[Show abstract][Hide abstract] ABSTRACT: Breakthrough cancer pain (BTcP) is a transient exacerbation of cancer pain in patients with otherwise stable, persistent background pain. This study evaluated the long-term effectiveness and tolerability of sublingual fentanyl orally disintegrating tablet (sublingual fentanyl ODT), for the treatment of BTcP in opioid-tolerant patients with cancer.
This was a non-randomized, open-label, multi-center, Phase III study conducted in opioid-tolerant patients (aged ≥17 years) with BTcP. The study comprised a 2-week titration phase, followed by a maintenance phase of up to 12 months. Patients self-administered sublingual fentanyl ODT for episodes of BTcP. Effectiveness was assessed using patients' global evaluation of medication (PGEM), the brief pain inventory (BPI) and the depression, anxiety and positive outlook scale (DAPOS). Adverse events were recorded throughout.
Of 139 recruited patients, 69% identified an effective dose of sublingual fentanyl ODT (a dosage that successfully treated all episodes of BTcP over two consecutive days) and entered the maintenance phase, during which they were treated for a median of 149.0 days (mean dose 507.5 µg). The study recorded a significant increase in reported satisfaction with pain medication at the 6-month and end-of-study visits, compared to screening (p ≤ 0.01). Evaluation of quality of life using BPI and DAPOS identified no deterioration in scores and significant improvements in certain parameters (p < 0.05). Sublingual fentanyl ODT was well tolerated, with no study drug-related deaths, and 49 patients (35.3%) experiencing ≥1 study drug-related adverse event. The most common of these included nausea (8.6%), constipation (5.8%) and somnolence (5.8%). There was no evidence of sublingual mucosal irritation due to the study medication. The pattern of adverse events was similar to that previously observed with transmucosal fentanyl.
Sublingual fentanyl ODT was effective and well tolerated for the long-term treatment of BTcP in opioid-tolerant cancer patients. There was an increase in satisfaction with pain medication during the study, and sublingual fentanyl ODT showed an acceptable safety profile over 12 months of treatment.
Current Medical Research and Opinion 03/2011; 27(3):519-30. DOI:10.1185/03007995.2010.545380 · 2.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite currently available treatments, postherpetic neuralgia continues to be a challenging pain condition to treat. Many patients remain in pain or suffer side effects from the (combination) therapies. A patch containing 8% capsaicin (research code NGX-4010 and marketed under the trade name Qutenza(®)), approved both in the EU and USA, provides a localized therapy with effects lasting up to 12 weeks after a single 60-min application. This review will summarize clinical trial evidence on the safety, efficacy and unique attributes of this capsaicin 8% patch in the treatment of postherpetic neuralgia. The action of capsaicin on the transient receptor potential cation channel, subfamily V, member 1 receptors will be discussed.
[Show abstract][Hide abstract] ABSTRACT: Herpes zoster infection is caused by a reactivation of the latent varicella zoster virus that causes chicken pox. It appears predominantly in older adults whose immunity for the virus has waned. The natural course of the disease is usually favorable, and the symptoms disappear spontaneously within a few weeks. Some patients, however, have prolonged pain: post-herpetic neuralgia. The diagnosis of acute zoster infection is made on the clinical signs including the appearance of rash. Post-herpetic neuralgia is described as sharp, burning, aching, or shooting constantly present in the dermatome that corresponds with the earlier rash. The objectives of treating herpes zoster are: (1) acute pain reduction; (2) promotion of recovery of epidermal defects and prevention of secondary infections; and (3) reduction or prevention of post-herpetic neuralgia. The objective of the treatment of post-herpetic neuralgia is primarily pain alleviation and improvement of the quality of life. Early treatment of the infection and the pain is believed to reduce the risk for post-herpetic neuralgia. This persistent pain syndrome is difficult to treat. Antiepileptic drugs and tricyclic antidepressants are the first choice. Interventional treatments, such as epidural injections of corticosteroids and local anesthetic drugs, have an effect on the acute pain but are of limited use in preventing post-herpetic neuralgia. When conservative treatment fails in providing satisfactory relief of post-herpetic neuralgia, a sympathetic block may be considered (2 C+); if this treatment provides unsatisfactory results, spinal cord stimulation may be considered, in a study context (2 C+).
