<b>Unlabelled: </b>This study examined the dose-related efficacy of disulfiram for treating cocaine dependence in methadone-stabilized cocaine dependent participants.<b>DESIGN: </b>One hundred and sixty-one cocaine- and opioid-dependent volunteers were entered into a 14-week, double blind, randomized, placebo-controlled clinical trial at two sites.<b>METHODS: </b>Participants were stabilized on methadone during weeks 1-2 and received disulfiram at 0, 62.5, 125 or 250 mg/day during weeks 3-14. All participants also received weekly cognitive behavioral therapy. Thrice-weekly urine samples and weekly self-reported drug use assessments were obtained.<b>RESULTS: </b>Baseline subject characteristics, retention and drug use did not differ across groups. Outcome analyses were performed on those who participated beyond week 2. Opioid-positive urine samples and self-reported opioid use did not differ by treatment group. The prevalence of alcohol use was low prior to and during the trial and did not differ by treatment group. Cocaine-positive urines increased over time in the 62.5 and 125 mg disulfiram groups and decreased over time in the 250 mg disulfiram and placebo groups (p < 0.0001). Self-reported cocaine use increased in the 125 mg disulfiram group relative to the other three treatment groups (p = 0.04).<b>CONCLUSIONS: </b>Disulfiram may be contraindicated for cocaine dependence at doses <250 mg/day. Whether disulfiram at higher doses is efficacious in reducing cocaine use in dually cocaine and opioid dependent individuals needs to be determined.
AIM: Disulfiram has been shown to be efficacious and safe in the treatment of alcohol relapse prevention. However, drinking alcohol while taking disulfiram can be harmful because of the resulting alcohol-disulfiram reaction/acetaldehyde reaction. Alcohol consumption of patients receiving a low disulfiram dose or low alcohol consumption in normal disulfiram dose can result in subclinical alcohol-disulfiram reactions. This undermines the learning of alcohol-associated punishment, might increase the risk to raise alcohol consumption, and can result in chronic acetaldehyde exposure, which has carcinogenic, neurotoxic, and cardiotoxic properties. Therefore, the use of an alcohol marker monitoring retrospective alcohol use is tested in this study.
METHOD: A total of 51 patients being treated with supervised disulfiram were unheralded measured for ethylglucuronide (EtG) if they attended at least for 2 weeks in the outpatient treatment program. Ethylglucuronide was measured with liquid chromatography-tandem mass spectrometry analysis (LC-MS/MS). Detection limit was 0.1 mg/L.
RESULTS: Urinary EtG was found positive in 5.9% (3/51) of the patients. Regularly conducted breathalyzer tests had been continuously negative in these patients. Moreover, vegetative withdrawal symptoms had not been found in these patients. Two of the positive EtG tests could be classified as covered relapses, whereas the third remained unclear but showed a negative EtG in a repetition of the test few days later.
CONCLUSIONS: Unheralded urinary EtG monitoring improved verification of abstinence in patients treated with disulfiram, was helpful in detecting covered consumption of alcoholic beverages or hidden alcohol exposition (eg, fruit juice or personal care products), and thereby improved safety by preventing chronic acetaldehyde reaction.
Chronic alcohol use has profound modulatory effects on the immune system. Both the innate and the acquired immunity are compromised. The use of pharmacotherapy is increasingly applied to enhance the percentage of success in maintaining alcoholic patients in remission. Disulfiram, naltrexone and gamma hydroxybutiric acid are the drugs used for this purpose in Italian Addiction Services. In this study we analyze the effect of pharmacotherapy of alcohol dependence on immune responses in alcoholics. Six groups were studied. Group A included 10 patients who were still using alcohol. Group B consisted of 10 patients abstinent from alcohol in treatment only with group therapy. Groups C, D and E were composed of 10 patients each, treated for at least 6 months with oral doses of gamma hydroxybutiric acid, naltrexone or disulfiram respectively. Ten age- and sex-matched healthy volunteers who never misused alcohol were included as a control group. Lymphoproliferation and peripheral mononuclear cell production of the Th1 cytokines IL-2 and IFN-gamma, the Th2 cytokine IL-4, and of the pro-inflammatory cytokines IL-1 and TNF-alpha were evaluated in all the patients and controls. The level of activity of the hypothalamus pituitary adrenal axis was assessed. Both ACTH and cortisol levels in plasma were elevated in alcoholic patients with no treatment. In this group a significant alteration of cytokine production was observed. TNF and IFN-gamma were lower than controls, while the Th2 cytokine IL-4 was increased. These altered levels state for a Th1/Th2 unbalance characterized by decreased Th1 response in the presence of Th2 predominance. In patients undergoing pharmacological treatment, none of the immune parameters were different from those observed in healthy controls, independently of the type of drug administered. These data indicate that pharmacotherapy more than group therapy treatment is able to ameliorate the immune system functioning in alcoholic patients.
