Neurobiological Basis of Craving and Anti-Craving Medications / 신경정신의학

Clinical studies published over the past two decades have consistently demonstrated the therapeutic efficacy and safety of anti-craving medications. To use anti-craving agents more effectively in clinical settings, it is important to set clear treatment goals. Because alcoholic patients have lost control of drinking alcohol, it is recommended to set ‘abstinence’ as a goal rather than ‘controlled drinking’. Indeed, the therapeutic effects of anti-craving medication are higher when abstinence is set as the target. On the other hand, if abstinence is the sole criterion, it is difficult to elicit the motivation of a patient who lacks motivation in clinical practice. In the case of patients who have not yet gained insight, the initial goal might be set to gradually reduce the amount of alcohol consumed and prevent at-risk heavy drinking. Even in this case, anti-craving can help clinically. To increase the effectiveness of anti-craving medications, it is best to start at least four to seven days after the patient has stopped drinking. If the patient has alcohol withdrawal symptoms, they should be treated first.

Evolución de pacientes con adicción al alcohol con el uso de acamprosato / Progression of patients with alcohol dependence using acamprosate

Introducción: los efectos del consumo excesivo de bebidas alcohólicas para el individuo, la familia y la sociedad son un problema de salud, convertido en la más trascendente toxicomanía en la actualidad. En el mercado existen tres fármacos que reducen el deseo de beber y son el disulfiram, la naltrexona y el acamprosato. El acamprosato es el medicamento que se propone estudiar, ya que en Cuba no existen referencias anteriores de estudios de la efectividad del acamprosato. Objetivo: valorar la evolución del alcoholismo y su tratamiento con acamprosato. Métodos: se diseñó un Estudio de Utilización de Medicamentos observacional y descriptivo, basado en las consecuencias prácticas del uso del acamprosato en pacientes diagnosticados con adicción al alcohol, con una dosis de dos cápsulas de 33,3 mg diarias por vía oral, durante seis meses de tratamiento, desde septiembre de 2012 a febrero de 2013. Resultados: de 44 pacientes evaluados, el 90,9 por ciento no tuvo recaídas, solamente el 9,1 por ciento de los pacientes tuvo deseos de consumir alcohol al inicio del tratamiento. Un paciente mostró intranquilidad como efecto adverso al acamprosato. La autovaloración de todos los pacientes fue positiva, refiriendo en su totalidad que cambiaron para una persona mejor. El 68,2 por ciento de los pacientes tuvieron una evolución excelente, lo que coincide con otros estudios internacionales con el acamprosato. Conclusiones: el tratamiento con acamprosato es efectivo para la prevención de las recaídas y la reducción del consumo de alcohol en el alcoholismo(AU)

Introduction: the effects of the excessive intake of alcohol beverages for the individual, the family and the society represent a health problem turned into the most transcendental toxicomania at present times. There are three drugs on the market which reduce the desire of drinking and are called disulfiram, naltrexone and acamprosate. The latter is the drug to be studied since there are no previous references in Cuba about effectiveness study of acamprosate. Objective: to assess the progression of alcoholism and its treatment with acamprosate. Methods: adescriptive and observational Study of Drug Use was designed on the basis of the practical consequences of the use of acamprosate in patients diagnosed with alcohol dependence, at a dose of two caplets of 33.3mg to be taken daily for six months from September 2012 to February 2013. Results: of 44 evaluated patients, 90.9 percent had no relapses, just 9.1 percent felt the desire of taking alcohol beverages at the onset of treatment. One patient showed restlessness as adverse effect of the drug. The self-assessment of all the patients was positive, stating that they changed into a better person after treatment. In the group, 68.2 percent had an excellent progress which agrees with other international study on this drug. Conclusions: the treatment with acamprosate is effective for the prevention of relapses and the reduction of alcohol dependence(AU)

Acamprosate-induced Extrapyramidal Symptoms in an Elderly Patient with Alcohol Dependence

Acamprosate reduces the craving for alcohol by decreasing glutamate activity and increasing gamma-aminobutyric acid (GABA) action in patients with alcohol dependence. Acamprosate has tolerable side effects that include diarrhea, headache, dizziness and pruritus. In this study, we report acamprosate-induced extrapyramidal symptoms in an elderly patient with no history of neurologic disease. Severe extrapyramidal symptoms developed two days after the administration of acamprosate and improved over one week after the acamprosate was stopped. Extrapyramidal symptoms are commonly associated with dopamine receptor antagonists. However, there have been several reports of extrapyramidal symptoms occurring with drugs targeting other systems, including GABA, glutamate and serotonin. Acamprosate may decrease dopamine levels in the ventral tegmental area mediated by glutamatergic action and thus cause extrapyramidal symptoms. We suggest that acamprosate carries the risk of causing extrapyramidal symptoms.

