title: Effectiveness and tolerability of low-dose oral oxycodone/naloxone added to anticonvulsant therapy for noncancer neuropathic pain: an observational analysis.
abstract: BACKGROUND
  Opioids may alleviate chronic neuropathic pain (NP), but are considered second/third-line analgesia due to their poor gastrointestinal (GI) tolerability. A fixed combination of prolonged-release oxycodone and naloxone (OXN) has been developed to overcome the GI effects. The aim of this analysis was to evaluate analgesic effectiveness and tolerability of low-dose OXN in patients with moderate-to-severe noncancer NP despite analgesia.
  
  
  METHODS
  This retrospective observation of consecutive adult patients, treated open-label for 8 weeks at a single Italian centre, evaluated effectiveness (pain intensity numerical rating scale [NRS], Patients' Global Impression of Change [PGIC], Douleur Neuropathique 4 inventory [DN4] and Chronic Pain Sleep Inventory [CPSI]), doses of daily OXN and adjuvant medication, rescue paracetamol use, bowel function index (BFI), laxative use, and safety.
  
  
  RESULTS
  Of 200 patients (mean age 65.9 years; 54% female) with NP included in the analysis; 97% completed 8 weeks' treatment. At the observation start, all patients were taking anticonvulsants and complained of constipation, and 60% were receiving opioids. Pain intensity and DN4 score decreased significantly by endpoint (NRS p < 0.0001; DN4 p < 0.0001) and need for rescue analgesics abated. Reduction in pain intensity throughout the observation was similar regardless of NP aetiology. According to PGIC, 87.8% of patients were much/extremely improved, CPSI (p < 0.0001) and BFI were significantly improved (p < 0.0001) and laxative use decreased. No differences were found between patients <65 years vs those ≥65 years. OXN was generally well tolerated.
  
  
  CONCLUSIONS
  Study limitations including the retrospective observational design, the lack of a control group and the single-centre design may limit the generalizability of our findings.
  
  
  CONCLUSIONS
  Low-dose OXN (25.0 ± 12.5 mg/day) added to anticonvulsants was highly effective in controlling noncancer NP of varied aetiology, with reduced need for rescue analgesia and improved quality of sleep, and was well tolerated, with improved bowel function and reduced laxative use. The efficacy and tolerability of OXN demonstrated in this real-world setting suggest its utility in this difficult to manage patient population.
authors.affiliation: Emergency Care, Critical Care Medicine, Pain Medicine and Anaesthesiology Department, Tor Vergata Polyclinic, University of Rome 'Tor Vergata' , Rome , Italy.
authors.forename: M
authors.initials: M
authors.lastname: Lazzari
authors.forename: A F
authors.initials: AF
authors.lastname: Sabato
authors.forename: C
authors.initials: C
authors.lastname: Caldarulo
authors.forename: M
authors.initials: M
authors.lastname: Casali
authors.forename: P
authors.initials: P
authors.lastname: Gafforio
authors.forename: C
authors.initials: C
authors.lastname: Marcassa
authors.forename: F
authors.initials: F
authors.lastname: Leonardis
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000009:adverse effects; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage* / Q000009:adverse effects; D009437:Neuralgia / Q000188:drug therapy*; D010098:Oxycodone / Q000008:administration & dosage* / Q000009:adverse effects; D012189:Retrospective Studies
chemical_list: D000927:Anticonvulsants; D004338:Drug Combinations; D009270:Naloxone; D010098:Oxycodone