The Use of Anticonvulsants for Treatment of Patients With Alcohol Dependence and Post Traumatic Stress Disorder

Sponsor

Yale University (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00571246

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Dependence Post Traumatic Stress Disorder	Drug: Topiramate Drug: lamotrigine Other: Placebo	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

The Use of Anticonvulsants for Treatment of Patients With Alcohol Dependence and Post Traumatic Stress Disorder

Study Start Date :

Jun 1, 2012

Anticipated Primary Completion Date :

Jun 1, 2016

Anticipated Study Completion Date :

Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Topiramate Participants will be randomized to topiramate (250mg)	Drug: Topiramate Participants are randomized to take Topiramate (250mg/day) 2 times a day
Experimental: Lamotrigine Participants will be randomized to lamotrigine (250mg)	Drug: lamotrigine Participants are randomized to take Lamotrigine (250 mg/day) 2 times a day
Placebo Comparator: Placebo Participants will be randomized placebo	Other: Placebo Participants are randomized to take placebo

Arm

Intervention/Treatment

Experimental: Topiramate

Participants will be randomized to topiramate (250mg)

Drug: Topiramate

Participants are randomized to take Topiramate (250mg/day) 2 times a day

Experimental: Lamotrigine

Participants will be randomized to lamotrigine (250mg)

Drug: lamotrigine

Participants are randomized to take Lamotrigine (250 mg/day) 2 times a day

Placebo Comparator: Placebo

Participants will be randomized placebo

Other: Placebo

Participants are randomized to take placebo

Outcome Measures

Primary Outcome Measures

drinking - measured using the TLFB [16 weeks]
craving - measured using the OCDS [16 weeks]
PTSD symptoms - measured using the CAPS [16 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Males and females between the ages of 18-60 years old.
Current alcohol abuse or dependence
Current PTSD
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 evaluation.
Individuals who are on a stable dose (no less than 2 weeks) of antidepressant medication.
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)
For women, negative pregnancy test and use of acceptable method of contraception.

Exclusion Criteria:

Females who are pregnant or lactating.
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, pyloric stenosis).
Patients who meet current SCID criteria for a major Axis I diagnosis (Bipolar Disorders, Schizophrenia and Schizophrenia-type Disorders).
History of substance dependence (other than alcohol, tobacco or cannabis) by DSM-IV criteria in the last 90 days.
Individuals taking mood stabilizers and antipsychotic medications.
Individuals with a history of allergies to topiramate or lamotrigine.