Titration with oxymorphone extended release to achieve effective long-term pain relief and improve tolerability in opioid-naive patients with moderate to severe pain. Continuous intrathecal morphine treatment for chronic pain of nonmalignant etiology: long-term benefits and efficacy. Safety, tolerability, and effectiveness of oxymorphone extended release for moderate to severe osteoarthritis pain: a one-year study. Evaluation of long-term efficacy and safety of transdermal fentanyl in the treatment of chronic noncancer pain. Long-term management of noncancer pain with transdermal therapeutic system-fentanyl. Long-term intrathecal infusion of drug combinations for chronic back and leg pain. Long-term intraspinal infusions of opioids in the treatment of neuropathic pain. Intrathecal opioid treatment for chronic non-malignant pain: a 3-year prospective study. Around-the-clock, controlled-release oxycodone therapy for osteoarthritis-related pain: placebo-controlled trial and long-term evaluation. Methadone in the intrathecal treatment of chronic nonmalignant pain resistant to other neuroaxial agents: the first experience. A randomized, double-blind, crossover comparison of the efficacy and safety of oral controlled-release tramadol and placebo in patients with painful osteoarthritis. Transdermal fentanyl versus sustained release oral morphine in strong-opioid naïve patients with chronic low back pain. Continuous intrathecal morphine infusion in patients with vertebral fractures due to osteoporosis. Long-term oral opioid therapy in patients with chronic nonmalignant pain. Maintenance of the long-term effectiveness of tramadol in treatment of the pain of diabetic neuropathy. Open-label study of the safety and effectiveness of long-term therapy with extended-release tramadol in the management of chronic nonmalignant pain. A prospective study of long-term intrathecal morphine in the management of chronic nonmalignant pain. [Long-term treatment of trigeminal neuralgia using valoron]. Opioid switching from oral slow release morphine to oral methadone may improve pain control in chronic non-malignant pain: a nine-month follow-up study. [Intrathecal opioids in chronic non-malignant pain: relief and life quality]. Intrathecal morphine pump as a treatment option in chronic pain of nonmalignant origin. Long-term use of controlled-release oxycodone for noncancer pain: results of a 3-year registry study. A Prospective, Randomized Trial of Intrathecal Injection vs. Epidural Infusion in the Selection of Patients for Continuous Intrathecal Opioid Therapy. Efficacy and safety of a once-daily morphine formulation in chronic, moderate-to-severe osteoarthritis pain: results from a randomized, placebo-controlled, double-blind trial and an open-label extension trial. Association of transdermal fentanyl and oral transmucosal fentanyl citrate in the treatment of opioid naive patients with severe chronic noncancer pain.
Assess the effectiveness and tolerability of a program of gradual dose titration with oxymorphone extended release (ER) for treatment of moderate to severe chronic pain in opioid-naive patients.
                Open-label, nonrandomized 6-month study with a titration/stabilization period of <or=1 month followed by a 5-month maintenance period.
                Multidisciplinary pain centers in the United States.
                Adult opioid-naive patients with moderate to severe chronic pain.
                Patients were gradually titrated from a 5-mg dose of oxymorphone ER (taken every 12 hours) to a stabilized dose that provided effective pain relief and was well tolerated.
                Brief Pain Inventory Short Form questions 5 and 9, patient and physician global assessments of pain relief, adverse events (AEs), and discontinuations.
                The majority (94/126; 75%) of patients were stabilized on a dose of oxymorphone ER that provided effective pain relief with tolerable AEs. Most (81/94; 86%) required <24 days to reach a stable dose. Sixteen percent of patients in the titration period and 17% of patients in the maintenance period discontinued because of AEs possibly or probably related to oxymorphone ER. Patients completing the entire 5-month maintenance period experienced effective pain relief with significant (>50%) reductions of pain interference with quality-of-life measures. There was minimal dose escalation over the 5 months and low use of rescue medication.
                Oxymorphone ER provided effective pain relief from moderate to severe chronic pain in opioid-naive patients. Gradual titration was well tolerated, with a low rate of discontinuations caused by AEs. To analyze, prospectively, the long-term effects of continuous intrathecal morphine infusion therapy in 16 patients with chronic nonmalignant pain syndromes.
