INCLUSION CRITERIA

To be admitted into this study patients must meet the following criteria:

1. DSM IV TR Diagnosis of Alcohol Dependence; minimal level of 14 drinks per week for women or 21 drinks per week for men over a 28 day consecutive period during the 90 day period prior to the screening session.
2. Male or Female 21-64 years of age.
3. Able to provide informed consent and comprehend study procedures.
4. Negative urine toxicological screen for opioids, psychomotor stimulants, sedative-hypnotics, and cannabinoids. If the urine tox screen was positive for any substance it may be repeated within two weeks.
5. Score of >8 on the Alcohol Use Disorder Identification Test (AUDIT) during screening.
6. Must be suitable for outpatient management of alcoholism.
7. Express desire to stop drinking or reduce alcohol consumption with a possible long-term goal of abstinence.
8. Provide contact information for themselves or an alternate contact that the staff will call in case of missed appointment.
9. Women must be postmenopausal for at least one year, be surgically sterile, be using an effective method of birth control (e.g. contraceptive injection, intrauterine device, spermicide with barrier, contraceptive patch, contraceptive ring, male partner sterilization, oral contraceptives) or completely abstinent (and agree to use one of the above mentioned methods of contraception if sexual activity is ever initiated).
10. Must be able to take oral medications, adhere to the regimen and be willing to return for follow up visits.
11. Must have breath alcohol concentration of no more than 0.01% when the informed consent is provided and the consent form is signed.
12. Must have resided at the same address for at least 3 months.

EXCLUSION CRITERIA

Patients meeting the following criteria will be excluded from the study:

1. Dependent on or extensive abuse of drugs or substances other than ethanol, nicotine, or caffeine.
2. DSM IV-TR diagnosis of any current Axis I diagnosis other than alcohol dependence, nicotine dependence, or caffeine dependence that in the opinion of the study physicians might require intervention with either pharmacological or non-pharmacological therapy that will interfere with the course of the study.
3. Receiving inpatient or outpatient treatment for alcohol dependence (with the exception of AA or other self-help groups) within 4 weeks prior to enrollment into this study.
4. Subjects with a score of 10 or greater on the CIWA-Ar (a withdrawal scale) on first or second visits.
5. Currently being treated with acamprosate, disulfiram or naltrexone.
6. Currently being treated with any of the following medications: a) Antipsychotic agents- including clozapine, risperidone, quetiapine, haloperidol b) Antimanic or anticonvulsant agents- including lithium carbonate, phenytoin, phenobarbital, carbamazepine, topiramate, valproic acid, divalproex, tiagabine c) Sedative-hypnotic or antianxiety agents-including triazolam, temazepam, zolpidem, zalepron, buspirone, alprazolam, diazepam, clonazepam, oxazepam, lorazepam d) chronic opioid treatment- including methadone, buprenorphine, oxycodone, morphine e) Psychomotor stimulants- amphetamine derivatives, methylphenidate
7. Subjects who are legally mandated to participate in an alcohol treatment program
8. Use of any medication known to inhibit or induce cytochrome P450 3A4 enzymes including macrolide antibiotics, fluoxetine, and carbamazepine.
9. Subjects who have attempted suicide or who have had suicidal ideation within 30 days of their first visit as assessed using responses from the SCID and Hamilton Depression scale.
10. Subjects with renal disease (including severe infection and cancer), impaired renal clearance (CrCl less than 50 ml/min), or history of kidney stones.
11. Subjects with AST or ALT >3 times the upper limit of the normal range during screening.
12. History of significant neurological disorder, including a history of seizures, stroke, dementia, multiple sclerosis, Parkinson's disease, brain tumors, or encephalitis.
13. Subjects who are pregnant (as assessed by serum HCG) or lactating.
14. Subjects known to have clinically significant medical conditions. These may include: symptomatic CAD or PVD, malignancy or history of malignancy in the last 5 years, significant pulmonary disease or endocrinological disorders.
15. Subjects with prior hypersensitivity to zonisamide or or related compounds, including sulfonamides (e.g. sulfisoxazole) carbonic anhydrase inhibitors (e.g. acetazolamide), sulfonylureas (e.g. chlorpropamide), sulfamates (e.g. topiramate), thiazide (e.g. hydrochlorothiazide), and loop diuretics (e.g. furosemide) except ethacrycrynic acid.
16. Subjects who in the opinion of the study physicians should not be enrolled based on the precautions, warnings, and contraindications stated on the package insert for zonisamide.
17. Impending incarceration.
18. Score of 25 or less on the Folstein Mini-Mental examination.
19. History of anticonvulsant-induced rash.