Pain Practice 12/2010; 11(1):88-97. DOI:10.1111/j.1533-2500.2010.00428.x · 2.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Postherpetic neuralgia (PHN) is a neuropathic pain syndrome that may develop subsequent to healing of herpes zoster rash.
This study aimed to determine the efficacy and safety of gabapentin extended-release (gabapentin ER) tablets for the treatment of patients with PHN and to determine whether optimal benefits might be achieved with once-daily (QD) or divided-dose (DD) administration.
This was a 10-week, randomized, double-blind, placebo-controlled, multicentre trial comparing gabapentin ER (total daily dose 1800 mg) either QD or as an asymmetrical DD with placebo in 407 patients with post-zoster pain for >or=3 months and a baseline average daily pain score (ADP)>or=4 on a 0-10 Likert numerical rating scale. The primary efficacy outcome was the ADP score mean change from baseline to week 10 using baseline observation carried forward (BOCF). Secondary efficacy outcomes included changes to week 10 in last observation carried forward (LOCF) ADP score, LOCF average daily sleep interference score, Short-Form McGill Pain Questionnaire score, Neuropathic Pain Scale score, and Brief Pain Inventory score.
Of 407 randomized patients, 400 were included in the intent-to-treat population (gabapentin ER QD, n=134; gabapentin ER DD, n=135; placebo, n=131). Between-group differences in the least squares (LS) mean changes in BOCF ADP scores did not reach statistical significance (gabapentin ER QD -1.85 [p=0.110 vs placebo]; gabapentin ER DD -1.72 [p=0.255 vs placebo]; placebo -1.42). In the LOCF analysis, the LS mean ADP score for the gabapentin ER QD group, but not for the DD group, improved compared with placebo (gabapentin ER QD, -2.28; p=0.032 vs placebo). Improvements compared with placebo were also observed in the gabapentin ER QD group, but not for the DD group, for mean daily sleep interference scores (gabapentin ER QD, -2.49; placebo, -1.63; p<0.001). Most adverse events (AEs) were mild or moderate. Among gabapentin-treated patients, 12% and 11% withdrew due to AEs, most commonly for dizziness (2% and 3%), in the gabapentin ER QD and DD groups, respectively. Treatment-related AEs in the gabapentin ER-treated groups occurred in 31% of patients. The most common AEs in the gabapentin ER QD and DD groups included dizziness (10% and 15%), headache (4% and 7%), somnolence (3% and 7%) and peripheral oedema (5% and 5%), respectively.
The primary efficacy endpoint for this study of gabapentin ER was not met, most likely due to the unexpectedly large placebo response. Outcomes on secondary endpoints suggest the potential efficacy of gabapentin ER QD. Gabapentin ER was well tolerated in this study. [Clinicaltrials.gov identifier NCT00335933].
Clinical Drug Investigation 11/2010; 30(11):765-76. DOI:10.2165/11539520-000000000-00000 · 1.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The heated lidocaine/tetracaine patch (Synera; ZARS Pharma, Inc, Salt Lake City, UT) is among the local topical anesthetic formulations used to prevent procedural pain. This study was conducted to determine the depth and duration of anesthesia provided by the patch and to evaluate safety and tolerability.
This randomized, double-blind, placebo-controlled, 2-period crossover study was conducted in healthy subjects. Subjects were randomized to receive either the heated lidocaine/tetracaine patch (active patch) in period 1 and placebo patch in period 2 or vice versa. Patches were applied for 30 mins to the volar aspect of the forearm. Pain and sensory depths were measured at baseline and at 30, 60, 90, and 150 mins after patch application. Duration of anesthesia was measured at 40, 70, 110, and 130 mins after patch application by evaluating thermal and mechanical sensation.
