Noncancer-related Pain Research Articles

Intrathecal ziconotide for the treatment of chronic pain: a collection of clinical experiences and literature review.

Despite the wide use of ziconotide in the USA for treating refractory cancer- and noncancer-related pain, this agent is little used in Europe, even if licensed by the European Medicines Agency (EMA). The reason could be attributed to the high, fixed starting dose required for ziconotide, as stated in the EMA Summary of Product Characteristics (SmPC). This dosage recommendation is based on the results of pivotal clinical studies of ziconotide, which utilized aggressive titration schedules. Thus, a reappraisal of the available evidence, as well as a reflection on real-life clinical experiences, might be useful to identify practice adjustments to improve the clinical application of ziconotide in the European scenario. In line with this need, this paper reports some clinical experiences of patients with chronic pain treated with ziconotide intrathecal (IT) therapy in Italy, particularly focusing on long-term treatment to further characterize and improve the use of this agent in real practice. Moreover, a literature review of the available data on the effectiveness and safety of IT ziconotide is provided. Collected clinical experiences suggested that the use of IT ziconotide represents a valuable option, particularly in cases where other treatments have been ineffective or poorly tolerated. Ziconotide was shown to not cause severe side effects in the long-term treatment, leading to a constant pain relief effect at stable doses, without adverse events that caused therapy interruption. The overall constant ziconotide dosages also suggest the absence of a tolerance effect. In parallel, the evidence in the literature aligns with real-world evidence and further supports the use of IT ziconotide as an important option for the management of chronic pain. IT ziconotide represents a valuable addition to the armamentarium of pain management strategies, offering hope for improved quality of life for patients suffering from chronic, treatment-resistant pain. Continued research and clinical experience will further elucidate its optimal use and role in comprehensive pain care.

Nanotechnology-Enhanced Naloxone and Alternative Treatments for Opioid Addiction.

Opioids are commonly prescribed to address intense, ongoing pain associated with cancer, as well as long-lasting noncancer-related pain when alternative methods have proven ineffective. Individuals who exhibit both chronic pain and misuse of opioids face a significant danger of experiencing adverse health outcomes and the potential loss of life related to opioid use. Thus, there is a current movement to prescribe naloxone to those considered high-risk for opioid overdose. Naloxone has been explored as an antidote to reverse acute respiratory depression. Conversely, naloxone can give rise to other problems, including hypertension and cardiac arrhythmias. Thus, the importance of nanotechnology-enabled drug delivery strategies and their role in mitigating naloxone side-effects are significant. In this review, we explore the latest advancements in nanotechnology-enabled naloxone and alternative methods for addressing the opioid crisis through the utilization of non-opioid natural alternatives for chronic pain management.

Utilization and dispensing patterns of medical cannabis products in a state with legalized medical cannabis.

e18844 Background: The medical uses of cannabis-based products have been proposed to include treatment of pain, various neurological, gastrointestinal and psychological conditions. Cancer patients are some of the highest utilizers of medical cannabis-based products. To understand real world use and impact of cannabis-based products, we analyzed the database from 4 dispensaries of a cannabis company licensed in New York state. We aim to evaluate the dose, average THC/CBD ratios, association of various medical conditions to THC/CBD dose and cost of products to individuals receiving cannabis-based products. Methods: A retrospective analysis of anonymized data was conducted on 422,201 dispensed products from 32,845 unique individuals aged 18 years and older between 1/1/2016 and 12/31/2020. The database included patient’s age, gender, qualifying medical condition, type of product, medication directions and amount of product dispensed. Results: Median age was 53 years old and 52% were females. Cancer and non-cancer related pain (85%) were the most common medical condition and inhalation (57%) the most common route. Individuals received a median of 6 prescriptions with median cost of $50/product. Average THC:CBD ratios were 28:0.5mg/day and 12:0.25mg/dose. Highest average cost [mean (95% CI): $73 ($71-$75)] and average CBD/dose per product [mean (95% CI):5.89 (5.38-6.40)] were dispensed for neurological conditions. Highest average THC/dose [mean (95% CI): 14.25 (13.36-15.14)] were found as use as alternative products for those with substance use disorders. Table 1 shows the comparison of gender and route to medical condition. Conclusions: More females received medical cannabis prescriptions while males used more products. Pain was the most common reason for medical cannabis prescriptions. Neurological conditions demonstrated highest average cost and CBD/dose and prescriptions for substance use disorder demonstrated highest THC/dose for products dispensed. Products prescribed had more THC as compared to CBD and inhalation was preferred. As cancer patients increasingly utilize medical cannabis products in conjunction with tumor directed and symptom therapy it will be important to have randomized studies to help guide oncologists. [Table: see text]

