Zonisamide Treatment of Alcohol Use Disorder: an Evaluation of Efficacy and Mechanism of Action

Inclusion Criteria:

• Female/male aged 21-70 years
• Regular heavy drinkers as defined by averaging 2 heavy drinking days per week over 90days baseline pre-treatment timeline follow-back (TLFB), and current DSM-IV-TR alcoholdependence that recognize a need to reduce or stop drinking (Note: heavy drinking dayswill be defined as follows; for men greater than or equal to 5 drinks in a day and forwomen greater than or equal to 4 drinks in a day)
• Women of child-bearing potential (i.e., no hysterectomy, bilateral oophorectomy, ortubal ligation or <2 years postmenopausal), must be non-lactating, practicing areliable method of birth control, and have a negative serum pregnancy test prior toinitiation of treatment;
• Willingness to provide signed, informed consent to participate in the study

Exclusion Criteria:

• A current, clinically significant physical disease or abnormality (i.e., neurologic,renal, rheumatologic, gastrointestinal, hematologic, pulmonary, endocrine,cardiovascular, hepatic, or autoimmune disease that, in the context of the study wouldrepresent a risk to the subject, or significant laboratory abnormalities such ashepatic aminotransferase levels (i.e., AST and ALT) greater than 300% of the upperlimit of normal or direct bilirubin levels >150% of the upper limit of normal) on thebasis of medical history, physical examination, or routine laboratory evaluation.Other specific exclusionary disorders include;
• History of clinically significant renal calculi or renal failure; a significantindication of renal compromise will be defined by an elevation of serum creatinineabove the investigators' laboratory's limit of normal, or a known history of renalfailure or chronic renal disease, or any current or chronic disease that couldreasonably be expected to result in renal failure
• History of hypersensitivity to ZNS or any sulfonamide, Stevens-Johnson Syndrome,penicillin allergy, or history of any severe drug allergic reaction; History ofsystemic autoimmune disease such as lupus erythematosis, fibromyalgia, or rheumatoidarthritis;
• Current blood dyscrasia or a history of such, with the exception of a past history ofiron deficiency anemia
• History of seizure disorder
• Use of any of a number of medications that might prominently influence drinkingpatterns or cause risk of harm or injury (e.g., topiramate, disulfiram, naltrexone,acetazolamide, stimulants such as amphetamine, or tramadol; Schizophrenia, bipolardisorder, PTSD, or substantial suicide or violence risk (i.e., can't be managed safelyin the outpatient setting) on the basis of history or psychiatric examination; j)currently dependent on opioids or benzodiazepines or other sedatives
• Considered by the investigators to be clinically inappropriate for study participationor have participated in another pharmacotherapy study in the past thirty days
• Subjects with prominent signs of physical dependence, and/or medical comorbiditiessuch that study physicians feel they should consider immediate detoxification, andreferred for medical detoxification in a normal treatment setting