buprenorphine and Low-Back-Pain

Buprenorphine is a partial agonist at the µ-opioid receptor and an antagonist at the delta and kappa opioid receptors. It has high affinity and low intrinsic activity at the µ-opioid receptor. Buprenorphine demonstrates no ceiling effect for clinical analgesia, but demonstrates this for respiratory depression and euphoria. It may provide effective analgesia while producing less adverse effects, making it a promising opioid analgesic. A systematic review and meta-analysis were performed to examine the analgesic efficacy of buprenorphine for patients with chronic noncancer pain.. PubMed, MEDLNE, Embase, and the Cochrane Library were searched up to January 2022. Randomized controlled trials were included if they compared buprenorphine versus placebo or active analgesic in patients with chronic noncancer pain, where pain score was an outcome. Nonrandomized controlled trials, observational studies, qualitative studies, case reports, and commentaries were excluded. Two investigators independently performed the literature search, study selection, and data collection. A random-effects model was used. The primary outcome was the effect of buprenorphine on pain intensity in patients with chronic noncancer pain based on standardized mean difference (SMD) in pain score. Quality of evidence was assessed using the Grade of Recommendations Assessment, Development, and Evaluation (GRADE) approach.. Two separate literature searches were conducted for patients with and without opioid use disorder (OUD). Only one study met the search criteria for those with OUD. Fourteen randomized controlled trials were included for those without OUD. Buprenorphine was associated with reduced pain score (SMD = -0.368, P < .001, I 2 = 89.37%) compared to placebo or active analgesic. Subgroup meta-analyses showed statistically significant differences in favor of buprenorphine versus placebo (SMD = -0.404, P < .001), for chronic low back pain (SMD = -0.383, P < .001), when administered via the transdermal route (SMD = -0.572, P = .001), via the buccal route (SMD = -0.453, P < .001), with length of follow-up lasting <12 weeks (SMD = -0.848, P < .05), and length of follow-up lasting 12 weeks or more (SMD = -0.415, P < .001). There was no significant difference when compared to active analgesic (SMD = 0.045, P > .05). Quality of evidence was low to moderate.. Buprenorphine was associated with a statistically significant and small reduction in pain intensity compared to placebo. Both the transdermal and buccal routes provided pain relief. There was more evidence supporting its use for chronic low back pain.

Topics: Analgesics, Opioid; Buprenorphine; Chronic Pain; Humans; Low Back Pain; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Receptors, Opioid

Pharmacological interventions are the most used treatment for low back pain (LBP). Use of evidence from systematic reviews of the effects of pharmacological interventions for LBP published in the Cochrane Library, is limited by lack of a comprehensive overview.. To summarise the evidence from Cochrane Reviews of the efficacy, effectiveness, and safety of systemic pharmacological interventions for adults with non-specific LBP.. The Cochrane Database of Systematic Reviews was searched from inception to 3 June 2021, to identify reviews of randomised controlled trials (RCTs) that investigated systemic pharmacological interventions for adults with non-specific LBP. Two authors independently assessed eligibility, extracted data, and assessed the quality of the reviews and certainty of the evidence using the AMSTAR 2 and GRADE tools. The review focused on placebo comparisons and the main outcomes were pain intensity, function, and safety.. Seven Cochrane Reviews that included 103 studies (22,238 participants) were included. There is high confidence in the findings of five reviews, moderate confidence in one, and low confidence in the findings of another. The reviews reported data on six medicines or medicine classes: paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, benzodiazepines, opioids, and antidepressants. Three reviews included participants with acute or sub-acute LBP and five reviews included participants with chronic LBP. Acute LBP Paracetamol There was high-certainty evidence for no evidence of difference between paracetamol and placebo for reducing pain intensity (MD 0.49 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -1.99 to 2.97), reducing disability (MD 0.05 on a 0 to 24 scale (higher scores indicate worse disability), 95% CI -0.50 to 0.60), and increasing the risk of adverse events (RR 1.07, 95% CI 0.86 to 1.33). NSAIDs There was moderate-certainty evidence for a small between-group difference favouring NSAIDs compared to placebo at reducing pain intensity (MD -7.29 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -10.98 to -3.61), high-certainty evidence for a small between-group difference for reducing disability (MD -2.02 on a 0-24 scale (higher scores indicate worse disability), 95% CI -2.89 to -1.15), and very low-certainty evidence for no evidence of an increased risk of adverse events (RR 0.86, 95% CI 0. 63 to 1.18). Muscle relaxants and benzodiazepines There was moderate-certainty evidence for a small between-group difference favouring muscle relaxants compared to placebo for a higher chance of pain relief (RR 0.58, 95% CI 0.45 to 0.76), and higher chance of improving physical function (RR 0.55, 95% CI 0.40 to 0.77), and increased risk of adverse events (RR 1.50, 95% CI 1. 14 to 1.98). Opioids None of the included Cochrane Reviews aimed to identify evidence for acute LBP. Antidepressants No evidence was identified by the included reviews for acute LBP. Chronic LBP Paracetamol No evidence was identified by the included reviews for chronic LBP. NSAIDs There was low-certainty evidence for a small between-group difference favouring NSAIDs compared to placebo for reducing pain intensity (MD -6.97 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI -10.74 to -3.19), reducing disability (MD -0.85 on a 0-24 scale (higher scores indicate worse disability), 95% CI -1.30 to -0.40), and no evidence of an in. We found no high- or moderate-certainty evidence that any investigated pharmacological intervention provided a large or medium effect on pain intensity for acute or chronic LBP compared to placebo. For acute LBP, we found moderate-certainty evidence that NSAIDs and muscle relaxants may provide a small effect on pain, and high-certainty evidence for no evidence of difference between paracetamol and placebo. For safety, we found very low- and high-certainty evidence for no evidence of difference with NSAIDs and paracetamol compared to placebo for the risk of adverse events, and moderate-certainty evidence that muscle relaxants may increase the risk of adverse events. For chronic LBP, we found low-certainty evidence that NSAIDs and very low- to high-certainty evidence that opioids may provide a small effect on pain. For safety, we found low-certainty evidence for no evidence of difference between NSAIDs and placebo for the risk of adverse events, and low-certainty evidence that opioids may increase the risk of adverse events.

