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Personality traits — especially impulsivity and sensation seeking — as related to dopaminergic and serotonergic drug challenge response in alcohol dependent men
Poster session I
BIOL. PSYCHIATRY 1997;42:15-2975
cortex was assessed in 20 alcoholic subjects and 23 controls. Samples were matched for age, gender, cause of death and postmortem delay. A positive correlation of MAQ-B sites with age was observed (r 0.370; p 0.015). No differences between alcoholic subjects (Bmax = 1263 ± 282 fmoVmg protein) and controls (Bm.. = 1131 ± 96 fmoVmg protein) were found. The lack of differences could not be ascribed to the influence of age (F [1, 41) =0.67; P = 0.417). In control brain, in vitro ethanol (10-4 M to 1 M; 10 points) inhibited [3H).R019-6327 binding at very high concentrations (~ = 338 :I:: 84 mM). The present results in human brain suggest that the catalytic binding site of the MAQ-B enzyme when quantified by radioligand binding techniques is not altered in chronic alcoholism. Supported by FIS (1731/95) and the Department of Health (Basque Govemment). A.I. Maeztu and L.F. Callado are fellowship of the Basque Govemment.
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1 14-75 1 SSRls In alcoholism: Fluvoxamine vs fluoxetine In
alcoholic outpatients
L. Janiri, A. Hadjichristos, U. Lombardi, R. Rago, P. Mannelli, E. Tempesta 1. Institute of Psychiatry. Catholic University. Rome, Italy, , Institute of Pharmacology, Catholic University. Rome, Italy The aim of this open study is to compare the effects of the selective 5-HT reuptake inhibitors (SSRls) fluvoxamine and fluoxetine, at antidepressant doses, on the alcohol-<>riented behavior of a sample of alcoholic outpatients. Methods: Fifty outpatients (MIF: 4; age: 43.7 ± 11.6), diagnosed as ale<>• hol-dependent according to DSM IV, entered the study and underwent the detoxification. After 7-15 days they were randomly assigned to either orally f1uvoxamine (100 mg/day) orfluoxetine (20 mg/day). Evaluation Instruments after 30 (T30), 60 (Teo) and 90 (T80) days of treatment consisted In: Alcohol Withdrawal Rating Scale (AWRS), Alcohol Questionnaire, Hamilton Scales for Depression (HDS) and Anxiety (HAS) and Visual Analog Scale for alcohol craving (VAS-10 em). Results: Out of 22 patients who completed the study, 12 were totally abstinent at T80 (fluoxetine: 9, fluvoxamlne: 3). The remaining 28 patients dropped out of the study before the end. As to T0-T80 comparison between the examined scales, AWRS score was significantly decreased in both groups of subjects, while HAS and HDS scores were significantly reduced only in the fluoxetine group. Among non-abstinent patients, those treated with f1uvoxamlne showed lower alcohol consumption then those treated with f1uoxetine. Conclusions: Fluoxetine showed a greater efficacy than fluvoxamlne on the abstinence rate and the anxious-depressed symptoms of the alcoholics, whereas f1uvoxamine was more effective on the consumed alcohol amount.
114-761 Craving for alcohol and dopamine activity P. Mannelli. M.C. Mizzonl, L. Janiri, U. Lombardi, S. De Rislo, E. Tempesta 1. Dept. of Psychiatry. Universitll Cattolica S. Cuore, Roma. Italy, , Dept. of Pharmacology, Unlversitll Cattolica S. Cuore. Roma, Italy Craving Is a multidimensional symptom considered as a cardinal feature of drug dependence. Dopamine (DA) transmission is central for the mecha• nisms of reinforcement of the main drugs of abuse and the perception of their hedonic effects. We present the results of a clinical Investigation evaluating the effects on craving for alcohol of drugs acting in different manners at the DA receptors. Methods: Sixty alcohol abusers attending ambulatory care for detoxifi• cation received either haloperidol, DA antagonist, amlneptine, DA uptake inhibitor. amisulpride, DA autoreceptor antagonist, or placebo, as part of a double-blind, 4-week trial. Weekly quantitative measures of alcohol con• sumption were taken, while visual analog scales were used to rate mood and craving. Craving for alcohol wes assessed evaluating six components representing distinct conceptualization of drug craving. Results: All the subjects showed a reduced amount of alcohol intake at the end of the study, but no significant differences were observed across treatments. Subjects assuming amisulpride showed reduced craVing, es• pecially in its dysphoric components. As to the results, the methodology employed needs to be discussed, as well as the Influence of DA manipula• tion on craving. the relationship between craving and alcohol assumption, and the utility of controlling craving for the compliance to treatment.
