CHICAGO – Naltrexone may have little positive effect either on drinking behavior in older women with alcoholism comorbid with depression or on drug-using behavior in women with alcoholism and comorbid cocaine dependence.
Data presented at the annual meeting of the Research Society for Alcoholism–a subanalysis of a 2005 drug trial and a preview of a trial in press–hint that naltrexone may have very different effects in women than men, according to William Dundon, Ph.D., of the University of Pennsylvania, Philadelphia.
“Women metabolize alcohol differently than men, and respond to naltrexone differently as well,” he said in an interview. Although most trials haven't seen a significant difference in gender response to the drug, that may reflect a demographic problem rather than a true drug response. “The number of women in most of these studies is generally less than men, so these studies are not necessarily powered to see a gender effect,” Dr. Dundon said.
Naltrexone blocks the mu-opiate receptors, moderating the sense of euphoria that alcohol provides, said Dr. Dundon, a researcher at the university's Center for the Studies of Addiction. Genetic makeup may also play a significant part in a given patient's response to the drug. Dr. David Oslin, also of the university, has recently identified a genetic variant–a polymorphism of the mu-receptor gene–that seems to predict naltrexone response (Addict. Biol. 2006;11:397–403).
Dr. Dundon presented a recent gender subanalysis of a 2005 study by Dr. Oslin, demonstrating a poor naltrexone response in older women with comorbid alcoholism and depression (Am. J. Geriatr. Psychiatry 2005;13:491–500).
This study comprised 74 older adults (mean age 63 years) with alcohol dependence and depressive disorder. Most subjects (59) were male; there were only 15 female subjects. All of the patients received sertraline (Zoloft) 100 mg/day for their depression, as well as 10 sessions of therapy focused on both alcohol use and depression. They were also randomized to either placebo or naltrexone (50 mg/day).
At the end of the 12-week trial, 42% of the patients were considered well, with no relapse to heavy drinking and with remission of depressive symptoms. An additional 24% remained depressed, but did not have a drinking relapse.
There were no significant differences between the placebo/sertraline group and the naltrexone/sertraline groups in terms of outcome measures: relapse to heavy drinking, abstinence, remission of depression, or overall improvement.
The gender subanalysis showed a slightly different picture, Dr. Dundon said.
Men with positive outcomes did equally well on either regimen, with 40% of the placebo/sertraline and 45% of the naltrexone/sertraline groups considered well by 12 weeks. In women, though, only about 25% of those in the naltrexone/sertraline group were considered well by the trial's end, compared with 70% of those in the placebo/sertraline group.
Because so few women were in the trial, Dr. Dundon said it's impossible to make clinical recommendations about naltrexone's suitability for older women with comorbid depression and alcoholism.