Clinical Characteristics of Noncancer-Related Upper Back Pain on Initiation of Palliative Care in Patients with Incurable Cancer.

Background: Cancer patients experience various types of pain unrelated to their malignancy. However, no previous study has reported the prevalence of noncancer-related pain among patients with incurable cancer.Objective: We aimed to investigate the frequency of noncancer-related upper back pain, the type of noncancer disease, and pain intensity among patients.Design: This is a multicenter cross-sectional survey.Setting/Subjects: Subjects were patients with incurable cancer who underwent initiation of palliative care at two university hospitals in Japan.Measurements: Data for patient characteristics were recorded, and the upper back pain intensity, duration, analgesic use, and opioid drug use with dose were determined. Appropriate statistical tests were also performed.Results: Among the 103 patients with upper back pain, 20 (19.4%) had cancer-related pain, 28 (27.2%) had both cancer- and noncancer-related pain, and 53 (51.5%) had only noncancer-related pain. Myofascial pain was suspected in the 72 (88.9%) participants with noncancer-related pain. The median pain numerical rating scale score was four in the cancer-related pain group and seven in the other two groups (p = 0.005).Conclusions: A high proportion of outpatients with incurable cancer undergoing palliative care initiation had noncancer-related upper back pain. Severe pain at the initiation of palliative care in patients with incurable cancer may include noncancer-related pain. Trial Registration: UMIN000038371. Registered December 1, 2019.

Single-Center Review of Celiac Plexus/Retrocrural Splanchnic Nerve Block for Non-Cancer Related Pain

Celiac plexus and retrocrural splanchnic nerve (CP/RSN) blocks are widely used for cancer-related abdominal pain, but there is limited literature on their efficacy for non-cancer related pain. Our aim was to determine the indications and effectiveness of CT-guided CP/RSN blocks performed on patients with abdominal pain from non-cancer related sources. CT-guided CP/RSN blocks for non-cancer related abdominal pain from 2011-2020 were retrospectively reviewed for patient demographics, procedure details, duration of pain relief, and complications. Effective blocks were defined as patient-reported pain relief or decrease in opioid use lasting 2 or more days for temporary blocks and 14 or more days for permanent blocks. Of 72 CT-guided CP/RSN blocks for non-cancer related abdominal pain, 48 (67%) were effective for a mean of 51 days (median 14, range 2-700). Of the 18 permanent blocks, 9 (50%) were effective for a mean of 111 days (median 90, range 14-390). Of the 54 temporary blocks, 39 (72%) were effective for a mean of 37 days (median 9, range 2-700). Indications included postural orthostatic tachycardia syndrome/dysautonomia (77% effective, 20/26), pancreatitis (86% effective, 12/14), postsurgical pain (62% effective, 8/13), median arcuate ligament syndrome (70% effective, 7/10), chronic pain syndrome (20% effective, 1/5), gastroparesis (80% effective, 4/5), and renal cystic disease (33% effective, 1/3). For postural orthostatic tachycardia syndrome /dysautonomia, pancreatitis, post-surgical pain, and MALS, there were no statistically significant differences in effectiveness between celiac vs. splanchnic blocks in groups matched by indication and intended duration (temporary/permanent). CT-guided CP/RSN blocks can effectively manage non-cancer related abdominal pain, though there is discrepancy in efficacy between temporary and permanent blocks.

A Proposed Opioid Tapering Tool.