355
114-771 Relapse prevention with flupenthlxol decanoate In alcohol dependence
G.A. Wiesbeck, H.-G. Weijers, J. Boening. Addiction Research Group. Department of Psychiatry. University of Wuerzburg, Germany This presentation will provide preliminary results of an ongoing double-blind, placebo-controlled German multicenter study on the effectiveness of flu• penthlxol decanoate in preventing relapse In detoxified alcoholics with the intention to remain abstinent. Methods: Flupenthixol decanoate (FD) Is a depot neuroleptic with mild antidepressant and anxlolytic activity and minimal sedation at low doses. It blocks dopamine binding at a number of receptor subtypes, primarily at 0.1, D2-, and Inhibitory D-2 autoreceptors as well as serotonin binding at 5-HT2 receptors. A total of 268 men and women meeting criteria for moderate or severe DSM-III·R alcohol dependence (303.90) will receive either 10 mg FD or placebo as intramuscular Injection every 14 days. The treatment phase will last 6 months followed by a drug-free 6 months follow-up period. 'Time to 1st relapse' is defined as the primary parameter of efficacy. Results: The recruitment phase will be completed in early 1997. At the moment more then 200 patients are already Included by 13 different centers. Flupenthixol is well tolerated with no severe side-effects so far. The drop-out rate is about 50% with half of the cases being 'early' drop-outs (within the first 4 weeks). Further results will be presented.
114-781 Personality traits - especially Impulsivity and sensation seeking - as related to dopamlnergic and serotonerglc drug challenge response In alcohol dependent men H.-G. Weijers, G.A. Wiesbeck, J. Boening. Addiction Research Group, Department of Psychiatry. University of Wuerzburg, Germany This presentation will provide preliminary results of an ongoing stUdy on biological correlates of personality traits In alcoholics. Methods: Based on the drug-ehallenge paradigm apomorphine and fsn• f1uramine were applied to neuroendocrinologically assess the overall central dopaminergic and serotonergic neurotransmission In adult men suffering from primary ICD-10 alcohol dependence. Both challenge tests were per• formed under standardized conditions with a placebo-eontrolled design during the 6th week of Inpatient treatment. Additionally, the subjects tem• perament and character traits were rated using Cloninger'S Temperament• and Character-Inventory (Tel), Zuckerman's Impulsive-Sensation-Seeklng• Scale (ImpSS), Eysenck's Impulsiveness Questionnaire (I 7), as well as the Matching Familiar Figures Test, a behavioral indicator for Impulsivity. Results: Unear correlations yielded a significant relationship between the subtrait 'Exploratory Excitability' and the both dopaminergic and sera• tonergic responsivity. Furthermore, the result of the serotonergic challenge correlated significantly with the impulsiveness-score of the I 7 and the sen• sation-seeking-score of the ImpSS. These findings suggest that impulsivity and sensation seeking are related - at least in part - to central serotonergic neurotransmission in primary alcohol dependence.
114-791 Alcoholics with and without positive family history and early age of onset: Differences In personality, biological and neurophysiological parameters U. PreuB, T. Bauch, M. Soyka, E. Benda, B. Bondy, J. Gallinat, U. Hegerl. Dept. of Psychiatry, Laboretory of Clinical Neurophysiology. Ludwig-Maximilians Universitllt Manchen. Nul3baumstr. 7. 80336 Manchen, Germany
Ob)ectlve: Alcoholics with positive family history and an age of onset before 25 years are supposed to show personality traits like high sensation seeking, high extroversion and antisocial personality traits. Two groups of alcoholics with and without these characteristics (FPEO and FNLO) and healthy controls were compared hypothesizing higher sensation seeking, higher extroversion scores, more antisocial personality traits, a more pronounced loudness dependence of auditory evoked potentials (LDAEP). reflecting a reduced serotonergic neurotransmission. smaller P300 amplitudes and lower MAQ-B activity in FPEO compared to FNLO and controls. Methods: 15 FPEO and 15 FNLO SUbjects were recruited as inpatients after alcohol withdrawal. 30 healthy controls were matched according to age and gender. Personality traits were assessed using Zuckermans Sensation Seeking Scale, the Five Factorial Inventory (FFI) and SCID II. Items of alcohol
BIOL. PSYCHIATRY 1997;42:15-2975
cortex was assessed in 20 alcoholic subjects and 23 controls. Samples were matched for age, gender, cause of death and postmortem delay. A positive correlation of MAQ-B sites with age was observed (r 0.370; p 0.015). No differences between alcoholic subjects (Bmax = 1263 ± 282 fmoVmg protein) and controls (Bm.. = 1131 ± 96 fmoVmg protein) were found. The lack of differences could not be ascribed to the influence of age (F [1, 41) =0.67; P = 0.417). In control brain, in vitro ethanol (10-4 M to 1 M; 10 points) inhibited [3H).R019-6327 binding at very high concentrations (~ = 338 :I:: 84 mM). The present results in human brain suggest that the catalytic binding site of the MAQ-B enzyme when quantified by radioligand binding techniques is not altered in chronic alcoholism. Supported by FIS (1731/95) and the Department of Health (Basque Govemment). A.I. Maeztu and L.F. Callado are fellowship of the Basque Govemment.
