Jodie A. Trafton

A pilot cohort study of the determinants of longitudinal opioid use after surgery.

BACKGROUND: Determinants of the duration of opioid use after surgery have not been reported. We hypothesized that both preoperative psychological distress and substance abuse would predict more prolonged opioid use after surgery. METHODS: Between January 2007 and April 2009, a prospective, longitudinal inception cohort study enrolled 109 of 134 consecutively approached patients undergoing mastectomy, lumpectomy, thoracotomy, total knee replacement, or total hip replacement. We measured preoperative psychological distress and substance use, and then measured the daily use of opioids until patients reported the cessation of both opioid consumption and pain. The primary end point was time to opioid cessation. All analyses were controlled for the type of surgery done. RESULTS: Overall, 6% of patients continued on new opioids 150 days after surgery. Preoperative prescribed opioid use, depressive symptoms, and increased self-perceived risk of addiction were each independently associated with more prolonged opioid use. Preoperative prescribed opioid use was associated with a 73% (95% confidence interval [CI] 0.51%–87%) reduction in the rate of opioid cessation after surgery (P = 0.0009). Additionally, each 1-point increase (on a 4-point scale) of self-perceived risk of addiction was associated with a 53% (95% CI 23%–71%) reduction in the rate of opioid cessation (P = 0.003). Independent of preoperative opioid use and self-perceived risk of addiction, each 10-point increase on a preoperative Beck Depression Inventory II was associated with a 42% (95% CI 18%–58%) reduction in the rate of opioid cessation (P = 0.002). The variance in the duration of postoperative opioid use was better predicted by preoperative prescribed opioid use, self-perceived risk of addiction, and depressive symptoms than postoperative pain duration or severity. CONCLUSIONS: Preoperative factors, including legitimate prescribed opioid use, self-perceived risk of addiction, and depressive symptoms each independently predicted more prolonged opioid use after surgery. Each of these factors was a better predictor of prolonged opioid use than postoperative pain duration or severity.

Presynaptic regulation of spinal cord tachykinin signaling via GABAB but not GABAA receptor activation

Internalization of spinal cord neurokinin-1 receptors following noxious stimulation provides a reliable measure of tachykinin signaling. In the present study, we examined the contribution of GABAergic mechanisms to the control of nociceptor processing involving tachykinins. Spinal administration of the GABA(B) receptor agonist R(+)-baclofen in the rat, at antinociceptive doses, significantly reduced the magnitude of neurokinin-1 receptor internalization in neurons of lamina I in response to acute noxious mechanical or thermal stimulation. By contrast, administration of even high doses of the GABA(A) receptor agonists, muscimol or isoguvacine, were without effect. CGP55845, a selective GABA(B) receptor antagonist, completely blocked the effects of baclofen, but failed to increase the incidence of internalization when administered alone. These results provide evidence for a presynaptic control of nociceptive primary afferent neurons by GABA(B) but not GABA(A) receptors in the superficial laminae of the spinal cord, limiting tachykinin release. Because CGP5584 alone did not increase the magnitude of neurokinin-1 receptor internalization observed following noxious stimulation, there appears to be little endogenous activation of GABA(B) receptors on tachykinin-releasing nociceptors under acute stimulus conditions. The contribution of pre- and postsynaptic regulatory mechanisms to GABA(B) receptor-mediated antinociception was also investigated by comparing the effect of baclofen on Fos expression evoked by noxious stimulation to that induced by intrathecal injection of substance P. In both instances, baclofen reduced Fos expression not only in neurons that express the neurokinin-1 receptor, but also in neurons that do not. We conclude that baclofen acts at presynaptic sites to reduce transmitter release from small-diameter nociceptive afferents. Presynaptic actions on non-tachykinin-containing nociceptors could similarly account for the reduction by baclofen of noxious stimulus-induced Fos expression in neurokinin-1 receptor-negative neurons. However, the inhibition of Fos expression induced by exogenous substance P indicates that actions at sites postsynaptic to tachykinin- and/or non-tachykinin-containing primary afferent terminals must also contribute to the antinociceptive actions of GABA(B) receptor agonists.

