Perspectives on the opioid crisis from pain medicine clinicians.

Patients experiencing a terminal drug related event reflect a sentinel event. If this pharmacotherapy is a widely used agent, it may be viewed as a catastrophic problem. If patients are dying from illegal drug use when the medical establishment fails them by withdrawing or minimizing their medically prescribed medication, then the burden rests with their health care providers, legislation, and insurance carriers to actively participate in a collegial fashion to achieve parity. Causing a decay in functionality in previously functional patients, may occur with appropriately prescribed opioid medications addressing non-cancer pain when withdrawing or diminishing either with or without patient consent. The members of the medical profession have diminished their prescribing of opioids for their patients out of apparent fear of reprisal, state or federal government sanctions, and other concerned groups. Diminishing former dosages or deleting the opioid medication, preferably in concert with the patient, often results in inequitable patient care. Enforcing sanctioned decreases or ceasing to prescribe from their former required/established opioid medications precipitate patient discord. In absence of opioid misuse, abuse, diversion or addiction based upon medical "guidelines" and with a poor foundation of Evidence Based Medicine the CDC guidelines, it may be masked as a true guideline reflecting a decrement of clinical judgment, wisdom, and compassion. This article also discusses the role of pharmacy chains, insurance carriers, and their pharmacy benefit managers (PBMs) contribution to this multidimensional problem. There may be a potential solution, identified in this paper, if all the associated political, medical and insurance groups work cohesively to improve patient care. This article and the CDC guidelines are not focused at hospice, palliative, end of life care pain management.

Responsible, Safe, and Effective Prescription of Opioids for Chronic Non-Cancer Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines.

BACKGROUND: Opioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl. Contrary to scientific evidence of efficacy and negative recommendations, a significant proportion of physicians and patients (92%) believe that opioids reduce pain and a smaller proportion (57%) report better quality of life. In preparation of the current guidelines, we have focused on the means to reduce the abuse and diversion of opioids without jeopardizing access for those patients suffering from non-cancer pain who have an appropriate medical indication for opioid use. OBJECTIVES: To provide guidance for the prescription of opioids for the management of chronic non-cancer pain, to develop a consistent philosophy among the many diverse groups with an interest in opioid use as to how appropriately prescribe opioids, to improve the treatment of chronic non-cancer pain and to reduce the likelihood of drug abuse and diversion. These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique. METHODS: The methodology utilized included the development of objectives and key questions. The methodology also utilized trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various specialties and groups. The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed, with a best evidence synthesis of the available literature, and utilized grading for recommendation as described by the Agency for Healthcare Research and Quality (AHRQ).Summary of Recommendations:i. Initial Steps of Opioid Therapy 1. Comprehensive assessment and documentation. (Evidence: Level I; Strength of Recommendation: Strong) 2. Screening for opioid abuse to identify opioid abusers. (Evidence: Level II-III; Strength of Recommendation: Moderate) 3. Utilization of prescription drug monitoring programs (PDMPs). (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 4. Utilization of urine drug testing (UDT). (Evidence: Level II; Strength of Recommendation: Moderate) 5. Establish appropriate physical diagnosis and psychological diagnosis if available. (Evidence: Level I; Strength of Recommendation: Strong) 6. Consider appropriate imaging, physical diagnosis, and psychological status to collaborate with subjective complaints. (Evidence: Level III; Strength of Recommendation: Moderate) 7. Establish medical necessity based on average moderate to severe (≥ 4 on a scale of 0 - 10) pain and/or disability. (Evidence: Level II; Strength of Recommendation: Moderate) 8. Stratify patients based on risk. (Evidence: Level I-II; Strength of Recommendation: Moderate) 9. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (Evidence: Level I-II; Strength of Recommendation: Moderate) 10. Obtain a robust opioid agreement, which is followed by all parties. (Evidence: Level III; Strength of Recommendation: Moderate)ii. Assessment of Effectiveness of Long-Term Opioid Therapy 11. Initiate opioid therapy with low dose, short-acting drugs, with appropriate monitoring. (Evidence: Level II; Strength of Recommendation: Moderate) 12. Consider up to 40 morphine milligram equivalent (MME) as low dose, 41 to 90 MME as a moderate dose, and greater than 91 MME as high dose. (Evidence: Level II; Strength of Recommendation: Moderate) 13. Avoid long-acting opioids for the initiation of opioid therapy. (Evidence: Level I; Strength of Recommendation: Strong) 14. Recommend methadone only for use after failure of other opioid therapy and only by clinicians with specific training in its risks and uses, within FDA recommended doses. (Evidence: Level I; Strength of Recommendation: Strong) 15. Understand and educate the patients of the effectiveness and adverse consequences. (Evidence: Level I; Strength of Recommendation: Strong) 16. Similar effectiveness for long-acting and short-acting opioids with increased adverse consequences of long-acting opioids. (Evidence: Level I-II; Strength of recommendation: Moderate to strong) 17. Periodically assess pain relief and/or functional status improvement of ≥ 30% without adverse consequences. (Evidence: Level II; Strength of recommendation: Moderate) 18. Recommend long-acting or high dose opioids only in specific circumstances with severe intractable pain. (Evidence: Level I; Strength of Recommendation: Strong)iii. Monitoring for Adherence and Side Effects 19. Monitor for adherence, abuse, and noncompliance by UDT and PDMPs. (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 20. Monitor patients on methadone with an electrocardiogram periodically. (Evidence: Level I; Strength of Recommendation: Strong). 21. Monitor for side effects including constipation and manage them appropriately, including discontinuation of opioids when indicated. (Evidence: Level I; Strength of Recommendation: Strong)iv. Final Phase 22. May continue with monitoring with continued medical necessity, with appropriate outcomes. (Evidence: Level I-II; Strength of Recommendation: Moderate) 23. Discontinue opioid therapy for lack of response, adverse consequences, and abuse with rehabilitation. (Evidence: Level III; Strength of Recommendation: Moderate) CONCLUSIONS: These guidelines were developed based on comprehensive review of the literature, consensus among the panelists, in consonance with patient preferences, shared decision-making, and practice patterns with limited evidence, based on randomized controlled trials (RCTs) to improve pain and function in chronic non-cancer pain on a long-term basis. Consequently, chronic opioid therapy should be provided only to patients with proven medical necessity and stability with improvement in pain and function, independently or in conjunction with other modalities of treatments in low doses with appropriate adherence monitoring and understanding of adverse events.Key words: Chronic pain, persistent pain, non-cancer pain, controlled substances, substance abuse, prescription drug abuse, dependency, opioids, prescription monitoring, drug testing, adherence monitoring, diversionDisclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

