Edgar L. Ross

Urine toxicology screening among chronic pain patients on opioid therapy: frequency and predictability of abnormal findings.

ObjectiveTo examine the incidence of abnormal urine toxicology screening among chronic pain patients prescribed opioids for their pain and to relate these results to patient descriptors and type, number, and dose of prescribed opioids. MethodsA retrospective analysis of data from 470 patients who had urine screening at a pain management program in an urban teaching hospital was performed. Urine samples were analyzed using gas chromatography-mass spectrometry. Patients were categorized as having urine screens that were “normal” (expected findings based on their prescribed drugs) or abnormal. Abnormal findings were those of (1) absence of a prescribed opioid, (2) presence of an additional nonprescribed controlled substance, (3) detection of an illicit substance, and (4) an adulterated urine sample. ResultsForty-five percent of the patients were found to have abnormal urine screens. Twenty percent were categorized as having an illicit substance in their urine. Illicit substances and additional drugs were found more frequently in younger patients than in older patients (P<0.001). No other variables were found to predict abnormal urine screen results. DiscussionThese results confirm past findings that random urine toxicology screens among patients prescribed opioids for pain reveal a high incidence of abnormal findings. Common patient descriptors, and number, type, and dose of prescribed opioids were found to be poor predictors of abnormal results.

Substance misuse treatment for high-risk chronic pain patients on opioid therapy: A randomized trial

&NA; Chronic pain patients who show aberrant drug‐related behavior often are discontinued from treatment when they are noncompliant with their use of opioids for pain. The purpose of this study was to conduct a randomized trial in patients who were prescribed opioids for noncancer back pain and who showed risk potential for or demonstration of opioid misuse to see if close monitoring and cognitive behavioral substance misuse counseling could increase overall compliance with opioids. Forty‐two patients meeting criteria for high‐risk for opioid misuse were randomized to either standard control (High‐Risk Control; N = 21) or experimental compliance treatment consisting of monthly urine screens, compliance checklists, and individual and group motivational counseling (High‐Risk Experimental; N = 21). Twenty patients who met criteria indicating low potential for misuse were recruited to a low‐risk control group (Low‐Risk Control). Patients were followed for 6 months and completed pre‐ and post‐study questionnaires and monthly electronic diaries. Outcomes consisted of the percent with a positive Drug Misuse Index (DMI), which was a composite score of self‐reported drug misuse (Prescription Drug Use Questionnaire), physician‐reported abuse behavior (Addiction Behavior Checklist), and abnormal urine toxicology results. Significant differences were found between groups with 73.7% of the High‐Risk Control patients demonstrating positive scores on the DMI compared with 26.3% from the High‐Risk Experimental group and 25.0% from the Low‐Risk Controls (p < 0.05). The results of this study demonstrate support for the benefits of a brief behavioral intervention in the management of opioid compliance among chronic back pain patient at high‐risk for prescription opioid misuse.

Craving of Prescription Opioids in Patients With Chronic Pain: A Longitudinal Outcomes Trial

UNLABELLED Little is known about whether patients with chronic pain treated with opioids experience craving for their medications, whether contextual cues may influence craving, or if there is a relationship between craving and medication compliance. We hypothesized that craving for prescription opioids would be significantly correlated with the urge for more medication, preoccupation with the next dose, and current mood symptoms. We studied craving in 62 patients with chronic pain who were at low or high risk for opioid misuse, while they were enrolled in an RCT to improve prescription opioid medication compliance. Using electronic diaries, patients completed ratings of craving at monthly clinic visits and daily during a 14-day take-home period. Both groups consistently endorsed craving, whose levels were highly correlated (P < .001) with urge, preoccupation, and mood. The intervention to improve opioid compliance in the high-risk group was significantly associated with a rate of decrease in craving over time in comparison to a high-risk control group (P < .05). These findings indicate that craving is a potentially important psychological construct in pain patients prescribed opioids, regardless of their level of risk to misuse opioids. Targeting craving may be an important intervention to decrease misuse and improve prescription opioid compliance. PERSPECTIVE Patients with noncancer pain can crave their prescription opioids, regardless of their risk for opioid misuse. We found craving to be highly correlated with the urge to take more medication, fluctuations in mood, and preoccupation with the next dose, and to diminish with a behavioral intervention to improve opioid compliance.

