of life, and work ability/sick leave. Methods: We carried out a systematic search of Web of Science, Cochrane Library, PubMed Central, EMBASE, and PsycINFO for English- and German-language literature published between January 2010 and July 2017. Study selection consisted of exclusion and inclusion phases. After screening for duplication, studies were excluded on the basis of criteria covering study design, number of participants, language of publication, and provision of information about the intervention. All the remaining articles dealing with the efficacy, utility, or cost-effectiveness of intensive (more than 25 hours per week) MBR encompassing at least 3 health domains and cognitive behavioral therapy–based psychological education were included. Results: The search retrieved 1199 publications of which 1116 were duplicates or met the exclusion criteria. Seventy of the remaining 83 articles did not meet the inclusion criteria; thus 13 studies were reviewed. All studies reporting changes in pain intensity or disability over 12 months after MBR reported moderate effect sizes and/or p-values for both outcomes. The effects on health-related quality of life were mixed, but MBR substantially reduced costs. Overall MBR produced an enduring improvement in work ability despite controversy and variable results. Conclusions: MBR is an effective treatment for nonspecific LBP, but there is room for improvement in cost-effectiveness and impact on sick leave, where the evidence was less compelling

A glimmer of hope in American pain medicine?

Michael E Schatman US Pain Foundation, Bellevue, WA, USAOver the past 8 years, I have acquired a degree of notoriety relating to my scathing criticism of the badly broken American pain care system. In the three-part series on the crisis in pain care in the United States that I coauthored with Dr Jim Giordano in 2008,1-3 we performed an ethical analysis of our system, examining the need for a paradigmatic revision if we were to adequately treat a disease as complex as is chronic pain, given the system's economic realities. Due to the insurance and hospital industries' adherence to the "business ethic" of cost-containment and profitability (as opposed to patient well-being), we were witnessing the profound undertreatment of pain in conjunction with a growing reliance upon technophilism, ie, an emphasis on technologically driven pain care sorely lacking a reasonable evidence-basis. Early in the following decade, Dr Alan Lebovits and I guest-edited a special series in Pain Medicine on the unfortunate devolution of the "profession" of pain medicine to the "business" of pain medicine.4&nbsp

The American chronic pain crisis and the media: about time to get it right?

Michael E SchatmanUS Pain Foundation, Bellevue, Washington/Middletown, Connecticut, USAOn November 23, 2015, the venerable Wall Street Journal published an article entitled "New Help for Back Pain".1 In this article, the author wrote of "an innovative approach to help patients cope and heal called functional restoration", suggesting that it helps avoid costly diagnostic tests, surgery and other expensive treatments, and the risks of problems potentially associated with opioid analgesics. While the author’s claims regarding interdisciplinary chronic pain management’s potential benefits are accurate, as is so often the case, the media’s inability to comprehend the "big picture" of the American crisis in pain medicine has resulted in yet another much-read yet highly biased and misinformative article that ultimately serves to exacerbate the difficulties with which our patients, and the system that they attempt to navigate, are faced

The health insurance industry: perpetuating the opioid crisis through policies of cost-containment and profitability

Michael E Schatman1, Lynn R Webster21Foundation for Ethics in Pain Care, Bellevue, WA, USA; 2PRA Health Sciences, Salt Lake City, UT, USA"People don’t trust private health insurance companies for all the right reasons." – Senator Bernie Sanders.Throughout the world, industrialized nations look at the USA and are befuddled by its opioid crisis. Between 1999 and 2011, we witnessed the number of opioid deaths in the USA increase from 4,030 to 16,917,1 with these figures having seemingly stabilized over the past several years.2 Many agree regarding the root causes of the crisis, with an analysis by Webster et al3 identifying health comorbidities (most prominently substance use disorders), payer policies mandating methadone as a first-line treatment option, physician error due to a lack of knowledge, patient nonadherence, unanticipated medical and mental health issues, concomitant utilization of other central nervous system depressants such as benzodiazepines, and sleep-disordered breathing as contributory

Terminology of chronic pain: the need to "level the playing field"

John F Peppin,1 Michael E Schatman2 1Center for Bioethics, Pain Management and Medicine, St Louis, MO, 2US Pain Foundation, Middletown, CT, USAPain medicine as a separate subspecialty is in its infancy, only fairly recently being recognized as such by the American Board of Medical Specialities.1 As it continues to find its way in the ever-changing world of medicine, terminology becomes an important consideration. Terms carry tremendous impact: for example, when a patient is told he or she has “cancer”, the impact emotionally will undoubtedly make further explanation difficult. To patients and their families, the word “cancer” has the effect of being hit with an emotional baseball bat. In the pain world, there was a recent, albeit failed, attempt to change the name of pain specialists to “algiatrists”.2 It was thought this would help define what such specialists did as opposed to other specialties. Accordingly, terminology matters, yet little attention has been paid to the terms we use to categorize and diagnose our patients. “Chronic cancer pain” and “chronic noncancer pain” are replete in the literature; however, the distinction here is actually obscure. A patient with pain from a cancer etiology has no different physiology than a patient with pain of noncancer etiologies

