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

Clinica Villa Maria Pia, Via del Forte Trionfale 36, Rome 00135 Italy.
Addiction (Impact Factor: 4.74). 02/2010; 105(2):288-99. DOI: 10.1111/j.1360-0443.2009.02792.x
Source: PubMed


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.
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.
On the CIWA-Ar score, all the groups showed a significant 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). Significant 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).
All the medications in the trial showed evidence of safety and efficacy in the treatment of uncomplicated forms of AWS, with some particular differences. The efficacy of pregabalin was superior to that of tiapride, used largely in research trials and, for some measures, to that of the 'gold standard', lorazepam. Accordingly, pregabalin may be considered as a potentially useful new drug for treatment of AWS, deserving further investigation.

Download full-text


Available from: Riccardo Guglielmo,
  • Source
    • "As to relief drinkers, Verheul et al. [14] proposed that Acamprosate (a glutamate antagonist), most likely via a reduction of neuronal hyperexcitability, may be effective. For relief drinkers, a role for Gabapentin [53], Pregabalin [54] [55], Baclofen [56] [57] and Acetyl-L-Carnetine [58] should be considered. With regard to obsessive craving, we believe that SSRIs [59] [60], some mood stabilizers [51], topiramate and baclofen may represent valid options. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction Craving is commonly thought to play a crucial role both in the transition from controlled drinking to alcohol dependence and in the mechanism underlying relapse. However there is no consensus on its definition, and on its correct assessment. Another significant hindrance is that craving is almost certainly a multi-faceted construct. To this respect a three pathway psychobiological model able to differentiate craving into a reward, relief, and obsessive component has been suggested. Methods CTQ was administered to 547 control subjects and to 100 alcohol dependent patients. The dimensional structure of the questionnaire, through the principal component analysis, the reliability and the threshold values were evaluated in both the control and clinical sample. Results The results showed and confirmed that the CTQ is composed of three dimensions. Cronbach's alpha coefficients suggest that the questionnaire is reliable. Alcohol-dependent subjects had a significantly higher mean score as compared to the normative sample in both Reward, Relief, Obsessive craving. Younger age correlated with higher scores on Reward craving (r=0.38; p<0.001) and males reported significantly higher scores than women on Reward craving (t=4.36; p<0.001). Discussion CTQ showed to be a reliable and valid questionnaire to distinguish a normative sample from pathological individuals. The average scores obtained represent the first normative data available for this questionnaire. Identifying a craving type may represent an important predicting or matching variable for anti-craving psychotropics. More research is needed with respect to CTQ's external validity, i.e. correlations with phenotypic, endophenotypic and genetic indicators of relief, reward and obsessive drinking.
    Comprehensive Psychiatry 10/2013; 54(7):925-932. DOI:10.1016/j.comppsych.2013.03.023 · 2.25 Impact Factor
  • Source
    • "Pregabalin 600 mg/die was an effective and well-tolerated treatment for social anxiety disorder. Martinotti et al. (2010) compared lorazepam with nonbenzodiazepine drugs, such as pregabalin, as treatment for AWS. Their results suggest that pregabalin has a better efficacy than lorazepam, normally considered the " gold standard " drug, in treating uncomplicated forms of AWS. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Pregabalin is an anticonvulsant drug that binds to the α2δ (alpha2delta) subunit of the voltage-dependent calcium channel in central nervous system (CNS). Pregabalin decreases the release of neurotransmitters, including glutamate, norepinephrine, substance P and calcitonin gene-related peptide. Purpose of this paper is to offer a qualitative overview of the studies currently available in literature about this drug, examining the effectiveness of pregabalin in its various fields of application. Our analysis, conducted on a final selection of 349 scientific papers, shows that pregabalin may help to reduce pain in diabetic neuropathy, in post-herpetic neuralgia and in some patients affected by fibromyalgia. It is also effective for the treatment of diverse types of seizures and has similar efficacy to benzodiazepines and venlafaxine in anxiety disorder. Moreover, pregabalin may be a therapeutic agent for the treatment of alcohol abuse, in both withdrawal phase and relapse prevention. Possible implications in the treatment of benzodiazepines dependence are emerging, but a potential abuse or misuse of the drug has also been reported. Range of dosage may fluctuate considerably, from 75 mg to 600 mg per day. Further studies are needed to completely understand pregabalin mechanism of action in the different diseases.
    Current pharmaceutical design 06/2013; 19(35). DOI:10.2174/13816128113199990425 · 3.45 Impact Factor
  • Source
    • "These selective effects of pregabalin are consistent with its antianxiety properties which have been demonstrated in randomized clinical trials (Feltner et al. 2008; Montgomery et al. 2008; Montgomery et al. 2006). Consistent with its effects on tobacco withdrawal, pregabalin attenuated alcohol withdrawal symptoms in clinical studies (Di Nicola et al. 2010; Martinotti et al. 2010). In our study, pregabalin, however, did not change the reactivity to smoking cues. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In preclinical and clinical studies, medications enhancing the GABA neurotransmission attenuate nicotine reward. Pregabalin, a GABA analogue, presumably interacts with brain glutamate and GABA neurotransmission. The goal of this study was to determine pregabalin's effects on smoking behavior, nicotine withdrawal, craving for cigarettes, and cognitive performance. Twenty-four smokers participated in an outpatient double-blind, placebo-controlled, crossover study. Subjects had a 4-day treatment period with either pregabalin (300 mg/day) or placebo and following a washout period were then crossed over for 4 days to the other treatment. In each treatment period, starting at midnight of day 1, participants were asked to stop smoking until the experimental session on day 4. During the experimental session measures of ad lib smoking behavior, tobacco withdrawal, craving for cigarettes, and cognitive performance were obtained. Pregabalin treatment, compared to placebo, did not reduce the smoking behavior during the first 3 days of treatment or during ad lib smoking period. Pregabalin treatment attenuated some tobacco withdrawal symptoms including ratings of anxious, irritable, and frustrated in abstinent smokers. Pregabalin treatment also attenuated the subjective ratings of "liking" in response to smoking. Under pregabalin treatment, smokers made more errors in a sustained attention task. These findings provide limited support for pregabalin as a treatment for nicotine addiction.
    Psychopharmacology 09/2011; 220(3):611-7. DOI:10.1007/s00213-011-2507-x · 3.88 Impact Factor
Show more