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Numerous guidelines targeting safe use of opioids for chronic pain have been published but substantial challenges persist in clinical application of best practice recommendations. This article describes a pragmatic approach to clinical care of adults with chronic pain receiving long-term opioid therapy. Three components of care are emphasized: (1) medical and mental health assessment before initiating opioid therapy, (2) clinical surveillance during the course of long-term opioid therapy, and (3) clinical considerations and strategies governing opioid tapering. A pressing need exists for ongoing research to further clarify the optimal role that long-term opioid therapy has in treatment of chronic pain.
Learn More >retrospective population-based cohort analysis.
Learn More >Ubrogepant is a novel, oral calcitonin gene-related peptide (CGRP) receptor antagonist intended for the acute treatment of migraine attacks. Ubrogepant has a chemical structure distinct from previous small-molecule CGRP receptor antagonists that were associated with elevated serum alanine aminotransferase (ALT) in clinical trials. Here, we report overall and hepatic safety data from two placebo-controlled phase I trials of ubrogepant, spray-dried oral compressed tablet (SD-OCT) in healthy male volunteers. Trial A was a pharmacokinetic (PK) trial of single (100-400 mg) and multiple (40-400 mg) ascending doses. Trial B was a dedicated hepatic safety trial assessing daily use of ubrogepant 150 mg for 28 days. Serum ALT (as hepatotoxicity biomarker) and PK data are reported. Ubrogepant was well-tolerated in both trials, with a low incidence of adverse events that did not differ greatly from placebo. Changes in mean ALT levels were minimal and similar to placebo. Over 28 days of treatment, the mean percentage change in ALT from baseline was < 5% at all time points. No participant in either trial demonstrated ALT ≥ 3× upper limit of normal at any time. Ubrogepant SD-OCT demonstrated linear PK appropriate for acute treatment of migraine, with rapid uptake (time of maximum plasma concentration (t ): 2-3 hours) and no accumulation with daily use. Overall, there was no evidence of ubrogepant-associated hepatotoxicity with daily doses up to 400 mg for 10 days or with daily ubrogepant 150 mg for 28 days. Supratherapeutic dosing is a useful strategy for characterizing hepatic safety in early drug development.
Learn More >The gabapentinoids are often recommended as first-line treatments for the management of neuropathic pain. The differing pharmacodynamic and pharmacokinetic profiles can have implications for clinical practice. This article has summarised these key differences. In addition to their use in managing neuropathic pain, gabapentinoids are increasingly being used for off-label conditions despite the lack of evidence. Prescription rates for off-label conditions have overtaken that for on-label use. Similarly, the use of gabapentinoids in the perioperative period is now embedded in clinical practice despite conflicting evidence. This article summarises the risks associated with this increasing use. There is increasing evidence of the potential to cause harm in vulnerable populations such as the elderly and increasing prevalence of abuse. The risk of respiratory depression in combination with opioids is of particular concern in the context of the current opioid crisis. This article describes the practical considerations involved that might help guide appropriate prescribing practices.
Learn More >Understanding nonsteroidal antiinflammatory drug (NSAID) use and impact on common rheumatic and arthritic conditions is critical to reconciling their appropriate use with their potentially serious adverse effects. NSAIDs have a profound impact on the treatment of connective tissue disorders because of their ability to address the underlying cause with specific benefits of decreasing stiffness and inflammation, and improving mobility. NSAID use is twice as common as opioid use, and inappropriate use of NSAIDs is widespread. NSAID use should be monitored and the impact understood to mitigate the risks. NSAID discontinuation should be evidence based and individualized to specific requirements.
Learn More >Ubrogepant (MK-1602) is a novel, oral, calcitonin gene-related peptide receptor antagonist in clinical development with positive Phase III outcomes for acute treatment of migraine. This paper describes the population exposure-response (E-R) modeling and simulations which were used to inform the Phase III dose-selection rationale, based on approximately 800 participants pooled across two Phase IIb randomized dose-finding clinical trials. The E-R model describes the placebo and ubrogepant treatment effects based on migraine pain endpoints (2-hour pain relief and 2-hour pain freedom) at various dose levels. Sensitivity analyses were conducted to evaluate various assumptions of placebo response in light of the high placebo response observed in one Phase II trial. A population PK model describing the effect of formulations was included in the E-R simulation framework to assess potential dose implications of a formulation switch from Phase II to Phase III. Model-based simulations predict that a dose of 25 mg or higher is likely to achieve significantly better efficacy than placebo with desirable efficacy levels. The understanding of E-R helped support the dose selection for the Phase III clinical trials.
Learn More >Pediatric chronic pain evaluation includes self-reports and/or caregiver proxy-reports across biopsychosocial domains. Limited data exist on the effects of caregiver-child discrepancies in pediatric pain assessment. In children with chronic pain, we examined associations among discrepancies in caregiver-child reports of child anxiety and depressive symptoms and child functional impairment.
Learn More >Chronic axial spinal pain is one of the major causes of significant disability and health care costs, with facet joints as one of the proven causes of pain.
Learn More >The Chronic pain epidemic is a pressing public health crises facing the United States. Currently, more than 100 million Americans suffer from chronic pain, with chronic pain being among the most prevalent conditions and the leading cause of disability. Chronic pain disproportionately affects certain populations including women, low-income individuals, and older adults. This article focuses primarily on new molecular entities in development targeting various chronic pain receptors and new delivery technologies.
Learn More >Many medically-refractory trigeminal neuralgia patients are non-responders to surgical treatment. Few studies have explored how trigeminal nerve characteristics relate to surgical outcome, and none have investigated the relationship between subcortical brain structure and treatment outcomes.
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