Naltrexone & SSRI in Alcoholics With Depression/PTSD

NCT00338962 | Completed Phase 3 Results DMC

• 1 other identifier: HIC # 11637
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

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.

Conditions

Alcoholism; Depression; PTSD

Keywords

SSRI; treatment; naltrexone; alcohol dependence; Desipramine; depression; PTSD

Outcome Measures

Primary Outcomes (4)

• Mean Self-report Weekly Craving Via Obsessive Compulsive Drinking Scale (OCDS)

  The OCDS is a 14-item (rated 0-4), self-administered questionnaire for characterizing and quantifying the obsessive and compulsive cognitive aspects of craving and heavy (alcoholic) drinking, such as drinking-related thought, urges to drink, and the ability to resist those thoughts and urges. A higher total score indicates higher craving and ranges from 0-48.

  beginning of treatment (week 1), and end of treatment (13 weeks)

• Clinician-Administered PTSD Scale (CAPS)

  The CAPS is the gold standard in PTSD assessment. The CAPS-5 is a 30-item structured interview that can be used to: Make current (past month) diagnosis of PTSD Make lifetime diagnosis of PTSD Assess PTSD symptoms over the past week Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). A higher score is associated with higher severity of PTSD. The score is interpreted as follows: 0-19=Asymptomatic/few symptoms 20-39=Sub-threshold/mild PTSD 40-59=Threshold PTSD/moderate 60-79=Severe PTSD \>80=Extreme PTSD

  beginning of treatment (week 1), and end of treatment (13 weeks)

• Hamilton Depression Rating Scale (HAM-D)

  The HAM-D ranges from 0 (Normal) to \>23 (Very Severe Depression)

  beginning of treatment (week 1), and end of treatment (13 weeks)

• Mean Number of Side Effects

  Differences in mean number of side effects reported for each group. Side effects and common adverse symptoms were evaluated by the research staff weekly, using a modified version of the ystematic Assessment for Treatment Emergent Events. The symptoms that are known to be associated with treatment with desipramine, paroxetine, and naltrexone were specifically screened or on a weekly basis. The symptoms were then clustered into the following categories: gastrointestinal, emotional, cold and flu symptoms, skin, sexual, neurological, and cardiac.

  12 weeks

Study Arms (4)

Paroxetine and naltrexone

ACTIVE COMPARATOR

Paroxetine was started at 10 mg per day and the dose was gradually increased over 2 weeks to 40 mg per day. Naltrexone was started at 25 mg the first day and 50 mg per day for the rest of the treatment.

Drug: paroxetine; Drug: Naltrexone

paroxetine and placebo

ACTIVE COMPARATOR

Paroxetine was started at 10 mg per day and the dose was gradually increased over 2 weeks to 40 mg per day.

Drug: paroxetine; Drug: Placebo

Desipramine and naltrexone

ACTIVE COMPARATOR

Desipramine was started at a dose of 25 mg per day. The dose was gradually increased over 2 weeks to 200 mg per day. Naltrexone was started at 25 mg the first day and 50 mg per day for the rest of the treatment.

Drug: desipramine; Drug: Naltrexone

Desipramine and placebo

ACTIVE COMPARATOR

Desipramine was started at a dose of 25 mg per day. The dose was gradually increased over 2 weeks to 200 mg per day.

Drug: desipramine; Drug: Placebo

Interventions

paroxetine DRUG

paroxetine (40mg/day)

Also known as: paxil

Paroxetine and naltrexone; paroxetine and placebo

desipramine DRUG

200 mg per day

Also known as: Norpramin

Desipramine and naltrexone; Desipramine and placebo

Naltrexone DRUG

50 mg per day

Also known as: Vivitrol

Desipramine and naltrexone; Paroxetine and naltrexone

Placebo DRUG

placebo

Desipramine and placebo; paroxetine and placebo

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

VA Connecticut Healthcare Systems

West Haven, Connecticut, 06516, United States

Location

Related Publications (1)

• 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.

  PMID: 22089316 DERIVED

Related Links

• Published paper

MeSH Terms

Conditions

Alcoholism; Depression; Stress Disorders, Post-Traumatic

Interventions

Paroxetine; Desipramine; Naltrexone; vivitrol

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Stress Disorders, Traumatic; Trauma and Stressor Related Disorders

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Elizabeth Ralevski
• Organization: Yale University

elizabeth.ralevski@yale.edu

203-932-5711

Study Officials

• Ismene Petrakis, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2006
• First Posted: June 20, 2006
• Study Start: October 1, 2001
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: February 5, 2016
• Results First Posted: February 5, 2016

Record last verified: 2016-01

Locations

US (1)