An analysis of the root causes for opioid-related overdose deaths in the United States.

OBJECTIVE: A panel of experts in pain medicine and public policy convened to examine root causes and risk factors for opioid-related poisoning deaths and to propose recommendations to reduce death rates. METHODS: Panelists reviewed results from a search of PubMed and state and federal government sources to assess frequency, demographics, and risk factors for opioid-related overdose deaths over the past decade. They also reviewed results from a Utah Department of Health study and a summary of malpractice lawsuits involving opioid-related deaths. RESULTS: National data demonstrate a pattern of increasing opioid-related overdose deaths beginning in the early 2000s. A high proportion of methadone-related deaths was noted. Although methadone represented less than 5% of opioid prescriptions dispensed, one third of opioid-related deaths nationwide implicated methadone. Root causes identified by the panel were physician error due to knowledge deficits, patient non-adherence to the prescribed medication regimen, unanticipated medical and mental health comorbidities, including substance use disorders, and payer policies that mandate methadone as first-line therapy. Other likely contributors to all opioid-related deaths were the presence of additional central nervous system-depressant drugs (e.g., alcohol, benzodiazepines, and antidepressants) and sleep-disordered breathing. CONCLUSIONS: Causes of opioid-related deaths are multifactorial, so solutions must address prescriber behaviors, patient contributory factors, nonmedical use patterns, and systemic failures. Clinical strategies to reduce opioid-related mortality should be empirically tested, should not reduce access to needed therapies, should address risk from methadone as well as other opioids, and should be incorporated into any risk evaluation and mitigation strategies enacted by regulators.

Open-label, multicenter study of combined intrathecal morphine and ziconotide: addition of morphine in patients receiving ziconotide for severe chronic pain.

OBJECTIVE: To assess the safety and efficacy of adding intrathecal morphine to intrathecal ziconotide in patients treated with stable ziconotide doses. DESIGN: Multicenter, open-label study with a 4-week morphine titration phase during which ziconotide was held constant and an extension phase during which dosing of either drug could vary. SETTING: Outpatient clinics. PATIENTS: Patients with suboptimal pain relief receiving stable ziconotide doses (> or = 4.8 microg/day) in one of two ongoing ziconotide trials. INTERVENTIONS: Ziconotide dosing remained constant during the titration phase; intrathecal morphine titration was based on each patient's daily systemic opioid dose at the study's start. During the extension phase, intrathecal ziconotide and morphine dosing were adjusted per investigator discretion. OUTCOME MEASURES: Safety was assessed primarily via adverse events. Efficacy was analyzed via percentage change on the visual analog scale of pain intensity and in weekly systemic opioid consumption. RESULTS: Twenty-five patients enrolled. The most common (> or = 10% of patients in either study phase) study drug-related (i.e., ziconotide/morphine combination [or ziconotide monotherapy in the extension phase only]) treatment-emergent adverse events included dizziness, peripheral edema, pruritus, and nausea. From the initial visit to week 4, visual analog scale of pain intensity scores improved by a mean of 26.3% (95% confidence interval: 15.6%-37.1%) but varied during the extension phase (mean percentage change from the initial visit ranged from -0.4% at week 16 to -35.0% at week 72). Mean percentage decrease in systemic opioid consumption from the initial visit was 49.1% at week 4 and 51.2% at week 56 of the extension phase. CONCLUSIONS: Intrathecal morphine, combined with stable intrathecal ziconotide doses, reduced pain in patients with previously suboptimal pain relief on ziconotide monotherapy.

Anti-inflammatory agents for the treatment of musculoskeletal pain and arthritis.

Pain produced by musculoskeletal disorders commonly misconceived as having mechanical etiology often is caused by inflammatory mechanisms. Simple analgesics (ie, those that lack anti-inflammatory action) often are used to treat musculoskeletal pain when an anti-inflammatory analgesic may be more effective for the painful condition. This review addresses the anti-inflammatory agents available for the symptomatic management of common inflammatory musculoskeletal conditions including osteoarthritis, rheumatoid arthritis, and low back pain.

Pharmacotherapy for pain in rheumatologic conditions: the neuropathic component.

Nociceptive and neuropathic types of pain occur in rheumatologic conditions. Most clinicians are familiar with the former, but many are not aware of the prevalence of the latter. The literature reports numerous examples of the occurrence of rheumatologic neuropathic pain, but little has been published on its management. In this article, neuropathic and nociceptive pain in rheumatologic conditions are differentiated and treatment recommendations are discussed. Common rheumatologic conditions and their pathophysiology in relation to pain mechanisms also are described. Pharmacotherapeutic recommendations for the treatment of both types of pain in the common rheumatologic conditions are presented.