                Twenty-five patients with severe, chronic, nonmalignant pain that had proven refractory to conservative management were considered candidates for trial of intrathecal spinal morphine. Sixteen patients achieved more than 50% pain relief after a trial period of intrathecal morphine infusion. They were implanted with fully implantable and programmable pumps through which morphine was delivered intrathecally on a continuous basis. These patients were followed prospectively and underwent careful evaluation of their functional and mental status, and pain intensity measurements using standardized techniques before treatment and every 6 months thereafter in the follow-up period. The follow-up period ranged from 13 months to 49 months (mean 29.14 months +/- 12.44 months) for the patients who had implanted morphine pumps.
                The mean morphine dosage initially administered was 1.11 mg/day (range 0.2--6.5 mg/day); after 6 months, it was 3.1 mg/day (range 0.4--8.75 mg/day). In long-term observation, no patient had a constant dosage history. The patients who received intrathecal morphine for longer than 2 years all showed an increase in morphine dosage to more than 10 mg/day. The best long-term results were seen with deafferentation pain and mixed pain, with 75% and 61% pain reduction (visual analog scale), respectively. Nociceptive pain patients had best pain relief initially (78% pain reduction) but it tended to decrease over the follow-up period to 57% pain reduction at final follow-up. The average pain reduction for all groups after 6 months was 67.5% and at last follow-up, it was 57.5%. Ten patients were satisfied with the delivery system and eleven reported improvement in their quality of life. In two patients, morphine was not able to adequately control the pain without producing undesirable side effects requiring the addition of clonidine to their infusion medication. In this series, 12 patients were considered successes and 4 patients were considered failures. In two patients, the intrathecal opioid therapy was unable to produce satisfactory pain relief and in the other two patients the pumps had to be explanted because of intolerable side effects.
                In our experience, the administration of intrathecal opioid medications for nonmalignant pain is justified in carefully selected patients. A 52-week, multicenter, open-label extension study was performed to evaluate the safety, tolerability, and effectiveness of oxymorphone extended release (ER), a novel tablet formulation of oxymorphone hydrochloride, in 153 patients with moderate to severe chronic osteoarthritis-related pain. Sixty-one patients (39.9%) completed the study. Common opioid-related nonserious adverse events (AEs) caused most withdrawals. However, approximately one-half of withdrawals due to AEs were among opioid-naive patients who received placebo in a previous trial and were started on a dose of 20 mg every 12 hours, suggesting that tolerability can be improved by titrating from a lower initial dose. Mean pain scores initially decreased as previously opioid-naive patients achieved adequate pain relief, reached stable levels after the first 6 weeks, and remained stable at mild levels throughout the remainder of the study (average pain, 20-25 mm on 100-mm Visual Analog Scale). Average daily dosing remained stable throughout the study (median, 40 mg/d). At each assessment, at least 80% of patients rated their global satisfaction with oxymorphone ER as "excellent," "very good," or "good." Oxymorphone ER provides a new 12-hour analgesic for the treatment of moderate to severe chronic osteoarthritis-related pain in patients who may require long-term opioid therapy. The objective of this international, multicenter, open-label trial was to assess the efficacy and safety of up to 12 months of therapy with transdermal therapeutic system (TTS) fentanyl in patients (n = 532) with chronic noncancer pain. The trial was completed by 301 (57%) of the patients. The main outcome measures were pain control assessment, global treatment satisfaction, patient preference for TTS fentanyl, and quality of life. The mean dose of transdermal fentanyl (TDF) increased from 48 to 90 microg/h during a period of 12 months. During treatment, on average 67% of patients within the efficacy analysis group (n = 524) reported very good, good, or moderate pain control. Global satisfaction (very good or good) was also stable at 42%. The majority (86%) of patients reported a preference for TDF over their previous treatment (P < .001, binomial test). Short Form 36 quality-of-life scores improved from baseline for bodily pain. The most frequent treatment-related adverse events were nausea (31%), constipation (19%), and somnolence (18%). With regard to opioid-specific adverse events (respiratory depression [< 1%], adrenal insufficiency [< 1%], drug abuse/dependence [1%], and opioid withdrawal syndrome [3%]), these were extremely rare and, with the exception of opioid withdrawal syndrome, none was considered definitively related to the treatment. Long-term treatment with TDF provided a stable degree of pain control in the majority of patients with moderate to severe chronic noncancer pain. It was preferred by the majority of patients compared with their previous opioid medication. Overall, long-term treatment with TDF was generally well tolerated, particularly in view of the low incidence of potentially serious side effects such as drug abuse/dependence and respiratory depression. However, at present, it is important that patients receiving TDF should still be subject to careful assessment and monitoring. Transdermal therapeutic system-fentanyl (TTS-F) has been extensively studied in cancer pain management. However, few studies have addressed the long-term management of noncancer pain, especially when it relates to neuropathic pain. A total of 529 patients were recruited into this prospective open-label study to determine the safety and effectiveness of TTS-F in relation to quality-of-life (QOL) stratified according to pain type and