Painful boney metastases.

Up to 90% of patients with metastatic or advanced stage cancer will experience significant cancer-related pain. Approximately half or more of patients diagnosed with cancer may experience bone pain. It has been estimated that tumor metastases to the skeleton affects roughly 400,000 US citizens annually. Carcinoma from breast, lung, and prostate cancers account for approximately 80% of secondary metastatic bone disease. Bone metastases may cause devastating clinical complications associated with dramatic reductions in quality of life, mobility, and independence, as well as excruciating refractory pain. Associated complications from osseous metastases also present a substantial economic burden. Currently, there are still a significantly high number of patients suffering with unrelieved pain from osseous metastases. Treatments for painful osseous metastases may not only diminish pain but also may improve quality of life and independence/mobility, and reduce skeletal morbidity, potential pathologic fractures, spinal cord compression, and other "skeletal-related events." Treatment strategies for painful osseous metastases include the following: systemic analgesics, intrathecal analgesics, glucocorticoids, radiation (external beam radiation, radiopharmaceuticals), ablative techniques (radiofrequency ablation and cryoablation), bisphosphonates, chemotherapeutic agents, inhibitors of RANKL-RANK interaction (eg, denosumab), hormonal therapies, interventional techniques (eg, kyphoplasty), and surgical approaches. Although the mechanisms underlying the development of bone metastases remain incompletely understood, there appears to be important bi-directional interactions between the tumor and the bone microenvironment. A greater understanding of the pathophysiology of painful osseous metastases may lead to better and more selective targeted analgesic therapy. Additionally, potential future therapeutic approaches to painful osseous metastases may revolutionize approaches to analgesia for this condition, leading to optimal outcomes with maximal pain relief and minimal adverse effects.

Options for treating postherpetic neuralgia in the medically complicated patient.

