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

Phase 3

Withdrawn

• Conditions: Alcohol Dependence; Post Traumatic Stress Disorder
• Interventions: Other: Placebo; Drug: Topiramate; Drug: lamotrigine

• Registration Number: NCT00571246
• Lead Sponsor: Yale University

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.

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 Timeline

• Study First Submitted: 2007-12-07
• Study First Submitted QC: 2007-12-07
• Study First Posted: 2007-12-11
• Study Start: 2012-06
• Primary Completion: 2016-06
• Study Completion: 2016-06
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-12
• Last Update Posted: 2020-11-16

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

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 evaluation.
5. Individuals who are on a stable dose (no less than 2 weeks) of antidepressant medication.
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.

Exclusion Criteria

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, pyloric stenosis).
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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants will be randomized placebo
Topiramate	Topiramate	Participants will be randomized to topiramate (250mg)
Lamotrigine	lamotrigine	Participants will be randomized to lamotrigine (250mg)

Primary Outcome Measures

Name	Time	Method
drinking - measured using the TLFB	16 weeks
craving - measured using the OCDS	16 weeks
PTSD symptoms - measured using the CAPS	16 weeks

Trial Locations

Locations (1)

VA Connecticut Healthcare System; 🇺🇸 West Haven, Connecticut, United States