etiology. TTS-F significantly improves QOL within 28 days, and pain management within 48 hours. The frequency of side effects rapidly decreases over time, and patients not experiencing adequate pain management are identified within 28 days. The median duration of therapy for effective pain management was 10 months, and 90% of patients sustained such efficacy. TTS-F offers statistically significant increases in QOL-Short Form 12 (including the Physical Component Scale and Mental Component Scale measures) and pain control (Greek Brief Pain Inventory) from one time point to the next (P <.0001). These improvements are not influenced by pain type or etiology. TTS-F is a safe and effective pain management system independent of patient characteristics and demographic factors. What is of most importance is that in those patients with neuropathic pain, for whom opioids have long been thought to be ineffective, similar effectiveness is demonstrated when compared to patients with nociceptive pain. Continuous intrathecal infusion of analgesic drugs by implantable pumps is recognized as an established treatment option for patients with chronic pain resistant to oral or parenteral medication. Polyanalgesia, the simultaneous use of more than one intrathecal analgesic drug, is practiced relatively often, but there are only a few published clinical studies on intrathecal polyanalgesia for chronic nonmalignant pain. This pilot study represents a long-term evaluation of a treatment regimen consisting of intrathecal morphine admixed with bupivacaine, clonidine, or midazolam in patients with chronic nonmalignant back and leg pain due to degenerative lumbar spinal disease. Twenty-six adult patients have been treated by intrathecal programmable pump-controlled infusion of analgesic drugs and followed for up to 3.5 years (27 +/- 11 months). Combination of morphine with a second drug was used in 10 cases, morphine with 2 additional drugs in 12 cases, and morphine with 3 additional drugs in 4 cases. Mean daily doses at 24 months after pump implantation were 6.2 +/- 2.8 mg for morphine, 2.5 +/- 1.5 mg for bupivacaine, 0.06 +/- 0.03 mg for clonidine, and 0.8 +/- 0.4 mg for midazolam. Nineteen patients reported excellent or good long-term treatment results, 6 patients had sufficient results, and only 1 patient complained of poor therapeutic efficacy. No long-term clinical side effects of intrathecal polyanalgesia were noted. Mean morphine dose had to be increased from 1.2 mg at baseline to 5.1 mg at 24 months due to tolerance development and disease progression. This experience suggests that intrathecal polyanalgesia employing morphine combined with additional nonopioid drugs can have a favorable analgesic efficacy in patients with complex chronic pain of spinal origin, and lacks major drug-related complications. Long-term intraspinal infusions of opioid drugs are being increasingly utilized in patients with noncancer pain. Despite this, there is a lack of long-term information, including success and failure rates for pain relief and technical problems. During a 5-year period, 18 noncancer patients underwent implantation of programmable infusion pumps for long-term intrathecal opioid infusion. Patients had (a) neuropathic pain, (b) had failed or been ineligible for noninvasive treatments, and (c) obtained greater than 50% pain relief with intrathecal trial infusions of morphine sulfate or sufentanil citrate. A disinterested third-party reviewer evaluated patients at the most recent follow-up. Sixty-one percent (11/18) of patients had good or fair pain relief with mean follow-up 2.4 +/- 0.3 years (0.8-4.7 years). Average numeric pain scores decreased by 39% +/- 4.3%. Five of the 11 responders required lower opioid doses (12-24 mg/day morphine) and the remaining six patients required higher opioid doses (> 34 mg/day morphine). Failure of long-term pain relief occurred in 39% (7/18) despite good pain relief in trial infusions and the use of both morphine and sufentanil. Technical problems developed in 6/18 patients but appeared to be preventable with further experience. Long-term intrathecal opioid infusions can be effective in treatment of neuropathic pain but might require higher infusion doses. Intrathecal (IT) opioid therapy is a treatment alternative for patients with severe chronic non-malignant pain. Several uncontrolled retrospective and prospective outcome studies have suggested a benefit in chronic non-malignant pain patients, but uncertainties about patient selection in these studies weaken the results. This study evaluated long-term outcome of IT opioid therapy in chronic non-malignant pain prospectively, and included two comparative groups to improve understanding of selection criteria and relative severity of intrathecal pump recipients (PRs). The study subjects included 38 PRs while the comparative groups included 31 intrathecal candidates who either had an unsuccessful trial, or declined the IT therapy, and another group of 41 newly referred patients. The following data were analyzed at study entry, and at 6 monthly intervals for a 3-year period: Symptom Check List 90 (SLC-90), SF-36 Health survey, Beck Depression Inventory, McGill Pain Questionnaire (short form), Oswestry Disability Index, Pain Drawings and Pain rating on visual analogue scale. Data analysis suggests the study group of PRs had improvements in pain, mood, and function from baseline to 36 months. These same parameters improved among new referrals (less severe patients receiving conservative pain management) while non-recipients significantly worsened. Although PRs improved, they were still worse off at 36 months than new referrals were at baseline. The study showed that when patients with extremely severe pain problems are selected as pump candidates, they will likely improve with the therapy, but their overall severity of pain and symptoms still remains high. Although opioid analgesics have well-defined efficacy and safety in treatment of chronic cancer pain, further research is needed to define their role in treatment of chronic noncancer pain.