Topics: Acetaminophen; Acute Pain; Adult; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Buprenorphine; Humans; Low Back Pain; Systematic Reviews as Topic; Tramadol

To evaluate the impact of buprenorphine (Butrans®) transdermal System (BTDS) treatment on sleep outcomes for patients with moderate-to-severe chronic low back pain (CLBP).. Two enriched-enrollment, randomized-withdrawal, double-blind, controlled trials examined BTDS treatment for patients with moderate-to-severe CLBP. Trial I evaluated BTDS 10 and 20 mcg/hour against a placebo control among opioid-naïve patients. Trial II compared BTDS 20 mcg/hour against a lower-dose control (BTDS 5 mcg/hour) among opioid-experienced patients. The patient-reported Medical Outcomes Study Sleep Scale (MOS-SS) assessed overall sleep quality (Sleep Problems Index [SPI]), Disturbance, and other sleep outcomes. In each trial, MOS-SS scores were compared between target treatment and control arms during the 12-week double-blind phase. Correspondence of changes in sleep outcomes and pain severity and the degree to which pain reduction mediates treatment impact on sleep outcomes were examined.. Medical Outcomes Study Sleep Scale scores were collected from 541 (Trial I) and 441 (Trial II) patients prior to randomization and from 369 (Trial I) and 274 (Trial II) patients at week 12. Patients receiving target treatment showed statistically significantly more improvement in SPI and Disturbance scores at 12 weeks than their respective controls (Ps < 0.05). Improvements in SPI and Disturbance for target treatment arms were statistically larger those of the controls by week 4 of the double-blind phase. The clinical significance of these differences was not determined. Pain reduction predicted improvements in sleep outcomes.. Buprenorphine Transdermal System improved sleep quality and disturbance for opioid-naïve and opioid-experienced patients with moderate-to-severe CLBP. Benefits of BTDS for these sleep outcomes emerged within 4 weeks and were maintained over the entire 12-week treatment period.

Topics: Administration, Cutaneous; Adult; Aged; Analgesics, Opioid; Buprenorphine; Double-Blind Method; Female; Humans; Low Back Pain; Male; Middle Aged; Pain Measurement; Sleep; Sleep Wake Disorders; Treatment Outcome

Buprenorphine HCl buccal film has been developed for treating chronic pain utilizing BioErodible MucoAdhesive (BEMA(®)) delivery technology. Buccal buprenorphine (BBUP; Belbuca(TM), Endo Pharmaceuticals) was evaluated for the management of moderate to severe chronic low back pain (CLBP) requiring around-the-clock analgesia in a multicenter, double-blind, placebo-controlled, enriched-enrollment, randomized-withdrawal study in opioid-naive patients.. Patients (n = 749) were titrated to a dose of BBUP (range, 150-450 µg every 12 h) that was generally well tolerated and provided adequate analgesia for ≥14 days, and then randomized to BBUP (n = 229) or placebo (n = 232), respectively. The primary efficacy variable was the change from baseline to week 12 of double-blind treatment in the mean of daily average pain intensity scores (numeric rating scale from 0 [no pain] to 10 [worst pain imaginable]).. Patients were experiencing moderate to severe pain at study entry: mean (SD) = 7.15 (1.05). Following titration, pain was reduced to the mild range; 2.81 (1.07). After randomization, mean (SD) pain scores increased from baseline to week 12 more with placebo (1.59 [2.04]) versus BBUP: (0.94 [1.85]) with a significant between-group difference (-0.67 [95% CI: -1.07 to -0.26]; p = 0.0012). A significantly larger percentage of patients receiving BBUP versus placebo had ≥30% pain reduction (63% vs 47%; p = 0.0012). During double-blind treatment, the most frequent adverse events (AEs) with BBUP were nausea (10%), constipation (4%) and vomiting (4%). The most common AEs with placebo were nausea (7%), upper respiratory tract infection (4%), headache (3%) and diarrhea (3%).. These findings demonstrate the efficacy and tolerability of BBUP among opioid-naive patients requiring around-the-clock opioid treatment for CLBP.