Patients with postherpetic neuralgia (PHN) are often of advanced age or immunocompromised and likely to have ≥1 comorbid medical condition for which they receive ≥1 medication (polypharmacy). Comorbidities affecting renal or hepatic function can alter pharmacokinetics, thereby impacting the efficacy or tolerability of PHN analgesic therapies. Cardiovascular, cerebrovascular, or psychiatric comorbidities may increase patient vulnerability to potential adverse events associated with some PHN analgesic therapies. Because PHN is a localized condition, localized therapy with a topical analgesic (lidocaine patch 5% and capsaicin 8% patch or cream) may provide adequate efficacy while mitigating the risk of systemic adverse events compared with oral analgesics (eg, tricyclic antidepressants, anticonvulsants, opioids). However, combined therapy with a topical and an oral analgesic or with >1 oral analgesic may be needed for optimal pain management in some patients. This review summarizes how comorbidities and concomitant medications should be taken into account when selecting among available pharmacotherapies for PHN and provides recommendations for the selection of therapies that will provide analgesia while minimizing the risk of adverse events.

Interview: The need to tailor pain management approaches to individual requirements.

Robert L Barkin talks to Roshaine Gunawardana, Commissioning Editor: Dr Barkin has authored over 150 publications including journals, book chapters and CD-Roms. He is a reviewer for over 30 journals, on the editorial board of nine journals and is an Associate Editor of the American Journal of Therapeutics. He received his BSc. Pharmacy degree from St Louis College of Pharmacy and Allied Science St Louis, MO, USA in 1963, an MBA in Healthcare Administration at DePaul University Chicago, IL, USA in 1976 and a doctorate in Clinical Pharmacy at Purdue University, IN, USA in 1985. Dr Barkin is engaged in a very active in-patient and out-patient practice with a collaborative arrangement with five anesthesiologist and consults with physical medicine and rehabilitation, rheumatology, oncology, neurology, neurosurgery, obstetrics and gynecology, psychiatry and chemical dependency/addiction specialists. He has presented over 500 formal lectures in the USA, Poland, India, China, Taiwan, Philippines, Puerto Rico, Australia and Canada. Dr Barkin's interest lies in pain, psychiatry, geriatrics, clinical pharmacology, clinical testing for medication and pain pharmacology. He has been the first to be granted scientific status with the American Academy of Pain Medicine.

Pharmacology of opioids in the treatment of chronic pain syndromes.

The perpetual pursuit of pain elimination has been constant throughout human history and pervades human cultures. In some ways it is as old as medicine itself. Cultures throughout history have practiced the art of pain management through remedies such as oral ingestion of herbs or techniques believed to have special properties. In fact, even Hippocrates wrote about the practice of trepanation, the cutting of holes in the body to release pain. Current therapies for management of pain include the pervasive utilization of opioids, which have an extensive history, spanning centuries. There is general agreement about the appropriateness of opioids for the treatment of acute and cancer pain, but the long-term use of these drugs for treatment of chronic non-malignant pain remains controversial. The pros and cons regarding these issues are beyond the scope of this review. Instead, the purpose of this review will be directed towards the pharmacology of commonly prescribed opioids in the treatment of various chronic pain syndromes. Opium, derived from the Greek word for "juice," is extracted from the latex sap of the opium poppy (Papaverum somniferum). The juice of the poppy is the source of some 20 different alkaloids of opium. These alkaloids of opioids can be divided into 2 chemical classes: phenanthrenes (morphine, codeine, and thebaine) and benzylisoquinolines (agents that do not interact with opioid receptors).

Fibromyalgia syndrome: a discussion of the syndrome and pharmacotherapy.

Fibromyalgia is a complex condition that is characterized by chronic widespread pain and multiple other symptoms, including fatigue, sleep disturbances, cognitive dysfunction, stiffness, and depressive episodes. Fibromyalgia may coexist and/or overlap with other conditions that may involve central sensitivity, including chronic fatigue syndrome, irritable bowel syndrome, irritable bladder syndrome or interstitial cystitis, and temporomandibular disorder. The pathophysiology of fibromyalgia remains uncertain but is believed to be partly the result of central systems affecting afferent processing as well as impaired endogenous pain-inhibitory systems. Abnormal central nociceptive processing may contribute to fibromyalgia, producing heightened responses to various noxious stimuli with resulting mechanical hyperalgesia. Fibromyalgia remains a clinical diagnosis. There has been a recent paradigm shift away from requiring 11 or more out of 18 tender points and instead focusing on the presence of chronic widespread pain as well as symptoms of fatigue, unrefreshed sleep, and other somatic complaints. Although there is no known cure for fibromyalgia, multidisciplinary team efforts using combined treatment approaches, including patient education, aerobic exercise, cognitive behavioral therapy, and pharmacologic therapies (serotonin norepinephrine reuptake inhibitors [eg, duloxetine, milnacipran] and alpha 2-delta receptor ligands [eg, pregabalin]) may improve symptoms as well as function of patients with fibromyalgia.

