Drug and Alcohol Dependence 63 (2001) 263–267 Relationship between central serotonergic neurotransmission and reduction in alcohol intake by citalopram Ulf Berggren a , Matts Eriksson a , Claudia Fahlke b , Jan Balldin a, * a Department of Psychiatry and Neurochemistry, Institute of Clinical Neuroscience, Go ¨teborg Uniersity, Sahlgrenska Uniersity Hospital /Mo ¨lndal, SE-43180 Mo ¨lndal, Sweden b Department of Psychology, Go ¨teborg Uniersity, P.O. Box 500, SE-40530 Go ¨teborg, Sweden Received 14 April 2000; received in revised form 15 September 2000; accepted 20 October 2000 Abstract The relationship between the effect of citalopram on alcohol intake and central serotonergic neurotransmission, as assessed by prolactin (PRL) response to fenfluramine, was investigated in 17 male heavy drinkers. A positive correlation was obtained, suggesting that the status of central serotonergic neurotransmission in individuals is associated with the treatment response to citalopram. When the group of subjects were divided into those with high and low PRL response (above and below median, respectively) to fenfluramine, those with high PRL response had a significant reduction in alcohol intake during citalopram treatment, whereas those with low PRL response had no such effect. Thus, in subjects with evidence of unimpaired or only slightly impaired central serotonergic neurotransmission (high PRL response) citalopram may have beneficial effect on alcohol consump- tion, whereas in those with more evidently impaired serotonergic neurotransmission (low PRL response) citalopram treatment may have no effect on or may even increase the alcohol consumption. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Alcohol; Prolactin; Fenfluramine; SSRI www.elsevier.com/locate/drugalcdep 1. Introduction Clinical double-blind placebo-controlled studies with SSRIs in individuals with heavy drinking or alcohol dependence have shown either a moderate decrease in alcohol consumption (Naranjo et al., 1984, 1987, 1989, 1990, 1992, 1995; Naranjo and Sellers, 1989; Gorelick and Paredes, 1992; Tiihonen et al., 1996) or no effect compared with placebo (Balldin et al., 1994a; Kranzler et al., 1995; Kabel and Petty 1996; Eriksson et al., 2000). It should be noted that in one study, fluoxetine treatment even seemed to reduce the beneficial effects of cognitive behavioural therapy in type B alcoholics (Kranzler et al., 1996). Furthermore, in some studies large interindividual variations in the response pattern to SSRIs have been observed (Naranjo et al., 1984, 1987; Balldin et al., 1994a). In one of these latter studies, a mean daily alcohol intake between 60 and 100 g pure alcohol appeared to be predictive for a fa- vourable response to citalopram (Balldin et al., 1994a). This finding has, however, not been replicated in a more recent study of ours (Eriksson et al., 2000), although the number of subjects might have been to small to reveal such an effect in that study. However, in this recent study (Eriksson et al., 2000), possession of the genotype dopamine D 2 receptor A 2 /A 2 seemed to predict a reduction in alcohol consumption, although transient, by citalopram treatment. It may thus be possible to distinguish subgroups of heavy drinkers or alcohol dependent subjects who are responsive or non- responsive to treatment with SSRIs. In clinical studies, central serotonergic dysfunction has been demonstrated in individuals with high alcohol consumption (for review see LeMarquand et al., 1994). Thus, lower cerebrospinal fluid (CSF) levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA); have been found in abstinent alcoholics (Ballenger et al., 1979; Banki, 1981; Borg et al., 1985). Moreover, recent studies have extended these findings by linking serotonin metabolism with age of onset of alcoholism. Thus, studies of individuals with early onset * Corresponding author. Tel.: +46-31-3432372; fax: +46-31- 3432348. 0376-8716/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII:S0376-8716(00)00218-0