Topics: Administration, Buccal; Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Buprenorphine; Chronic Pain; Double-Blind Method; Female; Follow-Up Studies; Humans; Low Back Pain; Male; Middle Aged; Pain Measurement; Severity of Illness Index; Treatment Outcome

A buccal film of buprenorphine (BBUP) was evaluated for safety and efficacy in a multicenter, double-blind, placebo-controlled, enriched-enrollment, randomized-withdrawal study in opioid-experienced patients (30 to ≤160 mg/d morphine sulfate equivalent) with moderate to severe chronic low back pain taking around-the-clock opioid analgesics. Patients' opioid doses were tapered to ≤30 mg morphine sulfate equivalent before open-label titration with BBUP (range, 150-900 μg every 12 hours). Patients who responded (received adequate analgesia that was generally well tolerated for 14 days) were randomized to receive buprenorphine (n = 254) or placebo (n = 257) buccal film. The primary efficacy variable was the change from baseline to week 12 of double-blind treatment in mean average daily pain-intensity scores using a rating scale of 0 (no pain) to 10 (worst pain imaginable). In the intent-to-treat population, mean pain scores were 6.7 after opioid taper and declined to 2.8 after the BBUP titration period. After randomization, mean pain scores were lower in the BBUP group than in the placebo group; the difference between groups in the mean change from baseline to week 12 was -0.98 (95% CI, -1.32 to -0.64; P < 0.001). A significantly larger percentage of patients receiving BBUP than placebo had pain reductions ≥30% and ≥50% (P < 0.001 for both). In the double-blind portion of the study, the only adverse event reported more frequently with BBUP than placebo and in ≥5% of patients was vomiting (5.5% vs 2.3%). These findings demonstrate the efficacy and tolerability of BBUP in opioid-experienced patients taking around-the-clock opioid treatment for chronic low back pain.

Topics: Administration, Buccal; Adult; Aged; Aged, 80 and over; Buprenorphine; Chronic Pain; Disability Evaluation; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Low Back Pain; Male; Middle Aged; Morphine; Narcotics; Pain Measurement; Severity of Illness Index

This study examines the efficacy of the buprenorphine transdermal system (BTDS) for reducing the interference of pain on physical and emotional functioning associated with chronic low back pain (CLBP).. A post-hoc analysis used data from a randomized, placebo-controlled, double-blind trial of patients with moderate-to-severe CLBP. The Brief Pain Inventory (BPI) measured pain interference at screening, following a run-in period, and during the 12-week double-blind treatment phase. Statistical analyses examined treatment arm differences (BTDS vs placebo) for the following: BPI Interference subscale items and subscale scores at the trial end point (week 12); patterns of change in the Interference subscale scores over time; proportions of patients indicating mild or no interference following treatment; and proportions of patients showing improvement (30%, 50%, 2-point, or 4-point change in score from screening to week 12) for each item and subscale.. Mean scores for BPI Interference items and Interference subscale were significantly lower (ie, indicated less interference) for BTDS than for placebo (all P < 0.001). Treatment arm differences in Interference subscale scores emerged within 4 weeks of treatment. The BTDS patients were significantly more likely to indicate mild/no interference on 5 of 7 Interference subscale items following treatment (P < 0.05). For most comparisons, BTDS patients were significantly more likely to show criterion-level improvements in Interference item and subscale scores (P < 0.05 for differences).. Results indicate the efficacy of BTDS treatment, compared with placebo, for reducing the interference of pain on physical and emotional functioning in patients with moderate-to-severe CLBP. The advantage of BTDS was observed within 4 weeks of treatment, and was maintained throughout the 12-week treatment phase.