A total of 25 subjects were enrolled in the study. Twenty-four subjects completed the study. Pain and sensory depths with the active patch were greater than with placebo (P < 0.001) at all postdose time points. Maximum mean pain depth achieved with the active patch was 8.22 mm; anesthesia lasted at least 100 mins after patch removal. Cool and warm sensations and hot pain thresholds were increased compared with placebo (P < 0.001). Light touch and pinprick were detectable by most subjects.
The heated lidocaine/tetracaine patch is well tolerated, and it provides favorable depth and duration of anesthesia without significant sensory loss for superficial venous access and minor dermatological procedures after a 30-min application.
Regional anesthesia and pain medicine 11/2010; 35(6):507-13. DOI:10.1097/AAP.0b013e3181fa69b8 · 3.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with malignancy sometimes develop painful mucositis and require patient-controlled analgesia (PCA) to treat their pain. Pain disrupts sleep and there is some evidence that analgesic medications also disrupt sleep. This study examined whether treatment with the sedative hypnotic eszopiclone could improve self-reports of sleep, fatigue, and pain as well as decrease opioid self-administered via PCA.
Inpatients who developed mucositis severe enough to require PCA treatment were randomized double-blind to a 2-day trial on eszopiclone or placebo-administered at bedtime. Patients completed questionnaires which assessed sleep, pain, and fatigue. PCA medication was calculated in terms of morphine equivalents. Data were analyzed with unpaired t tests and repeated measures analysis of variance.
Twenty-two patients were randomized to placebo and 23 to eszopiclone. Groups were comparable in age and treatment characteristics. Mean pain scores were lower in the eszopiclone group at all time points (morning p = 0.01, afternoon p = 0.04, evening p = 0.04). The eszopiclone group reported increased sleep time (p < 0.05), fewer nighttime awakenings (p < 0.001), better self-reported sleep quality (p = 0.01), and depth (p = 0.04). There were no significant differences between eszopiclone and placebo in terms of self-reports of fatigue or opioid usage.
Sedative hypnotic agents improve sleep and analgesia even in the setting of considerable pain and discomfort.
Supportive Care in Cancer 11/2010; 19(12):2015-20. DOI:10.1007/s00520-010-1052-1 · 2.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Quality improvement (QI) is a compilation of methods adapted from psychology, statistics, and operations research to identify factors that contribute to poor treatment outcomes and to design solutions for improvement. Valid and reliable measurement is essential to QI using rigorously developed and tested instruments. The purpose of this article is to describe the evolution of the American Pain Society Patient Outcome Questionnaire (APS-POQ) for QI purposes and present a revised version (R) including instrument psychometrics. An interdisciplinary task force of the APS used a step-wise, empiric approach to revise, test, and examine psychometric properties of the society's original POQ. The APS-POQ-R is designed for use in adult hospital pain management QI activities and measures 6 aspects of quality, including (1) pain severity and relief; (2) impact of pain on activity, sleep, and negative emotions; (3) side effects of treatment; (4) helpfulness of information about pain treatment; (5) ability to participate in pain treatment decisions; and (6) use of nonpharmacological strategies. Adult medical-surgical inpatients (n = 299) from 2 hospitals in different parts of the United States participated in this study. Results provide support for the internal consistency of the instrument subscales, construct validity and clinical feasibility. PERSPECTIVE: This article presents the initial psychometric properties of the APS-POQ-R for quality improvement purposes of hospitalized adult patients. Validation in additional groups of patients will be needed to demonstrate its generalizability.
The journal of pain: official journal of the American Pain Society 11/2010; 11(11):1172-86. DOI:10.1016/j.jpain.2010.02.012 · 4.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the efficacy, safety, and impact on quality of life of long-term administration of OROS hydromorphone ER (8-128mg) in patients with chronic low back pain.