Previous studies suggest a lack of confidence among primary care providers in managing patients on chronic opioid therapy (COT) for chronic non-cancer related pain (CNCP). The US Department of Health and Human Services (HHS) recently introduced guidelines on opioid tapering. In light of these recommendations, our group developed an opioid tapering software to assist healthcare providers in managing patients on COT. The initial iteration of our software utilizes RedCap for the application programming interface (API). This tool is designed to reduce a patient's prescribed chronic opioids by 5-10% every month, or 5 morphine milligram equivalents per day (MME), whichever is the greatest, in line with HHS guidelines. Users can also adjust the rate of taper. Our group plans to use this software in an upcoming pilot study to taper patients on COT for CNCP. We are exploring the possibility of transitioning our software into other available APIs with the goal of integrating this software into major electronic health record systems. Our group envisions that our software will provide an additional tool within a patient-centered, multi-modal framework in managing patients on COT for CNCP.

Le mésusage du fentanyl en France : 2010 à 2015

The aim of this study was to evaluate the French use, misuse and abuse/dependence of non-injectable forms of fentanyl (transdermal and transmucosal fentanyl formulations). Problematic use of transdermal and transmucosal fentanyl formulations was evaluated using an approach combining multiple sources of information: (1) spontaneous notifications recorded during 6years (2010-2015) for transdermal fentanyl form and 3years for transmucosal fentanyl forms and (2) data from annual epidemiological systematic surveys conducted by the French Addictovigilance Network during 6years (2010-2015). In all, 147cases were notified for transdermal fentanyl formulation and 109cases for transmucosal fentanyl formulations. According to the galenic formulation, analysis of these cases emphasizes different profiles: for transdermal fentanyl formulation, two consumption profiles: 1/mainly for analgesic effects (74%): women (61%), 47years, with addictive and/or psychiatric history (46%), treated for chronic non-cancer related pain (93%), 2/seeking positive psychic effects other than analgesia (26%): men (82%), 32years, with addictive and/or psychiatric history (87%) and having obtained the fentanyl patch illegally (60%) for non-medical use. For transmucosal fentanyl formulations, only one consumption profile was observed: women (52%), 48years, with addictive (24%) and/or psychiatric history (28%), off label indication (72%) (indications for non-cancer pain and/or no or insufficient opioid background treatment). The misuse of transmucosal fentanyl formulations implies a high risk of adverse effects: those already known of opioid-based drugs, sometimes lethal (withdrawal syndrome, respiratory and central nervous system depression…) but also serious reactions at the application site (buccal or nasal). For the transdermal fentanyl formulation, 27cases (18%) of involuntary intoxication were observed, of which 25were serious. Nineteen deaths involving both forms of fentanyl have been reported (2for the transmucosal formulations and 17for the transdermal formulation). Our results report significant and worrying misuse of transmucosal fentanyl formulations with wide off-label use and also primary dependence on fentanyl, regardless of galenic formulation, in patients treated for chronic non cancer pain. Given the significant risks of fentanyl, it is necessary to continue the monitoring of misuse, in particular, thanks to the activities of the French Addictovigilance network allowing a multisource approach and who provides information concerning cases of abuse, misuse and dependence.

Intrathecal Drug Delivery.

Targeted intrathecal (IT) drug delivery systems (IDDS) are well established as an effective treatment of patients with chronic nonmalignant or malignant pain, and as a tool for management of patients with severe spasticity. The risk to benefit ratio of IDD makes it a relatively safe therapy for both cancer- and noncancer-related pain, but it is not free of risks, so it should be managed at specific centers. Recent technological advances, new therapeutic applications, reported complications, and the costs as well as maintenance required for this therapy require the need to stay up to date about new recommendations that may improve outcomes. This chapter reviews all technological issues regarding IDDS implantation with follow-up and pharmacological recommendations published during recent years that provide evidence-based decision-making process in the management of chronic pain and spasticity in patients.