Topics: Administration, Cutaneous; Adult; Analgesics, Opioid; Buprenorphine; Chronic Pain; Double-Blind Method; Female; Humans; Low Back Pain; Male; Middle Aged; Pain Measurement; Transdermal Patch; Treatment Outcome

This open-label, phase 3b study evaluated the effectiveness and tolerability of oral tapentadol prolonged release (PR; 50-250 mg twice daily [b.i.d.]) for managing severe, chronic low back pain in patients responding to World Health Organization (WHO) step III opioids but tolerating treatment poorly. Equianalgesic ratios for tapentadol to prior strong opioids were calculated.. Patients rotated directly from prior WHO step III opioids to tapentadol. Patients received tapentadol PR (50-250 mg b.i.d.) during 5-week titration and 7-week maintenance periods. Tapentadol immediate release (IR) 50 mg (≤ twice/day, ≥ 4 h apart) was allowed (total daily dose of tapentadol PR and IR ≤ 500 mg/day). The primary endpoint was responder rate 1 at week 6 (percentage of patients with the same or less pain intensity [11-point numerical rating scale (NRS; 3-day average)] vs week -1).. Responder rate 1 at week 6 (last observation carried forward [LOCF]) was 80.9% (76/94; P < 0.0001 vs. the null responder hypothesis rate [<60%]), resulting in a positive trial despite premature termination (136 recruited of 180 planned). Significant improvements from baseline in pain intensity and neuropathic pain symptoms were observed at weeks 6 and 12 with tapentadol PR (P < 0.05). Equianalgesic ratios were calculated for PR formulations alone and for PR and IR formulations combined for tapentadol to oxycodone, buprenorphine, fentanyl, morphine, and hydromorphone. The prevalences of adverse events reported as the reason for switching to tapentadol (most commonly constipation and nausea) decreased over time.. Tapentadol PR (50-250 mg b.i.d.) provided at least comparable pain relief and improved tolerability versus prior strong opioids in patients with severe, chronic low back pain responding to WHO step III therapy. Conversion from strong opioids to tapentadol PR, with its two mechanisms of action, went smoothly considering overall effectiveness and tolerability outcomes. Equianalgesic ratios of tapentadol to oxycodone and other strong opioids were in line with other phase 3/3b studies.

Topics: Adult; Aged; Analgesics, Opioid; Buprenorphine; Chronic Pain; Constipation; Delayed-Action Preparations; Female; Fentanyl; Humans; Hydromorphone; Low Back Pain; Male; Middle Aged; Morphine; Neuralgia; Oxycodone; Pain Measurement; Phenols; Severity of Illness Index; Tapentadol

This study evaluated the impact of treatment with Buprenorphine Transdermal System (BTDS) on the health-related quality of life for patients with moderate-to-severe chronic low back pain (CLBP), and the correspondence between quality of life and pain. A multicenter, enriched, double-blind (DB), placebo-controlled, randomized trial evaluated BTDS 10 and 20 μg/hour for treatment of opioid-naïve patients with moderate-to-severe CLBP. The SF-36v2 survey, which measures 8 domains of quality of life, was administered at screening and following an open-label run-in period with BTDS and at weeks 4, 8, and 12 of the DB phase. Post hoc analyses compared SF-36v2 scores between BTDS and placebo groups during the DB phase. Condition burden was examined through comparisons with a U.S. general population sample. Correlations examined the correspondence between quality of life and pain measures. BTDS produced larger improvements than placebo at 12 weeks in all quality-of-life domains (Ps < .05). Treatment group differences in both physical and mental quality of life emerged by 4 weeks. Patients' pretreatment quality of life was worse than that in the general population (Ps < .05); only BTDS treatment eliminated deficits in pain, social functioning, and role limitations due to emotional health. Improvements in quality of life were moderately associated with pain reduction. These data suggest that moderate-to-severe CLBP patients receiving BTDS exhibited better quality of life than patients receiving placebo.. This post hoc analysis suggests that patients with moderate-to-severe CLBP treated with BTDS exhibit better health-related quality of life than those using placebo within 4 weeks of treatment, and were more likely to exhibit clinically meaningful improvements in quality of life following 12 weeks of treatment.

Topics: Administration, Cutaneous; Adult; Analgesics, Opioid; Buprenorphine; Cost of Illness; Double-Blind Method; Endpoint Determination; Female; Humans; Low Back Pain; Male; Motor Activity; Pain Measurement; Quality of Life

To evaluate the impact of 12 weeks of treatment with Butrans® (buprenorphine) transdermal system (BTDS) on the health-related quality of life (HRQoL) for patients with chronic low back pain (CLBP), and the maintenance of effects over 52 weeks.. A multicenter, enriched, double-blind (DB), randomized trial comparing BTDS 20 μg/h (BTDS 20) against 5 μg/h (BTDS 5) for treatment of opioid-experienced patients with moderate-to-severe CLBP, including a 52-week open-label (OL) extension phase.. QoL was measured with the SF-36v2 survey before and after an OL run-in period with BTDS 20, three times during the DB phase, and seven times over the extension phase. This post hoc analysis tested for SF-36v2 score differences between treatment groups during the DB phase and maintenance of effects over the extension phase.. At 12 weeks, BTDS 20 produced larger improvements than BTDS 5 in role limitations due to physical health, bodily pain and overall physical QoL (p < 0.01). Treatment group differences in overall physical QoL were sustained throughout the DB phase. Quality-of-life improvements associated with BTDS 20 persisted through the extension phase.. These data suggest that opioid-experienced moderate-to-severe CLBP patients receiving BTDS 20 exhibited better QoL than patients receiving BTDS 5.

