Pharmacoloeic maintenance of abstinence in patients Gith alcoholism: No efficacy of 5 -Lydroxytryptophanor levodopa Pharmacologic enhancement of central nervous system serotonin and dopamine functions has been pos- tulated to improve maintenance of abstinence in patients with alcoholism. To test this hypothesis, pa- tients with alcoholism who completed a 42-day inpatient treatment program were randomized to be ad- ministered, in a double-blind fashion, either 5-hydroxytryptophan and carbidopa, levodopa and carbidopa, or placebo for 1 year. Eight of 31 patients who entered the analysis remained abstinent from alcohol for 1 year; however, there was no significant effect of the treatment condition on maintenance of abstinence. Baseline psychologic measures showed that patients who abstained from alcohol had more education and higher scores on memory function tests. Measures of cerebrospinal fluid obtained before the start of the study indicated that all patients who had higher concentrations of the dopamine metab- olite homovanillic acid relapsed, suggesting that further research is needed to elucidate the role of dopa- mine in alcoholism. (CLIN PHARMACOL THER 1992;52:553-60.) David T. George, MD, Teresa Lindquist, MS, Robert R. Rawlings, MS, Michael J. Eckardt, PhD, Howard Moss, MD, Cynthia Mathis, MD, Peter R. Martin, MD, and Markku Linnoila, MD, PhD Bethesda, Md., Pittsburgh and Philadelphia, Pa., and N m h l l e , Tenn. The search for medications that can serve as ad- juncts in the maintenance of abstinence in patients with alcohol dependence is a growing area of interest and importance. Agents commonly used in the past include alcohol-sensitizing drugs (di~ulfiram'.~), anxiolytics (buspirone, diazepam, chlordiazepox- ide3-6), mood stabilizers (~ithium"~), P-blockers (atenol~l~~'~), and serotonin-uptake inhibitors (zimeli- dine, citalopram, fl~oxetine"~'~). Use of many of these medications has been predicated on the hypothe- sis that drinking behavior is maintained through rein- forcement, the basis of which is presumed to be neurochemical in origin, and is thus responsive to pharmacologic manipulations. l3 From the Laboratory of Clinical Studies, National Institute on Alco- hol Abuse and Alcoholism, National Institutes of Health, Bethesda; the Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh; the Hahnemann Medical School, Philadelphia; and the Department of Psychiatry, Vanderbilt University School of Medicine, Nashville. Received for publication April 28, 1992; accepted June 30, 1992. Reprint requests: David T. George, MD, Section of Clinical Sci- ence, National Institute on Alcohol Abuse and Alcoholism, 9000 Rockville Pike, Bldg. 10 Room 3B19, Bethesda, MD 20892. 13/1/4071 1 Some investigators have suggested that alcohol con- sumption may be regulated by several interacting cen- tral neurotransmitter systems, including dopamine and serotonin. In rats, for example, alcohol results in an increase in dopamine synthesis and release,I4 which is implicated in part for the intoxicating effects of alco- holI5 and the development of dependence.16 In addi- tion, rats that are bred to prefer alcohol have lower levels of dopamine in the brain than those that do not prefer alcohol. '* Major et a1. l9 found reduced levels of the major do- pamine metabolite, homovanillic acid (HVA), in the cerebrospinal fluid of men with alcoholism during withdrawal. Dopaminergic medicines have been used to modify acute alcohol intoxication in normal volun- teers and to reduce the intensity of the withdrawal syndrome and alcohol "craving" in alcoholic subjects who are abstinent.2092'Dopamine agonists apomor- phine,21 b r o m ~ c r i ~ t i n e , ~ ~ and amantadine,23 and the apomorphine-levodopa-carbidopa ~ombination~~ have been used in clinical trials to modify the short-term and prolonged symptoms of abstinence of alcohol- dependent patients. A dysregulation of serotonin metabolism may also be involved in the pathophysiology of alcoholism. 553