PMID- 36877492
OWN - NLM
STAT- MEDLINE
DCOM- 20230717
LR  - 20230718
IS  - 1872-6623 (Electronic)
IS  - 0304-3959 (Linking)
VI  - 164
IP  - 8
DP  - 2023 Aug 1
TI  - Combination analgesic development for enhanced clinical efficacy (the CADENCE 
      trial): a double-blind, controlled trial of an alpha-lipoic acid-pregabalin 
      combination for fibromyalgia pain.
PG  - 1783-1792
LID - 10.1097/j.pain.0000000000002875 [doi]
AB  - Drug therapy for fibromyalgia is limited by incomplete efficacy and dose-limiting 
      adverse effects (AEs). Combining agents with complementary analgesic 
      mechanisms-and differing AE profiles-could provide added benefits. We assessed an 
      alpha-lipoic acid (ALA)-pregabalin combination with a randomized, double-blind, 
      3-period crossover design. Participants received maximally tolerated doses of 
      ALA, pregabalin, and ALA-pregabalin combination for 6 weeks. The primary outcome 
      was daily pain (0-10); secondary outcomes included Fibromyalgia Impact 
      Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression 
      Inventory (BDI-II), adverse events, and other measures. The primary outcome of 
      daily pain (0-10) during ALA (4.9), pregabalin (4.6), and combination (4.5) was 
      not significantly different ( P = 0.54). There were no significant differences 
      between combination and each monotherapy for any secondary outcomes, although 
      combination and pregabalin were both superior to ALA for measures of mood and 
      sleep. Alpha-lipoic acid and pregabalin maximal tolerated doses were similar 
      during combination and monotherapy, and AEs were not frequent with combination 
      therapy. These results do not support any additive benefit of combining ALA with 
      pregabalin for fibromyalgia. The observation of similarly reached maximal 
      tolerated drug doses of these 2 agents (which have differing side-effect 
      profiles) during combination and monotherapy-without increased side 
      effects-provides support for future development of potentially more beneficial 
      combinations with complementary mechanisms and nonoverlapping side effects.
CI  - Copyright (c) 2023 International Association for the Study of Pain.
FAU - Gilron, Ian
AU  - Gilron I
AUID- ORCID: 0000-0002-5293-8792
AD  - Department of Anesthesiology and Perioperative Medicine, Queen's University, 
      Kingston, ON, Canada.
AD  - Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      ON, Canada.
AD  - School of Policy Studies, Queen's University, Kingston, ON, Canada.
AD  - Providence Care Hospital, Queen's University, Kingston, ON, Canada.
FAU - Robb, Sylvia
AU  - Robb S
AD  - Department of Anesthesiology and Perioperative Medicine, Queen's University, 
      Kingston, ON, Canada.
FAU - Tu, Dongsheng
AU  - Tu D
AD  - Departments of Public Health Sciences and Mathematics & Statistics, Queen's 
      University, Kingston, ON, Canada.
FAU - Holden, Ronald R
AU  - Holden RR
AD  - Departments of Psychology, Queen's University, Kingston, ON, Canada.
FAU - Milev, Roumen
AU  - Milev R
AD  - Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.
AD  - Departments of Psychology, Queen's University, Kingston, ON, Canada.
AD  - Departments of Psychiatry, Queen's University, Kingston, ON, Canada.
AD  - Providence Care Hospital, Queen's University, Kingston, ON, Canada.
FAU - Towheed, Tanveer
AU  - Towheed T
AD  - Division of Rheumatology, Department of Medicine, Queen's University, Kingston, 
      ON, Canada.
LA  - eng
GR  - CIHR/Canada
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20230306
PL  - United States
TA  - Pain
JT  - Pain
JID - 7508686
RN  - 55JG375S6M (Pregabalin)
RN  - 73Y7P0K73Y (Thioctic Acid)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 0 (Analgesics)
SB  - IM
MH  - Humans
MH  - Pregabalin/therapeutic use
MH  - *Fibromyalgia/drug therapy/complications
MH  - *Thioctic Acid/therapeutic use
MH  - gamma-Aminobutyric Acid/therapeutic use
MH  - Analgesics
MH  - Pain/drug therapy
MH  - Treatment Outcome
MH  - Double-Blind Method
EDAT- 2023/03/07 06:00
MHDA- 2023/07/17 06:42
CRDT- 2023/03/06 11:24
PHST- 2022/11/03 00:00 [received]
PHST- 2023/01/13 00:00 [accepted]
PHST- 2023/07/17 06:42 [medline]
PHST- 2023/03/07 06:00 [pubmed]
PHST- 2023/03/06 11:24 [entrez]
AID - 00006396-202308000-00015 [pii]
AID - 10.1097/j.pain.0000000000002875 [doi]
PST - ppublish
SO  - Pain. 2023 Aug 1;164(8):1783-1792. doi: 10.1097/j.pain.0000000000002875. Epub 
      2023 Mar 6.