Despite the fact that alcoholism is a severe public health problem of worldwide proportions, only a limited number of medications is used as coadjuvant treatment. The objectives of this study were to analyse the use of disulfiram for alcohol-dependent patients and the immediate interruption of treatment following medication prescription. This is a transversal study of 810 patients who attended the Alcohol and Drug Research Unit (UNIAD) during the 2000-2006 period. The study showed that both male and female patients who had remained under treatment during the first year used proportionally more disulfiram than those who remained for lesser time under treatment, and immediate treatment interruption was statistically more significant in this latter group of patients after prescription of this medication. Although disulfiram is an old medication, it seems that this drug can be useful for keeping alcohol-dependent patients under outpatient treatment.
AIMS: To compare the long-term effectiveness of acamprosate (ACP) and disulfiram (DSF) in the treatment of alcohol dependence and their effectiveness in regard to patient characteristics, within a naturalistic outpatient treatment setting.
METHOD: Retrospective data from 2002 to 2007 were analysed on 353 alcohol-dependent subjects in outpatient treatment, who, according to the patient's and the clinician's mutual decision, received either supervised DSF (with thrice-weekly appointments) or ACP (once-weekly appointments) following an inpatient alcohol detoxification treatment. Abstinence was assessed by alcohol breathalyzer, patients' self-report, urine and serum analyses, and overall physicians' rating.
RESULTS: Baseline data in terms of current addictive behaviour and course of disease differed between groups to the disadvantage of the DSF group; compared to the ACP group, subjects treated with DSF showed a longer duration of alcohol dependence, higher amounts of daily alcohol consumption and more alcohol detoxification treatments in their history. In follow-up, Kaplan-Meier survival analysis revealed significant differences between groups in the primary and secondary measures of outcome (P always <0.01). Time elapsed before the first alcohol relapse as well as attendance to outpatient treatment and cumulative alcohol abstinence achieved within outpatient treatment was explicitly longer in the DSF group. A longer duration of alcohol dependence predicted a favourable treatment outcome in the DSF group, while for the ACP group the chances for a successful treatment increased with shorter duration of alcohol dependence.
CONCLUSIONS: This study supports the thesis that supervised DSF is an important component of alcoholism treatment, and it appears to be more effective than the treatment with ACP particularly in patients with a long duration of alcohol dependence.
AIMS: Disulfiram is widely used to prevent alcoholic relapse. However, due to the intended adverse reaction with ethanol, some believe that its use is dangerous for patients with personality disorders or psychiatric comorbidities because of their increased risk of impulsivity or suicidal behaviour. We examined the safety and efficacy in relapse prevention of a series of alcoholics with borderline personality disorder (BPD).
METHODS: Case history study of patients diagnosed with BPD, prescribed disulfiram in a dose of 1.5-2.5 g/week, supervised by a physician in up to three brief contacts per week.
RESULTS: Two out of eight patients remained completely abstinent during the supervised disulfiram therapy over a mean period of 9.25 months. Adherence to treatment was 18.44 +/- 21.78 months. The first relapse occurred after 1.38 +/- 1.41 months. The cumulated time of abstinence was 16.88 +/- 20.48 months. The overall tolerability was considered to be high; dizziness and fatigue appeared in all patients at the beginning of the therapy but did not persist. No serious adverse events or ethanol-disulfiram interactions were observed. No suicidal behaviour was reported.
CONCLUSIONS: Although case observations should be interpreted with caution, supervised disulfiram seems to deserve further investigation in patients with comorbid BPD, for whom it appears to help prevent alcoholic relapse.