Actualización del tratamiento farmacológico de la dependencia alcohólica / Pharmacological review of alcoholic dependence treatment

El objetivo de la presente actualización farmacológica es abordar la problemática de la dependencia alcohólica. Partiendo de las bases biológicas y del impacto del etanol sobre los sistemas neurobiológicos y de neurotransmisión, se hará una revisión de las principales herramientas farmacológicas para el tratamiento de la dependencia alcohólica. El disulfiram, la naltrexona y el acamprosato, todas ellas con aprobación por la FDA (Food and Drug Administration) han mostrado mecanismos de acción, perfiles de eficacia, tolerabilidad y adherencia dispares. También nos referiremos al topiramato, el que está siendo estudiado actualmente con relación a esta indicación.

The aim of the present pharmacological update is to revise the problem of alcohol dependence. Starting from the biological bases and the impact of alcohol on the neurobiological and neurotransmission systems, a revision of the main pharmacological tools for alcohol dependence treatment will be done. Disulfiram, naltrexone, acamprosate, all of them approved by the FDA (Food and Drug Administration), have shown mechanisms of action, efficacy, tolerance and adherence dissimilar. We will also refer to topiramate, which is being studied for this indication.

Pharmacotherapy for Alcohol Dependence: Anticraving Medications for Relapse Prevention

Alcohol dependence is a chronic disorder that results from a variety of genetic, psychosocial, and environmental factors. Relapse prevention for alcohol dependence has traditionally involved psychosocial and psychotherapeutic interventions. Pharmacotherapy, however, in conjunction with behavioral therapy, is generating interest as another modality to prevent relapse and enhance abstinence. Naltrexone and acamprosate are at the forefront of the currently available pharmacological options. Naltrexone is an opioid receptor antagonist and is thought to reduce the rewarding effect of alcohol. Acamprosate normalizes the dysregulation of N-methyl-D-aspartate (NMDA)-mediated glutamatergic excitation that occurs in alcohol withdrawal and early abstinence.These different mechanisms of action and different target neurotransmitter systems may endow the two drugs with efficacy for different aspects of alcohol use behavior. Since not all patients seem to benefit from naltrexone and acamprosate, there are ongoing efforts to improve the treatment outcomes by examining the advantages of combined pharmacotherapy and exploring the variables that might predict the response of the medications. In addition, novel medications are being investigated to assess their efficacy in preventing relapse and increasing abstinence.

Effect of Olanzapine on Alcohol Consumption of C57BL-6 Type Rats / 대한정신약물학회지

OBJECTIVE: This study compared the effect of anticraving agent acamprosate and atypical antipsychotics that has serotonin-dopamine receptor antagonistic property, olanzapine on reduction of alcohol consumption level of alcohol intake reinforced C57BL-6 type rat. METHODS: Small amount of alcohol and water were applied to the 28 rats for 2 hours per day during 30 days. On the 31th day, the rats were divided into four groups and provided different medication by intraabdominal route 30 minutes before the alcohol consumption. For the next 7 weeks, the each subject group was applied with acamprosate 200 mg/kg, olanzapine 0.1 mg/kg and olanzapine 1.0 mg/kg respectively and the control group was done with saline. RESULTS: In contrast to control group, acamprosate 200 mg/kg group and olanzapine 0.1 mg/kg showed the reduction of alcohol consumption from 3rd to 7th week period, significantly. Although olanzapine 1 mg/kg group showed a momentary decrease of the consumption during the from 3rd to 6th weeks, the group did not show significant difference at 7th week. Olanzapine 0.1 mg/kg was more effective in reducing the alcohol consumption than olanzapine 1 mg/kg. CONCLUSION: This results suggest that low dose of olanzapine may reduce the alcohol intake in C57BL-6 type rats, as well as acamprosate.

Effect of Combined Administration of Acamprosate and Naltrexone on Alcohol Intake in C57BL/6 Mice / 신경정신의학

OBJECTIVES: For the relapse prevention in alcohol dependence, a lot of studies suggested that combined administration of two or more drugs which have different mechanism of action is more effective than each drug alone. In order to investigate the effectiveness of combined administration of naltrexone and acamprosate in comparison with naltrexone alone, this study was carried out by comparing the amount of alcohol intake in C57BL/6 mice co-administered with naltrexone and acamprosate with that in C57BL/6 mice with naltrexone alone. METHODS: In 42 C57BL/6 mice in the state of alcohol dependence, naltrexone 0.025mg/kg or 1.0mg/kg alone or with acamprosate 50mg/kg or 200mg/kg were administrated for ten days. The amounts of alcohol consumption for 2 hour, water consumption for 22 hours, and food intake for 24 hours were measured. RESULTS: 1) A significant reduction of alcohol intake for 2 hours was observed when the mice were treated with naltrexone 0.025mg/kg or 1.0mg/kg and acamprosate 50mg/kg or 200mg/kg simultaneously compared with naltrexone 0.025mg/kg or 1.0mg/kg alone. This effect was significant on the eighth and tenth days of drug administration. 2) Naltrexone administration of 1.0mg/kg was significantly more effective than that of 0.025 mg/kg in reducing alcohol intake from the second day of drug administration up to the tenth day. 3) No significant difference was revealed between the effect of naltrexone alone and that of naltrexone with acamprosate on 22 hour water consumption and 24 hour food intake. CONCLUSION: From these results, it is suggested that the effect of combined treatment with naltrexone and acamprosate is superior to that of naltrexone alone in prevention of relapse in alcohol dependence.