Zonisamide Treatment of Alcohol Use Disorder: an Evaluation of Efficacy and Mechanism of Action
Zonisamide Treatment of Alcohol Use Disorder: an Evaluation of Efficacy and Mechanism of Action
This is a randomized, placebo-controlled, double-blind, 16 week trial of the medication
 zonisamide for the treatment of heavy drinking alcoholic civilians.
This is a 16-week randomized, double blind, placebo-controlled trial designed to determine
 the effectiveness of zonisamide treatment for reducing heavy drinking and overall drinking in
 160 treatment-seeking, regularly heavy drinking, alcohol-dependent civilians who want to quit
 drinking or reduce consumption to non-hazardous levels. The investigators will use
 state-of-the-art methodology and outcome assessments, including medical management (MM)
 therapy (a minimal behavioral intervention aimed at reinforcing treatment goals and adherence
 to medication), which is simple and easily implemented in primary care settings. The use of
 MM in the study will increase the generalizability of results, allowing a more accurate
 assessment of zonisamide's effectiveness than if a more intensive behavioral intervention
 were to be used. To demonstrate zonisamide's effectiveness in a representative civilian
 sample, the investigators will include civilians with co-morbid mood and anxiety disorders.
Inclusion Criteria:

 -  Female/male aged 21-70 years

 -  Regular heavy drinkers as defined by averaging 2 heavy drinking days per week over 90
 days baseline pre-treatment timeline follow-back (TLFB), and current DSM-IV-TR alcohol
 dependence that recognize a need to reduce or stop drinking (Note: heavy drinking days
 will be defined as follows; for men greater than or equal to 5 drinks in a day and for
 women greater than or equal to 4 drinks in a day)

 -  Women of child-bearing potential (i.e., no hysterectomy, bilateral oophorectomy, or
 tubal ligation or <2 years postmenopausal), must be non-lactating, practicing a
 reliable method of birth control, and have a negative serum pregnancy test prior to
 initiation 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 would
 represent a risk to the subject, or significant laboratory abnormalities such as
 hepatic aminotransferase levels (i.e., AST and ALT) greater than 300% of the upper
 limit of normal or direct bilirubin levels >150% of the upper limit of normal) on the
 basis of medical history, physical examination, or routine laboratory evaluation.
 Other specific exclusionary disorders include;

 -  History of clinically significant renal calculi or renal failure; a significant
 indication of renal compromise will be defined by an elevation of serum creatinine
 above the investigators' laboratory's limit of normal, or a known history of renal
 failure or chronic renal disease, or any current or chronic disease that could
 reasonably 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 of
 systemic autoimmune disease such as lupus erythematosis, fibromyalgia, or rheumatoid
 arthritis;

 -  Current blood dyscrasia or a history of such, with the exception of a past history of
 iron deficiency anemia

 -  History of seizure disorder

 -  Use of any of a number of medications that might prominently influence drinking
 patterns or cause risk of harm or injury (e.g., topiramate, disulfiram, naltrexone,
 acetazolamide, stimulants such as amphetamine, or tramadol; Schizophrenia, bipolar
 disorder, PTSD, or substantial suicide or violence risk (i.e., can't be managed safely
 in 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 participation
 or have participated in another pharmacotherapy study in the past thirty days

 -  Subjects with prominent signs of physical dependence, and/or medical comorbidities
 such that study physicians feel they should consider immediate detoxification, and
 referred for medical detoxification in a normal treatment setting