Efficacy of a Combination of Flumazenil and Gabapentin in the Treatment of Alcohol Dependence

Anton, Raymond F.; Myrick, Hugh; Baros, Alicia M.; Latham, Patricia K.; Randall, Patrick K.; Wright, Tara; Stewart, Scott H.; Waid, Randy; Malcolm, Robert

doi:10.1097/jcp.0b013e3181aba6a4

Cited by 73 publications

(79 citation statements)

References 40 publications

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“…Anton et al [89] studied 60 alcohol-dependent patients who received 2 days of intravenous flumazenil (2 mg incremental bolus × 20 min) to ensure complete withdrawal followed by gabapentin (up to 1200 mg at bedtime for 39 days) or intravenous/oral placebos. The low-alcohol withdrawing group had an increased percentage of drinking days and hastened time to first HDD when randomized to the active medication while the high-alcohol withdrawing subjects displayed the reverse profile.…”

Section: Anticonvulsants For the Treatment Of Harmful Drinking Pattmentioning

confidence: 99%

Anticonvulsants for the Treatment of Alcohol Withdrawal Syndrome and Alcohol Use Disorders

et al. 2015

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Alcoholic patients suffer from harmful allostatic neuroplastic changes in the brain causing an acute withdrawal syndrome upon cessation of drinking followed by a protracted abstinence syndrome and an increased risk of relapse to heavy drinking. Benzodiazepines have long been the treatment of choice for detoxifying patients and managing alcohol withdrawal syndrome (AWS). Non-benzodiazepine anticonvulsants (NBACs) are increasingly being used both for alcohol withdrawal management and for ongoing outpatient treatment of alcohol dependence, with the goal of either abstinence or harm reduction. This expert narrative review summarizes the scientific basis and clinical evidence supporting the use of NBACs in treating AWS and for reducing harmful drinking patterns. There is less evidence in support of NBAC therapy for AWS, with few placebo-controlled trials. Carbamazepine and gabapentin appear to be the most promising adjunctive treatments for AWS, and they may be useful as monotherapy in select cases, especially in outpatient settings and for the treatment of mild-to-moderate low-risk patients with the AWS. The body of evidence supporting the use of the NBACs for reducing harmful drinking in the outpatient setting is stronger. Topiramate appears to have a robust effect on reducing harmful drinking in alcoholics. Gabapentin is a potentially efficacious treatment for reducing the risk of relapse to harmful drinking patterns in outpatient management of alcoholism. Gabapentin's ease of use, rapid titration, good tolerability, and efficacy in both the withdrawal and chronic phases of treatment make it particularly appealing. In summary, several NBACs appear to be beneficial in treating AWS and alcohol use disorders.

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Section: Anticonvulsants For the Treatment Of Harmful Drinking Pattmentioning

confidence: 99%

Anticonvulsants for the Treatment of Alcohol Withdrawal Syndrome and Alcohol Use Disorders

et al. 2015

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“…Others reported that gabapentin worked better than placebo in preventing relapse in patients who had undergone benzodiazepine detoxification, but did not compare them to non-detoxified individuals (10). Our group recently reported that gabapentin worked significantly better than placebo only in those with clinically significant alcohol withdrawal at the time of study entry (11). In that study gabapentin was adjunctive to an initial intravenous flumazenil, so the direct effect of gabapentin, by itself could not be validly affirmed.…”

Section: Discussionmentioning

confidence: 99%

“…Since clinician soften cannot predict, a priori, what sort of symptoms specific individuals will exhibit as well as what sort of craving (withdrawal based versus reward based) will be the most salient, it might be wise to attempt to reduce both in order to improve treatment efficacy. We and others have previously shown that anticonvulsants in general (5) (6) (7) and gabapentin in particular (1) (8) (9) were able to ameliorate acute alcohol withdrawal and could actually be useful in preventing relapse (10) especially in those with previous alcohol withdrawal symptoms (11). Gabapentin, which works by modulating both GABA and glutamate tone, is an especially appealing drug since it hypothetically can “normalize” the known GABA deficits and glutamate excess that is thought to underlie alcohol withdrawal (12) and perhaps parts of the early abstinence, or protracted withdrawal syndrome (13).…”