                To evaluate the effects of controlled-release oxycodone (OxyContin tablets) treatment on pain and function and its safety vs placebo and in long-term use in patients with moderate to severe osteoarthritis pain.
                One hundred thirty-three patients experiencing persistent osteoarthritis-related pain for at least 1 month were randomized to double-blind treatment with placebo (n = 45) or 10 mg (n = 44) or 20 mg (n = 44) of controlled-release oxycodone every 12 hours for 14 days. One hundred six patients enrolled in an open-label, 6-month extension trial; treatment for an additional 12 months was optional.
                Use of controlled-release oxycodone, 20 mg, was superior (P<.05) to placebo in reducing pain intensity and the interference of pain with mood, sleep, and enjoyment of life. During long-term treatment, the mean dose remained stable at approximately 40 mg/d after titration, and pain intensity was stable. Fifty-eight patients completed 6 months of treatment, 41 completed 12 months, and 15 completed 18 months. Common opioid side effects were reported, several of which decreased in duration as therapy continued.
                Around-the-clock controlled-release oxycodone therapy seemed to be effective and safe for patients with chronic, moderate to severe, osteo-arthritis-related pain. Effective analgesia was accompanied by a reduction in the interference of pain with mood, sleep, and enjoyment of life. Analgesia was maintained during long-term treatment, and the daily dose remained stable after titration. Typical opioid side effects were reported during short- and long-term therapy. Intrathecal drug delivery is a widely used and effective method of treatment for chronic intractable pain. Unfortunately all currently used agents can not provide adequate pain relief in all patients. A prospective study of neuroaxial methadone was performed in 24 patients, all of whom had failed treatment with multiple previous intrathecal drugs. Thirteen patients experienced improvement of their pain control with methadone, nine continued to receive this agent for 6 months with good pain relief, improved quality of life and no side effects. The final rates of methadone infusion were 2.2 times higher than preceding morphine rates. The only observed possible side effect of methadone was transient blurred vision in one patient. Methadone is a promising alternative neuroaxial agent in the treatment of chronic pain. To compare the efficacy and safety of controlled-release (CR) tramadol (Zytram XL, Purdue Pharma, Canada) and placebo in patients with painful osteoarthritis.
                Patients underwent analgesic washout for two to seven days before random assignment to 150 mg daily of CR tramadol or placebo, and were titrated weekly to 200 mg, 300 mg or a maximum of 400 mg once daily. After four weeks, patients crossed over to the alternate treatment for another four weeks. Plain acetaminophen was provided as a rescue analgesic. All patients who completed the crossover study were eligible to receive open label CR tramadol for six months.
                Seventy-seven of 100 randomly assigned patients were evaluable for efficacy. CR tramadol resulted in significantly lower visual analogue scale pain intensity scores (37.4+/-23.9 versus 45.1+/-24.3, P=0.0009). Western Ontario and McMaster Universities osteoarthritis index subscale scores for pain (189.0+/-105.0 versus 230.0+/-115.4; P=0.0001) and physical function (632.4+/-361.3 versus 727.4+/-383.4; P=0.0205) were significantly better with CR tramadol. Total pain and disability (22.8+/-14.5 versus 27.2+/-14.8; P=0.0004), and overall pain and sleep (104.7+/-98.0 versus 141.0+/-108.2; P=0.0005) scores in the Pain and Sleep Questionnaire were significantly lower for CR tramadol. Short-form 36 Health Survey scores were significantly better during CR tramadol treatment for the pain index (38.8+/-10.8 versus 35.6+/-9.0; P=0.0100), general health perception (46.5+/-11.2 versus 44.4+/-11.6; P=0.0262), vitality (43.1+/-13.2 versus 40.2+/-13.7; P=0.0255) and overall physical components (40.8+/-8.9 versus 37.8+/-7.7; P=0.0002). CR tramadol treatment was preferred by 55.8% of patients (P=0.0005) versus 20.8% and 23.4% of patients who chose placebo or had no preference, respectively. These improvements were sustained for up to six months, and 86.5% of patients reported at least moderate benefit from CR tramadol during long-term treatment.
