Anticonvulsant Drug Cuts Drinking In Bipolar Alcoholics, Shows University Of Pittsburgh Research

Results of the research, the first randomized controlled trial to date that addresses this difficult problem, are detailed in today’s Archives of General Psychiatry, and show the drug valproate is effective at reducing drinking when combined with a patient’s regular treatment program.

Approximately 61 percent of bipolar patients abuse alcohol or other substances, a higher proportion than in any other psychiatric illness, including schizophrenia, major depression and anxiety disorders, and a rate that is ten times higher than that of the general population.

These patients are at greater risk for suicide and have more profound manic and depressive episodes. In addition, they have a difficult time adhering to treatments, which contributes to a Catch-22 of worsening health and cognitive functioning and increasing incidences of hospitalizations and use of costly psychiatric services.

“Patients with bipolar disorder and alcoholism are in a very precarious situation,” said lead author Ihsan Salloum, M.D., associate professor of psychiatry at the University of Pittsburgh School of Medicine. “They have high disability rates and ultimately the presence of these two disorders lead to higher death rates. Substance abuse makes it much more difficult for these individuals to stick with medication regimens. Our results show that valproate could be an important element to getting control of this dangerous combination of illnesses.”

The study followed 54 patients diagnosed with bipolar disorder and alcoholism for 24 weeks. Everyone in the study continued to receive their standard treatment, usually a combination of lithium and counseling therapy, and was assigned to receive either valproate or placebo to address their alcoholism.

The researchers found that patients who were given valproate in addition to their normal treatments drank less often and drank less overall.

Alcohol use was defined by heavy drinking days – days in which men had five or more drinks per day and women four or more. Additional alcohol use outcomes were determined by the number of drinking days and the period of time before patients relapsed into sustained heavy drinking.

Of the subjects taking valproate, 12, or 44 percent, reported heavy drinking days, compared with 17, or 68 percent, of the placebo group. In addition, those on valproate drank less on heavy drinking days, an average of 5.6 drinks vs. the 10.2 drinks consumed by those in the placebo group. In addition, the valproate group had significantly fewer total heavy drinking days during the study, 11.3, compared to 18.4 for those in the placebo group. Finally, the group on valproate had a longer time before relapse to sustained heavy drinking – 93 days to 62 days for the placebo group.

Despite the serious nature of bipolar disorder combined with alcoholism, very few interventions to address both illnesses have been looked at. A number of issues have complicated the effort, including ethical problems relating to taking bipolar patients off of their medications to participate in a research study and problems relating to the difficulty in isolating the effects of a particular treatment on one set of symptoms, such as mania or drinking. This situation has created a serious gap in knowledge of how best to treat patients with both bipolar disorder and an addiction.

This study was designed to address both issues. Patients were kept on their normal medication and therapy routine to avoid the danger of triggering mania or depression, and the study medication was added in a way that would allow the researchers to accurately measure its impact on drinking.

“This finding could have a significant impact on the quality of life for these patients,” said Dr. Salloum. “Most treatments for these individuals are designed to concentrate on the bipolar disorder with the hope that the alcoholism will ease as well. While common drugs used to treat bipolar disorder, such as lithium, can have a positive effect on regulating mood and preventing episodes of mania and depression, studies have shown it has no meaningful effect on drinking, a treatment rationale that leaves much to be desired in its effect on the associated, but equally significant illness of alcoholism.”

This study showed that valproate appears to decrease heavy drinking independent of measurable effect on mood state. Researchers believe the drug works by affecting the GABAergic system in the brain, affecting mechanisms involved in reducing both alcohol use and withdrawal symptoms.

The study group was made up of individuals aged 18-65 who had been diagnosed with both bipolar disorder and alcoholism. Approximately half of the participants had a history of other substance abuse disorders as well, including marijuana and cocaine. Nearly two-thirds smoked cigarettes.

Other researchers, all of the University of Pittsburgh, are Jack R. Cornelius, M.D., professor of psychiatry; Dennis C. Daley, Ph.D., associate professor of psychiatry; Levent Kirisci, Ph.D., associate professor of pharmaceutical sciences; Jonathan M. Himmelhoch, M.D., professor of psychiatry; and Michael E. Thase, M.D., professor of psychiatry.

The study was funded by grants from the National Institute of Alcohol Abuse and Alcoholism and the National Institute of Mental Health.