Abstract

The alcohol withdrawal syndrome (AWS) has been treated for nearly forty years with the remarkably safe and effective benzodiazepines (BZs). In the outpatient treatment of AWS, interactions with alcohol and the abuse liability of BZs invite comparisons with agents that do not share these susceptibilities. In our original Alcohol Research Center component comparing Lorazepam (LZ) to Carbamazepine (CBZ), the latter was significantly more effective in suppressing the acoustic startle response, and anxiety and depressive symptoms during treatment. In the immediate seven-day post treatment, LZ subjects showed higher levels of multiple dimensions of AWS symptoms, including higher withdrawal scores, poor sleep, and greater subjective discomfort than CBZ. CBZ, useful in research has limited clinical applications because of its widespread interactions and uncommon but serious toxicities. In the present application, we propose a double-blind controlled trial of gabapentin (GBP, 80) vs. LZ (N=80) in treatment seeking outpatients experiencing AWS. Multiple domains of AWS will be evaluated during a five-day outpatient treatment interval and a seven-day post treatment phase. Serial measures include electrophysiologic tests of eye blink acoustic startle response, aggregate withdrawal symptoms as evaluated by the CIWA-Ar, subjective assessments of sleep, global discomfort, anxiety, depression, and need for additional medications. Side effects and safety will be compared. GMP, a unique anticonvulsant, is not a controlled substance, soon will be generic, has benign side effects, has no interactions with other drugs, and has limited interactions with alcohol. Side effects and safety will be compared. GBP, a unique anticonvulsant, is not a controlled substance, soon will be generic, has benign side effects, has no interactions with other drugs, and has limited interactions with alcohol. Should GBP be superior to LZ for the treatment of AWS, it could revise the way AWS is managed in outpatients.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Specialized Center (P50)
Project #
5P50AA010761-07
Application #
6563196
Study Section
Project Start
2002-01-01
Project End
2002-12-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
7
Fiscal Year
2002
Total Cost
$242,857
Indirect Cost

  Institution

Name
Medical University of South Carolina
Department
Type
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425

  Publications

Dowdle, Logan T; Brown, Truman R; George, Mark S et al. (2018) Single pulse TMS to the DLPFC, compared to a matched sham control, induces a direct, causal increase in caudate, cingulate, and thalamic BOLD signal. Brain Stimul 11:789-796
Zamudio-Bulcock, Paula A; Homanics, Gregg E; Woodward, John J (2018) Loss of Ethanol Inhibition of N-Methyl-D-Aspartate Receptor-Mediated Currents and Plasticity of Cerebellar Synapses in Mice Expressing the GluN1(F639A) Subunit. Alcohol Clin Exp Res 42:698-705
Cannady, Reginald; Rinker, Jennifer A; Nimitvilai, Sudarat et al. (2018) Chronic Alcohol, Intrinsic Excitability, and Potassium Channels: Neuroadaptations and Drinking Behavior. Handb Exp Pharmacol 248:311
Harlan, Benjamin A; Becker, Howard C; Woodward, John J et al. (2018) Opposing actions of CRF-R1 and CB1 receptors on VTA-GABAergic plasticity following chronic exposure to ethanol. Neuropsychopharmacology 43:2064-2074
Hanlon, Colleen A; Dowdle, Logan T; Henderson, J Scott (2018) Modulating Neural Circuits with Transcranial Magnetic Stimulation: Implications for Addiction Treatment Development. Pharmacol Rev 70:661-683
Hanlon, Colleen A; Dowdle, Logan T; Gibson, Nicole B et al. (2018) Cortical substrates of cue-reactivity in multiple substance dependent populations: transdiagnostic relevance of the medial prefrontal cortex. Transl Psychiatry 8:186
Gioia, Dominic A; Xu, Minfu; Wayman, Wesley N et al. (2018) Effects of drugs of abuse on channelrhodopsin-2 function. Neuropharmacology 135:316-327
Anton, Raymond F; Latham, Patricia K; Voronin, Konstantin E et al. (2018) Nicotine-Use/Smoking Is Associated with the Efficacy of Naltrexone in the Treatment of Alcohol Dependence. Alcohol Clin Exp Res 42:751-760
Anderson, Ethan M; Larson, Erin B; Guzman, Daniel et al. (2018) Overexpression of the Histone Dimethyltransferase G9a in Nucleus Accumbens Shell Increases Cocaine Self-Administration, Stress-Induced Reinstatement, and Anxiety. J Neurosci 38:803-813
Osterndorff-Kahanek, Elizabeth A; Tiwari, Gayatri R; Lopez, Marcelo F et al. (2018) Long-term ethanol exposure: Temporal pattern of microRNA expression and associated mRNA gene networks in mouse brain. PLoS One 13:e0190841

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