                CR tramadol is effective for the management of painful osteoarthritis. Open, randomized, parallel group multicenter study.
                To compare the efficacy and safety of transdermal fentanyl (TDF) and sustained release morphine (SRM) in strong-opioid naïve patients with chronic low back pain (CLBP).
                Most studies of TDF and SRM have involved patients already receiving strong opioids. This is the first large-scale study focusing on strong-opioid naïve patients with CLBP.
                Adults with CLBP requiring regular strong opioid therapy received either TDF or SRM for 13 months. Starting doses were 25 microg/hr fentanyl patches every 72 hours or 30 mg oral morphine every 12 hours. Doses were adjusted according to response. Participants assessed pain relief and bowel function using weekly diaries. Other assessments, including quality of life, disease progression, and side effects, were made by patients and investigators.
                Data from 680 patients showed that TDF and SRM provided similar levels of pain relief, but TDF was associated with significantly less constipation than SRM, indicating a greater likelihood of satisfactory pain relief without unmanageable constipation for patients receiving TDF. Other ratings were similar for TDF and SRM, but TDF provided greater relief of pain at rest and at night.
                TDF and SRM provided equivalent levels of pain relief, but TDF was associated with less constipation. This study indicates that sustained-release strong opioids can safely be used in strong-opioid naïve patients. Vertebral fractures are the most common consequences of severe osteoporosis. The chronic pain from collapse of osteoporotic vertebrae affects quality of life (QOL) and autonomy of patients. The management of pain with oral or transdermal opiates can cause severe side effects. Continuous intrathecal administration of morphine via an implantable pump might represent an alternative therapy to conventional oral or transdermal administration of opioids and has some advantages and disadvantages for pain relief and improvement in QOL when compared with conventional opioid delivery. It is our objective to report our experience using intrathecal delivery of analgesics in a population of patients with refractory pain due to vertebral fractures.
                In 24 patients, refractory to conventional delivery of opioids, we used intrathecal analgesic therapy. To test for efficacy and improvement in QOL, we administered the visual analog scale for pain and the Questionnaire of the European Foundation of Osteoporosis (QUALEFFO). Before patients were selected for pump implantation, an intraspinal drug delivery trial was performed to monitor side effects and responses to intrathecal therapy.
                Significant pain relief was obtained in all implanted patients. Using the QUALEFFO, we observed significant improvement of all variables such as quality of daily life, domestic work, ambulation, and perception of health status, before and after 1 year after pump implantation. With intrathecal morphine infusion, none of the 24 patients required additional systemic analgesic medication. The mean morphine dose during the spinal trial was 11.28 mg/d, 7.92 mg/d at pump implantation, and 16.32 mg/d at 1-year follow-up.
                Our results show that intrathecal administration of morphine efficiently relieves the symptoms of pain and improves QOL. Continuous intrathecal administration of morphine appears to be an alternative therapy to conventional analgesic drug delivery and has advantages in those patients who have severe side effects with systemic administration of analgesics. In contrast to the use of opioids for the treatment of acute and chronic cancer pain, the administration of chronic opioid therapy for pain not due to malignancy remains controversial. We describe 100 patients who were chronically given opioids for treatment of nonmalignant pain. Most patients experienced neuropathic pain or back pain. We used sustained-release dihydrocodeine, buprenorphine, and sustained-release morphine. Pain reduction was measured with visual analogue scales (VAS), and the Karnofsky Performance Status Scale was used to assess the patient's function. Good pain relief was obtained in 51 patients and partial pain relief was reported by 28 patients. Only 21 patients had no beneficial effect from opioid therapy. There was a close correlation between the sum and the peak VAS values (r = 0.983; p less than 0.0001) and pain reduction was associated with an increase in performance (p less than 0.0001). The most common side effects were constipation and nausea. There were no cases of respiratory depression or addiction to opioids. Our results indicate that opioids can be effective in chronic nonmalignant pain, with side effects that are comparable to those that complicate the treatment of cancer pain. The objective of this study was to evaluate the efficacy and safety of tramadol in a 6-month open extension following a 6-week double-blind randomized trial.
