Naltrexone and disulfiram in patients with alcohol dependence and current depression.
OBJECTIVE
Although disulfiram and naltrexone have been approved by the Food and Drug Administration for the treatment of alcoholism, no medications have been approved for individuals with alcohol dependence and comorbid psychiatric disorders. In particular, the effect of these medications on alcohol use outcomes and on specific psychiatric symptoms is still unknown in patients with the most common co-occurring disorder, major depression.


METHODS
Two hundred fifty-four patients with a major Axis I psychiatric disorder and comorbid alcohol dependence were treated for 12 weeks in an outpatient medication study conducted at 3 Veterans Administration outpatient clinics. Randomization included (1) open randomization to disulfiram or no disulfiram, and (2) double-blind randomization to naltrexone or placebo. This resulted in 4 groups: (1) naltrexone alone, (2) placebo alone, (3) disulfiram and naltrexone, and (4) disulfiram and placebo. Primary outcomes were measures of alcohol use. Secondary outcomes included psychiatric symptoms assessed by the Hamilton Depression Rating Scale, alcohol craving, gamma-glutamyltransferase levels, and adverse events.


RESULTS
One hundred thirty-nine subjects (54.7%) met the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression. There was no relationship between the diagnosis of depression and medication treatment on alcohol use outcomes, psychiatric symptoms, or the reporting of side effects for these medications. There was a significant interaction between diagnosis, medication group, and craving, where subjects with depression on disulfram reported lower craving over time than subjects with depression on naltrexone.


CONCLUSIONS
The results suggest that disulfiram and naltrexone are safe pharmacotherapeutic agents for dually diagnosed individuals with depression for the treatment of alcohol use disorders.
Petrakis
Ismene
I
Department of Psychiatry, Yale University School of Medicine, Veterans Affairs Connecticut Healthcare System, West Haven Campus, West Haven, CT 06516, USA. ismene.petrakis@yale.edu
Ralevski
Elizabeth
E
Nich
Charla
C
Levinson
Carolyn
C
Carroll
Kathleen
K
Poling
James
J
Rounsaville
Bruce
B
D000427:Alcohol Deterrents / Q000009:adverse effects / Q000627:therapeutic use; D000437:Alcoholism / Q000188:drug therapy* / Q000453:epidemiology; D001714:Bipolar Disorder / Q000188:drug therapy / Q000453:epidemiology; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000453:epidemiology; D015897:Comorbidity; D003237:Connecticut / Q000453:epidemiology; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000453:epidemiology; D004221:Disulfiram / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D009271:Naltrexone / Q000009:adverse effects / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000009:adverse effects / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000188:drug therapy / Q000453:epidemiology; D012559:Schizophrenia / Q000188:drug therapy / Q000453:epidemiology; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy / Q000453:epidemiology; D016896:Treatment Outcome; D014728:Veterans; D005723:gamma-Glutamyltransferase / Q000097:blood
D000427:Alcohol Deterrents; D009292:Narcotic Antagonists; D009271:Naltrexone; D005723:gamma-Glutamyltransferase; D004221:Disulfiram