ANTECEDENTES: Disulfiram se utiliza en gran medida en Dinamarca para tratar el alcoholismo, pero la evidencia es limitada.
Objetivo: Estudiar el efecto del tratamiento con disulfiram supervisado en la dependencia del alcohol. Los sujetos fueron reclutados de una sala de emergencia psiquiátrica después de un tratamiento de abstinencia de alcohol.
MÉTODOS: Un total de n = 39 pacientes fueron asignados al azar a cualquiera de disulfiram abiertamente 800 mg dos veces por semana durante 26 semanas (n = 19) o no disulfiram (n = 20). Todos los pacientes fueron tratados con la terapia cognitivo-conductual (TCC) en grupos.
RESULTADOS: La tasa de abstinencia fue de 20% y 26% en el grupo control y disulfiram, respectivamente. Esta diferencia no fue estadísticamente significativa (NS). Una tendencia hacia el aumento de tiempo medio hasta la primera bebida se encontró en el grupo de disulfiram (96 vs. 76 días en el grupo de control, NS), mientras que un menor número de pacientes en este grupo completaron la terapia de grupo CBT (41% vs. 67% en el grupo control , NS). Días libres de alcohol fueron de 100 días en ambos grupos (NS).
CONCLUSIÓN: Supervisado administración disulfiram no tuvo ningún impacto en el resultado del tratamiento.
OBJETIVOS: Este estudio tiene como objetivo comparar la eficacia del disulfiram (DSF) y naltrexona (NTX) para la prevención de la recaída alcohólica en adolescentes con dependencia del alcohol en la práctica clínica habitual. DISEÑO: 58 adolescentes con dependencia del alcohol que tienen miembros de la familia que fomentarían el cumplimiento médica y acompañarían a ellos para su seguimiento se asignaron al azar a los 6 meses de tratamiento con DSF o NTX. También se proporcionó semanal psicoeducación. El psiquiatra, paciente, y miembro de la familia estaban al tanto del tratamiento prescrito. MEDIDAS: El consumo de alcohol, las ansias y los eventos adversos fueron registrados la semana durante 3 meses y luego cada dos semanas. Gamma glutamil transferasa en suero (GGT) se midió al comienzo y al final del estudio. RESULTADOS: Al final del ensayo 54 pacientes todavía estaban en contacto. La recaída se produjo en una media de 84 días con DSF en comparación con 51 días para NTX. Un total de 79,31% de los pacientes en DSF se mantuvo abstinente en comparación con 51,72% con NTX. Los pacientes asignados con NTX sin embargo tenían menos ansia que el grupo DSF. CONCLUSIÓN: DSF fue así resultó ser superior a NTX en la prevención de la recaída en adolescentes con dependencia del alcohol que tiene un buen apoyo familiar. Otras comparaciones entre estos medicamentos junto con tratamientos psicosociales solos o en diferentes escenarios están garantizados.
OBJETIVO: Comparar los efectos en pacientes dependientes del alcohol de tres tratamientos farmacológicos, disulfiram (DIS), naltrexona (NTX), y el acamprosato (ACA), cuando se utiliza con una breve intervención cognitivo-conductual basada en manual.
MÉTODO: Se realizó un, abierto, aleatorizado, multicéntrico naturalista en dos fases; primero, un 12-semanas supervisado continuamente medicación, seguido por la medicación específica (TM) hasta 52 semanas además de un período de seguimiento de 67 semanas; un total de 119 semanas (2,5 años), en 243 pacientes adultos ambulatorios dependientes del alcohol tratamiento de búsqueda de voluntarios. Los sujetos fueron aleatorizados 1: 1: 1 para recibir supervisada NTX, ACA o DIS, 50, 1998, o 200 mg, respectivamente, por día, además de una breve intervención cognitivo-conductual basada en manual. Los pacientes se encontraron en las segunda y sexta semana, y después de 3, 6, y 12 meses. Las medidas de resultado primarias fueron el tiempo (días) para el primer día un consumo alto (HDD), y el tiempo durante los primeros 3 meses hasta el primer día de consumo después de la medicación comenzó. Las variables secundarias fueron días de abstinencia / semana (0 bebidas / día), la ingesta de alcohol semanal promedio, consumo de alcohol Trastorno de identificación de prueba (AUDIT), severidad de la dependencia del alcohol de Datos (SADD), y la calidad de vida (CV) medidas.