                Patients with painful diabetic neuropathy who completed the double-blind study were eligible for enrollment in an open extension of up to 6 months. All patients received tramadol 50-400 mg/day. Self-administered pain intensity scores (scale 0-4; none to extreme pain) and pain relief scores (scale -1-4; worse to complete relief) were recorded the first day of the open extension (last day of the double-blind phase) and at 30, 90, and 180 days.
                A total of 117 patients (56 former tramadol and 61 former placebo) entered the study. On the first day of the study, patients formerly treated with placebo had a significantly higher mean pain intensity score (2. 2+/-1.02 vs. 1.4+/-0.93, P<0.001) and a lower pain relief score (0. 9+/-1.43 vs. 2.2+/-1.27, P<0.001) than former tramadol patients. By Day 90, both groups had mean pain intensity scores of 1.4, which were maintained throughout the study. Mean pain relief scores (2. 4+/-1.09 vs. 2.2+/-1.14) were similar after 30 days in the former placebo and former tramadol groups, respectively and were maintained for the duration of the study. Four patients discontinued therapy due to ineffective pain relief; 13 patients discontinued due to adverse events. The most common adverse events were constipation, nausea, and headache.
                Tramadol provides long-term relief of the pain of diabetic neuropathy. Tramadol ER* is a once-daily oral analgesic for management of moderate-to-moderately severe chronic pain in adults who require around-the-clock treatment of pain. This study evaluated long-term safety of tramadol ER and effectiveness outcomes in the management of chronic, nonmalignant pain.
                Patients enrolled directly for approximately 1 year of open-label tramadol ER treatment if they had chronic, nonmalignant pain (n = 919), or 'rolled over' for 38 weeks of open-label tramadol ER treatment if they completed either of two 12-week, placebo-controlled studies of tramadol ER for low back pain (n = 72) or osteoarthritis (n = 61). Tramadol ER was titrated to a dose of 300 mg once daily (patients >or= 75 years) or 300-400 mg once daily (patients < 75 years).
                A total of 257 (24%) patients completed the study. Common adverse events, regardless of treatment relationship, were nausea, dizziness (excluding vertigo), and constipation. Mean scores for current pain intensity (from 0 = no pain to 100 = extreme pain) and least, worst, and average pain intensity over the past week improved at every post-baseline visit. At each post-baseline visit, > 50% of patients provided a global assessment rating of good, very good, or excellent. Study limitations were mandatory titration to 400 mg in some patients, concomitant analgesic therapy as a confounding variable, and lack of a placebo comparator.
                Individualized dose titration and limiting once-daily therapy with tramadol ER to the maximum recommended daily dose of 300 mg may balance tolerability and analgesic effects of tramadol ER in patients with chronic, nonmalignant pain. To examine in a prospective manner the long-term safety and efficacy of chronic intrathecal morphine in patients with severe, nonmalignant pain refractory to less invasive modalities.
                Forty patients with severe, chronic nonmalignant pain poorly managed by systemic medications were identified as candidates for intraspinal trial of morphine. Thirty participants reported successful pain relief during trial and were implanted with an intraspinal delivery system. Standardized measures of pain and functional status were assessed before treatment was begun and at defined intervals during the subsequent 24 months. Intrathecal opioid use and pharmacological and device-related complications were also monitored.
                The participants had a mean age of 58 +/- 13 years and a mean pain duration of 8 +/- 9 years. Fifty-three percent of the study participants were women. Pain type was characterized as mixed neuropathic-nociceptive (15 of 30 patients, 50%), peripheral neuropathic (10 of 30 patients, 33%), deafferentation (4 of 30 patients, 13%), or nociceptive (1 of 30 patients, 3%). Forty-seven percent of the patients were diagnosed with failed back surgery syndrome. Significant improvement over baseline levels of visual analog scale pain was measured at each follow-up examination after implant. Overall, 50% (11 of 22 patients) of the population reported at least a 25% reduction in visual analog scale pain after 24 months of treatment. In addition, the McGill Pain Questionnaire, visual analog scale measures of functional improvement and pain coping, and several subscales of the Chronic Illness Problem Inventory showed improvement throughout the follow-up period. Pharmacological side effects were managed medically by morphine dose reduction, addition of bupivacaine, or replacement of morphine with hydromorphone. Device-related complications requiring repeat operations were experienced by 20% of the patients.