Beliefs and attitudes about opioid prescribing and chronic pain management: Survey of primary care providers

OBJECTIVE There is growing concern of medication misuse and noncompliance among patients with chronic pain prescribed opioids for pain. The aim of this survey was to obtain information from primary care providers (PCPs) about their perception of prescribing opioids for patients with chronic pain. METHODS PCPs were invited to complete a packet of questionnaires about attitudes and concerns about opioids for chronic pain. These questionnaires included 1) General Health Questionnaire, 2) Test of Opioid Knowledge (TOK), 3) Opioid Therapy Provider Survey, and 4) Concerns About Analgesic Prescription Questionnaire. RESULTS Fifty-six (N = 56) PCPs from eight centers participated in this study. In general, the PCPs showed adequate opioid knowledge on the KOT and their general health was unrelated to prescription attitudes. Most expressed concern about medication misuse (89 percent) and felt that managing patients with chronic pain was stressful (84 percent). Most were worried about addiction (82 percent) and less than half felt that they were sufficiently trained in prescribing opioids (46 percent). Younger providers felt more reluctant to prescribe opioids, experienced more stress in managing patients with pain, had less overall confidence in managing patients with pain, and worried more about opioid dependence than older providers (p < 0.05). Younger providers were also less knowledgeable about opioids, but opioid knowledge was not found to be related to concerns about analgesic prescriptions. CONCLUSION This study indicates a general concern and reluctance of primary care physicians to manage the prescribing of opioids among their patients with chronic pain and younger providers expressed more concern about opioids than older providers.

Randomized trial comparing polymer-coated extended-release morphine sulfate to controlled-release oxycodone HCl in moderate to severe nonmalignant pain

ABSTRACT Objective: To assess the long-term efficacy, tolerability and safety of polymer-coated extended- release morphine sulfate (P-ERMS) (KADIAN*) compared with controlled-release oxycodone HCl (CRO) (OxyContin†) in treating chronic, nonmalignant, moderate to severe pain in a community- based outpatient population. * KADIAN is a licensed trademark of Alpharma Branded Products Division Inc., Piscataway, NJ, USA † OxyContin is a registered trademark of Purdue Pharma L.P., Stamford, CT, NJ, USA Design: Phase IV, prospective, randomized, open-label. Participants: Adults (N = 112) with chronic, nonmalignant, moderate to severe pain with visual numeric scale (VNS) scores ≥ 4 (0 = no pain; 10 = worst pain). Interventions: Patients were randomized to receive either P-ERMS once-daily (QD) dosing or CRO twice-daily (BID) dosing for a 24‐week treatment period. Upward titration of dose and switching P-ERMS to BID or CRO to thrice-daily (TID) dosing was allowed Weeks 2–24. Main outcome measures: Quality of life (Physical [PCS] and Mental [MCS] Component Summary scores of the SF-36v2 Health Survey), pain and sleep scores (0–10), and patient and clinician assessments of current therapy (–4 to +4). Results: Patients in both treatment groups experienced significant improvements in PCS scores (P-ERMS, +2.6; CRO, +3.1; p < 0.05 vs. baseline); patients taking CRO also demonstrated improvements in MCS scores (+4.7, p < 0.05 vs. baseline). Both groups attained significant reductions from baseline to 24 weeks in pain (P-ERMS, –2.0; CRO, –1.4; p ≤ 0.001 vs. baseline); the reduction with P-ERMS was clinically meaningful (as defined by at least a 2‐point reduction in VNS score). Patients attained significant improvement in sleep scores (P-ERMS, –2.6; CRO, –1.6; p < 0.001 vs. baseline; p < 0.05, P-ERMS vs. CRO). At Week 24, both groups indicated significantly increased patient (P-ERMS, +2.6; CRO, +1.7; p < 0.001 vs. baseline) and clinician (P-ERMS, +4.0; CRO, +3.1; p < 0.001 vs. baseline) global assessments of therapy. After 24 weeks, all patients on P-ERMS were dosing within the FDA-approved frequencies (65% QD, 35% BID); 56% of patients on CRO dosed BID, but 38% dosed TID and 6% dosed four times daily (QID). Most common adverse events were constipation, nausea, and somnolence, with no significant difference between treatment groups. Conclusions: P-ERMS and CRO both relieved chronic nonmalignant pain in this community-based population; however, patients taking P-ERMS dosed in accordance with FDA-approved frequencies (QD/BID); 44% of those taking CRO dosed more frequently (TID/QID).

