Pregabalin, tiapride and lorazepam in alcohol withdrawal syndrome: a multi-centre, randomized, single-blind comparison trial.

Introduction The aim of this trial was to compare lorazepam with non-benzodiazepine medications such as pregabalin and tiapride in the treatment of alcohol withdrawal syndrome (AWS). These drugs were chosen for their inhibitorial effects on the hypersecretion of neurotransmitters usually observed in AWS. Craving reduction and improvement of psychiatric symptoms were the secondary end-points. Methods One hundred and ninety subjects affected by current alcohol dependence were considered consecutively: 111 were enrolled and divided into three groups of 37 subjects each. Within a treatment duration of 14 days, medication was given up to the following maximum doses (pregabalin 450 mg/day; tiapride 800 mg/day; lorazepam 10 mg/day). Withdrawal (CIWA-Ar), craving [visual analogue scale (VAS); Obsessive and Compulsive Drinking Scale (OCDS)], psychiatric symptoms [Symptom Check List 90 Revised (SCL-90-R)] and quality of life (QL-index) rating scales were applied. Results On the CIWA-Ar score, all the groups showed a signi\ufb01cant reduction between times (P < 0.001) with a higher reduction for the pregabalin group (P < 0.01) on items regarding headache and orientation. Retention in treatment was lower in the tiapride group (P < 0.05), while the number of subjects remaining alcohol free was higher in the pregabalin group (P < 0.05). Signi\ufb01cant reduction between baseline and the end of the treatment was found in all the groups at the OCDS and the VAS for craving, at the SCL-90-R and QL-index (P < 0.001). Discussion All the medications in the trial showed evidence of safety and ef\ufb01cacy in the treatment of uncomplicated forms of AWS, with some particular differences. The ef\ufb01cacy of pregabalin was superior to that of tiapride, used largely in research trials and, for some measures, to that of the \u2018gold standard\u2019, lorazepam. Accordingly, pregabalin may be considered as a potentially useful new drug for treatment of AWS, deserving further investigation

Blunted endogenous opioid release following an oral dexamphetamine challenge in abstinent alcohol-dependent individuals

Addiction has been proposed as a ‘reward deficient’ state, which is compensated for with substance use. There is growing evidence of dysregulation in the opioid system, which plays a key role in reward, underpinning addiction. Low levels of endogenous opioids are implicated in vulnerability for developing alcohol dependence (AD) and high mu-opioid receptor (MOR) availability in early abstinence is associated with greater craving. This high MOR availability is proposed to be the target of opioid antagonist medication to prevent relapse. However, changes in endogenous opioid tone in AD are poorly characterised and are important to understand as opioid antagonists do not help everyone with AD. We used [11C]carfentanil, a selective MOR agonist positron emission tomography (PET) radioligand, to investigate endogenous opioid tone in AD for the first time. We recruited 13 abstinent male AD and 15 control participants who underwent two [11C]carfentanil PET scans, one before and one 3 h following a 0.5 mg/kg oral dose of dexamphetamine to measure baseline MOR availability and endogenous opioid release. We found significantly blunted dexamphetamine-induced opioid release in 5 out of 10 regions-of-interest including insula, frontal lobe and putamen in AD compared with controls, but no significantly higher MOR availability AD participants compared with HC in any region. This study is comparable to our previous results of blunted dexamphetamine-induced opioid release in gambling disorder, suggesting that this dysregulation in opioid tone is common to both behavioural and substance addictions