Different subgroups of alcoholics respond differently to serotonin-acting medication
Serotonin, a brain chemical, influences mood, emotions, sleep, appetite and temperature regulation.
Both short- and long-term alcohol consumption can damage serotonin functioning.
Selective serotonin reuptake inhibitors (SSRIs) help to maintain optimal levels of serotonin.
New findings indicate that Type A alcoholics respond better to an SSRI called sertraline (Zoloft®) than do Type B alcoholics, both during treatment and for six months following treatment.
Alcoholism typologies are constructed according to a set of one or more variables such as age of onset, family history of alcoholism, and presence/absence of antisocial behavior. According to one such typology by Thomas Babor, Type A alcoholics are considered to be at lower risk/severity, Type B alcoholics at higher risk/severity. In previous research, the authors of a study in the July issue of Alcoholism: Clinical & Experimental Research showed that Type A alcoholics had a better treatment response to a selective serotonin reuptake inhibitor (SSRI) called sertraline than did Type B alcoholics. In their latest study, the authors have found that during the six months following treatment, Type A alcoholics maintained their gains, whereas Type B alcoholics who had taken sertraline did not.
"SSRIs are the most widely prescribed class of anti-depressants," said William Dundon, senior research investigator in the department of psychiatry at the University of Pennsylvania School of Medicine and first author of the study. "SSRIs work by affecting the level of serotonin in the brain and elsewhere in the body. In the brain, serotonin is thought to influence mood, emotions, sleep, appetite, and temperature regulation. When the level of serotonin is too low, SSRIs can prevent the re-use (or re-uptake) to help maintain an optimal level of this neurochemical. Since we know from research with animals and humans that the serotonin system is affected by both acute and chronic alcohol consumption, it makes sense to investigate the use of SSRIs for alcohol-use disorders."
"Individuals with alcohol problems frequently present to their family physicians with complaints of depression or anxiety and receive prescriptions for SSRIs," added Darlene H. Moak, a psychiatrist and assistant professor at the Medical University of South Carolina. However, SSRIs have not performed well in previous studies of individuals with serious alcohol problems.
For this study, 100 alcoholics were given a three-month course of either sertraline (200 mg/day) or placebo capsules and AA-based individual therapy. During the next six months, researchers used the Timeline Followback method to interview the alcoholics, classified as either Type A (n=55) or Type B (n=45), about their alcohol consumption, if any. After gathering data at two, four, six, 12 and 24 weeks after treatment, researchers compared monthly alcohol consumption for the six months following treatment to alcohol consumption during the last month of treatment.
The Type A alcoholics who had been treated with sertraline instead of a placebo maintained – for at least six months after treatment had ceased – the positive results they had obtained during treatment. Type B alcoholics who had been treated with sertraline instead of a placebo continued to show no observable pharmacotherapeutic benefits during the six-month period following treatment. In fact, heavy drinking increased during that six-month post-treatment period among those Type B alcoholics treated with sertraline.
"We appear to have identified a subgroup of alcoholics, Type As, who responded well to sertraline during treatment and maintained their gains over a six-month period after ending treatment," said Dundon. "However, there is another subgroup, Type Bs, for whom SSRIs may not be appropriate. This subgroup seemed to maintain their gains from the AA-based individual therapy only if they had not received sertraline."
"The rationale for looking at these two types of alcoholism separately was rooted in earlier research that suggested there were differences in serotonin metabolism between the two groups," said Moak. "What is very interesting about the results that were obtained in earlier work by these authors is that the group found to have more abnormalities in serotonin metabolism – that is, Type B alcoholics – and would have been thought to be more likely to respond to the SSRIs in fact did worse on the SSRIs. [Nonetheless,] these new results are consistent with those obtained previously by the authors, in that the Type A alcoholics who received sertraline continue to do well after treatment, while the Type B alcoholics who received sertraline do poorly."
Furthermore, she noted, "these findings may help explain some of the inconsistencies that have occurred in earlier studies of the SSRIs, in alcoholics both with and without co-occurring independent depression."
Dundon and Moak agreed that developing a more "user-friendly" method by which clinicians could decide if an individual under evaluation were either a Type A or B alcoholic before they enter treatment is an important area for further research.
"I think our study clearly suggests that there may be ways to subtype alcoholics, and that these different subgroups of alcoholics may respond differently to the same treatment," said Dundon. "Numerous classification schemes have been proposed to differentiate types of alcoholics. Our study supports the usefulness of the Babor Type A and Type B classification system. If we can identify subgroups that may have different post-treatment outcomes, then clinicians may be able to make more precise ongoing treatment recommendations and better allocate limited resources."
Dundon added that this is a fruitful time for developments in alcohol-treatment research. "The most promising areas," he said, "focus on the combinations of medicines and psychotherapies to treat alcohol dependence and other drug dependencies."
Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Co-authors of the ACER paper, "Treatment outcomes in Type A and B alcohol dependence six months after serotonergic pharmacotherapy," were Kevin G. Lynch, Helen M. Pettinati, and Craig Lipkin of the Center for the Studies of Addiction in the Department of Psychiatry at the University of Pennsylvania School of Medicine. The study was funded by the National Institute on Alcohol Abuse and Alcoholism.