Alpha-2 Adrenergic Recipients, Valproic and Carbamazepine Acids as an Adjuvant Treatment in Moderate-Grave Alcoholic Abstinence: Systematic Review View PDF

Castellano Fabricio Jose
Department Of Toxicology, Juan A. Fernández Hospital, Argentina

Published on: 2024-11-05

Abstract

Alcohol dependence is among the main risk factors for health in most developed and developing countries. Therapeutic success in moderate-grave abstinence could be increased with adjuvant treatment to benzodiazepines. In our environment, agonists α-2 (clonidine and dexmedetomidine), valproic acid and carbamazepine are the most used. The objective of this work was to carry out the thorough search, critical analysis and summary of the evidence to provide an overview of the effectiveness of these drugs when used without a certain time of treatment compared to each other, against any intervention, placebo or other interventions. A bibliographic search was carried out in databases (PubMed/Medline, Lilacs, and Embase). Two reviewers selected, extracted the data and evaluated the bias risk of independently included studies using the covidence software. The disagreements were resolved by consensus. We perform meta-analysis using revman 5.3 and subgroup analysis by study design. 22 studies were included where none of them presented a risk of bias in all domains, and most studies presented at least one domain with high bias risk. Studies with statistically low results showed that dexmedetomidine and valproic acid decrease the requirements of benzodiazepines in patients receiving placebo. In addition, when valproic acid is combined with benzodiazepines achieve a stable and continuous decrease in abstinence measured in CIWA-AR scale. Clonidine was the only one described that presented a decrease in heart rate against placebo with high significance, clinical situation to be in mind in front of the sympathomimetic syndrome that characterizes alcohol withdrawal syndrome.

Keywords

Alcohol, Abstinence, Carbamazepine, Valproic acid, Dexmedetomidine, Clonidine, Substance consumption

Introduction

Alcohol consumption disorders are among the most prevalent mental disorders worldwide, being highly disabling and are associated with many physical and psychiatric comorbidities. This causes them to contribute substantially to increase morbidity and mortality worldwide. Argentina is one of the countries with the greatest alcohol consumed in the region. In our country there are consumption data of 9.8 L of pure alcohol per capita, for an 8 L regional average and with increasing projections for the year 2025 [1].

The consumption of this substance in moderate condition in most people considered healthy may not be detrimental, however, in some people, due to different genetic and/or environmental issues they lose control capacity developing dependence. Chronic alcohol exposure produces in the central nervous system (CNS) adaptive changes in various neurotransmitter systems, including GABA, glutamate and norepinephrine roads to compensate for alcohol-induced destabilization and restore a neurochemical balance. This adaptive phenomenon results in long-term reductions in the effects of alcohol in the CNS, that is, it generates tolerance. The abrupt reduction or cessation of alcohol intake produces an acute imbalance due to both the acute reduction of GABA’s activity and the increase in glutamergic action, with the consequent hyperexcitability and development of abstinence symptoms that can begin in a few hours after the last alcohol intake. The positive regulationof dopaminergic and noradrenergic pathways could be responsible for the development of hallucinations and autonomous hyperactivity during alcoholic withdrawal syndrome [2-6].