The objective of this study is to evaluate the efficacy of topiramate (250mg) or lamotrigine
(250mg) versus placebo in reducing alcohol consumption and decreasing symptoms of PTSD in
patients with comorbid AD and PTSD.
There is a high rate of comorbidity with alcohol dependence (AD) and post traumatic stress
disorder (PTSD). The rates of PTSD among individuals with AD are at least twice as high as
those in the general population. In addition, alcohol dependence is the most common comorbid
condition in men with PTSD. Despite this, little is known about how to best treat
individuals with comorbid AD and PTSD. The use of anticonvulsants represents a novel
approach to treatment that may target symptoms of both AD and PTSD. Both Topiramate and
Lamotrigine act on the GABAergic and glutamatergic systems. Topiramate has GABAergic
effects by robustly increasing brain GABA, and antiglutamatergic effects by inhibiting
glutamate function that might antagonize alcohol's rewarding effects in AD and could
contribute to the regulating of reexperiencing and arousal symptoms in PTSD. Lamotrigine is
a glutamate-inhibiting anticonvulsant that has shown efficacy in some dually diagnosed
patients with alcohol dependence, and in patients with PTSD. Neither topiramate nor
lamotrigine have been used to treat patients with comorbid PTSD and AD. Methods: Ninety
men and women with a current diagnosis of AD and PTSD will be enrolled in a 16-week trial.
They will be assigned, in a double-blind fashion, to either topiramate, lamotrigine or
placebo. Significance: This project will be the first to compare anticonvulsants
(topiramate and lamotrigine) to placebo as effective treatments for reducing alcohol
consumption and PTSD symptoms in patients with AD and PTSD.
1. Males and females between the ages of 18-60 years old.
2. Current alcohol abuse or dependence
3. Current PTSD
4. Patients with current alcohol dependence, with at least one recent episode of heavy
drinking (defined as 5 or more drinks per drinking episode) over the past 14 days,
and during a consecutive 30-day period within the 90 days prior to baseline
5. Individuals who are on a stable dose (no less than 2 weeks) of antidepressant
6. Medically and neurologically healthy on the basis of history, physical examination,
EKG, screening laboratories (CBC w/ differential, TSH, Free-T4, ASAT, ALAT, GGT, BUN,
creatinine, calcium, phosphorous, magnesium, total protein, albumin, electrolytes,
VDRL, urinalysis, beta-HCG)
7. For women, negative pregnancy test and use of acceptable method of contraception.
1. Females who are pregnant or lactating.
2. Individuals with a current unstable medical condition such as neurological,
cardiovascular, endocrine, renal, liver, or thyroid pathology (LFT > 3 times normal,
abnormal BUN and creatinine, and unmanaged hypertension with BP > 200/120) which in
the opinion of the physician would preclude the patient from fully cooperating or be
of potential harm during the course of the study (includes those with a history of
glaucoma, prostatic hypertrophy, urethral obstruction, cerebral arteriosclerosis,
3. Patients who meet current SCID criteria for a major Axis I diagnosis (Bipolar
Disorders, Schizophrenia and Schizophrenia-type Disorders).
4. History of substance dependence (other than alcohol, tobacco or cannabis) by DSM-IV
criteria in the last 90 days.
5. Individuals taking mood stabilizers and antipsychotic medications.
6. Individuals with a history of allergies to topiramate or lamotrigine.