Antonio Gatti

Controlled-Release Oxycodone and Pregabalin in the Treatment of Neuropathic Pain: Results of a Multicenter Italian Study

Aims: The aim of our study was to compare the efficacy, safety, and quality of life of combination therapy with controlled-release (CR) oxycodone plus pregabalin versus monotherapy with either CR oxycodone or pregabalin in patients with neuropathic pain. Materials and Methods: Patients with moderate to severe neuropathic pain, despite the use of various pharmacologic treatments prior to study entry, were enrolled (n = 409) and treated with CR oxycodone plus pregabalin (n = 169), CR oxycodone (n = 106), and pregabalin (n = 134). Pain intensity was rated on an 11-point numerical rating scale (NRS). Results: The combination of CR oxycodone plus pregabalin and CR oxycodone monotherapy were both more effective for alleviating neuropathic pain than pregabalin monotherapy (reduction in NRS value: 80, 76, and 46%, respectively; p ≤ 0.003). Significantly greater improvements from baseline in quality of life were reported with combination therapy than with monotherapy (p = 0.0009). At the end of treatment, the majority (91.2%) of patients receiving CR oxycodone plus pregabalin found that the treatment had been ‘effective’ or ‘very effective’. Combination therapy also allowed a dose reduction of both agents (22% for CR oxycodone and 51% for pregabalin) compared with the dosages of the respective monotherapies. Combination therapy had a superior safety profile compared with pregabalin monotherapy. Conclusions: The combination of CR oxycodone plus pregabalin may represent a valuable addition to the existing pharmacotherapy for neuropathic pain and warrants further investigation.

Clinical and psychosocial correlates of post-herpetic neuralgia

Post‐herpetic neuralgia is the most challenging and debilitating complication of herpes zoster in the immunocompetent host. Because the effect of treatment is disappointing once the syndrome has developed, it is important to know which factors predict post‐herpetic neuralgia occurrence to facilitate selection of herpes zoster patients with a higher risk of developing neuralgia and undertake preventative strategies. The present study aimed at identifying demographic, clinical and psychosocial correlates of post‐herpetic neuralgia in a sample of 219 immunocompetent patients, who were examined by dermatologists in private practice in Italy and who completed a questionnaire designed to evaluate their clinical and psychosocial profile at the time of clinical diagnosis of herpes zoster and at a follow‐up visit 6 months later. In a univariate analysis, post‐herpetic neuralgia was associated significantly with older age, longer duration of prodromal pain, greater acute pain intensity, greater extent of rash, presence of abnormal sensations and use of systemic antiviral therapy. Compared to the values at herpes zoster onset, at the follow‐up visit patients with post‐herpetic neuralgia presented with similar high mean scores of pain intensity, anxiety and depression and greatly reduced quality of life, whereas patients without neuralgia presented with improved scores. In a multivariate model, older age, greater acute pain intensity, greater extent of rash and longer duration of prodromal pain were independently associated with post‐herpetic neuralgia. The results of this study may help physicians to identify patients with a higher risk of developing post‐herpetic neuralgia and undertaking preventative strategies. J. Med. Virol. 80:1646–1652, 2008.

Effectiveness and safety of tapentadol prolonged release for severe, chronic low back pain with or without a neuropathic pain component: results of an open-label, phase 3b study

