title: Randomised, double-blind controlled trial by dose reduction of implanted intrathecal morphine delivery in chronic non-cancer pain.
abstract: OBJECTIVE
  This study aimed to investigate the efficacy of intrathecal morphine in the long term by hypothesising that a reduction of the intrathecal opioid dose following long-term administration would increase the level of pain intensity.
  
  
  METHODS
  Randomised, double-blind, controlled, parallel group trial.
  
  
  METHODS
  Department of Pain Management, Russells Hall Hospital, Dudley, UK.
  
  
  METHODS
  24 patients with non-cancer pain implanted with morphine reservoirs were assessed for eligibility.
  
  
  METHODS
  Participants were randomly allocated to one of two parallel groups in which one of the groups had no change in morphine dose and the other group had a small reduction (20%) in dosage every week during a 10-week follow-up.
  
  
  RESULTS
  Primary outcomes were visual analogue scale (VAS) pain score change and withdrawal from the study due to lack of efficacy.
  
  
  RESULTS
  9 of the patients assessed for eligibility declined to participate in the study. 15 patients were randomised to control (n=5) or intervention (n=10) and included in an intention-to-treat analysis. Owing to worsening of pain, seven patients withdrew from the study prematurely. None knew prior to withdrawal which arm of the study they were in, but all turned out to be in the dose-reduction arm. The calculation of dropout rates between groups indicated a significant statistical difference (p=0.026) and recruitment was ceased. The VAS change between baseline and the last observation was smaller in the control group (median, Mdn=11) than in the intervention group (Mdn=30.5), although not statistically significant, Z=-1.839, p=0.070; r=-0.47. Within groups, VAS was significantly lower at baseline (Mdn=49.5) than at the last observation (Mdn=77.5) for the reduction group, Z=-2.805, p=0.002; r=-0.627 but not for the control group (p=0.188).
  
  
  CONCLUSIONS
  This double-blind randomised controlled trial of chronic intrathecal morphine administration suggests the effectiveness of this therapy for the management of chronic non-cancer pain. However, owing to the small number of patients completing the study (n=8), further studies are warranted.
  
  
  BACKGROUND
  International Standard Randomised Controlled Trials Centre (ISRCTN 33733462).
authors.affiliation: Faculty of Health, Birmingham City University, Birmingham, UK.
authors.forename: Jon H
authors.initials: JH
authors.lastname: Raphael
authors.forename: Rui V
authors.initials: RV
authors.lastname: Duarte
authors.forename: Jane L
authors.initials: JL
authors.lastname: Southall
authors.forename: Peter
authors.initials: P
authors.lastname: Nightingale
authors.forename: George D
authors.initials: GD
authors.lastname: Kitas
keywords: chronic pain; drug delivery systems, implantable; morphine; randomised controlled trial; treatment efficacy
references.citation: J Pain Symptom Manage. 2000 Aug;20(2):S12-36
references.pmid: 10989255
references.citation: Pain. 2004 Jun;109(3):242-249
references.pmid: 15157684
references.citation: Lancet. 1979 May 26;1(8126):1141-2
references.pmid: 86861
references.citation: Science. 1976 Jun 25;192(4246):1357-8
references.pmid: 1273597
references.citation: J Clin Oncol. 2002 Oct 1;20(19):4040-9
references.pmid: 12351602
references.citation: J Neurosurg. 1996 Sep;85(3):458-67
references.pmid: 8751633
references.citation: J Pain Symptom Manage. 2000 Mar;19(3):209-15
references.pmid: 10760626
references.citation: Pain Med. 2002 Dec;3(4):300-12
references.pmid: 15099235
references.citation: J Psychopharmacol. 1991 Jan;5(4):342-51
references.pmid: 22282839
references.citation: Pain. 1993 Oct;55(1):119-123
references.pmid: 8278204
references.citation: Health Technol Assess. 1997;1(6):i-iv, 1-135
references.pmid: 9483161
references.citation: Surg Neurol. 2001 Feb;55(2):79-86; discussion 86-8
references.pmid: 11301086
references.citation: Science. 1973 Mar 9;179(4077):1011-4
references.pmid: 4687585
references.citation: Mayo Clin Proc. 1981 Aug;56(8):516-20
references.pmid: 6894954
references.citation: J Pain Symptom Manage. 1996 Feb;11(2):71-80
references.pmid: 8907137
references.citation: Pain Med. 2010 Jul;11(7):1010-6
references.pmid: 20492572
references.citation: Pain. 1983 Sep;17(1):45-56
references.pmid: 6226917
references.citation: Neuromodulation. 1999 Apr;2(2):55-66
references.pmid: 22151109
references.citation: Lancet. 1979 Mar 10;1(8115):527-9
references.pmid: 85109
references.citation: Pain Physician. 2012 Sep-Oct;15(5):363-9
references.pmid: 22996848
references.citation: J Pain. 2008 Feb;9(2):105-21
references.pmid: 18055266
references.citation: Anesthesiology. 2006 Mar;104(3):570-87
references.pmid: 16508405
references.citation: J Psychosom Res. 2002 Feb;52(2):69-77
references.pmid: 11832252
references.citation: Spine (Phila Pa 1976). 2000 Nov 15;25(22):2940-52; discussion 2952
references.pmid: 11074683
references.citation: J Neurosurg Anesthesiol. 2012 Jan;24(1):63-70
references.pmid: 21904220
references.citation: Anesthesiology. 1979 Feb;50(2):149-51
references.pmid: 373503
references.citation: Acta Psychiatr Scand. 1983 Jun;67(6):361-70
references.pmid: 6880820
references.citation: Pain. 1983 May;16(1):87-101
references.pmid: 6602967
references.citation: Neuromodulation. 2012 Sep-Oct;15(5):467-82; discussion 482
references.pmid: 22849581
references.citation: Physiotherapy. 1980 Aug;66(8):271-3
references.pmid: 6450426
references.citation: J Pain Symptom Manage. 2006 May;31(5):393-406
references.pmid: 16716870
references.citation: Pain. 1996 Mar;64(3):455-462
references.pmid: 8783309
references.citation: Cochrane Database Syst Rev. 2010 Jan 20;(1):CD006605
references.pmid: 20091598
references.citation: Neuromodulation. 2012 Sep-Oct;15(5):436-64; discussion 464-6
references.pmid: 22748024
references.citation: Pain. 1983 Sep;17(1):33-44
references.pmid: 6226916
references.citation: Clin J Pain. 2007 Feb;23(2):180-95
references.pmid: 17237668
references.citation: Br J Pain. 2016 May;10(2):67-9
references.pmid: 27551415
references.citation: Pain Physician. 2011 May-Jun;14(3):219-48
references.pmid: 21587327