=
=
1 14-75 1 SSRls In alcoholism: Fluvoxamine vs fluoxetine In
alcoholic outpatients
L. Janiri, A. Hadjichristos, U. Lombardi, R. Rago, P. Mannelli, E. Tempesta 1. Institute of Psychiatry. Catholic University. Rome, Italy, , Institute of Pharmacology, Catholic University. Rome, Italy The aim of this open study is to compare the effects of the selective 5-HT reuptake inhibitors (SSRls) fluvoxamine and fluoxetine, at antidepressant doses, on the alcohol-<>riented behavior of a sample of alcoholic outpatients. Methods: Fifty outpatients (MIF: 4; age: 43.7 ± 11.6), diagnosed as ale<>• hol-dependent according to DSM IV, entered the study and underwent the detoxification. After 7-15 days they were randomly assigned to either orally f1uvoxamine (100 mg/day) orfluoxetine (20 mg/day). Evaluation Instruments after 30 (T30), 60 (Teo) and 90 (T80) days of treatment consisted In: Alcohol Withdrawal Rating Scale (AWRS), Alcohol Questionnaire, Hamilton Scales for Depression (HDS) and Anxiety (HAS) and Visual Analog Scale for alcohol craving (VAS-10 em). Results: Out of 22 patients who completed the study, 12 were totally abstinent at T80 (fluoxetine: 9, fluvoxamlne: 3). The remaining 28 patients dropped out of the study before the end. As to T0-T80 comparison between the examined scales, AWRS score was significantly decreased in both groups of subjects, while HAS and HDS scores were significantly reduced only in the fluoxetine group. Among non-abstinent patients, those treated with f1uvoxamlne showed lower alcohol consumption then those treated with f1uoxetine. Conclusions: Fluoxetine showed a greater efficacy than fluvoxamlne on the abstinence rate and the anxious-depressed symptoms of the alcoholics, whereas f1uvoxamine was more effective on the consumed alcohol amount.
114-761 Craving for alcohol and dopamine activity P. Mannelli. M.C. Mizzonl, L. Janiri, U. Lombardi, S. De Rislo, E. Tempesta 1. Dept. of Psychiatry. Universitll Cattolica S. Cuore, Roma. Italy, , Dept. of Pharmacology, Unlversitll Cattolica S. Cuore. Roma, Italy Craving Is a multidimensional symptom considered as a cardinal feature of drug dependence. Dopamine (DA) transmission is central for the mecha• nisms of reinforcement of the main drugs of abuse and the perception of their hedonic effects. We present the results of a clinical Investigation evaluating the effects on craving for alcohol of drugs acting in different manners at the DA receptors. Methods: Sixty alcohol abusers attending ambulatory care for detoxifi• cation received either haloperidol, DA antagonist, amlneptine, DA uptake inhibitor. amisulpride, DA autoreceptor antagonist, or placebo, as part of a double-blind, 4-week trial. Weekly quantitative measures of alcohol con• sumption were taken, while visual analog scales were used to rate mood and craving. Craving for alcohol wes assessed evaluating six components representing distinct conceptualization of drug craving. Results: All the subjects showed a reduced amount of alcohol intake at the end of the study, but no significant differences were observed across treatments. Subjects assuming amisulpride showed reduced craVing, es• pecially in its dysphoric components. As to the results, the methodology employed needs to be discussed, as well as the Influence of DA manipula• tion on craving. the relationship between craving and alcohol assumption, and the utility of controlling craving for the compliance to treatment.