Abstract Objective: This open-label, phase 3b study evaluated the effectiveness and tolerability of tapentadol prolonged release and tapentadol immediate release (for acute pain episodes) for severe, chronic low back pain with or without a neuropathic pain component that was inadequately managed in patients taking World Health Organization (WHO) Step I or II analgesics or who were not regularly treated with analgesics. Research design and methods: Average baseline pain intensity was greater than 5 (11-point numerical rating scale-3 [NRS-3; 3-day average pain intensity]) with WHO Step I or II analgesics and greater than 6 with no regular analgesic regimen. WHO Step II analgesics were discontinued before starting study treatment; WHO Step I analgesics or co-analgesics were continued at the same dose. Patients received tapentadol prolonged release (50–250 mg bid) during a 5-week titration and 7-week maintenance period. Tapentadol immediate release was permitted for acute pain episodes (tapentadol prolonged release and immediate release maximum combined dose, ≤500 mg/day). The painDETECT questionnaire was used to define subsets of patients based on the probability of a neuropathic pain component to their low back pain as ‘negative’, ‘unclear’, or ‘positive’. Clinical trial registration: NCT00983385. Main outcome measure: The primary endpoint was the change from baseline to week 6 in average pain intensity (NRS-3), using the last observation carried forward to impute missing scores. Results: In the painDETECT negative (n = 49) and unclear/positive (n = 126) subsets, respectively, mean (SD) changes in pain intensity from baseline to week 6 were −2.4 (2.18) and −3.0 (2.07; both p < 0.0001). Among patients who had not received prior WHO Step II treatment, lower doses of tapentadol prolonged release were generally required with increasing likelihood of a neuropathic pain component. Based on the painDETECT questionnaire and the Neuropathic Pain Symptom Inventory (NPSI), tapentadol prolonged release treatment was also associated with significant improvements in neuropathic pain symptoms, with decreases in the number of pain attacks and the duration of spontaneous pain in the last 24 hours in patients with low back pain with a neuropathic pain component (painDETECT unclear or positive score at baseline or screening). The most common treatment-emergent adverse events (incidence ≥10%, n = 176) were nausea, dizziness, headache, dry mouth, fatigue, constipation, diarrhea, nasopharyngitis, and somnolence. Conclusions: Tapentadol prolonged release was well tolerated and effective for managing severe, chronic low back pain with or without a neuropathic pain component.

Palmitoylethanolamide in the Treatment of Chronic Pain Caused by Different Etiopathogenesis

OBJECTIVE To assess the efficacy and safety of palmitoylethanolamide (PEA), an endogenous fatty acid amide belonging to the N-acylethanolamines family, in reducing pain severity in patients with pain associated to different pathological conditions. METHODS This was an observational study conducted on 610 patients who were unable to effectively control chronic pain with standard therapies. PEA (600 mg) was administered twice daily for 3 weeks followed by single daily dosing for 4 weeks, in addition to standard analgesic therapies or as single therapy. The primary outcome measure was the mean score pain severity evaluated by the numeric rating scale. Safety was also evaluated. RESULTS PEA treatment significantly decreased the mean score pain intensity evaluated in all patients who completed the study. The PEA effect was independent of the pain associated pathological condition. PEA-induced decrease of pain intensity was present also in patients without concomitant analgesic therapy. Importantly, PEA showed no adverse effects. CONCLUSIONS In this study, PEA was effective and safe in the management of chronic pain in different pathological conditions.

Dosing fentanyl buccal tablet for breakthrough cancer pain: dose titration versus proportional doses

Abstract Objectives: The aim of this study was to compare the efficacy and safety of doses of fentanyl buccal tablet (FBT) proportional to doses of opioids used for background analgesia versus dose titration starting with the minimal dose for the management of breakthrough cancer pain (BTcP). Methods: A total of 82 cancer patients with BTcP who were receiving strong opioids in doses of at least 60 mg of oral morphine equivalents and having acceptable background analgesia, were selected for a multicenter unblinded study. Forty-one patients were randomized to receive FBT in doses proportional to the daily opioid doses for four consecutive episodes of BTcP (group P). Forty-one patients underwent dose titration of FBT, with an initial dose of 100 µg, for four consecutive episodes (group T). Pain intensity and symptoms associated with opioid therapy were measured before administering any dose of FBT (T0) and 15 minutes after (T15). Results: In all, 80 patients were considered for analysis (39 and 41 patients in group P and T, respectively). Patients were receiving a mean of 126 ± 100 mg of oral morphine equivalents (range 60–480 mg) for background analgesia. A total of 293 episodes of BTcP (144 and 149 in group P and T, respectively) were treated and considered for analysis. No differences were found in the decrease of pain intensity between the two groups. However, in patients receiving doses of oral morphine equivalents of >120 mg/day, a significant number of patients obtained a decrease in pain intensity >50% in group P in comparison with group T (p = 0.040). Also, the need for rescue medication was significantly more frequently reported in group T for the first episode of BTcP (p < 0.0005). No differences in the level of adverse effects were observed between the two groups. No differences in patients’ satisfaction were reported. Conclusion: According to the data obtained in this study, there is no evidence for the use of dose titration in the management of BTcP in opioid-tolerant patients. Indeed, doses proportional to basal opioid regimen for background pain seem to be effective and safe in the majority of patients. Further studies should confirm this data in patients receiving higher doses of opioids, with other rapid-onset opioids, and in other settings.