Topics: Administration, Cutaneous; Adult; Analgesics, Opioid; Buprenorphine; Chronic Pain; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Low Back Pain; Male; Middle Aged; Quality of Life; Severity of Illness Index; Transdermal Patch; Treatment Outcome

In this enriched design study, 1,160 opioid-experienced patients with chronic, moderate to severe low back pain entered an open-label run-in period; 660 demonstrated analgesic benefit from and tolerability to buprenorphine transdermal system 20 mcg/hour (BTDS 20) treatment and were randomized to receive either BTDS 20, BTDS 5 mcg/hour (BTDS 5), or the active control (immediate release oxycodone 40-mg/day) during an 84-day double-blind phase. The primary endpoint, "average pain in the last 24 hours" during double-blind weeks 4, 8, and 12, was significantly lower for patients receiving BTDS 20 compared with patients receiving BTDS 5 (P < .001, treatment difference of -.67). A treatment difference of -.75 in favor of oxycodone 40 mg/day versus BTDS 5 (P < .001) indicated the assay sensitivity of the study. Four sensitivity analyses, secondary, and exploratory analyses supported the results of the primary analysis. Incidences of treatment-emergent adverse events were 56% during the open-label period, and 59, 77, and 73% for the BTDS 5, BTDS 20, and oxycodone 40 mg/day treatment groups, respectively, during the double-blind phase. One death considered unrelated to study treatment occurred in a patient receiving BTDS 10 during the run-in period. BTDS 20 treatment was demonstrated to be efficacious and generally well tolerated.. This article presents results of a pivotal Phase 3 study that assesses a new treatment for the management of chronic low back pain: a transdermal patch containing the opioid buprenorphine (BTDS). In this active controlled, superiority study with an enriched design, BTDS 20 was found to be efficacious and generally well tolerated.

Topics: Administration, Cutaneous; Analgesics, Opioid; Buprenorphine; Chronic Pain; Double-Blind Method; Female; Humans; Low Back Pain; Male; Middle Aged; Oxycodone; Transdermal Patch; Treatment Outcome

This article presents the results of a pivotal Phase 3 study that assesses a new treatment for the management of chronic low back pain: a transdermal patch containing the opioid buprenorphine. In this randomized, placebo-controlled study with an enriched enrollment design, the buprenorphine transdermal system (BTDS) was found to be efficacious and generally well tolerated.. This enriched, multicenter, randomized, double-blind study evaluated the efficacy, tolerability, and safety of BTDS in opioid-naïve patients who had moderate to severe chronic low back pain.. Patients who tolerated and responded to BTDS (10 or 20 mcg/hour) during an open-label run-in period were randomized to continue BTDS 10 or 20 mcg/hour or receive matching placebo. The primary outcome was "average pain over the last 24 hours" at the end of the 12-week double-blind phase, collected on an 11-point scale (0=no pain, 10=pain as bad as you can imagine). Sleep disturbance (Medical Outcomes Study subscale) and total number of supplemental analgesic tablets used were secondary efficacy variables.. Fifty-three percent of patients receiving open-label BTDS (541 of 1024) were randomized to receive BTDS (n=257) or placebo (n=284). Patients receiving BTDS reported statistically significantly lower pain scores at Week 12 compared with placebo (least square mean treatment difference: -0.58, P=0.010). Sensitivity analyses of the primary efficacy variable and results of the analysis of secondary efficacy variables supported the efficacy of BTDS relative to placebo. During the double-blind phase, the incidence of treatment-emergent adverse events was 55% for the BTDS treatment group and 52% for the placebo treatment group. Laboratory, vital sign, and electrocardiogram evaluations did not reveal unanticipated safety findings.. BTDS was efficacious in the treatment of opioid-naïve patients with moderate to severe chronic low back pain. Most treatment-emergent adverse events observed were consistent with those associated with the use of opioid agonists and transdermal patches.

