Harmen Beurmanjer

80 Chapter 6 Methods Study design The effectiveness of baclofen was assessed in a multicentre, open-label, non-randomized, controlled clinical trial (see protocol publication, Kamal et al, 2015). After detoxification from GHB, patients received TAU or TAU combined with baclofen, based on patient preference. Participants provided written informed consent. The study was approved by the Medical Ethics Committee, Twente Medical School (METC /14015.am) study number NL40321.044.13. The study was registered in the Netherlands Trial Register with number NTR4528. Participants GHB-dependent patients (according to DSM-IV criteria of substance dependence) were recruited at six addiction care facilities (IrisZorg, Mondriaan, Novadic-Kentron, Tactus, Victas and VNN) in The Netherlands, when admitted for detoxification. Inclusion criteria: completed GHB detoxification, wish for abstinence, continuing out-patient treatment after detoxification, age between 18-40 years, and comprehension of Dutch. Exclusion criteria: physical contra-indications for baclofen (e.g. liver problems, renal impairment, hypertension, diabetes, seizure disorder, pregnancy), severe psychiatric conditions (e.g. bipolar disorder, major depression, psychotic disorders, suicidal ideations), use of anxiolytics, stimulants or hypnotics after detoxification, or previous misuse of baclofen. Of 137 GHB-dependent patients admitted for detoxification, 107 were eligible for participation. Thirty-seven patients received baclofen on top of TAU; 70 received TAU only. During admission, a physician informed patients about the baclofen study. A flowchart is shown in figure 1. Sample size calculation Sample size calculation was based on the effectiveness of baclofen in alcohol use disorders. Though the literature on baclofen’s efficacy in alcohol use disorders is contradictory, several studies do suggest a beneficial response of baclofen versus placebo (abstinence rates 70% versus 20-30% )(Giovanni Addolorato et al., 2002, 2007). Anticipating a smaller effectiveness in GHB dependence (three month abstinence rates 60% versus 40%) based on our previous studies(Dijkstra et al., 2017), approximately 30 patients per group are needed in order to detect any significant effects of baclofen, with α=.05 and β=.80 (Kamal, Schellekens, et al., 2015) Treatment intervention Baclofen Participants initially received 15mg per day, divided over three doses, which was gradually increased over a period of 10 days to 45mg daily. When patients reported no or limited effects of baclofen on anxiety and craving after two weeks without side effects, the dose