Mu and delta opioid receptor-like immunoreactivity in the cervical spinal cord of the rat after dorsal rhizotomy or neonatal capsaicin : an analysis of pre- and postsynaptic receptor distributions

Opioid compounds have powerful analgesic properties when administered to the spinal cord. These effects are exerted through mu and delta opioid receptors, and both pre- and postsynaptic mechanisms have been implicated. To specifically address the relative pre- and postsynaptic contribution to spinal opioid analgesia, we have quantitatively assessed the pre- vs. postsynaptic distribution of the mu-opioid (MOR-1, MOP(1)) and delta-opioid receptors (DOR-1, DOP(1)). We also examined the rostro-caudal arborization of MOR-1 and DOR-1 immunoreactive primary sensory neurons, using an isolated dorsal root preparation. These results were compared to those obtained by labeling for calcitonin gene-related peptide (CGRP), a neuropeptide whose expression in the spinal cord is restricted to the terminals of small diameter primary sensory neurons. We estimate that approximately one half of MOR-1 and two thirds of DOR-1 immunoreactivity in the cervical spinal cord is located on primary afferent fibers. These fibers have a broad rostro-caudal distribution, extending at least three segments rostral and caudal to their segment of entry. Regardless of marker used, the rostral projection was greatest, however, the distribution of CGRP-immunoreactive fibers differed somewhat in that they had a much smaller projection to the most caudal segments examined. Our results suggest that presynaptic delta opioid actions predominate, but that there are mixed pre- and postsynaptic inhibitory effects exerted by opioid analgesics that act at the spinal cord mu opioid receptor.

Trends and regional variation in opioid overdose mortality among Veterans Health Administration patients, fiscal year 2001 to 2009.

Objectives:Opioid-related mortality has increased in the United States in the past decade. The purpose of this study was to examine trends and regional variation in opioid prescribing and overdose rates in a national health system, the Veterans Health Administration. Materials and Methods:Annual cohorts of Veterans Health Administration patients were identified on the basis of medical records, and overdose mortality was determined from National Death Index records. State-level prescribing and overdose rates were mapped to provide information on regional variability. Results:There were significant increases between 2001 and 2009 in the rate of overdoses associated with nonsynthetic opioids (&bgr;=0.53, 95% confidence interval, 0.35, 0.70) and methadone (&bgr;=0.63, 95% confidence interval, 0.37, 0.90) but not synthetic/semisynthetic opioids. State-level overdose rates had a moderate correlation with the average proportion of patients in that state receiving opioids (r=0.29). Discussion:The present study demonstrates that the increases in prescription opioid overdoses observed in the general population are also found in the patient population of a national health system and provides further evidence of the population-level association between trends in opioid prescribing and opioid overdose deaths. There is substantial regional variation in both opioid prescribing and opioid-related overdose rates, and these data can inform region-specific overdose prevention strategies and opioid policy.

Evaluation of the Acceptability and Usability of a Decision Support System to Encourage Safe and Effective Use of Opioid Therapy for Chronic, Noncancer Pain by Primary Care Providers

