title: The role of benzodiazepines in breathlessness: a single site, open label pilot of sustained release morphine together with clonazepam.
abstract: BACKGROUND
  Breathlessness at rest or on minimal exertion despite optimal treatment of underlying cause(s) is distressing and prevalent. Opioids can reduce the intensity of chronic refractory breathlessness and an anxiolytic may be of benefit. This pilot aimed to determine the safety and feasibility of conducting a phase III study on the intensity of breathlessness by adding regular benzodiazepine to low-dose opioid.
  
  
  METHODS
  This is a single site, open label phase II study of the addition of regular clonazepam 0.5 mg nocte orally to Kapanol(R) 10 mg (sustained release morphine sulphate) orally mane together with docusate/sennosides in people with modified Medical Research Council Scale ≥2. Breathlessness intensity on day four was the efficacy outcome. Participants could extend for another 10 days if they achieved >15% reduction over their own baseline breathlessness intensity.
  
  
  RESULTS
  Eleven people had trial medication (eight males, median age 78 years (68 to 89); all had COPD; median Karnofsky 70 (50 to 80); six were on long-term home oxygen. Ten people completed day four. One person withdrew because of unsteadiness on day four. Five participants reached the 15% reduction, but only three went on to the extension study, all completing without toxicity.
  
  
  CONCLUSIONS
  This study was safe, feasible and there appears to be a group who derive benefits comparable to titrated opioids. Given the widespread use of benzodiazepines for the symptomatic treatment of chronic refractory breathlessness and its poor evidence base, there is justification for a definitive phase III study.
authors.affiliation: Southern Adelaide Palliative Services, Repatriation General Hospital, Daw Park, South Australia, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Allcroft
authors.forename: Vera
authors.initials: V
authors.lastname: Margitanovic
authors.forename: Aine
authors.initials: A
authors.lastname: Greene
authors.forename: Meera R
authors.initials: MR
authors.lastname: Agar
authors.forename: Katherine
authors.initials: K
authors.lastname: Clark
authors.forename: Amy P
authors.initials: AP
authors.lastname: Abernethy
authors.forename: David C
authors.initials: DC
authors.lastname: Currow
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use; D001569:Benzodiazepines / Q000008:administration & dosage / Q000627:therapeutic use; D002998:Clonazepam / Q000008:administration & dosage* / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D004359:Drug Therapy, Combination; D004417:Dyspnea / Q000188:drug therapy* / Q000209:etiology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D009020:Morphine / Q000008:administration & dosage* / Q000627:therapeutic use; D010166:Palliative Care / Q000379:methods; D010865:Pilot Projects; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy*; D013021:South Australia
chemical_list: D000701:Analgesics, Opioid; D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D001569:Benzodiazepines; D002998:Clonazepam; D009020:Morphine