Relationship of negative affect and outcome of an opioid therapy trial among low back pain patients.

Objectives:  Patients with chronic noncancer pain frequently report symptoms of depression and anxiety (negative affect), which are associated with higher ratings of pain intensity and a greater likelihood of being prescribed chronic opioid therapy. The purpose of this secondary analysis was to test the hypothesis that initial levels of negative affect can predict treatment‐related outcomes in a double‐blind, placebo‐controlled study of extended‐release (ER) hydromorphone among opioid‐tolerant patients with chronic low back pain.

Considerations for extrapolating evidence of acute and chronic pain analgesic efficacy

1. IntroductionEvidence of the efficacy of analgesic treatments is typicallybased on double-blind randomized clinical trials (RCTs) conductedin patients with a specific pain diagnosis, disease, or condition[1,2,9–11,40]. The results of these RCTs provide evidence of effi-cacy in the specific condition investigated, especially when thereis replication of the results. However, little attention has been de-voted to considering whether evidence of efficacy in one particularconditioncan be extrapolatedto otherswith a reasonabledegreeofconfidence that the treatment will be efficacious. For example, canit be assumed that the results of RCTs demonstrating that a medi-cation is efficacious for knee osteoarthritis (OA) pain indicate thatthis medication would also be efficacious for hip OA pain, or thatefficacy in postherpetic neuralgia (PHN) predicts efficacy in painfuldiabetic peripheral neuropathy (DPN)? In considering such gener-alization of efficacy, it would be important to specify the bound-aries of extrapolation, especially between pain conditions withdifferent neurobiological mechanisms, for example, neuropathicand musculoskeletal pain.The extrapolation of analgesic treatment efficacy to unstudiedconditions has broad implications. Most importantly, if efficacy isextrapolated to conditions in which treatments are truly not effec-tive, patients will be exposed to ineffective treatments that may beassociated with undesirable side effects, safety risks, and financialcosts. Conversely, if efficacy is not extrapolated to conditions inwhich treatments are truly efficacious but have not yet beenstudied, patients may be denied effective treatments that couldprovide meaningful relief. This is an important concern becausemany efficacious analgesics have been studied in relatively fewconditions, and there are numerous acute and chronic pain condi-tions for which effective treatments have not been identified.The United States Food and Drug Administration convened aworkshop to initiate discussion of the issues involved in consider-ingthe extrapolationof analgesic efficacy.The meetingincluded16pain specialists representing diverse disciplines and medical spe-cialties, all of whom are authors of this article. Participants wereasked to discuss the types of evidence that could provide the basisfor extrapolating efficacy to pain conditionsin which the treatmenthas not been studied. These discussions did not address the extrap-olation of safety, and also did not consider migraine headachegiven distinct regulatory and research design issues involving itsprevention and acute treatment [25].This article summarizes the conclusions from the workshop—which was held on December 2, 2009—and subsequent discussionsamong the participants. The considerations contained in thisarticle are not intended to serve as ‘‘consensus recommendations’’or to represent the views of the Food and Drug Administration orany other public or private agency or organization. Mostimportantly, given the major limitations of the evidence base forconsidering the extrapolation of analgesic efficacy, the material

Treatment of chronic moderate-to-severe non-malignant pain with polymer-coated extended-release morphine sulfate capsules.