Oxymorphone and oxymorphone extended release: a pharmacotherapeutic review.

The treatment of chronic pain remains an enormous challenge in the United States. Opioid analgesics are an important component of pharmacotherapy for chronic pain and have proven efficacy in the management of cancer and noncancer chronic pain. The newest addition to oral opioid pharmacotherapy is oral oxymorphone, a semisynthetic opioid agonist that is now available in oral immediate-release (IR) and extended-release (ER) formulations. This review discusses the pharmacology, pharmacokinetics, pharmacodynamics, pharmacotherapeutics, and clinical use of oral oxymorphone IR and ER formulations for the management of moderate to severe pain for different types of patients in a variety of settings. Two published studies evaluated the efficacy and safety of oxymorphone IR in patients with moderate to severe postoperative pain and demonstrated that it provides rapid and effective analgesia and is generally well tolerated. Six published randomized controlled trials and three published open-label studies evaluated the efficacy and safety of oxymorphone ER for chronic cancer or noncancer pain. These trials found analgesic efficacy and tolerability comparable to that provided by morphine controlled release (CR) or oxycodone CR; treatment effects with oxymorphone ER were durable for treatment periods of 12 weeks at the same dose or up to 1 year with little dose escalation. Titrated doses of oxymorphone ER were effective and generally well tolerated in both opioid-experienced and opioid-naïve patients. Aspects of oxymorphone metabolism and limited protein binding may simplify treatment in certain populations.

Proposal for a medical master class system of medical education for common complex medical entities.

It is imperative that the management of complex outpatient medical problems be taught using an apprentice system of education. The implementation of highly experienced and outcome successful "master physicians" to train outpatient practicing clinicians will provide a powerful frame of reference and a highly imitatable model on which clinicians can base their presentations of information and medications to patients with complex medical problems such as type 2 diabetes, cardiovascular disease, chronic pain, obesity, or tobacco addiction. Because doctors have always learned by observation, we must ensure that those who they observe will be "worth watching" and that those watched can provide skills of patient management currently not taught in the Flexnor-styled medical educational system, which effectively ended the apprentice system of training. The reintroduction of a carefully crafted apprentice system will foreseeably improve patient care and reduce morbidity, mortality, medical errors, and medical expenses.

The pharmacist's role in the nonsteroidal anti-inflammatory drug selection process.

The pharmacist provides an integral role in pain management and treatment by focusing on the selection and evaluation of analgesic agents in a process that is patient specific and patient centered. Counseling patients (and the families of patients) who are using nonsteroidal anti-inflammatory drugs (NSAIDs) for acute musculoskeletal pain and inflammation regarding the appropriate use of these agents is a key component of the pharmacist's overall pharmacotherapeutic role. This article reviews the importance of explaining the therapeutic and nontherapeutic effects of NSAIDs and cautions, contraindications, dosing parameters, and the avoidance of multiple NSAID use to patients and prescribers. The article also discusses the need to evaluate the cytochrome P450 system and the patient's pharmacotherapy and comorbid disease history to identify potential drug interactions. Evaluation of patients for comorbidities, allergies, and gastrointestinal, renal, hepatic, hematologic, and cardiovascular risks is also addressed, as are essential laboratory tests and the special needs of elderly patients.

Urine drug test interpretation: what do physicians know?