Topics: Administration, Cutaneous; Adult; Aged; Analgesics, Opioid; Buprenorphine; Double-Blind Method; Electrocardiography; Female; Humans; Low Back Pain; Male; Middle Aged; Pain Measurement; Treatment Outcome

Buprenorphine is a mixed-activity, partial mu-opioid agonist. Its lipid solubility makes it well suited for transdermal administration.. This study assessed the efficacy and safety profile of a 7-day buprenorphine transdermal system (BTDS) in adult (age >18 years) patients with moderate to severe chronic low back pain previously treated with > or =1 tablet daily of an opioid analgesic.. This was a randomized, double-blind, placebo-controlled crossover study, followed by an open-label extension phase. After a 2- to 7-day washout of previous opioid therapy, eligible patients were randomized to receive BTDS 10 microg/h or matching placebo patches. The dose was titrated weekly using 10- and 20-microg/h patches (maximum, 40 microg/h) based on efficacy and tolerability. After 4 weeks, patients crossed over to the alternative treatment for another 4 weeks. Patients who completed the double-blind study were eligible to enter the 6-month open-label phase. Rescue analgesia was provided as acetaminophen 325 mg to be taken as 1 or 2 tablets every 4 to 6 hours as needed. The primary outcome assessments were daily pain intensity, measured on a 100-mm visual analog scale (VAS), from no pain to excruciating pain, and a 5-point ordinal scale, from 0 = none to 4 = excruciating. Secondary outcome assessments included the Pain and Sleep Questionnaire (100-mm VAS, from never to always), Pain Disability Index (ordinal scale, from 0 = no disability to 11 = total disability), Quebec Back Pain Disability Scale (categorical scale, from 0 = no difficulty to 5 = unable to do), and the 36-item Short Form Health Survey (SF-36). Patients and investigators assessed overall treatment effectiveness at the end of each phase; they assessed treatment preference at the end of double-blind treatment. After implementation of a precautionary amendment, the QTc interval was measured 3 to 4 days after randomization and after any dose adjustment. All assessments performed during the double-blind phase were also performed every 2 months during the open-label extension. Adverse events were collected by non-directed questioning throughout the study.. Of 78 randomized patients, 52 (66.7%) completed at least 2 consecutive weeks of treatment in each study phase without major protocol violations (per-protocol [PP] population: 32 women, 20 men; mean [SD] age, 51.3 [11.4] years; mean weight, 85.5 [19.5] kg; 94% white, 4% black, 2% other). The mean (SD) dose of study medication during the last week of treatment was 29.8 (12.1) microg/h for BTDS and 32.9 (10.7) microg/h for placebo (P = NS). During the last week of treatment, BTDS was associated with significantly lower mean (SD) pain intensity scores compared with placebo on both the VAS (45.3 [21.3] vs 53.1 [24.3] mm, respectively; P = 0.022) and the 5-point ordinal scale (1.9 [0.7] vs 2.2 [0.8]; P = 0.044). The overall Pain and Sleep score was significantly lower with BTDS than with placebo (177.6 [125.5] vs 232.9 [131.9]; P = 0.027). There were no treatment differences on the Pain Disability Index, Quebec Back Pain Disability Scale, or SF-36; however, BTDS was associated with significant improvements compared with placebo on 2 individual Quebec Back Pain Disability Scale items (get out of bed: P = 0.042; sit in a chair for several hours: P = 0.022). Of the 48 patients/physicians in the PP population who rated the effectiveness of treatment, 64.6% of patients (n = 31) rated BTDS moderately or highly effective, as did 62.5% of investigators (n = 30). Among the 50 patients in the PP population who answered the preference question, 66.0% of patients (n = 33) preferred the phase in which they received BTDS and 24.0% (n = 12) preferred the phase in which they received placebo (P = 0.001), with the remainder having no preference; among investigators, 60.0% (n = 30) and 28.0% (n = 14) preferred the BTDS and placebo phases, respectively (P = 0.008), with the remainder having no preference. The mean placebo-adjusted change from baseline in the QTc interval ranged from -0.8 to +3.8 milliseconds (P = NS). BTDS treatment was associated with a significantly higher frequency of nausea (P < 0.001), dizziness (P < 0.001), vomiting (P = 0.008), somnolence (P = 0.020), and dry mouth (P = 0.003), but not constipation. Of the 49 patients completing 8 weeks of double-blind treatment, 40 (81.6%) entered the 6-month, open-label extension study and 27 completed it. Improvements in pain scores achieved during the double-blind phase were maintained in these patients.. In the 8-week, double-blind portion of this study, BTDS 10 to 40 microg/h was effective compared with placebo in the management of chronic, moderate to severe low back pain in patients who had previously received opioids. The improvements in pain scores were sustained throughout the 6-month, open-label extension. (Current Controlled Trials identification number: ISRCTN 06013881).

