This is a competing continuation proposal to extend results from a 5- year NIAAA-funded project on sertraline for depressed alcoholics. Comorbidity in substance abusers traditionally has been associated with a more severe clinical picture and a poorer prognosis for drinking outcome, compared to cases of uncomplicated alcoholism. In clinical populations, one-third to one-half of patients seeking alcohol treatment have a lifetime major depressive disorder. Persistent depression in abstinent alcoholics is both disabling and a risk factor for relapse to drinking, and further clinical deterioration that may result in suicide. Because we have effective, FDA-approved pharmacotherapy for alleviating depressive symptoms, it is important that we are fully informed about the advantages (or disadvantages) of treating primary or secondary depression in alcoholics with antidepressant medications. Results from our initial, project suggested that comorbidly depressed alcoholics appeared to have reduced antidepressant effects from sertraline and sertraline did not reduce their drinking (more than placebo). To address these results, we propose a study that will examine if we can achieve a more optimal outcome in comorbidly depressed alcoholics by directly treating the alcoholism with naltrexone, and combining this pharmacotherapy with the use of sertraline for treating depression. Thus, the primary aim of this proposal is to examine in depressed alcoholic outpatients whether combining naltrexone (an FDA-approved pharmacological intervention to reduce drinking) with sertraline (an FDA-approved pharmacological intervention to treat depression) will result in greater reductions in both drinking and depression over either medication alone or placebo. A secondary aim is to examine whether certain patient features, e.g., extent of pre-treatment drinking or severity of depression, will predict response to sertraline, naltrexone, or the combination. Patients who present to the University of Pennsylvania Treatment Research Center will be recruited for participation in this study over a 5-year period. There will be 160 males and females with a current DSM-IV diagnosis of alcohol dependence and also of major depression (via PRISM) who will be randomized to one of four treatment groups (40 per group): 1) the combination of 100mg/day naltrexone and 200mg/day sertraline, 2) 100mg/day naltrexone, 3) 200mg/day sertraline, or 4) placebo. Subjects will also receive once- weekly sessions of Cognitive Behavioral Therapy that has been adapted to include a medication compliance enhancement component. The treatment phase will last 16 weeks (includes a week of baseline, and a week of single-blind, placebo lead-in, and 14 weeks of double-blind pharmacotherapy). The follow-up phase includes two visits at 6 and 9 months post-treatment entry. Overall, this project will determine if combining pharmacotherapies results in a better response in comorbidly depressed alcoholics than either medication alone or placebo.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA009544-07
Application #
6168269
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Litten, Raye Z
Project Start
1992-09-30
Project End
2004-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
7
Fiscal Year
2000
Total Cost
$389,545
Indirect Cost
Name
University of Pennsylvania
Department
Psychiatry
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Pettinati, Helen M; Oslin, David W; Kampman, Kyle M et al. (2010) A double-blind, placebo-controlled trial combining sertraline and naltrexone for treating co-occurring depression and alcohol dependence. Am J Psychiatry 167:668-75
Ahmadi, Jamshid; Kampman, Kyle M; Oslin, David M et al. (2009) Predictors of treatment outcome in outpatient cocaine and alcohol dependence treatment. Am J Addict 18:81-6
Suh, Jesse J; Pettinati, Helen M; Kampman, Kyle M et al. (2006) The status of disulfiram: a half of a century later. J Clin Psychopharmacol 26:290-302
Pettinati, Helen M; O'Brien, Charles P; Rabinowitz, Amanda R et al. (2006) The status of naltrexone in the treatment of alcohol dependence: specific effects on heavy drinking. J Clin Psychopharmacol 26:610-25
Pettinati, Helen M; Rabinowitz, Amanda R (2006) Choosing the right medication for the treatment of alcoholism. Curr Psychiatry Rep 8:383-8
Dundon, William; Lynch, Kevin G; Pettinati, Helen M et al. (2004) Treatment outcomes in type A and B alcohol dependence 6 months after serotonergic pharmacotherapy. Alcohol Clin Exp Res 28:1065-73
Pettinati, Helen M; Dundon, William; Lipkin, Craig (2004) Gender differences in response to sertraline pharmacotherapy in Type A alcohol dependence. Am J Addict 13:236-47
Pettinati, Helen M (2004) Antidepressant treatment of co-occurring depression and alcohol dependence. Biol Psychiatry 56:785-92
Pettinati, Helen M; Kranzler, Henry R; Madaras, Julie (2003) The status of serotonin-selective pharmacotherapy in the treatment of alcohol dependence. Recent Dev Alcohol 16:247-62
Pettinati, Helen M; Monterosso, John; Lipkin, Craig et al. (2003) Patient attitudes toward treatment predict attendance in clinical pharmacotherapy trials of alcohol and drug treatment. Am J Addict 12:324-35

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