Drug Treatment for Depressed Alcoholics (Naltrexone/Fluoxetine)
Summary
This study will examine the effects of combing naltrexone and fluoxetine (Prozac) versus fluoxetine and placebo in alcoholics with co-occurring major depression. Both groups will actively participate in the 6-month study, which includes weekly individual Dual Disorders Recovery Counseling during the first month and every two weeks during the second through sixth months, plus the naltrexone and fluoxetine or fluoxetine and placebo. Subjects will complete follow-up assessments at 9 and 12 months.
Description
We propose to test the efficacy of the combination of naltrexone and fluoxetine versus fluoxetine alone in the treatment of patients with alcoholism and co-morbid major depression in a double-blind, placebo- controlled, randomized, parallel group trial. With nearly eight million affected individuals in the U.S., co-morbid alcoholism and major depressive disorder represent a significant public health problem. The presence of co-morbidity has a significant negative impact on treatment response and outcome, resulting in increased risk for suicide and increased rates of costly inpatient psychiatric care. Effective pharmacologic treatments addressing thee dual disorders are lacking. Only partial response has been obtained in studies evaluating anti- depressant monotherapy in depressed alcoholics. Our previous work with the SSRI fluoxetine has demonstrative the positive results published to date in severely depressed alcoholics. Our previous work with the SSRI fluoxetine has demonstrative the most positive results published to date in severely depressed alcoholics. The fluoxetine group in that study, however, displayed only a partial treatment response, with low abstinence rates and persistent depressive symptoms and alcohol abuse. However, our original and extended pilot work evaluating the usefulness of combined naltrexone and fluoxetine suggest a robust response, with a significant decrease in alcohol use and depressive symptoms. Our study of potential interactions between these two medications documents that naltrexone does not increase fluoxetine or norfluoxetine blood levels in most patients. Our proposed study will build on our previous work and established record both in conducting medication efficacy trials in this complex and high risk population, and in developing fundamental pharmacological methodologies necessary to investigate the proposed rug interaction studies. The timeliness of our proposed study is underscored by the high prevalence of this co-morbid condition and by the widely but untested use of the combined medication treatment in clinical practice. Thus, our study our will fill an important gap in our knowledge regarding the treatment of high risk clinical population. We hypothesize that combined fluoxetine and naltrexone treatment will offer enhanced treatment for alcoholics with co-morbid major depression. While the fluoxetine will target the depressive disorders in addition to the compulsive consumatory behavior related to alcoholism, the naltrexone will target the positive reinforcing effect and release risk related to pathological alcohol use. We request five years of support to achieve the following aims: 1) Examine the efficacy of naltrexone plus fluoxetine compared to fluoxetine and placebo in the treatment of patients with co- morbid DSM-IV alcohol dependence and unipolar major depression.; 2) Assess specific predictors of medication response; 3) Conduct a prospective assessment of the effect of persistent depressive symptoms on alcohol use. One hundred and six acutely depressed and actively drinking subjects will be randomized and prospectively followed during a 6 month double-blind study, and a 6-month post-treatment follow-up phase.
Study Design
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
Conditions
Alcoholism
Intervention
naltrexone (Revia), fluoxetine (Prozac)
Location
Department of Psychiatry, Western Psychiatric Institute and Clinic of the University of Pittsburgh Medical Center
Pittsburgh
Pennsylvania
United States
15213
Status
Completed
Source
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00006204
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Naltrexone
Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.
Alcoholism
A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. (Morse & Flavin for the Joint Commission of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism: in JAMA 1992;268:1012-4)
Fluoxetine
The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants.
National Institute On Alcohol Abuse And Alcoholism (u.s.)
Component of the NATIONAL INSTITUTES OF HEALTH. It conducts research focused on improving the treatment and prevention of alcoholism and alcohol-related problems to reduce the health, social, and economic consequences of this disease. NIAAA, NIMH, and NIDA were created as coequal institutes within the Alcohol, Drug Abuse and Mental Health Administration in 1974. It was established within the NATIONAL INSTITUTES OF HEALTH in 1992.
Pueraria
A plant genus of the family FABACEAE a common weed of the southeast US. There has been folk use for alcoholism and liver protection. It contains puerarin, kakkalide, daidzein (isoflavonoids), and kudzusaponins (oleanene-type triterpene glycosides).
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PubMed Articles
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Characterization of the subcritical water extraction of Fluoxetine-Hydrochloride.
The characteristics of using Subcritical Water Extraction (SWE) to recover Fluoxetine-Hydrochloride from both standard solutions and the contents of commercial capsule formulations were investigated....
Fluoxetine administration to pregnant rats increases anxiety-related behavior in the offspring.
RATIONALE: Fluoxetine (Prozac®) is the most frequently prescribed drug to battle depression in pregnant women, but its safety in the unborn child has not yet been established. Fluoxetine, a selective...
Chronic exposure to fluoxetine (Prozac) causes developmental delays in Rana pipiens larvae.
Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, are among the many pharmaceuticals detected in aquatic ecosystems. Although the acute effects of SSRIs on select organisms have bee...
Cravings as a mediator and moderator of drinking outcomes in the COMBINE Study.
AIMS: Investigators of the COMBINE (Combining Medications and Behavioral Interventions for Alcoholism) Study examined whether combining medications with a behavioral intervention would improve outcome...