Resultados: Todos los tres grupos de estudio mostraron una marcada reducción en la bebida, desde el inicio hasta el final del estudio. Durante la fase de medicación continua, el tratamiento con DIS fue más eficaz en la reducción de unidades de disco duro y el consumo semanal promedio de alcohol, y aumentar el tiempo hasta la primera bebida, así como el número de días de abstinencia. Durante el período de TM, no hubo diferencias significativas entre los grupos en el tiempo hasta la primera unidad de disco duro y los días a primera beber, pero los días de abstinencia fueron significativamente más frecuentes en el grupo DIS de ACA y NTX. No hubo diferencias entre los grupos de NTX y ACA en cualquiera de las fases del estudio de los resultados de beber. Sin embargo, las puntuaciones de SADD mejoraron más en el grupo de NTX que el grupo de ACA.
CONCLUSIONES: Los pacientes asignados a la ACA, NTX y DIS combinado con una breve intervención cognitivo conductual basada en el manual reducir significativamente su consumo de alcohol y reportan mejorado QL. Supervisado DIS apareció superior, especialmente durante el período de medicación continua, a NTX y ACA.
ANTECEDENTES: Este es un estudio doble ciego, controlado con placebo que evaluó la eficacia del disulfiram, la naltrexona y su combinación en pacientes con co-produciendo la cocaína y la dependencia del alcohol. Métodos: 208 pacientes fueron asignados aleatoriamente a disulfiram (250 mg / día), la naltrexona (100 mg / día), la combinación, o un placebo durante 11 semanas. Los resultados fueron, en espera de juicio la abstinencia de cocaína y / o alcohol. RESULTADOS: Las preocupaciones de seguridad se reportaron pocos, a pesar de adherencia a la medicación fue baja en el número de pacientes de ambos medicamentos, solos o en combinación. En los análisis primarios (modelos GEE), la abstinencia de la cocaína, medida por la cocaína-las orinas negativas y días de auto-reporte de la abstinencia de la cocaína o el alcohol no fue diferente entre el placebo y ninguno de los grupos de medicamentos. Sin embargo, los pacientes que toman disulfiram (solo o en combinación) tenían más probabilidades de lograr la abstinencia combinado de cocaína y el alcohol. Los análisis secundarios revelaron que los pacientes que tomaban la combinación de disulfiram-naltrexona tenían más probabilidades de lograr 3 semanas consecutivas de abstinencia de la cocaína y el alcohol. CONCLUSIÓN: Se observó una asociación entre el tratamiento con disulfiram y la abstinencia de la cocaína y el alcohol. Más pacientes tratados con la combinación de disulfiram-naltrexona consigue 3 semanas consecutivas de abstinencia en el tratamiento de pacientes tratados con placebo.
Unlabelled: This study examined the dose-related efficacy of disulfiram for treating cocaine dependence in methadone-stabilized cocaine dependent participants.
DESIGN:
One hundred and sixty-one cocaine- and opioid-dependent volunteers were entered into a 14-week, double blind, randomized, placebo-controlled clinical trial at two sites.
METHODS:
Participants were stabilized on methadone during weeks 1-2 and received disulfiram at 0, 62.5, 125 or 250 mg/day during weeks 3-14. All participants also received weekly cognitive behavioral therapy. Thrice-weekly urine samples and weekly self-reported drug use assessments were obtained.
RESULTS:
Baseline subject characteristics, retention and drug use did not differ across groups. Outcome analyses were performed on those who participated beyond week 2. Opioid-positive urine samples and self-reported opioid use did not differ by treatment group. The prevalence of alcohol use was low prior to and during the trial and did not differ by treatment group. Cocaine-positive urines increased over time in the 62.5 and 125 mg disulfiram groups and decreased over time in the 250 mg disulfiram and placebo groups (p < 0.0001). Self-reported cocaine use increased in the 125 mg disulfiram group relative to the other three treatment groups (p = 0.04).
CONCLUSIONS:
Disulfiram may be contraindicated for cocaine dependence at doses <250 mg/day. Whether disulfiram at higher doses is efficacious in reducing cocaine use in dually cocaine and opioid dependent individuals needs to be determined.