OBJECTIVE To develop and evaluate a clinical decision support system (CDSS) named Assessment and Treatment in Healthcare: Evidenced-Based Automation (ATHENA)-Opioid Therapy, which encourages safe and effective use of opioid therapy for chronic, noncancer pain. DESIGN CDSS development and iterative evaluation using the analysis, design, development, implementation, and evaluation process including simulation-based and in-clinic assessments of usability for providers followed by targeted system revisions. RESULTS Volunteers provided detailed feedback to guide improvements in the graphical user interface, and content and design changes to increase clinical usefulness, understandability, clinical workflow fit, and ease of completing guideline recommended practices. Revisions based on feedback increased CDSS usability ratings over time. Practice concerns outside the scope of the CDSS were also identified. CONCLUSIONS Usability testing optimized the CDSS to better address barriers such as lack of provider education, confusion in dosing calculations and titration schedules, access to relevant patient information, provider discontinuity, documentation, and access to validated assessment tools. It also highlighted barriers to good clinical practice that are difficult to address with CDSS technology in its current conceptualization. For example, clinicians indicated that constraints on time and competing priorities in primary care, discomfort in patient-provider communications, and lack of evidence to guide opioid prescribing decisions impeded their ability to provide effective, guideline-adherent pain management. Iterative testing was essential for designing a highly usable and acceptable CDSS; however, identified barriers may limit the impact of the ATHENA-Opioid Therapy system and other CDSS on clinical practices and outcomes unless CDSS are paired with parallel initiatives to address these issues.

Prevalence of Cannabis Use Disorder Diagnoses Among Veterans in 2002, 2008, and 2009

The present investigation sought to document current rates and trends of cannabis use disorder (CUD) diagnoses among patients of the Veterans Affairs Health Care System (VA) during fiscal years 2002, 2008, and 2009. Results indicated that the prevalence of CUD diagnoses within VA has increased more than 50% (from 0.66% to 1.05%) over the past 7 years. The prevalence of patients with a CUD diagnosis but no other illicit SUD diagnosis rose 115.41% (from 0.27% to 0.58%) during the same time period. States with laws allowing for the legal use of cannabis for medicinal purposes had significantly higher rates of Cannabis-Disorder diagnoses within VA in 2002, 2008, and 2009 (p < .01). Though rates of psychiatric diagnoses, and posttraumatic stress disorder (PTSD) specifically, were higher among patients with a Cannabis-Disorder diagnosis compared with other SUD groups (p < .001), rates of specialty SUD treatment utilization among those with a Cannabis-Disorder diagnosis have decreased within VA. Results indicate that interventions to motivate treatment engagement among patients with CUD, particularly among those with co-occurring psychological problems, are needed for Veterans.

Pharmacotherapy of Alcohol Use Disorders by the Veterans Health Administration: Patterns of Receipt and Persistence

OBJECTIVE This study assessed changes since 2007 at Veterans Health Administration (VHA) facilities (N=129) in use of the medications approved by the U.S. Food and Drug Administration for treatment of alcohol use disorders. METHODS VHA data from fiscal years (FYs) 2008 and 2009 were used to identify patients with a diagnosis of an alcohol use disorder who received oral or extended-release naltrexone, disulfiram, or acamprosate as well as the proportion of days covered (PDC) in the 180 days after initiation and the time to first ten-day gap in possession (persistence) for each medication. Multilevel, mixed-effects logistic regression models examined the association between patient and facility characteristics and use of medications. RESULTS Nationally, 3.4% of VHA patients with an alcohol use disorder received medications in FY 2009 (11,165 of 331,635 patients), up from 3.0% in FY 2007. Use of medications by patients at the facilities ranged from 0% to 12%. In fully adjusted analyses, facilities offering evening and weekend services had higher rates of medication receipt, but other facility characteristics, such as having prescribers on the addiction programs staff or using medication to treat opioid or tobacco dependence, were unrelated to medication receipt. The mean PDC of acamprosate was significantly lower than mean PDCs of the other medications (p<.05), and persistence in use of naltrexone was significantly greater than use of acamprosate and significantly less than use of disulfiram (p<.05). CONCLUSIONS Use of these medications is increasing but remains variable across the VHA system. Interventions are needed to optimize initiation of and persistence in use of these medications.

Determining effective methadone doses for individual opioid-dependent patients.