No Evidence of Family History as a Risk Factor for Herpes Zoster in Patients with Post-Herpetic Neuralgia

Little is known about reactivation of latent varicella zoster virus as herpes zoster in individuals with no underlying immunosuppression. Risk factors include age, sex, ethnicity, exogenous boosting of immunity from varicella contacts, underlying cell‐mediated immune disorders, mechanical trauma, psychological stress, and immunotoxin exposure. An association between herpes zoster and family history of zoster has been proposed. A case‐control study involving patients affected by post‐herpetic neuralgia, which usually follows more severe acute herpes zoster, was performed. The patients with post‐herpetic neuralgia were enrolled at the Pain Clinic of the Policlinico Tor Vergata in Rome, Italy, within 1 year from the onset of acute zoster. The controls matched for sex and age were chosen among healthy subjects without a history of herpes zoster presenting at the Internal Medicine Outpatient Clinic for hypertension in the same time period. All the participants in the study gave informed consent and were interviewed by medically trained and blinded investigators using a questionnaire. Similar proportions of the patients and the controls reported a family history of herpes zoster irrespective of the degree of relationship, i.e., 17.4% and 18.2%, respectively, by analyzing only the first‐degree relatives [RR 1.03 (CI 95%: 0.78–1.37)], and 28.4% and 29.6%, respectively, by analyzing the total number of relatives [RR 1.03 (CI 95%: 0.81–1.31)]. Further and larger prospective cohort studies are needed to ascertain whether a family history of herpes zoster is really an independent predictor of zoster in different geographical settings. J. Med. Virol. 82:1007–1011, 2010.

Acute Pain and Availability of Analgesia in the Prehospital Emergency Setting in Italy: A Problem to be Solved

Objectives:  The treatment of acute pain in the prehospital emergency setting remains a significant problem. We evaluated the incidence, site, and possible cause of acute pain in the prehospital period and also the current state of prehospital pain management by evaluating analgesic availability in emergency vehicles in Italy.

Adequacy assessment of oxycodone/paracetamol (acetaminophen) in multimodal chronic pain: A prospective observational study

AbstractBackground: Multimodal pain is comprised of nociceptive/inflammatory and neuropathic components. Pharmacological pain therapies from different classes provide pain relief using different mechanistic actions; often a combination of such therapies provides more effective pain relief than monotherapy. To assess whether pain management is adequate requires a comprehensive pain scoring system. Objective: To evaluate the adequacy of a low-dose combination of oxycodone and paracetamol (acetaminophen) in patients with multimodal, chronic, non-malignant pain using the Pain Management Index (PMI). Methods: During this prospective, observational study, consecutive patients were classified according to the presence of prevalent osteoarticular pain (group A, n = 78) or prevalent neuropathic pain (group B, n = 72). Existing pain-relief medications were discontinued and both groups received oxycodone 5 mg and paracetamol 325 mg up to 8 hourly for a planned duration of ≥6 weeks. Patients in group B who were receiving gabapentin continued this treatment up to a maximum daily dosage of 2400 mg during the observation period. Pain intensity was evaluated using a visual analogue scale (VAS from 0 to 10). Functional limitation for patients in group A was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The intensities of dynamic allodynia and hyperalgesia in patients in group B were evaluated by a VAS. Results from the WOMAC, dynamic allodynia, and hyperalgesia assessments were evaluated using the PMI. Results: In group A, 64.3% of patients showed improvements in pain symptoms after 15 days of treatment in the WOMAC categories of “pain preventing sleep” and “walks with aid”. The PMI showed that the oxycodone/paracetamol therapy was adequate in patients with osteoarticular pain. In group B, 83.3% of patients reported improvement in the category of “pain preventing sleep”, and all patients rated the remaining four categories (“spontaneous pain”, “burning pain”, “painful paresthesia”, and “pinprick”) as either stable or improved after 15 days of treatment. Using the PMI, hyperalgesia resolved with oxycodone/paracetamol therapy. 37.1% and 58.3% of patients did not complete the study in group A and B, respectively. Conclusion: The PMI was an effective tool for assessment of pain management efficacy. Oxycodone/paracetamol improved pain symptoms in the majority of compliant patients. In patients with neuropathic pain, rescue therapy with oxycodone/paracetamol showed a lesser, but significant, improvement of pain symptoms.