                Continuous intrathecal morphine can be a safe, effective therapy for the management of severe, nonmalignant pain among a carefully selected patient population and can result in long-term improvement in several areas of daily function. nan Twelve patients with poor pain control or unacceptable side effects during treatment with morphine were switched to methadone and followed for nine months in this open prospective study. Primary outcomes were patient preference for opioid and pain control while physical, cognitive and role functioning were secondary outcomes. The morphine dose was decreased by 1/3 daily and was replaced with an equianalgesic dose of methadone over a three-day period. During switching and a one-week dose titration period, patients were given additional methadone if required. During dose titration one patient experienced sedation requiring naloxone. Four patients were switched back to morphine due to poor pain control, drowsiness or sweating. Seven patients preferred long-term (>nine months) treatment with methadone and reported reduced pain and improved functioning while cognition was not improved. This study brings novel information on the long-term consequences for pain control, health-related quality of life and cognitive functioning with a switch from morphine to methadone in the treatment of chronic non-malignant pain. The use of opioids for treatment of non-malignant pain is controversial. The evaluation of pain relief and of the quality of life of 11 severely incapacitated chronic non-cancer pain patients treated with long term intrathecal infusion of opioids trought implantable pumps was performed. The mean duration of pain complaints was 5.3 years. The mean pain intensity was 8.6. In 7 patients, pain episodes lasted at least 6 hours daily. The mean duration of the therapy was 19.6 months. After the treatment the mean pain score became 3.9. In only 1 patient, the duration of pain episodes was still longer than 6 hours. Quality of life improved in 36.36% of the cases. The long term spinal opioids through implantable pumps for non-malignant pains results in pain relief but not necessarily improves the quality of life. Implantable pumps for the delivery of intrathecal morphine have become a common option for administering opiate medication for the management of pain in patients with terminal cancer. Options for treating chronic pain of non-malignant origin are more controversial. This study describes responses to intrathecal morphine administration for managing chronic pain in patients without an underlying malignancy.
                Eleven patients between the ages of 29 and 81 years, nine with failed back syndrome (FBS) and two with neuropathic pain (NP) from other causes, were chosen from 15 consecutive individuals referred to neurosurgery clinic. The presenting levels of pain and a functional-economic outcome level were determined for each patient. Patients were admitted to the hospital for therapeutic trials and were assessed for the appropriateness of their analgesic response and for adverse responses to the medication. A morphine pump was implanted in five males and six females who were followed for up to 3 years.
                A good to excellent analgesic response was seen in 8 (73%) patients (6 FBS; 2 NP). In the remaining three patients (27%), the analgesic response was judged poor (3 FBS). In patients with FBS, the total effective response was 67%. Two patients experienced bladder dysfunction requiring pump removal. Other adverse effects of pump placement were rare.
                The morphine pump was found to be a viable alternative in the management of failed back syndrome. Its use in long-term therapy, however, is not without limitations and should be a last choice option. To evaluate the outcomes associated with the use of controlled-release (CR) oxycodone for up to 3 years in the treatment of noncancer pain.
                Adult patients who previously participated in controlled trials of CR oxycodone for osteoarthritis pain, diabetic neuropathy pain, or low back pain, and who continued to require opioid analgesia for moderate or severe pain, were enrolled in an open-label, uncontrolled, registry study. Data collected over time included dose, pain severity on a numeric scale, treatment acceptability, adverse events, and descriptions of problematic drug-related behavior.
                Two hundred thirty-three patients were enrolled. When the study closed, 141, 86, and 39 patients had taken CR oxycodone for at least 1, 2, and 3 years, respectively; mean duration of treatment was 541.5 days. Among the 219 intent-to-treat patients (received at least 1 dose and provided at least 1 postdose study observation), the mean (SD, range) daily dose was 52.5 (+/-38.5, 10.0 to 293.5) mg. Before the end of month 3, 44% required an increase in total daily dose; this dropped to 23% during months 4 to 6, to 17% during months 10 to 12, and remained at approximately 10% for each time interval thereafter (range 8% to 13%). Among the large majority of patients with stable or lower dose requirements after the initial 3 months of treatment, the average pain intensity ratings were unchanged or improved for approximately 70% to 80% of patients at all subsequent time points through month 33, and for 54% (7/13 patients) at month 36. A decrease in pain was initially seen by the end of month 3, and for the majority of patients, the Average Pain Intensity score remained the same, better, or minimally worse (<3 points) for the remainder of the 3-year study period. The most common adverse events were constipation and nausea, and the incidence of these events declined over time on treatment. Investigators reported 6 cases (2.6%) of possible drug misuse but no evidence of de novo addiction was observed.
