In a preliminary study, among patients prescribed opioids for chronic pain, the ORT exhibited a high degree of sensitivity and specificity for determining which individuals are at risk for opioid-related, aberrant behaviors. Further studies in a variety of pain and nonpain settings are needed to determine the ORT's universal applicability.

Treatment with naloxegol, as compared with placebo, resulted in a significantly higher rate of treatment response, without reducing opioid-mediated analgesia. (Funded by AstraZeneca; KODIAC-04 and KODIAC-05 ClinicalTrials.gov numbers, NCT01309841 and NCT01323790, respectively.).

Background Opioids are effective for acute and chronic pain conditions, but their use is associated with often difficult-to-manage constipation and other gastrointestinal (GI) effects due to effects on peripheral μ-opioid receptors in the gut. The mechanism of opioid-induced constipation (OIC) differs from that of functional constipation (FC), and OIC may not respond as well to most first-line treatments for FC. The impact of OIC on quality of life (QoL) induces some patients to decrease or stop their opioid therapy to relieve or avoid constipation. Purpose At a roundtable meeting on OIC, a working group developed a consensus definition for OIC diagnosis across disciplines and reviewed current OIC treatments and the potential of treatments in development. By consensus, OIC is defined as follows: ‘A change when initiating opioid therapy from baseline bowel habits that is characterized by any of the following: reduced bowel movement frequency, development or worsening of straining to pass bowel movements, a sense of incomplete rectal evacuation, or harder stool consistency’. The working group noted the prior validation of a patient response outcome and end point for clinical trials and recommended future efforts to create treatment guidelines and QoL measures specific for OIC. Details from the working group’s discussion and consensus recommendations for patient care and research are presented in this article.

Safety and efficacy data from a study of slow intrathecal (IT) ziconotide titration for the management of severe chronic pain are presented. Patients randomized to ziconotide (n = 112) or placebo (n = 108) started IT infusion at 0.1 microg/hour (2.4 microg/day), increasing gradually (0.05-0.1 microg/hour increments) over 3 weeks. The ziconotide mean dose at termination was 0.29 microg/hour (6.96 microg/day). Patients' baseline Visual Analogue Scale of Pain Intensity (VASPI) score was 80.7 (SD 15). Statistical significance was noted for VASPI mean percentage improvement, baseline to Week 3 (ziconotide [14.7%] vs. placebo [7.2%; P = 0.036]) and many of the secondary efficacy outcomes measures. Significant adverse events (AEs) reported in the ziconotide group were dizziness, confusion, ataxia, abnormal gait, and memory impairment. Discontinuation rates for AEs and serious AEs were comparable for both groups. Slow titration of ziconotide, a nonopioid analgesic, to a low maximum dose resulted in significant improvement in pain and was better tolerated than in two previous controlled trials that used a faster titration to a higher mean dose.

Opioid analgesics are recognized as a legitimate medical therapy for selected patients with severe chronic pain that does not respond to other therapies. However, opioids are associated with risks for patients and society that include misuse, abuse, diversion, addiction, and overdose deaths. Therapeutic success depends on proper candidate selection, assessment before administering opioid therapy, and close monitoring throughout the course of treatment. Risk assessment and prevention include knowledge of patient factors that may contribute to misuse, abuse, addiction, suicide, and respiratory depression. Risk factors for opioid misuse or addiction include past or current substance abuse, untreated psychiatric disorders, younger age, and social or family environments that encourage misuse. Opioid mortality prevalence is higher in people who are middle aged and have substance abuse and psychiatric comorbidities. Suicides are probably undercounted or frequently misclassified in reports of opioid-related poisoning deaths. Greater understanding and better assessment are needed of the risk associated with suicide risk in patients with pain. Clinical tools and an evolving evidence base are available to assist clinicians with identifying patients whose risk factors put them at risk for adverse outcomes with opioids.