(288) Reducing High Dose Narcotic Therapy for Chronic Non-Cancer Related Pain

Following the release of the 2016 CDC Guidelines for Prescribing Opioids for Chronic Pain, there have been intense efforts to reduce the utilization of high dose narcotic therapy for the management of non-cancer related chronic pain. Most prior research on prescription narcotic over-utilization has focused on geographical and community-based statistics, including investigating prescribers with inconsistent prescribing practices and guidelines. To date, there have been few published reports of these efforts in a large health system. In our presentation, we fill this gap by sharing the results of an intervention designed to reduce high dose narcotic therapy for non-cancer related chronic pain in a high-volume hospital-based pain center (census 5,000 patients) embedded within a large health system (11,000 employees). Our multi-modality pain intervention included the development of well-defined prescribing guidelines that enforced a maximum 100 Morphine Equivalent Dose (MED) daily threshold for narcotic therapy in patients with non-cancer related chronic pain. Our team openly communicated the goals of this intervention and related monitoring procedures to pain center patients and staff, as well as care providers across the health system. Outcome measures were collected for 30 months, from January 2016 through June 2018. During this study period, high dose narcotic prescriptions decreased from 20.5% to 0.5%, in established patients with non-cancer related chronic pain undergoing therapy in our pain center. The results suggest our approach – well-defined prescribing guidelines, 100 MED max daily narcotic dosing, and strategic system-wide and patient level communication – should be considered by other health systems as a method to improve adherence with CDC guidelines for opioid prescription.

(385) The Evaluation of Blended Codeine Phosphate with Hydroxyzine Pamoate, Gabapentin, Ondansetron, and Docusate for the Treatment of Chronic Pain: A Patient-Centered Approach to the Pain Management “State of Emergency”

The United States is suffering from a so-called opioid epidemic. It has been proposed that the onset of this epidemic occurs in physician offices. In November 2016, the Centers for Disease Control published guidelines for the treatment of non-cancer related pain. In this guideline, they suggested limitations as to the amount of morphine milligram equivalencies that are allowed for adequate pain relief, while limiting the complication rate. In this study, we evaluate the effectiveness of a Codeine preparation for the treatment of moderate to severe pain. The study evaluates the effectiveness of reducing MME through substituting medication with a low MME rather than weaning the patient. A trial of 20 patients was carried out. The patients were required to score their pain while on their previous medications. The score was the standardized one -10/10 methodology. The patients were then switched to a Codeine blended therapy and were asked to report on their pain, using the same methodology. The effectiveness of this treatment program is presented. P values are calculated. Of the 20 patients, 19 had excellent results with equal pain relief and no significant adverse reactions. The use of a blended codeine therapy can lower the MME without change in pain or withdrawal.

What Affects the Completion of Ecological Momentary Assessments in Chronic Pain Research? An Individual Patient Data Meta-Analysis.

BackgroundEcological momentary assessment (EMA) involves repeated sampling of people’s current experiences in real time in their natural environments, which offers a granular perspective on patients’ experience of pain and other symptoms. However, EMA can be burdensome to patients, and its benefits depend upon patients’ engagement in the assessments.ObjectiveThe goal of this study was to investigate factors affecting EMA-completion rates among patients with chronic pain.MethodsThis individual patient data meta-analysis was based on 12 EMA datasets that examined patients with chronic noncancer-related pain (n=701). The EMA-completion rates were calculated on a daily basis for each patient. Multilevel models were used to test the following predictors of completion rates at different levels: within-patient factors (days into the study and daily pain level), between-patient factors (age, sex, pain diagnosis, and average pain level per person), and between-study EMA design factors (study duration, sampling density, and survey length).ResultsAcross datasets, an EMA-completion rate of 85% was observed. The strongest results were found for the between-patient factor age: Younger respondents reported lower completion rates than older respondents (P=.002). One within-patient factor, study day, was associated with completion rates (P<.001): over the course of the studies, the completion rates declined. The two abovementioned factors interacted with each other (P=.02) in that younger participants showed a more rapid decline in EMA completion over time. In addition, none of the other hypothesized factors including gender, chronic pain diagnoses, pain intensity levels, or measures of study burden showed any significant effects.ConclusionMany factors thought to influence the EMA-completion rates in chronic pain studies were not confirmed. However, future EMA research in chronic pain should note that study length and young age can impact the quality of the momentary data and devise strategies to maximize completion rates across different age groups and study days.