A practical and ethical solution to the opioid scheduling conundrum

Michael E Schatman,1 Beth D Darnall21Foundation for Ethics in Pain Care, Bellevue, WA, USA; 2Stanford University School of Medicine, Division of Pain Medicine, Palo Alto, CA, USAAbuse-deterrent formulations (ADFs) of opioids have been in existence since the 1970s,1 with abuse-deterrent mechanisms including physical barriers (eg, barriers to crushing), chemical additives such as opioid antagonists or irritants, and prodrugs that require conversion of the medication into their active forms in the gastrointestinal tract.2 A recent systematic review and meta-analysis3 found no difference between ADFs and non-ADFs in terms of efficacy or adverse events including nausea, vomiting, dizziness, headache, somnolence, constipation, and pruritus. Notably, the efficacy of ADFs in preventing abuse is not yet established, and therefore the authors could only comment on their "potential … to deter or resist some of the common forms of tampering associated with opioid misuse and abuse". While Turk et al2 have elucidated the complexity of producing high-quality research on the efficacy of ADFs to reduce opioid abuse, recent data are encouraging. For example, since Purdue Pharma’s (Stamford, CT, USA) voluntary reformulation of OxyContin® to an ADF in 2010, abuse of the medication has decreased significantly.4–6 As a specific example, National Poison Data System statistics indicated a 36% reduction in abuse exposure for OxyContin following ADF reformulation. Meanwhile, researchers for Purdue Pharma found an increase in abuse exposure for other single-entity oxycodone products and a 42% increase in abuse exposure for heroin during the same time frame.7 Although OxyContin has been the most investigated abuse deterrent formulation, ADFs of other opioids have demonstrated promise in preliminary investigations.8,

Pain management, prescription opioid mortality, and the CDC: is the devil in the data?

Michael E Schatman,1,2 Stephen J Ziegler31Research and Network Development, Boston Pain Care, Waltham, MA, 2Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, 3Department of Public Policy, Purdue University, Fort Wayne, IN, USATransparency, freedom from bias, and accountability are, in principle, hallmarks of taxpayer-funded institutions. Unfortunately, it seems that at least one institution, the Centers for Disease Control and Prevention (CDC), continues to struggle with all three.What began with a prescribing guideline created in secrecy has now evolved to the use of statistical data and public statements that fail to capture not only the complexity of the problem but also the distinction between licit and illicit opioids and their relationship to the alarming increase in unintentional overdose. This is unfortunately consistent with Mark Twain’s assertion that “There are lies, there are damn lies, and then there are statistics.”

EMA401: an old antagonist of the AT2R for a new indication in neuropathic pain

Jan M Keppel Hesselink,1 Michael E Schatman2 1Institute of Neuropathic Pain, Bosch en Duin, the Netherlands; 2Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA Abstract: EMA401 is an old molecule, synthesized by Parke-Davis in the last century and characterized at that time as an AT2R antagonist. Professor Maree Smith and her group from the University of Queensland (Australia) patented the drug and many related derivatives and other compounds with high affinity for the AT2R for the indication neuropathic pain in 2004, an example of drug repositioning. After some years of university work, the Australian biotech company Spinifex Pharmaceuticals took over further research and development and characterized the S-enantiomer, code name EMA401, and related compounds in a variety of animal models for neuropathic and cancer pain. EMA401 was selected as the lead compound, based on high selectivity for the AT2R and good oral bioavailability (33%). EMA401, however, was only administered once in a chronic neuropathic pain model, and no data have been published in other pain models, or during steady state, although such data were available for the racemate EMA400 and some related compounds (EMA200, EMA400). A pilot phase IIa study demonstrated the efficacy and safety of the drug taken twice daily as two capsules of 50 mg (400 mg/day). In 2015, Novartis took over the clinical development. Two phase IIb studies designed by Spinifex Pharmaceuticals were put on hold, probably because Novartis wanted to improve the clinical design or collect additional preclinical data. Further data are eagerly awaited, especially since EMA401 is first-in-class in neuropathic pain. Keywords: angiotensin II type 2 receptor, antagonist, neuropathic pain, EMA401, novel, development, drug repositioning&nbsp

Rediscovery of old drugs: the forgotten case of dermorphin for postoperative pain and palliation

Jan M Keppel Hesselink,1,2 Michael E Schatman3,4 1Department of Health, University of Witten/Herdecke, Witten, Germany; 2Institute for Neuropathic Pain, Bosch en Duin, the Netherlands; 3Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA; 4Research and Network Development, Boston Pain Care, Waltham, MA, USA Abstract: The repurposing of old drugs for new indications is becoming more accepted as a cost-efficient solution for complicated health problems. However, older drugs are often forgotten when they are not repositioned. This analysis makes a case for re-exploration of dermorphin for intrathecal use in postoperative pain and in a palliative context, with the goal of re-establishing this compound. Dermorphin was isolated from the skin of an Amazonian frog, characterized and identified as a bioactive heptapeptide by Vittorio Erspamer’s research group in the early 1980s. It was traditionally called “Kambo” or “Sapo” by Amazon tribes and was used to improve their physical and psychic skills as hunters. Its structure is rather enigmatic, containing a D-amino acid, and its pharmacological activity in a number of assays was found to be quite impressive and superior to morphine. Moreover, it has been established as more selective and potent with long-lasting analgesia compared to morphine after intracerebroventricular administration in animal models. In 1985, the first clinical trial results of a randomized, placebo-controlled study in postoperative pain were reported, and dermorphin administered via the intrathecal route was again impressively superior over the placebo and the reference compound morphine. This milestone study was apparently minimally read by clinicians, as the study has never been referenced; only 15 pharmacological and review papers after 1985 mentioned the results, with not one being a clinical paper. The interest in dermorphin decreased after 1985, and the compound was never again introduced in the clinical setting. Considering the enormous pressure to find superior acting opioids, this is quite puzzling. We suggest new clinical studies to further evaluate the safety and efficacy of dermorphin, especially administered via the intrathecal route in postoperative pain or for palliative use in terminal patients. Keywords: Kambo, Sapo, peptides, postoperative, analgesia, palliative, pain&nbsp