Long-Term Controlled-Release Oxycodone and Pregabalin in the Treatment of Non-Cancer Pain: An Observational Study

Aims: This study evaluates the efficacy and tolerability of long-term controlled-release (CR) oxycodone + pregabalin in patients with non-cancer pain, in a real-life setting. Methods: Patients (n = 1,051) with chronic uncontrolled non-cancer pain received CR oxycodone + pregabalin for 1 year. Pain intensity was rated on an 11-point numerical rating scale (NRS) at months 1, 2, 4, 6, 9 and 12. Results: Throughout the study period, the NRS score decreased significantly (baseline: 7.02 ± 1.26; 12 months: 1.45 ± 0.92; p = 0.00001). Following an initial increase in the mean daily doses of CR oxycodone (starting dose: 12.5 ± 8.4 mg) and pregabalin (starting dose: 121.7 ± 97.2 mg), dose reductions were seen for both drugs with the trend particularly evident for CR oxycodone. 23% of patients withdrew from the study, mainly due to adverse events (67.9% of withdrawn subjects). However, 19.7% of withdrawn patients were removed from the study due to complete relief from chronic pain. The combination was generally well tolerated and there were no reports of addiction. Conclusion: The combination of CR oxycodone + pregabalin could represent a valuable long-term therapeutic addition to existing pharmacological options for the treatment of non-cancer pain.

Prolonged-release oxycodone/naloxone in nonmalignant pain: Single-center study in patients with constipation

IntroductionOpioid treatment for chronic malignant and nonmalignant pain of moderateto-severe intensity is associated with bowel dysfunction leading to constipation; this often requires opioid dose reduction or interruption. Combination opioid agonist/antagonist therapy can restore normal bowel function. A prolonged-released (PR) fixed-dose combination of oxycodone and naloxone has been developed and efficacy has been demonstrated in phase 3 clinical trials.MethodsThis 2-month, retrospective, singlecenter, observational study assessed the effectiveness and safety of PR oxycodone/naloxone in consecutive nononcological patients with constipation and chronic pain despite analgesic treatment; specific subgroup analyses were performed in opioid-experienced or opioid-naïve patients and in age subgroups. Efficacy was assessed by: intensity of pain; bowel function; effective oxycodone/naloxone dose; Patients’ Global Impression of Change (PGIC) scale; rescue paracetamol; and laxative use. Safety evaluations were also performed.ResultsOf 1,051 patients starting on the oxycodone/naloxone combination (32.0% male; mean age 67 ± 13 years, 53.9% opioid naïve), 1,012 completed 2 months of treatment. Overall, PR oxycodone/naloxone was associated with a significant decrease in pain intensity (P < 0.001), a reduced need for rescue paracetamol (P < 0.001), and PGIC score of “very much improved” or “much improved” in 84.0% of patients. Constipation markedly decreased (P < 0.001) despite reduced laxative use (P < 0.001 vs. baseline). The most frequent treatment-emergent adverse events were somnolence (2.0%), dizziness (1.1%), and confusion (1.0%). Clinical differences in endpoints were seen between opioid-naïve and opioid-experienced patients, and among agestratified groups, but efficacy was similar to the overall population.ConclusionsFixed combination PR oxycodone/naloxone was effective and well tolerated in moderate-to-severe chronic pain in patients with constipation, providing analgesia and relief from bowel dysfunction. Consistent efficacy across patient subgroups provides guidance for daily management of chronic pain when therapy options are limited due to bowel dysfunction, regardless of age or previous medication. Supplementary material belonging to this paper is available on SpringerLink.