Accuracy of Self-reported Prescribed Analgesic Medication Use: Linkage Between the Quebec Pain Registry and the Quebec Administrative Prescription Claims Databases.

OBJECTIVES: The validity of studies conducted with patient registries depends on the accuracy of the self-reported clinical data. As of now, studies about the validity of self-reported use of analgesics among chronic pain (CP) populations are scarce. The objective of this study was to assess the accuracy of self-reported prescribed analgesic medication use. This was attained by comparing the data collected in the Quebec Pain Registry (QPR) database to those contained in the Quebec administrative prescription claims database (Régie de l'assurance maladie du Québec [RAMQ]). METHODS: To achieve the linkage between the QPR and the RAMQ databases, the first 1285 patients who were consecutively enrolled in the QPR between October 31, 2008 and January 27, 2010 were contacted by mail and invited to participate in a study in which they had to provide their unique RAMQ health insurance number. Using RAMQ prescription claims as the reference standard, κ coefficients, sensitivity, specificity, and their respective 95% confidence intervals were calculated for each therapeutic class of prescribed analgesic drugs that the participants reported taking currently and in the past 12 months. RESULTS: A total of 569 QPR patients responded to the postal mailing, provided their unique health insurance number, and gave informed consent for the linkage (response proportion=44%). Complete RAMQ prescription claims over the 12 months before patient enrollment into the QPR were available for 272 patients, who constituted our validated study population. Regarding current self-reported prescribed analgesic use, κ coefficients measuring agreement between the 2 sources of information ranged from 0.66 to 0.78 for COX-2-selective nonsteroidal anti-inflammatory drugs, anticonvulsants, antidepressants, skeletal muscle relaxants, synthetic cannabinoids, opiate agonists/partial agonists/antagonists, and antimigraine agents therapeutic classes. For the past 12-month self-reported prescribed analgesic use, QPR patients were less accurate regarding anticonvulsants (κ=0.59), opiate agonists/partial agonists/antagonists (κ=0.57), and antimigraine agents use (κ=0.39). DISCUSSION: Information about current prescribed analgesic medication use as reported by CP patients was accurate for the main therapeutic drug classes used in CP management. Accuracy of the past year self-reported prescribed analgesic use was somewhat lower but only for certain classes of medication, the concordance being good on all the others.

Is the deficit in pain inhibition in fibromyalgia influenced by sleep impairments?

It has been proposed that a deficit in inhibitory conditioned pain modulation (ICPM) underlies the pathophysiology of fibromyalgia (FM), but there is high variability in ICPM efficacy in this syndrome that remains poorly understood. Based on emerging data showing that age, anxiety, depression and sleep can modulate ICPM efficacy, the main objective of this study was to determine the clinical correlates of experimentally-induced pain perception in FM. Fifty FM patients and 39 healthy controls (HC) were tested. Anxiety, depression, sleep and FM symptoms were measured with questionnaires or interview-type scales. Experimental pain testing consisted of two tonic heat pain stimulations separated by a 2-minute cold pressor test (CPT). Thermal pain thresholds and tolerance were higher in HC compared to FM patients. Pain ratings during the CPT were lower in HC relative to FM patients. ICPM efficacy was stronger in HC compared to FM patients. Finally, sleep quality was the only factor significantly related to ICPM efficacy. To our knowledge, this is the first study to report this association in FM. Future studies will need to replicate this finding, to determine whether impaired sleep is primary or secondary to deficient pain inhibition, and to characterize the neurobiological mechanisms underlying this association.

Add-on treatment of quetiapine for fibromyalgia: a pilot, randomized, double-blind, placebo-controlled 12-week trial.

Recently, second-generation antipsychotic drugs have attracted interest in the treatment of chronic pain, including fibromyalgia (FM). Preliminary uncontrolled studies have shown that quetiapine treatment may be helpful for FM patients. In this trial, we sought to examine-for the first time-the efficacy and tolerability of quetiapine as a treatment for FM and its associated psychiatric symptoms. This was a 12-week double-blind, randomized, placebo-controlled trial of quetiapine XR as an add-on treatment for FM syndrome. Fifty-one female FM patients were randomized, and a flexible dosage of 50 to 300 mg/d was used. The primary outcome was the change from baseline to end point in the Fibromyalgia Impact Questionnaire total score. Secondary outcomes included mood symptoms, sleep disturbances, and tender points. Using a low dose (mean = 132.2 mg) of quetiapine, we observed significant benefits of drug treatment on sleep, uncertain effects on FM and mood symptoms, but no effects on pain, in a small group of polymedicated FM patients. Quetiapine was generally well tolerated.

Reduced analgesic effect of acupuncture-like TENS but not conventional TENS in opioid-treated patients.

UNLABELLED: Evidence from recent animal studies indicates that the analgesic effect of low-frequency transcutaneous electrical nerve stimulation (TENS) is reduced in opioid-tolerant animals. The aim of the present study was to compare the analgesic effect of conventional (high frequency) and acupuncture-like (low frequency) TENS between a group of opioid-treated patients and a group of opioid-naive patients in order to determine if this cross-tolerance effect is also present in humans. Twenty-three chronic pain patients (11 who took opioids and 12 who did not) participated in the study. Participants were assigned in a randomized crossover design to receive alternately conventional and acupuncture-like TENS. There was a significant reduction in pain during and after conventional TENS when compared to baseline for both the opioid and nonopioid group (P < .01). For acupuncture-like TENS however, the analgesic effect of TENS was only observed in the nonopioid group (P < .01), with opioid-treated patients showing no change in pain scores during and after TENS when compared to baseline (P > .09). The reduced analgesic effect of acupuncture-like TENS in opioid-treated patients is coherent with previous animal studies and suggests that conventional TENS should be preferred in patients taking opioids on a regular basis. PERSPECTIVE: This study shows that patients taking opioids on a regular basis are less susceptible to benefit from acupuncture-like TENS. This phenomenon is probably attributable to the fact that the analgesia induced by acupuncture-like TENS and opioids are mediated by the same receptors (ie, µ opioid receptors).

Buprenorphine transdermal system in adults with chronic low back pain: a randomized, double-blind, placebo-controlled crossover study, followed by an open-label extension phase.

BACKGROUND: Buprenorphine is a mixed-activity, partial mu-opioid agonist. Its lipid solubility makes it well suited for transdermal administration. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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).

The efficacy and safety of pregabalin in the treatment of neuropathic pain associated with chronic lumbosacral radiculopathy.

We evaluated the efficacy of pregabalin in patients with chronic lumbosacral radiculopathy. This randomized, controlled, withdrawal trial included five phases: screening (4-18 days); run-in (4-10 days) to screen out placebo responders; single-blind (28 days) to identify pregabalin responders; double-blind to randomize responders to pregabalin or placebo (35 days); and final study medication taper (7 days). The primary endpoint was time to loss of response (LOR) during the double-blind phase (1-point increase in pain, discontinuation, or rescue-medication use). In the single-blind phase, 58% of patients had 30% pain reduction. In the double-blind phase, pregabalin (n=110) and placebo (n=107) groups did not differ significantly in time to LOR. Adverse events caused the discontinuation of 9.9% and 5.6% of pregabalin-treated and placebo-treated patients, respectively. Most patients with chronic lumbosacral radiculopathy responded to pregabalin therapy; however, time to LOR did not significantly differ between pregabalin and placebo. Considering the results of all phases of the study, it is difficult to draw definitive conclusions from it, suggesting a need for further work to understand the clinical potential of pregabalin treatment for lumbosacral radiculopathy.