ABSTRACT Objective: To demonstrate the efficacy and tolerability of polymer-coated extended-release morphine sulfate (P-ERMS) (KADIAN*) for the treatment of chronic, moderate-to-severe, non-malignant pain in a community-based outpatient population not satisfactorily relieved with their current therapies. * KADIAN is a registered trademark of Alpharma Branded Products Division Inc., Piscataway, NJ Design: Phase IV, prospective, randomized, open-label, blinded endpoint. Participants: Adults (N = 1428) with chronic, moderate-to-severe, non-malignant pain with visual numeric scale scores ≥ 4 (0 = no pain; 10 = worst pain). Interventions: Patients were randomized to P‐ERMS once daily in am or pm for a 4‐week treatment period. Dose increases were allowed; however, switching to twice-daily dosing was reserved until week 2. Main outcome measures: Improvement from baseline in pain and sleep scales (0–10) (after weeks 2 and 4), quality of life (physical and mental component summary scores of the SF-36v2 Health Survey) (week 4), and patient (weeks 2 and 4) and clinician (week 4) assessments of current therapy (–4 to +4). Patient satisfaction was assessed again 1 month after the study. Results: Approximately 70% of patients completed the study, with 2.4% (n = 34) discontinuing due to lack of efficacy, and 9.6% (n = 136) discontinuing due to an adverse event. Improvements were seen in pain and sleep scores, physical and mental component scores of the SF-36v2, and patient and clinician global assessment scores ( p < 0.0001, all assessments). Patients attained similar results regardless of am vs. pm dosing. More than half (55.4%) of patients were maintained on once-daily therapy, with the remainder on a twice-daily regimen, in accordance with the prescribing information. Most adverse events (71.6%) were mild to moderate in severity, the most common being constipation (11.6%) and nausea (9.2%). One‐month follow-up indicated continued satisfaction with P‐ERMS vs. previous medication ( p < 0.0001). Conclusions: P‐ERMS was efficacious and well tolerated in patients with chronic, moderate-to-severe, non-malignant pain when used once or twice daily.

Treatment of Chronic Pain in Failed Back Surgery Patients with Spinal Cord Stimulation: a Review of Current Literature and Proposal for Future Investigation

Objective. The authors attempted to design and conduct a randomized, prospective study to investigate the efficacy of spinal cord stimulation (SCS) for patients with chronic back and leg pain following at least one previous surgery. While the scientific advantages of the randomized, prospective trial are considerable, the authors encountered numerous practical and ethical difficulties with conducting these trials.

The state of implantable pain therapies in the United States: A nationwide survey of academic teaching programs

UNLABELLED The purpose of this questionnaire survey was to provide an overview of anesthesiology pain fellowship programs in the United States with regard to implantation of spinal cord stimulators (SCS) and opioid infusion devices. Of the 95 programs solicited, 80% responded to questions pertaining to the prevalence of use and technical considerations of implantation. Of the responding programs, 87% report implanting SCS, and 84% report implanting neuraxial infusion pumps. All programs perform a stimulation or infusion trial before implantation, although the duration varied from a trial in the operating room at the time of implantation to 25 days. Of the programs, 83% implant cylindrical leads, and 17% implant flat leads via laminectomy for their nonrevision SCS implants. Morphine, bupivacaine, hydromorphone, and baclofen are the most commonly used drugs and are used in implanted pumps by >50% of respondents. The question of industry-sponsored pain fellow education in implantable techniques is addressed. IMPLICATIONS Of the pain teaching programs in the United States, 80% responded to a questionnaire eliciting information about the implantation of spinal cord-stimulating and opioid infusion devices. The range and diversity of responses imply a lack of agreement about implantation techniques, drugs, and protocols.