A total of 113 adults with chronic low back pain who completed a 6-week open-label study were enrolled in this 6-month extension study.
The primary end point was the daily pain relief rating obtained during monthly study visits. Secondary end points included Investigator and Patient Global Evaluations, Brief Pain Inventory scores obtained at monthly study visits, and quality-of-life measures (Medical Outcomes Study Questionnaire and 36-Item Short-Form Health Survey score) obtained at monthly intervals.
Mean±SD change from baseline in pain relief with OROS hydromorphone ER for the Month 6 visit was 0.9±2.55 (P=0.0007) and for the last assessment of the extension study was 0.9±2.53 (P=0.0002). At the Month 6 visit, 81.3% of investigators and 71.0% of patients rated their satisfaction of pain relief with OROS hydromorphone ER treatment as good, very good, or excellent. Changes on the 36-item Short Form Health Survey, a quality-of-life measure, were statistically significant for the physical composite scores for all extension phase time points, including Month 6 (2.1±5.34; P<0.0001) and the last assessment (2.4±5.56; P<0.0001) and mental composite scores for all extension phase time points, including Month 6 (3.3±9.52; P=0.0006) and the last assessment (3.1±9.5; P=0.0008). Treatment with OROS hydromorphone ER also resulted in significant improvement in sleep disturbances. Adverse events included gastrointestinal and central nervous system symptoms.
The results support the long-term use of OROS hydromorphone ER in managing chronic moderate to severe low back pain.
Pain Medicine 10/2010; 11(10):1477-88. DOI:10.1111/j.1526-4637.2010.00956.x · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study evaluated the effects of topical lidocaine on skin sensation and on intradermal capsaicin-induced pain and hyperalgesia. A randomized, double-blinded, placebo controlled methodology was used. After baseline sensory testing, a placebo patch and a lidocaine patch were randomized to the volar aspect of the left or right forearm for 4 hours. The right forearm patch was removed, the sensory testing was repeated, and capsaicin was injected intradermally at the site. Pain scores were measured at the time of injection and every 2.5 minutes for 10 minutes followed by measurement of the hyperalgesic area to von Frey hair and stroking, flare response, and repeat sensory testing. At the completion of the testing on the right forearm, the left forearm patch was removed and the procedures described for the right forearm were repeated for the left forearm. There was a significant reduction in cool sensation, warm sensation, and touch thresholds in the lidocaine but not placebo patch arm. The lidocaine patch had no significant effect on hot pain or mechanical pain thresholds. Intradermal capsaicin resulted in a significant decrease in hot pain and mechanical pain thresholds; however, lidocaine was unable to significantly reverse the thermal or mechanical hyperalgesia induced by capsaicin. The lidocaine patch did not reduce flare area, nor areas of hyperalgesia or allodynia. This study suggests that the sodium channels and the capsaicin receptors function independently to control peripheral terminal depolarization. PERSPECTIVE: The sodium channel and the transient receptor potential vanilloid 1 (TRPV1) receptor coexist on peripheral terminals of unmyelinated fibers. This study showed that activation of the TRPV1 receptor can depolarize the fibers in the presence of sodium channel blockade. This suggests that the sodium channel and TRPV1 receptor function independently in depolarizing the fibers.
The journal of pain: official journal of the American Pain Society 10/2010; 12(3):323-30. DOI:10.1016/j.jpain.2010.07.013 · 4.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: to assess the long-term safety, tolerability, and consistency of effect of fentanyl pectin nasal spray (FPNS) in patients with breakthrough cancer pain (BTCP).
a multicenter, open-label study.
patients with chronic cancer pain treated with > or = 60 mg/d oral morphine or equivalent experiencing 1-4 episodes per day of BTCP.
all patients entered into a 16-week treatment phase after undergoing a dose-titration phase with FPNS.
safety and tolerability were assessed by adverse events (AEs) and by nasal tolerability assessments. Consistency of effect was monitored through additional rescue medication use and FPNS dose change.