Methylnaltrexone: Peripherally Acting μ-Opioid Receptor Antagonist

Opioid-induced constipation (OIC) is a common adverse effect associated with opioid therapy, with many patients never developing tolerance to this effect. There are many traditional laxatives available to help patients combat this symptom, yet OIC may not reliably respond to conventional treatment. Peripherally acting µ-opioid receptor antagonists (PAMORAs) have a place in the treatment of refractory OIC, when traditional laxatives have not resulted in effective laxation. There are a number of PAMORAs now available, and methylnaltrexone is the only PAMORA indicated for the treatment of OIC in adults with advanced illness, as well as for patients with chronic noncancer pain, including patients with chronic pain related to prior cancer treatment who do not require frequent opioid escalation. Advanced practitioners need to have an understanding of how and when to best use these medications for the different indications in patients with advanced illness or chronic noncancer-related pain.

Cancer and non-cancer pain opioid utilization in Medicare and Medicaid populations.

139 Background: Limited data exist comparing opioid use patterns in Medicare and Medicaid patients with cancer-related (CP) and non-cancer-related pain (NCP). Methods: A retrospective analysis of Medicare and Medicaid claims data (MarketScan Research Databases) investigated opioid use patterns in patients with CP and NCP. Adults (age ≥18 yr) with ≥1 pharmacy claim for an opioid (index date), continuous plan eligibility for 6 months pre- and 12 months post-index date, and duration of opioid use of ≥4 weeks were identified. CP patients were identified by medical claim for a cancer diagnosis within 30 days before index date. Results: A total of 4,009 Medicare and 551 Medicaid patients with CP and 98,631 Medicare and 25,163 Medicaid patients with NCP were analyzed. The most common cancer diagnoses were breast, lung, prostate, and colorectal. Medicare patients with CP and NCP had similar mean age; in the Medicaid cohort, patients with CP were older than those with NCP. In the Medicare cohort, NCP patients were more likely to be women; sex distribution was similar among Medicaid patients. Higher rates of comorbidity in the CP cohorts were observed in both datasets. Median index and post-index opioid doses were consistent between the CP and NCP cohorts. The post-index pattern of change in opioid dose was consistent between CP and NCP in both Medicare and Medicaid patients. The most common pattern observed was up to a doubling of index dose. Conclusions: Similar opioid utilization patterns in Medicare and Medicaid populations, including dose escalation, were observed regardless of pain etiology (cancer or non-cancer). [Table: see text]

Opioid-induced bowel dysfunction in cancer-related pain: Causes, consequences, and a novel approach for its management

Opioids are the mainstay of management for patients with cancer-related pain. Although the analgesic efficacy of opioid therapy is well documented, the recent European Pain in Cancer survey demonstrated that the management of moderate-to-severe pain in patients with cancer is far from optimal. Bowel dysfunction, and importantly constipation, is a common side effect and has a significant impact on the patient's morbidity and quality of life. Nonpharmacological strategies and laxatives are often not effective in the management of opioid-induced constipation (OIC), making it necessary to search for new strategies for the treatment of opioid-induced bowel dysfunction. One promising strategy is the prevention of OIC with peripherally acting opioid antagonists that specifically target the underlying cause of this condition, without affecting centrally mediated analgesia. In recent studies, the novel combination of prolonged-release oral oxycodone and prolonged-release oral naloxone provided effective analgesia with improved bowel function in patients suffering from severe cancer-related and noncancer-related pain. The combination has the potential to improve the quality of pain management significantly in these patients.

Opioid utilization patterns among patients with cancer and noncancer pain.

