Clinical trial NCT00338962: Naltrexone & SSRI in Alcoholics With Depression/PTSD
Official title: Naltrexone & SSRI in Alcoholics With Depression/PTSD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alcoholism
Depression
PTSD
Keywords: SSRI
treatment
naltrexone
alcohol dependence
Desipramine
depression
PTSD
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2006-06-20
Enrollment: 88
Sex: ALL
Minimum age (years): 21
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy of naltrexone in combination with an SSRI to reduce alcohol consumption in alcoholic patients with comorbid PTSD and depression.

We hypothesize that the combination of naltrexone and SSRI will exhibit a greater decrease in alcohol consumption than that seen with treatment with SSRI alone, or with a combination of another class of antidepressant and naltrexone. We also hypothesize that SSRI will be effective in treating PTSD and depressive symptoms and naltrexone will be well tolerated.

Detailed description: OBJECTIVE: Alcoholics with current comorbid mental disorders constitute the majority of alcoholics in clinical settings. Although there are two FDA approved medications for the treatment of alcoholism (naltrexone and disulfiram), there are no established pharmacotherapies for individuals with comorbid alcoholism and psychiatric illnesses. Studies suggest that the class of antidepressants known as serotonin selective reuptake inhibitors (SSRIs) is effective in reducing alcohol use in depressed individuals. In addition, a small open label study has shown that SSRIs have similar effects on individuals with comorbid PTSD and alcoholism. Preclinical studies have shown that the combination of a serotonergic agent and naltrexone was more effective than either medication alone in suppressing alcohol intake. To address this issue, we are conducting a 13 week randomized clinical trial evaluating the effects of paroxetine, desipramine and naltrexone in reducing alcohol use in alcohol dependent individuals who currently meet DSM-IV diagnosis for Depressive Disorder or PTSD. RESEARCH PLAN: One hundred and twenty subjects who are alcohol dependent patients with comorbid PTSD or Depressive Disorder will be recruited from the following West Haven VA sources: the Substance Abuse Treatment program, the PTSD clinic, the Women's clinic, clinical referrals and advertisement. These subjects will be randomized in a double-blind fashion to one of four cells. We will compare paroxetine versus desipramine and naltrexone versus placebo. The antidepressant will be started at a low dose and titrated upward on a fixed schedule. The target dose will be 40mg for paroxetine and 200mg for desipramine. Minimum dosage permitted for study retention will be 20mg for paroxetine and 150mg for desipramine. Pharmacological treatments will last 13 weeks. Psychosocial treatment will involve medication compliance therapy, using the Microelectric Event Monitoring (MEMS) bottle caps. The specific aim of the research is to compare the relative effectiveness of paroxetine versus desipramine and naltrexone versus placebo in reducing the quantity and frequency of alcohol consumption. METHODOLOGY: The primary outcome measures of major interest will include: frequency and quantity of alcohol consumption, self-reported craving, self-reported psychiatric and emotional distress, diagnostic assessment or psychiatric symptoms and side effects. These outcomes will be measured by the following: self-assessments, Timeline Followback, Hamilton Depression and anxiety scales, CAPS, ASI, Quality of Life, breathalyzer tests and monthly liver function tests.

Eligibility criteria: Inclusion Criteria:

* DSM-IV diagnosis of alcohol dependence and current DSM-IV depressive disorder or PTSD
* a recent episode of heavy drinking
* outpatient, sober from alcohol and other abused substance for at least 2 days before randomization
* stable medication regiment for at least 2 weeks
* women on adequate methods of contraception

Exclusion Criteria:

* current opioid dependence or abuse
* history (within the last 3 months) of opioid dependence or abuse
* pregnant
* history of psychotic disorders or current treatment with antipsychotic medications
* medication thought to influence drinking including: acamprosate, disulfiram, naltrexone, ondansetron, valproic acid or tegretol
* current (within the lst 6 months) use of MAO inhibitors
* suicidal active ideation or intent
* significant underlying medical condition
* history of cardiac condition abnormalities

Primary outcomes:
measure: Mean Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS)
timeFrame: beginning of treatment (week 1), and end of treatment (13 weeks)
measure: Clinician-Administered PTSD Scale (CAPS)
timeFrame: beginning of treatment (week 1), and end of treatment (13 weeks)
measure: Hamilton Depression Rating Scale (HAM-D)
timeFrame: beginning of treatment (week 1), and end of treatment (13 weeks)
measure: Mean Number of Side Effects
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: West Haven
country: United States
facility: VA Connecticut Healthcare Systems
state: Connecticut
Study officials:
affiliation: Yale University
name: Ismene Petrakis, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Petrakis IL, Ralevski E, Desai N, Trevisan L, Gueorguieva R, Rounsaville B, Krystal JH. Noradrenergic vs serotonergic antidepressant with or without naltrexone for veterans with PTSD and comorbid alcohol dependence. Neuropsychopharmacology. 2012 Mar;37(4):996-1004. doi: 10.1038/npp.2011.283. Epub 2011 Nov 16.