four hundred three patients were included in the safety analyses. Of these, 356 patients entered the treatment phase and 110 patients completed the study. FPNS was self-administered for 42,227 episodes. During the treatment phase, 99 patients (24.6 percent) reported treatment-related AEs; most were mild or moderate and typical of opioids. Serious AEs were reported by 61 patients (15.1 percent), but only five were considered related to study drug. Of the 80 deaths that occurred during this study, one was assessed as possibly related to study drug. Nasal assessments revealed no significant local effects. No additional rescue medication was required after 94 percent of FPNS-treated episodes. More than 90 percent of patients required no increase in their initial dose of FPNS.
FPNS use for BTCP was associated with AEs, typical of opioids, with no evidence of nasal toxicity. A large proportion of BTCP episodes were treated with a single dose, and doses remained stable over the 4-month period.
Journal of opioid management 09/2010; 6(5):319-28. DOI:10.5055/jom.2010.0029
[Show abstract][Hide abstract] ABSTRACT: Ziconotide is a nonopioid intrathecal analgesic used to manage moderate to severe chronic pain. Although ziconotide is approved in the United States for intrathecal monotherapy only, it is often used in combination with other intrathecal drugs in clinical practice.
The need exists for a critical assessment of the currently available published literature on ziconotide combination therapy. This review summarizes and evaluates the publications from preclinical and clinical peer-reviewed experiments that have investigated the safety and effectiveness of ziconotide in combination with a variety of other drugs.
Eleven relevant publications were identified through a systematic search of multiple databases.
In preclinical studies, additive or synergistic antinociceptive effects were discovered when ziconotide was used in combination with morphine, clonidine, or baclofen; however, no additional antinociceptive effects were observed when bupivacaine was added to ziconotide therapy. Safety data from animal studies revealed that ziconotide did not exacerbate morphine-induced respiratory depression, or clonidine-induced hypotension or bradycardia; however, ziconotide did potentiate morphine-induced hypotension and inhibition of gastrointestinal tract motility. Results from 2 open-label trials indicated that combination ziconotide and morphine therapy produced greater analgesia than was produced by the use of either drug alone. Preliminary support for the use of ziconotide in combination with morphine, baclofen, or hydromorphone was provided by case studies.
Although clinical and preclinical studies provide some support for the use of ziconotide in combination with morphine, hydromorphone, clonidine, or baclofen, strong evidence-based data are limited. Controlled, long-term clinical trials are warranted.
The Clinical journal of pain 09/2010; 26(7):635-44. DOI:10.1097/AJP.0b013e3181e017df · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This pooled analysis was designed to determine whether the analgesic response to treatment with OROS hydromorphone, as measured by the "pain on average" scale of the Brief Pain Inventory (BPI), was different in patients with neuropathic pain compared to those with nociceptive pain, after adjusting for differences in baseline characteristics. Three open-label studies on patients with neuropathic and nociceptive malignant and nonmalignant chronic pain were analyzed. A mixed model for repeated measures linear regression analysis was used to compare the effect of OROS hydromorphone on patients with neuropathic and nociceptive pain, adjusting for potentially confounding factors. Data from patients with pure neuropathic pain and mixed pain were also compared. Safety and tolerability was assessed by recording the number of adverse events. The primary outcome was "pain on average" (BPI item 5) over time. Secondary outcomes were the effect of OROS hydromorphone on other BPI items including "pain relief" and "interference with sleep." Patients with neuropathic pain showed a similar response to treatment with OROS hydromorphone to those patients with nociceptive pain. There was no statistically significant difference between the pain groups (difference between groups -0.552 at visit 7; P = .060 for overall difference between groups). For some outcome variables, treatment was more effective for patients with neuropathic pain. The treatment was generally well tolerated. This pooled analysis shows that treatment with OROS hydromorphone had similar efficacy for neuropathic and nociceptive pain.
