Song Guo1, Victoria Manning2, Yi Yang3, Puay Kee Koh4, Edwin Chan5, Nurun Nisa de Souza5, Pryseley Nkouibert Assam5, Rehena Sultana6, Ruki Wijesinghe6, Julius Pangjaya7, Gomathinayagam Kandasami8, Christopher Cheok9, Kae Meng Lee10, Kim Eng Wong8. 1. National Addictions Management Service, Institute of Mental Health, 10 Buangkok View, 539747, Singapore. Electronic address: song_guo@imh.com.sg. 2. Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia. 3. National Addictions Management Service, Institute of Mental Health, 10 Buangkok View, 539747, Singapore; Clinical Governance and Quality, Institute of Mental Health, Singapore. 4. National Addictions Management Service, Institute of Mental Health, 10 Buangkok View, 539747, Singapore; Ministry of Communications and Information, 140 Hill Street, #01-01A, Old Hill Street Police Station, Singapore 179369. 5. Singapore Clinical Research Institute, 31 Biopolis Way, #02-01, Nanos, 138669, Singapore. 6. Centre for Quantitative Medicine, Duke-NUS Medical School, 20 College Road, 169856, Singapore. 7. Department of Pharmacy, Institute of Mental Health, 10 Buangkok View, 539747, Singapore. 8. National Addictions Management Service, Institute of Mental Health, 10 Buangkok View, 539747, Singapore. 9. National Addictions Management Service, Institute of Mental Health, 10 Buangkok View, 539747, Singapore; Department of General and Forensic Psychiatry, Institute of Mental Health, 10 Buangkok View, 539747, Singapore. 10. Resilienz Clinic, 10 Sinaran Drive #10-03, Novena Medical Center, 307506, Singapore.
Abstract
BACKGROUND: Many individuals leave costly inpatient detoxification programs prematurely because of the severity of withdrawal symptoms experienced. In the absence of opioid-assisted detoxification in Singapore, diazepam is used to manage withdrawal. However since diazepam is addictive, there is a need to explore the effectiveness of alternative medications. DESIGN AND PROCEDURES: The study aimed to examine the safety and efficacy of lofexidine, a non-opiate, non-addictive, alpha 2-adrenergic agonist in assisting opioid detoxification in Singapore, using a randomized, double-blind, investigator-initiated placebo-controlled trial comparing lofexidine against diazepam. Opioid dependent patients (n = 111) were randomized to receive a 10-day course of lofexidine (n = 56) or diazepam (n = 55). The primary endpoint was the Objective Opioid Withdrawal Scale (OOWS) score on days 3 and 4 and secondary outcomes were the Short Opioid Withdrawal Scale (SOWS) score, program retention rate, and ratings of opiate craving. MAIN FINDINGS: The OOWS, SOWS and opiate craving scores were consistently lower in the lofexidine group relative to the diazepam group over the 14-day study period; however no statistically significant differences were found on days 3 and 4 (peak withdrawal). Changes in mean pupil size during peak withdrawal were significantly smaller in the lofexidine group and more participants in the lofexidine group remained in treatment and completed detoxification. CONCLUSIONS:Lofexidine was at least as effective as diazepam in reducing the opioid withdrawal syndrome and increased treatment retention. In addition to its non-addictive and non-abuse properties, lofexidine has several clinical advantages over diazepam. The use of lofexidine is recommended when opioid-assisted medications are not available.
RCT Entities:
BACKGROUND: Many individuals leave costly inpatient detoxification programs prematurely because of the severity of withdrawal symptoms experienced. In the absence of opioid-assisted detoxification in Singapore, diazepam is used to manage withdrawal. However since diazepam is addictive, there is a need to explore the effectiveness of alternative medications. DESIGN AND PROCEDURES: The study aimed to examine the safety and efficacy of lofexidine, a non-opiate, non-addictive, alpha 2-adrenergic agonist in assisting opioid detoxification in Singapore, using a randomized, double-blind, investigator-initiated placebo-controlled trial comparing lofexidine against diazepam. Opioid dependent patients (n = 111) were randomized to receive a 10-day course of lofexidine (n = 56) or diazepam (n = 55). The primary endpoint was the Objective Opioid Withdrawal Scale (OOWS) score on days 3 and 4 and secondary outcomes were the Short Opioid Withdrawal Scale (SOWS) score, program retention rate, and ratings of opiate craving. MAIN FINDINGS: The OOWS, SOWS and opiate craving scores were consistently lower in the lofexidine group relative to the diazepam group over the 14-day study period; however no statistically significant differences were found on days 3 and 4 (peak withdrawal). Changes in mean pupil size during peak withdrawal were significantly smaller in the lofexidine group and more participants in the lofexidine group remained in treatment and completed detoxification. CONCLUSIONS:Lofexidine was at least as effective as diazepam in reducing the opioid withdrawal syndrome and increased treatment retention. In addition to its non-addictive and non-abuse properties, lofexidine has several clinical advantages over diazepam. The use of lofexidine is recommended when opioid-assisted medications are not available.
Authors: Melvyn W B Zhang; Sandor Heng; Syidda B Amron; Zaakira Mahreen; Guo Song; Daniel S S Fung; Helen E Smith Journal: Int J Environ Res Public Health Date: 2020-01-24 Impact factor: 3.390
Authors: Francisco Navarrete; María Salud García-Gutiérrez; Ani Gasparyan; Amaya Austrich-Olivares; Jorge Manzanares Journal: Front Pharmacol Date: 2021-05-20 Impact factor: 5.810
Authors: Ivan Urits; Anjana Patel; Robbie Zusman; Celina Guadalupe Virgen; Mohammad Mousa; Amnon A Berger; Hisham Kassem; Jai Won Jung; Jamal Hasoon; Alan D Kaye; Omar Viswanath Journal: Psychopharmacol Bull Date: 2020-07-23