Levetiracetam for the Treatment of Alcohol Dependence and Anxiety

Alcohol dependence is frequently associated with anxiety disorders. Treatment studies of
individuals suffering from both alcohol dependence and anxiety have been limited.
Anti-seizure medications have been used for the treatment of alcohol withdrawal for three
decades. More recently, anti-seizure medications have been shown to reduce drinking and
promote abstinence, and reduce drinking in abstinent alcoholics. Levetiracetam is a newer
anti-seizure medication, with a structure different than that of other anti-seizure
medications, that is safe and generally well tolerated. The Food and Drug Administration
(FDA) has approved levetiracetam for use with other anti-seizure medications in the treatment
of epilepsy in adults. The metabolism of levetiracetam is less complicated than older
anti-seizure medications, which makes it easier to use and better tolerated, and it is not
likely to interact with other medicines. Levetiracetam has been shown to prevent anxiety
during sedative withdrawal, which is similar to alcohol withdrawal, in a laboratory study
using mice. Levetiracetam also had anti-anxiety effects in laboratory study using mice. Given
that other anti-seizure medications have been shown to be helpful in treating alcohol
dependence, that levetiracetam is not likely to have interactions with other medications, and
that in animals levetiracetam appeared to be helpful for treating a condition similar to
alcohol dependence and anxiety, we believe it should be studied for the treatment of alcohol
dependent patients with anxiety disorders.

Inclusion Criteria:

- Men and women between the ages of 18-65 who meet Diagnostic and Statistical Manual of
Mental Disorders, Fourth Edition (DSM-IV) criteria for alcohol dependence and a
comorbid anxiety disorder, including: panic disorder, social phobia, generalized
anxiety disorder, substance-induced anxiety disorder and anxiety disorder, no
otherwise specified (NOS).

- Individuals capable of giving informed consent and capable of complying with study
procedures.

- Individuals must have clinically significant anxiety.

- Individuals must have current average alcohol use over past 28 days with > 4 drinking
days per week and >4 standard drinks/drinking day for women and > 5 standard
drinks/drinking day for men.

- Women of child-bearing age will be included provided that they are not pregnant, based
on the results of a blood pregnancy test done at the time of screening and agree to
use a method of contraception with proven efficacy and not to become pregnant during
the study. To confirm this, blood pregnancy tests will be repeated monthly. Women will
be provided a full explanation of the potential dangers of pregnancy while on the
study. If a woman becomes pregnant the study medication will be discontinued.

- Individual's breathalyzer reading at the time of signing consent must be < 0.04%.

Exclusion Criteria:

- Subjects with any current Axis I psychiatric disorder as defined by DSM-IV-Text
Revision (DSM-IV-TR) supported by the Structured Clinical Interview for DSM-IV-TR Axis
I Disorders, Research Version, Patient Edition (SCID-I/P) that in the investigator's
judgment might require pharmacological intervention, with the exceptions of alcohol
dependence and a comorbid anxiety disorder (panic disorder, social phobia, generalized
anxiety disorder, substance-induced anxiety disorder and anxiety disorder, NOS).
Current diagnoses of post-traumatic stress disorder (PTSD) or obsessive-compulsive
disorder are exclusionary.

- Individuals with evidence of moderate to severe alcohol withdrawal that would require
pharmacologic intervention.

- Individuals meeting DSM IV criteria for current cocaine or opioid dependence.

- Unstable physical disorders which might make participation hazardous such as
uncontrolled hypertension and tachycardia (systolic blood pressure [SBP] > 150 mm Hg,
diastolic blood pressure [DBP] > 90 mm Hg, or a sitting quietly heart rate [HR] > 100
bpm), acute hepatitis (patients with chronic mildly elevated transaminase levels ((2-3
x upper limit of normal) are acceptable) or poorly controlled diabetes.

- Patients currently taking prescribed psychotropic medications.

- Patients with a known sensitivity to levetiracetam.

- Individuals who have exhibited suicidal or homicidal behavior within the past two
years or have current active suicidal ideation.

- Women who are pregnant or nursing.

- Individuals physiologically dependent on any other drugs (excluding nicotine,
caffeine).

- Individuals with a history of a hazardous drinking behavior (e.g., driving while
intoxicated convictions, violent crimes committed while intoxicated) will be excluded.