                These registry data demonstrate that a subgroup of patients with noncancer pain experienced prolonged relief with tolerable side effects and modest need for dose escalation during long-term therapy with CR oxycodone. The objective of this study was to compare the cost and safety of intrathecal injection (IN) vs. epidural infusion (CE) trial and to provide a preliminary assessment of the prognostic value of each in the selection of patients for long-term continuous intrathecal opioid therapy (CIOT). Thirty-seven patients with chronic nonmalignant pain who were being considered for CIOT were randomized to morphine trial by IN or CE. Analgesic response and complications were monitored throughout trial. Sixty-seven percent of IN (12/18) and 79% (15/19) of CE subjects reported good pain relief (defined as ≥ 50% pain reduction) and were implanted with a permanent infusion system. Eighty-nine percent (24/27) of subjects provided six-month CIOT follow-up data. Cost of trial and health care utilization during six months of CIOT were compared between groups. Analgesic and functional response during CIOT was also compared between IN and CE groups. The cost of IN trial was significantly less than CE trial (p < 0.001). Complications were generally mild in both groups, although opioid-related side effects tended to be more common in the IN group. Successful pain relief after six months of CIOT was reported by 10 (60%) and 14 (64%) patients who underwent IN and CE trial, respectively (p = 0.32; Fisher's exact test). There was no difference between IN and CE groups in McGill Pain rating, quality of life (VAS), mood (Profile of Mood States), or function (Sickness Impact Profile) after six months of CIOT. We conclude that intrathecal injection is a safe procedure for use in selection of patients for CIOT and is less costly than epidural infusion. Differences in pain and functional response to long-term opioids among patients selected by either trial method are not large. A randomized, 4-week, double-blind trial followed by an open-label extension trial assessed the efficacy and safety of a once-daily, extended-release morphine formulation (Avinza (previously referred to as Morphelan)) in 295 patients with chronic, moderate-to-severe osteoarthritis pain who had failed to obtain adequate pain relief with NSAIDs and acetaminophen. Participants received one of four treatments: Avinza 30 mg once daily (QAM or QPM), MS Contin(R) 15 mg twice daily, or placebo twice daily. Patients (n =181) received Avinza QAM or QPM during the 26-week open-label extension trial and could increase their dose to optimize pain control. Avinza and MS Contin reduced pain and improved several sleep measures versus placebo. Analgesic efficacy was comparable between Avinza and MS Contin; however, Avinza QAM demonstrated greater improvements in overall quality of sleep. The most common adverse events were constipation and nausea. The majority of AEs occurred at a similar incidence among the active treatment groups. Chronic noncancer pain is often undertreated.
                To assess the efficacy of fentanyl transdermal therapeutic system (TTS) associated with oral transmucosal fentanyl citrate (OTFC) for breakthrough pain in patients with chronic noncancer pain.
                A total of 215 patients with chronic (> or =6 months), severe (VAS > or = 8) noncancer pain participated in a 6-month prospective study. The starting dose of 12 microg/h fentanyl TTS was titrated in 25 microg/h increments to a visual analog scale (VAS) score < or = 4. OTFC was administered as single-unit doses of 400 microg.
                The mean (SD) VAS score decreased from 9.86 (0.35) at baseline to 2.05 (0.96) at 6 months. The percentage of patients with poor quality of sleep decreased from 99 percent at baseline to 2.8 percent at the end of the study. The percentage of patients with inadequate pain control decreased from 16.2 percent at month 1 to 2.3 percent at month 6. Pain control was achieved with the 50 microg/h dose in 48 percent of patients, the 75 microg/h dose in 18 percent, and the 100 microg/h dose in 5 percent (only two patients required >100 microg/h). The daily use of single-unit doses of OTFC decreased from 4.64 at month 1 to 2.62 at month 6. Headache, nausea/vomiting, constipation, and somnolence of mild or moderate intensity were the most common side effects. Treatment was discontinued because of nausea/vomiting in seven patients, somnolence in three, and dermatitis in two.
                Fentanyl TTS associated with OTFC for breakthrough pain is a feasible and effective strategy in opioid naïve patients with severe chronic nonmalignant pain.
Many patients discontinue long-term opioid therapy (especially oral opioids) due to adverse events or insufficient pain relief; however, weak evidence suggests that patients who are able to continue opioids long-term experience clinically significant pain relief. Whether quality of life or functioning improves is inconclusive. Many minor adverse events (like nausea and headache) occurred, but serious adverse events, including iatrogenic opioid addiction, were rare.