355
114-771 Relapse prevention with flupenthlxol decanoate In alcohol dependence
G.A. Wiesbeck, H.-G. Weijers, J. Boening. Addiction Research Group. Department of Psychiatry. University of Wuerzburg, Germany This presentation will provide preliminary results of an ongoing double-blind, placebo-controlled German multicenter study on the effectiveness of flu• penthlxol decanoate in preventing relapse In detoxified alcoholics with the intention to remain abstinent. Methods: Flupenthixol decanoate (FD) Is a depot neuroleptic with mild antidepressant and anxlolytic activity and minimal sedation at low doses. It blocks dopamine binding at a number of receptor subtypes, primarily at 0.1, D2-, and Inhibitory D-2 autoreceptors as well as serotonin binding at 5-HT2 receptors. A total of 268 men and women meeting criteria for moderate or severe DSM-III·R alcohol dependence (303.90) will receive either 10 mg FD or placebo as intramuscular Injection every 14 days. The treatment phase will last 6 months followed by a drug-free 6 months follow-up period. 'Time to 1st relapse' is defined as the primary parameter of efficacy. Results: The recruitment phase will be completed in early 1997. At the moment more then 200 patients are already Included by 13 different centers. Flupenthixol is well tolerated with no severe side-effects so far. The drop-out rate is about 50% with half of the cases being 'early' drop-outs (within the first 4 weeks). Further results will be presented.
114-781 Personality traits - especially Impulsivity and sensation seeking - as related to dopamlnergic and serotonerglc drug challenge response In alcohol dependent men H.-G. Weijers, G.A. Wiesbeck, J. Boening. Addiction Research Group, Department of Psychiatry. University of Wuerzburg, Germany This presentation will provide preliminary results of an ongoing stUdy on biological correlates of personality traits In alcoholics. Methods: Based on the drug-ehallenge paradigm apomorphine and fsn• f1uramine were applied to neuroendocrinologically assess the overall central dopaminergic and serotonergic neurotransmission In adult men suffering from primary ICD-10 alcohol dependence. Both challenge tests were per• formed under standardized conditions with a placebo-eontrolled design during the 6th week of Inpatient treatment. Additionally, the subjects tem• perament and character traits were rated using Cloninger'S Temperament• and Character-Inventory (Tel), Zuckerman's Impulsive-Sensation-Seeklng• Scale (ImpSS), Eysenck's Impulsiveness Questionnaire (I 7), as well as the Matching Familiar Figures Test, a behavioral indicator for Impulsivity. Results: Unear correlations yielded a significant relationship between the subtrait 'Exploratory Excitability' and the both dopaminergic and sera• tonergic responsivity. Furthermore, the result of the serotonergic challenge correlated significantly with the impulsiveness-score of the I 7 and the sen• sation-seeking-score of the ImpSS. These findings suggest that impulsivity and sensation seeking are related - at least in part - to central serotonergic neurotransmission in primary alcohol dependence.
114-791 Alcoholics with and without positive family history and early age of onset: Differences In personality, biological and neurophysiological parameters U. PreuB, T. Bauch, M. Soyka, E. Benda, B. Bondy, J. Gallinat, U. Hegerl. Dept. of Psychiatry, Laboretory of Clinical Neurophysiology. Ludwig-Maximilians Universitllt Manchen. Nul3baumstr. 7. 80336 Manchen, Germany
Ob)ectlve: Alcoholics with positive family history and an age of onset before 25 years are supposed to show personality traits like high sensation seeking, high extroversion and antisocial personality traits. Two groups of alcoholics with and without these characteristics (FPEO and FNLO) and healthy controls were compared hypothesizing higher sensation seeking, higher extroversion scores, more antisocial personality traits, a more pronounced loudness dependence of auditory evoked potentials (LDAEP). reflecting a reduced serotonergic neurotransmission. smaller P300 amplitudes and lower MAQ-B activity in FPEO compared to FNLO and controls. Methods: 15 FPEO and 15 FNLO SUbjects were recruited as inpatients after alcohol withdrawal. 30 healthy controls were matched according to age and gender. Personality traits were assessed using Zuckermans Sensation Seeking Scale, the Five Factorial Inventory (FFI) and SCID II. Items of alcohol