OBJECTIVE: To determine the level of urine drug test (UDT) interpretive knowledge of physicians who use these instruments to monitor adherence in their patients on chronic opioid therapy. METHODS: A seven-question instrument consisting of six five-option, single-best-answer multiple choice questions and one yes/no question was completed by 114 physicians (77 who employ UDT and 37 who do not) attending one of three regional opioid education conferences. We calculated frequencies and performed chi2 analyses to examine bivariate associations between UDT utilization and interpretive knowledge. RESULTS: The instrument was completed by 80 percent of eligible respondents. None of the physicians who employ UDT answered all seven questions correctly, and only 30 percent answered more than half correctly. Physicians who employ UDT performed no better on any of the questions than physicians who do not employ UDT. CONCLUSIONS: Physicians who employ UDT to monitor patients receiving chronic opioid therapy are not proficient in test interpretation. This study highlights the need for improved physician education; it is imperative for physicians to work closely with certified laboratory professionals when ordering and interpreting these tests.

Perception, assessment, treatment, and management of pain in the elderly.

Twenty to 50% of community elderly suffer from pain. Up to 80% of the institutionalized elderly report at least one pain problem. Multiple pain etiologies that occur in elderly patients may be the occurrence of multiple chronic diseases: osteoarthritis, RA, cancer, DJD, bone/joint disorders, osteoporosis, surgical pain, trauma, neuropathic pain, and nociceptive pain. The incidence of unrelieved pain inhibits respiration, decreases mobility, and decreases their functional status, which may lead to iatrogenic events, which include pneumonia, constipation and deep vein thrombosis. Prolonged inpatient stays and extended care facilities or nursing homes may decrease the elderly patient's expectations of quality of life and initiate social isolation. There exists some roadblocks or barriers to the detection of pain in the elderly client. These include social, emotional, cognitive, and subjective issues with the patient.

Tender points as predictors of distress and the pharmacologic management of fibromyalgia syndrome.

The object of this study was to determine the association between tender point pain ratings, tender point counts and distress in people with fibromyalgia and to review the pharmacotherapy of fibromyalgia. Demographic, psychosocial, and health status information was collected from 316 health maintenance organization members with fibromyalgia. A manual tender point exam was conducted. Tender point counts predicted 3.0%, and tender point severity ratings predicted 8.3%, of the variance in distress. Little difference was found between the variance predicted for physical versus psychologic distress. A principal components analysis of all measures produced four distinct factors: global-physical functioning, tender points, psychologic, and physical. Tender point pain ratings and counts predicted a small but significant amount of variance in distress. In addition, FMS involves at least four rather distinct factors, one of which is related to tender points. Pharmacotherapeutic management is provided on a patient-specific basis including pharmacokinetics, pharmacodynamic, pathophysiologic, and psychosocial needs designed and modulated for each individual patient.

A Trilogy Case Review Highlighting the Clinical and Pharmacologic Applications of Mirtazapine in Reducing Polypharmacy for Anxiety, Agitation, Insomnia, Depression, and Sexual Dysfunction.

BACKGROUND: Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), is characterized by a unique receptor-specific pharmacologic profile and tolerable side-effect profile in comparison to other antidepressants. It has been reported to have a low incidence of agitation, anxiety, and insomnia, which may be due to blockade of 5-HT(2) and 5-HT(3) receptors. This unique multireceptor-mediated clinical pharmacologic profile may reduce the need for polypharmacy in selected patients. CASE REPORTS: Three cases are presented. In case 1, mirtazapine was able to rapidly treat anxiety and agitation in a 90-year-old woman. This was confirmed with 3 consecutive challenges with mirtazapine. In case 2, both a mood disorder and insomnia were successfully treated with rapid resolution in a patient by using mirtazapine. In case 3, the patient experienced sexual dysfunction while receiving sertraline and developed insomnia with the addition of bupropion. The addition of mirtazapine and the discontinuation of sertraline and bupropion resolved the sexual dysfunction and insomnia. Polypharmacy interventions were decreased in these patients through receptor-specific events from mirtazapine. CONCLUSION: The new antidepressant mirtazapine appears to be an effective strategy for treating anxiety, agitation, and insomnia and for diminishing SSRI-related sexual dysfunction without compromising the patient's therapeutic response to the medication while decreasing the need for additional pharmacotherapies. More than 70% of patients with major depression will have anxiety symptoms. The 5-HT(2) receptor seems to play a major role in the regulation of anxiety. The anxiolytic properties of mirtazapine may be due to its antagonism of 5-HT(2) receptors and can appear as early as the first week of treatment.