194 Background: Opioids are used to manage moderate to severe pain in patients with cancer and non-cancer pain. Limited data exist comparing opioid utilization patterns between these two patient populations. Methods: This retrospective, commercial administrative claims database analysis (HealthCore Integrated Research Environment) investigated opioid use patterns, including opioid dose escalation, in adult patients with cancer-related (CP) and non-cancer-related pain (NCP). Adults (age ≥18 years) with at least one pharmacy claim for an opioid between July 1, 2006, and September 30, 2014, were identified (index date). Patients selected for analysis had to have continuous plan eligibility for 6 months pre- and 12 months post-index date and opioid use for at least 4 weeks. Patients with opioid use related to cancer pain were identified by a medical claim for a cancer diagnosis coded within 30 days prior to the index opioid date. Results: A total of 9,209 patients with CP and 409,703 patients with NCP were analyzed. Patients with CP were older than patients with NCP (mean [SD]: 62.6 [12.9] yrs vs. 49.3 [15.3] yrs); other demographics were similar between cohorts. The most common cancer diagnoses were breast, lung, and prostate. Hydrocodone was the most common opioid prescribed for both cohorts. Total mean (SD) days of opioid therapy were 167.1 (341.8) for CP and 196.6 (421.1) for NCP, with similar rates of opioid use for ≥1 year (10.6% for CP; 13.6% for NCP). Median index opioid doses were consistent between the cohorts (CP: 51.7 morphine-equivalent units (MEU); NCP: 45.0 MEU). Median post-index (after the first 30 days) opioid doses were also similar (CP: 55.8 MEU; NCP: 45.3 MEU). Post-index opioid dose reductions occurred in approximately one-third of both cohorts. Opioid dose escalations (up to dose doubling) occurred in 31.8% of CP and 28.3% of NCP patients. More patients died during the follow-up period in the CP cohort (24.1%) compared with the NCP cohort (0.02%). Conclusions: The use of opioids bears many similarities between patients with cancer pain and non-cancer pain, including clinically similar rates of chronic opioid utilization and dose escalation. This study was supported by AstraZeneca.

Long-term administration of opioids for non-tumor pain - LONTS guideline provides an orientation

The long-term usage of opioid analgesics (> 3 months) for chronic, non-cancer related pain is critically discussed nationally and internationally. There are indications of under- and oversupply as well as misuse of opioids in Germany, but an "opioid epidemic" such as is evident in the USA cannot be detected at present.The S3-guideline LONTS (long-term usage of opioid analgesics for non-cancer related pain)serves as an orientation to improve provision of opioids and contains statements about the available evidence, indications and contraindications of use, as well as practical recommendations for managing a long-term opioid therapy.

New Formulation of Sustained Release Naloxone Can Reverse Opioid Induced Constipation Without Compromising the Desired Opioid Effects.

An international double-blind randomized placebo controlled study evaluated the safety and efficacy of four doses of a new sustained release naloxone capsule to treat Opioid Induced Constipation (OIC). Forty patients taking opioids for noncancer related pain, and experiencing OIC, were randomized into 4 cohorts of 10 patients. A multiple ascending dose design was used to evaluate the safety and efficacy of 2.5 mg, 5 mg, 10 mg, and 20 mg naloxone sustained release (NSR) capsules vs placebo. Drug was given once-daily for 3 weeks followed by twice daily (bid) dosing between weeks 4 and 6. The incidence of treatment emergent adverse events was highest in the placebo group. The incidence of adverse events among the four active treatment groups were similar. There were no serious adverse events. The number of severe events was low overall but highest in the placebo group. Significant improvements were seen in Spontaneous Bowel Movements with 5 mg, 10 mg, and 20 mg NSR capsules. Mean change in SBMs from baseline of 2.21 (P = 0.052), 2.37 (P = 0.032); 4.11 (P = 0.0005); 5.19 (<0.0001) was noted with NSR 2.5 mg, 5 mg, 10 mg, and 20 mg, respectively, when taken once daily, compared with 1.38 (P = 0.2) for patients on placebo therapy. No changes in subjective or objective measures of opioid withdrawal as measured by the Subjective Opioid Withdrawal Scale or Clinical Opioid Withdrawal Scale were observed. There was no increase in patient reported pain as measured daily using a visual analogue scale. This Phase II study has shown that using a new sustained release formulation to deliver oral naloxone to the colon allows successful treatment of OIC without comprising the desired opioid effects.