Topics: Administration, Cutaneous; Adult; Aged; Analgesics, Opioid; Buprenorphine; Chronic Disease; Cross-Over Studies; Double-Blind Method; Electrocardiography; Female; Humans; Low Back Pain; Male; Middle Aged

Topics: Analgesics, Opioid; Buprenorphine; Chronic Pain; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Substitution; Humans; Low Back Pain; Male; Middle Aged; Oxycodone

Topics: Analgesics, Opioid; Buprenorphine; Deglutition Disorders; Esophageal Spasm, Diffuse; Esophageal Sphincter, Lower; Female; Humans; Low Back Pain; Manometry; Middle Aged; Transdermal Patch

To evaluate utilization patterns in patients initiating buprenorphine transdermal system (BTDS), CIII, and estimate the proportion decreasing their total opioid dose over time.. This retrospective cohort study used data from the Truven Health Analytics MarketScan® Commercial Claims and Encounters Database from 1 January 2011 through 31 December 2015. Eligible individuals were adults aged 18-64 years newly dispensed BTDS (index prescription) who had at least six months of insurance coverage prior to (baseline period) and following (study period) the index prescription.. Back and neck pain was the most common pain condition in the study population (n = 31,533) and 88% were dispensed opioids in the baseline period. Nearly half (48%) received BTDS in a strength of 10 mcg/hour as their index prescription. Most (80%) patients prescribed BTDS had concomitant prescriptions for other opioids, chiefly immediate-release (IR) opioids (77%). During the baseline period, median opioid dose among patients prescribed opioids was 50 morphine-equivalent doses (MED), with 33% of patients using nonsteroidal anti-inflammatory drugs and 44% adjuvant analgesics. During the study period, BTDS use lasted a median 30 days and mean 100 days. Median dose of BTDS remained largely constant, and median dose of all opioids during continuous use of BTDS was 65.6 units MED. However, 24% of patients reduced total units MED from the baseline period (median mean dose, 74.5 units MED) until the end of the study period (42.8).. Most patients initiating treatment with BTDS had a history of treatment with IR opioids. Though the average change in total opioid daily dose after patients were prescribed BTDS was modest, an important subpopulation of approximately one-quarter of patients were able to markedly reduce their total units MED compared with prior opioid therapy. BTDS should be investigated as an option to help patients step down from higher opioid doses.

Topics: Administration, Cutaneous; Adolescent; Adult; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Buprenorphine; Chronic Pain; Cohort Studies; Dose-Response Relationship, Drug; Female; Humans; Low Back Pain; Male; Middle Aged; Neck Pain; Practice Patterns, Physicians'; Retrospective Studies; United States; Young Adult

Chronic pain (CP) patients with depression typically exhibit worse post-treatment outcomes than nondepressed CP patients. The cause is often assumed to reflect a differential response to treatment, neglecting other potential explanations, such as the continuation of differences in pretreatment outcomes. This post hoc analysis examines whether worse post-treatment outcomes for depressed patients with chronic low back pain (CLBP) are driven by reduced treatment efficacy.. Data were from opioid-naïve adult patients with moderate-to-severe CLBP who participated in a randomized, placebo-controlled, double-blind clinical trial of Butrans(®) (buprenorphine) Transdermal System (BTDS) for pain relief. Depression screening was based on baseline SF-36v2 Mental Health subscale scores. Patient-reported measures of pain severity, pain interference, quality of life, sleep problems, and functional disability were administered at screening and during the study. Differential treatment efficacy for each outcome was examined using analysis of covariance models that included interaction terms between treatment arm and depression status.. At baseline, patients classified as depressed showed greater pain interference, lower quality of life, more sleep problems, and greater functional disability than nondepressed patients; the two groups did not differ in pain severity. No statistically significant interactions between treatment arm and depression status were observed. The direction of improvement post-treatment favored the depressed group on nine of seventeen outcomes.. Results do not support a differential response to BTDS treatment between depressed and nondepressed CLBP patients across a variety of patient-reported outcomes. These findings raise the question of whether depressed mood actually moderates the effectiveness of treatment in CP patients.

Topics: Administration, Cutaneous; Adult; Analgesics, Opioid; Buprenorphine; Chronic Pain; Depression; Double-Blind Method; Female; Humans; Low Back Pain; Male; Middle Aged; Pain Measurement; Quality of Life; Treatment Outcome