Background Randomized clinical trials of methadone maintenance have found that on average high daily doses are more effective for reducing heroin use, and clinical practice guidelines recommend 60 mg/d as a minimum dosage. Nevertheless, many clinicians report that some patients can be stably maintained on lower methadone dosages to optimal effect, and clinic dosing practices vary substantially. Studies of individual responses to methadone treatment may be more easily translated into clinical practice. Methods and Findings A volunteer sample of 222 opioid-dependent US veterans initiating methadone treatment was prospectively observed over the year after treatment entry. In the 168 who achieved at least 1 mo of heroin abstinence, methadone dosages on which patients maintained heroin-free urine samples ranged from 1.5 mg to 191.2 mg (median = 69 mg). Among patients who achieved heroin abstinence, higher methadone dosages were predicted by having a diagnosis of posttraumatic stress disorder or depression, having a greater number of previous opioid detoxifications, living in a region with lower average heroin purity, attending a clinic where counselors discourage dosage reductions, and staying in treatment longer. These factors predicted 42% of the variance in dosage associated with heroin abstinence. Conclusions Effective and ineffective methadone dosages overlap substantially. Dosing guidelines should focus more heavily on appropriate processes of dosage determination rather than solely specifying recommended dosages. To optimize therapy, methadone dosages must be titrated until heroin abstinence is achieved.

What do patients do with unused opioid medications

Objectives:The volume of opioid medications being prescribed in the United States is increasing rapidly. Problems associated with the misuse of opioid medications are also increasing, in part because of medication diversion from legitimate prescriptions. However, little is known about what patients do with any unused opioid medications. This paper uses a qualitative analysis of patients’ self-report of medication storage and retention habits to begin to address this gap. Methods:We analyzed responses to the Prescription Drug Use Questionnaire in conjunction with other data on prescription opioid use in a sample of 191 Veteran patients (83% of whom had a preexisting factor associated with higher rates of opioid misuse) who received one or more opioid prescriptions in the previous 12 months. Results:Only 6.3% of participants disposed of extra medications and 24.1% reported having no extra opioids. A total of 65.4% of participants reported retaining some or all opioids even if they ceased taking the medication, and some participants accumulated large amounts of medication. A total of 34.0% of participants described engaging in sharing or diversion of opioids at least once, most often receiving them from a family member or a friend. Discussion:A majority of patients retain unused opioids, and medication sharing is common. Interventions to improve monitoring of patient experience with opioid medication, educate patients about the dangers of opioid use by nonprescribed others, and increase information about medication disposal options could decrease the supply of opioid medications available for misuse.

Reasons for Under-Use of Prescribed Opioid Medications by Patients in Pain

BACKGROUND With the growth in opioid therapy for the treatment of chronic pain, health care providers have focused their attention on avoiding over-use of opioid medications, specifically to avoid addiction, dependency, and other misuse. Qualitative and quantitative reviews of medication adherence, in contrast, focus primarily on why patients under-use or do not take their medications as prescribed and find nonadherence rates of approximately 25%. OBJECTIVE To identify the prevalence of under-use of opioid medications and the reasons and implications of under-use. DESIGN As part of a variety of structured assessments, subjects were asked detailed questions about how they used their opioid medication in their daily lives. PARTICIPANTS One hundred ninety-one veterans who received an opioid prescription for any pain problem within the 12 months before the interview. MEASURES We defined a patient who under-used his/her medication as one who took less than their prescribed dose of medication and reported that pain impaired their ability to engage in normal daily activities. RESULTS Under-use of opioids (20%) was more common than over-use (9%), consistent with research on medication adherence. Patients who under-used their opioids offered the same reasons for under-use that patients report for other medications. However, while under-users reported more pain than other opioid users they filled only slightly fewer opioid prescriptions. Communication problems between patients and providers about opioids were common. CONCLUSIONS Improved communication between patients and providers and shared decision-making regarding opioid prescriptions may improve pain management and minimize the problems associated with over-prescription of opioids (i.e., diversion).