Section: Introductionmentioning

confidence: 99%

Gabapentin Combined With Naltrexone for the Treatment of Alcohol Dependence

Anton

Myrick²,

Wright³

et al. 2011

AJP

Self Cite

133

112

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Objective Naltrexone, an efficacious medication for alcohol dependence, does not work for everyone. Symptoms (e.g. insomnia, mood instability), most evident during early abstinence, might respond better to a different pharmacotherapy. Gabapentin may reduce these symptoms and early relapse. This clinical trial evaluated whether gabapentin, in conjunction with naltrexone, was better than naltrexone alone and/or placebo during the early drinking cessation phase (first six weeks) and whether this effect persisted. Method A total of 150 alcohol-dependent individuals randomly received sixteen weeks of naltrexone alone (50 mg/day [N= 50]), with gabapentin (up to 1200 mg/day [N=50] for the first six weeks), or double placebo (N= 50) while receiving medical management. Results During the first six weeks, the naltrexone/gabapentin group had 1) a longer delay to heavy drinking than the naltrexone-alone group (p =0.04) which was similar to the placebo group, 2) had less heavy drinking days than the naltrexone-alone group (p= 0.0002) which did worse than placebo, and 3) had less drinks/drinking day than the naltrexone-alone group (p=0.02) and the placebo group (p=0.01). These differences faded over the remaining study weeks. Poor sleep was associated with more drinking in the naltrexone-alone group, but not in the combined group, while an alcohol withdrawal history was associated with better response in the combined group. Conclusion The addition of gabapentin to naltrexone improved drinking outcomes over naltrexone alone during the first six weeks after cessation of drinking. This effect did not endure once gabapentin was discontinued. Future studies should evaluate gabapentin alone and over longer durations of treatment.

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“…Los pacientes efectuaron un seguimiento ambulatorio con determinaciones de sustancias en la orina 3 veces por semana (lunes, miércoles y viernes) y 1 visita médica cada 4 semanas, durante 12 semanas. El resultado del tratamiento fue evaluado mediante la variable tiempo hasta el primer consumo excesivo de alcohol (TPCEA), de acuerdo con otros estudios de tratamiento del alcoholismo 22,23 .…”

Section: Procedimientounclassified

“…Urine samples were collected for analysis three times a week (Monday, Wednesday and Friday). Outcome was assessed by means of the time to first heavy drinking day (TFHD) variable 22,23 .…”

Section: Methodsmentioning

confidence: 99%

La Escala Multidimensional de Craving de Alcohol y el SPECT con yodobenzamida[I123] como predictores de recaída precoz en pacientes que presentan dependencia del alcohol

Guardia-Serecigni¹,

Estorch

Surkov³

et al. 2011

Adicciones

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with 123 I-iodobenzamide ( 123 I-IBZM) can be useful tools for assessing relapse risk in early recovery from alcohol-dependency. The aim of this study was to assess possible relationships between MACS score, 123 I-IBZM binding and time to first heavy drinking day (TFHD) after detoxification treatment. Methods:Nineteen alcohol-dependent in-patients were evaluated by MACS scale and an 123 I-IBZM-SPECT, performed following alcohol detoxification treatment. At discharge, participants were advised to take naltrexone 50 mg/day for relapse prevention. TFHD was assessed over a 12-week follow up. Results:The MACS score at the beginning of the detoxification process and naltrexone treatment after detoxification were independent predictive factors for TFHD. Conclusions:The MACS scale is a better predictor of TFHD than IBZM binding. It is simple, non-invasive and inexpensive and appears to be a useful instrument both for clinical practice and for research. I-yodobenzamida (IBZM) pueden ser instrumentos válidos para evaluar el riesgo de recaída, durante la etapa inicial de la recuperación del trastorno por dependencia del alcohol. El objetivo de este estudio es evaluar las posibles relaciones entre la escala EMCA y la captación de IBZM y el tiempo hasta el primer consumo excesivo de alcohol (TPCEA) una vez finalizado el tratamiento de desintoxicación. Metodología: Diecinueve pacientes hospitalizados han sido evaluados mediante la escala EMCA y la SPECT con IBZM al finalizar el tratamiento de desintoxicación del alcohol. En el momento del alta se les aconsejó seguir un tratamiento con naltrexona 50 mg/día para la prevención de recaídas. El TPCEA ha sido evaluado durante 12 semanas de seguimiento. Resultados: La puntuación de la escala EMCA, al inicio del proceso de desintoxicación, y el seguimiento de un tratamiento con naltrexona, posteriormente a dicho proceso, fueron factores predictivos independientes del TPCEA. Conclusiones: La escala EMCA se ha mostrado como un buen predictor del TPCEA mientras que la captación de IBZM parece no serlo. La escala EMCA parece presentar una mayor utilidad, tanto clínica como para la investigación, frente a evaluaciones más complejas, invasivas y costosas.Palabras Clave: tomografía computarizada por emisión de fotón simple (SPECT) con yodobenzamida-I 123 , escala multidimensional de craving de alcohol (EMCA), tiempo hasta el primer consumo excesivo de alcohol, dependencia del alcohol.

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Efficacy of a Combination of Flumazenil and Gabapentin in the Treatment of Alcohol Dependence

Cited by 73 publications

References 40 publications

Anticonvulsants for the Treatment of Alcohol Withdrawal Syndrome and Alcohol Use Disorders

Anticonvulsants for the Treatment of Alcohol Withdrawal Syndrome and Alcohol Use Disorders

Gabapentin Combined With Naltrexone for the Treatment of Alcohol Dependence

La Escala Multidimensional de Craving de Alcohol y el SPECT con yodobenzamida[I123] como predictores de recaída precoz en pacientes que presentan dependencia del alcohol

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