Improving GHB withdrawal with baclofen: study protocol for a feasibility study for a randomised controlled trial.
BACKGROUND
GHB (gamma-hydroxybutyrate) and its pro-drugs GBL (gamma-butyrolactone) and 1,4-butanediol (1,4-BD) are central nervous system depressants whose street names include 'G' and 'liquid ecstasy'. They are used recreationally predominately for their stimulant and pro-sexual effects or for sedation to help with sleep and/or to 'come down' after using stimulant recreational drugs. Although overall population prevalence is low (0.1 %), in some groups such as men who have sex with men, GHB/GBL use may reach 20 %. GHB/GBL dependence may be associated with severe withdrawal with individuals presenting either acutely to emergency departments or to addiction services for support. Benzodiazepines are currently prescribed for GHB/GBL detoxification but do not prevent all complications, such as behavioural disinhibition, that may require hospitalisation or admission to a high dependency/intensive care unit. The GABABreceptor mediates most effects of GHB/GBL and the GABABagonist, baclofen, has shown promise as an adjunct to benzodiazepines in reducing withdrawal severity when prescribed both during withdrawal and as a 2-day 'preload' prior to detoxification. The key aim of this feasibility study is provide information about recruitment and characteristics of the proposed outcome measure (symptom severity, complications including delirium and treatment escalation) to inform an application for a definitive randomised placebo controlled trial to determine the role of baclofen in the management of GHB/GBL withdrawal and whether starting baclofen 2 days earlier improves outcomes further.


METHODS
This is a prospective, randomised, double-blind, placebo-controlled feasibility study that will recruit participants (aged over 18 years) who are GHB/GBL-dependent and wish to undergo planned GHB/GBL detoxification or are at risk of acute withdrawal and are inpatients requiring unplanned withdrawal. We aim to recruit 88 participants: 28 unplanned inpatients and 60 planned outpatients. During detoxification we will compare baclofen 10 mg three times a day with placebo as an adjunct to the usual benzodiazepine regimen. In the planned outpatient arm, we will also compare a 2-day preload of baclofen 10 mg three times a day with placebo. Ratings of GHB/GBL withdrawal, sleep, depression, anxiety as well as GHB/GBL use will be collected. The main data analyses will be descriptive about recruitment and characterising the impact of adding baclofen to the usual benzodiazepine regimen on measures and outcomes of GHB/GBL withdrawal to provide estimates of variability and effect size. A qualitative approach will evaluate research participant and clinician acceptability and data collected to inform cost-effectiveness.


CONCLUSIONS
This feasibility study will inform a randomised controlled trial to establish whether adding baclofen to a benzodiazepine regimen reduces the severity and complications of GHB/GBL withdrawal.


BACKGROUND
ISRCTN59911189 . Registered 14 October 2015.


METHODS
v3.1, 1 February 2016.
Central North West London NHS Foundation Trust's Club Drug Clinic, 69 Warwick Rd, London, SW5 9HB, UK. anne.lingford-hughes@imperial.ac.uk.|Centre for Psychiatry, Division of Brain Sciences, Imperial College London, Burlington Danes Building, Hammersmith Hospital site, Du Cane Rd, London, W12 0NN, UK. anne.lingford-hughes@imperial.ac.uk.
Anne
http://orcid.org/0000-0003-4512-3453
A
Lingford-Hughes
Central North West London NHS Foundation Trust's Club Drug Clinic, 69 Warwick Rd, London, SW5 9HB, UK.
Yash
Y
Patel
Central North West London NHS Foundation Trust's Club Drug Clinic, 69 Warwick Rd, London, SW5 9HB, UK.
Owen
O
Bowden-Jones
Central North West London NHS Foundation Trust's Club Drug Clinic, 69 Warwick Rd, London, SW5 9HB, UK.|Centre for Psychiatry, Division of Brain Sciences, Imperial College London, Burlington Danes Building, Hammersmith Hospital site, Du Cane Rd, London, W12 0NN, UK.
Mike J
MJ
Crawford
Guy's and St. Thomas NHS Foundation Trust, London, UK.|Faculty of Life Sciences and Medicine, King's College, London, UK.
Paul I
PI
Dargan
Statistical Advisory Service, School Of Public Health, Imperial College London, London, UK.
Fabiana
F
Gordon
Department of Health Sciences, The University of York, York, UK.
Steve
S
Parrott
Department of Mental Health, Social Work and Integrative Medicine, Middlesex University, London, UK.
Tim
T
Weaver
Guy's and St. Thomas NHS Foundation Trust, London, UK.|Faculty of Life Sciences and Medicine, King's College, London, UK.
David M
DM
Wood
Baclofen; Benzodiazepine; GABAB; GBL; GHB; GHB/GBL dependence; GHB/GBL withdrawal; Gamma-butyrolactone; Gamma-hydroxybutyrate
Drug Alcohol Depend. 2004 Jul 15;75(1):3-9
15225884
J Gen Intern Med. 2001 Sep;16(9):606-13
11556941
Trends Pharmacol Sci. 2004 Jan;25(1):29-34
14723976
Mol Pharmacol. 2012 Aug;82(2):226-35
22561075
Gen Hosp Psychiatry. 2009 Jul-Aug;31(4):394-6
19555805
Br J Addict. 1989 Nov;84(11):1353-7
2597811
Drug Test Anal. 2011 Jul-Aug;3(7-8):417-25
21548140
Am J Drug Alcohol Abuse. 2012 Mar;38(2):121-9
22175869
J Psychopharmacol. 2012 Jul;26(7):899-952
22628390
Drug Alcohol Depend. 2001 Jun 1;63(1):1-22
11297827
Eur Addict Res. 2012;18(1):40-5
22142784
Addiction. 2008 Sep;103(9):1450-60
18783500
Drug Alcohol Depend. 2002 Jun 1;67(1):89-94
12062782
Int J STD AIDS. 2016 Dec;27(14 ):1309-1316
26553307
Psychopharmacology (Berl). 2005 May;179(3):678-87
15645222
Int J Psychiatry Clin Pract. 2013 Jun;17(2):154-6
23485126
Addiction. 1997 Jan;92(1):89-96
9060200
Addiction. 1993 Jun;88(6):791-804
8329970
Arch Intern Med. 2006 May 22;166(10):1092-7
16717171
Psychol Med. 1978 May;8(2):325-9
26096
Ann Emerg Med. 2001 Feb;37(2):147-53
11174231
J Psychopharmacol. 2005 Mar;19(2):195-204
15871147
Neurocrit Care. 2008;8(3):430-3
18266111
BMJ. 2015 Nov 03;351:h5790
26537832
J Addict Med. 2011 Dec;5(4):302-3
21817917
Emerg Med Australas. 2011 Dec;23(6):732-40
22151672
Eval Program Plann. 1979;2(3):197-207
10245370
Curr Neuropharmacol. 2015 Jan;13(1):47-70
26074743
CJEM. 2008 Jan;10(1):69-74
18226321
Eur J Emerg Med. 2013 Aug;20(4):263-7
22850087
Addiction. 2011 Feb;106(2):442-7
20925687