Journal of Pain & Palliative Care Pharmacotherapy 09/2010; 24(3):200-12. DOI:10.3109/15360288.2010.502213
[Show abstract][Hide abstract] ABSTRACT: Intrathecal therapy offers an invasive alternative for the long-term management of select patients with intractable pain associated with various disease states, including those of noncancer origin. It is commonly accepted that proper patient selection is essential to optimizing treatment outcomes, yet the practice of candidate selection for device implantation varies widely. A multifaceted approach--with consideration of preexisting medical comorbidities; psychological status; associated social, technical, and economic issues; and response to intrathecal trialing--enables practitioners to fully evaluate the appropriateness of implanting a patient with an intrathecal drug delivery system. Yet, to date no standard set of guidelines have been developed to aid practitioners in navigating this evaluation process. Using experience- and knowledge-based expert opinion to systematically evaluate the available evidence, this article provides consensus guidelines aimed at optimizing the selection of patients with noncancer pain for intrathecal therapy. In conclusion, complete assessment of a patient's physical, psychological, and social characteristics, can guide practitioners in determining the appropriateness of initiating intrathecal therapy. These consensus guidelines are intended to assist with weighing this risk/benefit ratio of intrathecal therapy, thereby minimizing the potential for treatment failure, unacceptable adverse effects, and excess mortality.
[Show abstract][Hide abstract] ABSTRACT: Since the late 1980s, intrathecal (IT) analgesic therapy has improved, and implantable IT drug delivery devices have become increasingly sophisticated. Physicians and patients now have myriad more options for agents and their combination, as well as for refining their delivery. As recently as 2007, The Polyanalgesic Consensus Conference of expert panelists updated its algorithm for drug selection in IT polyanalgesia. We review this algorithm and the emerging therapy included. This article provides an update on newly approved as well as emerging IT agents and the advances in technology for their delivery.
Current Pain and Headache Reports 02/2010; 14(1):8-16. DOI:10.1007/s11916-009-0092-z · 2.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The UV-B pain model utilizes ultraviolet light to induce a small area of inflammation allowing assessment of mechanical and thermal thresholds. Pharmacologic testing has mainly focused on reduction of primary hyperalgesia, although the effect of analgesics on secondary hyperalgesia has also been investigated. The model requires an instrument to precisely generate controlled UV-B tissue hyperalgesia. Initially, a minimum dose to induce tissue hyperalgesia is determined; subsequently, dosages are delivered in set quantities. Tissue is then assessed for inflammation using color Doppler imaging or flare measurements. Heat pain thresholds and pain tolerance are often evaluated using a commercially available thermal sensory testing device. Analgesics can be administered to determine the influence on these clinical endpoints.
[Show abstract][Hide abstract] ABSTRACT: The cold pressor test is a reliable pain model in which subjects submerge their hands and forearms into ice water while onset to pain, pain intensity, and tolerance are assessed. Although originally developed as a model for hypertension, the paradigm leads to development of reproducible pain responses allowing assessment to analgesic medications. However, analgesic variability to various medications has been observed. A recent study suggests that methodological discrepancies may contribute to such inconsistencies. The model may be more reproducible by utilizing consistent protocols.
[Show abstract][Hide abstract] ABSTRACT: The heat/capsaicin sensitization and intradermal capsaicin injection models are safe and noninvasive paradigms to generate stable, long-lasting, and reproducible injury capable of producing an area of both primary and secondary hyperalgesia. Risk of skin injury is substantially reduced since lower levels of thermal and chemical irritation produce long-lasting cutaneous hyperalgesia. Rekindling sustains central sensitization by providing peripheral nociceptive input. The intradermal capsaicin model has been widely used to test analgesic efficacy for a wide range of analgesics. Unlike the heat/capsaicin sensitization model, intradermal capsaicin results in a brief painful stimulus followed by a long lasting area of secondary hyperalgesia. The intradermal injection of capsaicin results in a transient, intense stinging sensation at the site of injection (e.g. heat allodynia) followed by a persistent area of secondary tactile allodynia.