β2-Adrenergic receptor functionality and genotype in two different models of chronic inflammatory diseases: Liver Cirrhosis and Osteoarthrosis

August 2015 e13 MAnAgeMent Of IAtrOgenICAlly InduCed OpIOId dependenCe A.M. Peiro; C. Puga; B. Planelles; L. Mira; M. Puerto; L. Gomez; J.F. Horga; and C. Margarit Hospital General Universitario de Alicante (HGUA), Spain; The Foundation for the Promotion of Health and Biomedical Research of the Valencian. Community (FISABIO), Spain; and Occupational Observatory, University Miguel Hernandez (UMH), Spain Introduction: Opioids are valuable analgesics, capable of providing pain relief and functional improvement also in chronic non–cancerrelated pain (NCP) patients. However, recent data have shown that the increasing prescription of opioids is associated with a rise in aberrant drug-related behaviour. Methodology: A prospective study was performed with 70 NCP outpatients diagnosed with opioid iatrogenic DSMIV dependence and severe pain intensity. The study focused on analgesic efficacy, opioid withdrawal syndrome prevention, adverse side effects, functional status, and aberrant drug-related behaviour. We design a contractual agreement on opioid therapy, including goals, side effects, and criteria to finish the opioid therapy. Genotyping of the OPRM (rs1799971), COMT (rs4680), and ABCB (rs1045642) genes was performed. Results: Results from 73% (50 of 70) of the patients are presented. After a structured and progressive opioid conversion to buprenorphine/tramadol, a significant reduction of 47% of the total daily dose (TDD) with no withdrawal symptoms (OWS reduction of 9 points) was achieved, maintaining a moderate relief and pain intensity score. Quality of life tends to improve, as do the number of adverse reactions reported by the patients throughout the visits. OPRM and COMT gene variant distribution but ABCB variants were more prevalent (9% C/C, 65% C/T, 26% T/T) vs general population distribution (21% C/C, 49% C/T, 25% T/T). Psychosocial risk was associated to a high prevalence of opioid iatrogenic dependence. Conclusions: The indication for the prescription of opioids must be very carefully weighed in the presence of any risk factors. In these cases the integration into a multimodal, interdisciplinary therapy program is mandatory.

(462) Humanistic burden of constipation among chronic opioid users: an analysis of the National Health and Wellness Survey

Opioids are used in the management of chronic pain and are associated with significant tolerability issues, including constipation. Our objective was to demonstrate the self-reported humanistic burden (work productivity, health related quality of life [HRQoL]) of constipation among chronic opioid users. Data from the U.S. 2012 National Health and Wellness Survey, a web-based, patient-reported survey were examined. Respondents who reported using opioids chronically (>30 days) for diagnoses of non-cancer related pain were included.

Intrathecal Ziconotide: A Review of Its Use in Patients with Chronic Pain Refractory to Other Systemic or Intrathecal Analgesics

Ziconotide (Prialt(®)) is a synthetic conopeptide analgesic that acts by selectively antagonizing N-type voltage-gated calcium channels. Intrathecal ziconotide is the only non-opioid intrathecal analgesic that is FDA-approved for use in patients with treatment-refractory, chronic pain. The efficacy of intrathecal ziconotide was demonstrated in randomized, double-blind, placebo-controlled trials in patients with treatment-refractory noncancer-related pain or cancer- or AIDS-related pain. Across trials, ziconotide recipients had significantly greater reductions in pain intensity during ziconotide treatment than those receiving placebo (primary endpoint). At the end of the titration period, approximately one-sixth to one-third of patients with noncancer chronic pain and one-half with cancer- or AIDS-related pain who received ziconotide reached a pain response threshold (≥30 % reduction in the pain intensity score). In ziconotide responders, analgesic effects were enduring, with some patients continuing treatment over extended periods. Across trials, the chief tolerability concerns in ziconotide recipients during the titration phase and during extended treatment were related to CNS adverse events. These were mostly of mild to moderate intensity, although serious adverse events were commonly attributed to ziconotide treatment, especially in trials with rapid ziconotide titration and that permitted higher dosages. In general, clinically important non-CNS adverse events were infrequent, and during the ziconotide titration phase, relatively few patients discontinued treatment because of adverse events. Ongoing research will assess various strategies for selecting patients for ziconotide treatment and for enhancing its efficacy and tolerability. At the present time, intrathecal ziconotide provides a treatment option for patients with severe, unremitting pain who have failed to respond to other intensive analgesic regimens.