The buprenorphine transdermal delivery system (BTDS) is indicated for reduction of pain in moderate to severe chronic low back pain (CLBP), which can affect patients' ability to perform routine activities of daily living (ADLs). This post hoc analysis of clinical trial data examines the impact of BTDS treatment on CLBP patients' ability to perform ADLs that relate to functioning with low back pain.. Data are drawn from a multicenter, enriched enrollment, randomized, placebo-controlled, double-blind 12-week trial of BTDS for pain control among opioid-naive patients with moderate to severe CLBP. The 23 selected ADLs are those that (1) appear in the Low Back Pain Core Set of the International Classification of Functioning, Disability and Health and (2) link to the content of 3 patient-reported outcome instruments administered during the trial. Logistic regression models estimated the odds ratios (ORs) of BTDS patients' ability to perform each ADL at 12 weeks, controlling for baseline ability, relative to placebo.. The ORs for 10 ADLs related to sleeping, lifting, bending, and working reached multiplicity-adjusted statistical significance and indicated a greater ability to perform ADLs among BTDS users than among the placebo group. These 10 ORs ranged from 1.9 (no physical health-related restrictions on the kind of work performed) to 2.4 (being able to sleep undisturbed by pain).. These results suggest that for patients with moderate to severe CLBP, 12 weeks use of BTDS improves the ability to carry out certain ADLs related to sleeping, lifting, bending, and working.

Topics: Activities of Daily Living; Administration, Cutaneous; Analgesics, Opioid; Buprenorphine; Chronic Disease; Disabled Persons; Double-Blind Method; Female; Humans; International Classification of Diseases; Logistic Models; Low Back Pain; Male; Pain Measurement; Sleep; Treatment Outcome; Walking; Work

In Japan, indications for opioid analgesics, once exclusively used as pain killers for patients suffering from malignant cancer, have been expanded for a wide range of pain. Herein we report a patient with opioid-induced delirium associated with the administration of buprenorphine patches that was well below the indicated therapeutic range limit. An 82-year-old woman was referred to us from an orthopaedic practitioner for uncontrollable behavioural problems apparently caused by the beginning of dementia; the patient had gradually developed disorientation, visual hallucinations, and delusions. Laboratory and imaging findings excluded common causes of delirium including Alzheimer's disease and diffuse Lewy body disease. Detailed questioning revealed that the patient's confused state appeared following a buprenorphine patch dose increase and subsequently disappeared after administration was stopped. Delirium has not been reported as a side-effect in clinical trials of buprenorphine patches. However, our findings in this case show that even topical opioids can precipitate the development of a delirious state in elderly patients.

Topics: Aged, 80 and over; Analgesics, Opioid; Buprenorphine; Confusion; Delirium; Dementia; Female; Hallucinations; Humans; Japan; Low Back Pain; Transdermal Patch; Treatment Outcome

In monitoring a patient with chronic pain who was taking high-dose morphine and oxycodone with weekly urine enzymatic immunoassay (EIA) toxicology testing, the authors noted consistent positives for buprenorphine. The patient was not taking buprenorphine, and gas chromatography/mass spectroscopy (GCMS) testing on multiple samples revealed no buprenorphine, indicating a case of false-positive buprenorphine EIAs in a high-dose opiate case. The authors discontinued oxycodone for a period of time and then discontinued morphine. Urine monitoring with EIAs and GCMS revealed false-positive buprenorphine EIAs, which remained only when the patient was taking morphine. When taking only oxycodone and no morphine, urine samples became buprenorphine negative. When morphine was reintroduced, false-positive buprenorphine results resumed. Medical practitioners should be aware that high-dose morphine (with morphine urine levels turning positive within the 15,000 to 28,000 mg/mL range) may produce false-positive buprenorphine EIAs with standard urine EIA toxicology testing.

Topics: Analgesics, Opioid; Buprenorphine; Chronic Disease; Enzyme Assays; False Positive Reactions; Gas Chromatography-Mass Spectrometry; Humans; Low Back Pain; Male; Middle Aged; Morphine; Oxycodone; Reagent Kits, Diagnostic

We report two unusual cases of septic sacroiliitis resulting from intravenous Subutex abuse that initially masqueraded as low back pain. Both patients, a 48-year-old Malay man and a 30-year-old Malay woman, presented with chills, rigor and progressive lower back pain, and eventually experienced difficulty in ambulating. The Malay woman also developed severe pain in her left elbow, with swelling and restriction of movement. Blood investigations and cultures revealed an infective process. Imaging of the pelvis and lower back confirmed the diagnosis of septic arthritis of the sacroiliac joints. The first patient underwent computed tomography-guided drainage of the abscess and was administered intravenous antibiotics via a peripherally-inserted central catheter (PICC) line. The second patient underwent an arthrotomy for her elbow and her left sacroiliac joint was managed conservatively with intravenous antibiotics, also via a PICC line. The diagnostic difficulty and the need for a high index of suspicion are discussed.

Topics: Adult; Arthritis, Infectious; Buprenorphine; Elbow Joint; Humans; Low Back Pain; Male; Middle Aged; Opioid-Related Disorders; Radiography; Sacroiliac Joint; Substance Abuse, Intravenous