Efficacy and safety of high-dose baclofen for the treatment of alcohol dependence: A multicentre, randomised, double-blind controlled trial

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• 作者：Esther M. Beraha^a ; Elske Salemink^a ; ¹ ; Anna E. Goudriaan^b ; ^c ; ^d ; ¹ ; Abraham Bakker^h ; David de Jong^a ; Natasha Smits^e ; Jan Willem Zwart^e ; Dick van Geest^f ; Pieter Bodewits^g ; Tom Schiphof^f ; Harma Defourny^e ; Mirjam van Tricht^b ; Wim van den Brink^b ; ^c ; ² ; Reinout W. Wiers^a ; ² ; ^{R.W.H.J.Wiers@uva.nl}
• 关键词：Randomised placebo-controlled trial ; Alcohol dependence ; High-dose baclofen
• 刊名：European Neuropsychopharmacology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：26
• 期：12
• 页码：1950-1959
• 全文大小：614 K
• 卷排序：26

文摘

Previous randomised placebo-controlled trials with low-to-medium doses of baclofen (30–60 mg) showed inconsistent results, but case studies suggested a dose-response effect and positive outcomes in patients on high doses of baclofen (up to 270 mg). Its prescription was temporary permitted for the treatment of alcohol dependence (AD) in France, and baclofen is now widely prescribed. Recently, a small RCT found a strong effect of a mean dose of 180 mg baclofen. In the present study the efficacy and safety of high doses of baclofen was examined in a multicentre, double-blind, placebo-controlled trial. 151 patients were randomly assigned to either six weeks titration and ten weeks high-dose baclofen (N=58; up to 150 mg), low-dose baclofen (N=31; 30 mg), or placebo (N=62). The primary outcome measure was time to first relapse. Nine of the 58 patients (15.5%) in the high-dose group reached 150 mg and the mean baclofen dose in this group was 93.6 mg (SD=40.3). No differences between the survival distributions for the three groups were found in the time to first relapse during the ten-weeks high-dose phase (χ2=0.41; p=0.813) or the 16-weeks complete medication period (χ2=0.04; p=0.982). There were frequent dose-related adverse events in terms of fatigue, sleepiness, and dry mouth. One medication related serious adverse event occurred in the high-dose baclofen group. Neither low nor high doses of baclofen were effective in the treatment of AD. Adverse events were frequent, although generally mild and transient. Therefore, large-scale prescription of baclofen for the treatment of AD seems premature and should be reconsidered.