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P-10-22 Tianeptine in the treatment of alcohol dependence syndrome
P-I O Alcolhlism, drug dependence and abuse
400 References
References
Amit Z, Smith BR (i 992) Neurot'ansmnter systems ,egulat ng alcohol inta
C' Malley. S S , et al Naltrexone and Coping Skills Therapy for Alcohol Dependence A Controlled Study Arch Gen Psychiatry Vol 49, Nov 1992, p 881 887 Volpicelb J R , et al Naltrexone in the Treatment of Alcohol Dependence Arch Gen. Psych~atrv Vol 49, Nov 1992, p 876 880.
I
Experimentally induced expectations interfering IP" 10-24 I with nicotine effects induced by oral absorption and inhalation of smoke in nicotine dependent subjects
]
P-10-22 j Tianeptine in the treatment of alcohol dependence syndrome
P Netter, J. Hennig, T. Bbckling, R Olbrich. Department of Psycho/ogy,
N N Ivanets. State Research Center on Add/ctsons, 121921 Moscow
i./n/versi~ of GIessen, FRG
Russ/a
/~troduct/on In spite of the well established fact that reinforcing properties
AffectJve d~sorders are known t:) ~; ay an m]portant "die in trle clinical p~c ture of alcoholism Pathological c'av ng for alcohol is often unreal,zeal and manifested by depresswe s y m p t o m s Biological bases for neurochem~cal mechanisms of depressive states and alcoholism have much in common The goal of this work was to study, by the chnlco b~ochemicai m e t h o d the efficacy of a PeW antidepressant tlaneptme, in treating alcoholsm w~th chnical symptoms of depression and pathological craving for alcohol Tianeptine tablets (12.5 mg) were given to 35 alcohohc patients 3 braes a day over a period of 60 days The results showed high efficacy of tlaneptme depresswe symptorTs :~ sappeared, emotional state was normahzed and pathological crav nc tor alcoholdeactualized The estimates of the neurotransmittercontent rq the b~ooo plasma showed that the improvement of the clinical condition was accomoanied by the normalization of the serotonm and dooamlne concert Vat,on under the influence o; tlaneptlne The data obtained permit us :o recommend tlaneotlne as a drug that stabilizes remission and prevents early alcohohs~ relapse
of smoking do not only concern the content of nicotine but many additional nonpharmacologicat factors, it has not been tried to disentangle different reinforcing components of cigarettes in a systematic manner. In particular, effects of expectancy, widely investigated in alcohol and placebo research have not been analyzed for their interactions with the pharmacological action of mcotine [1]. The smoker's expectations concern the knowledge of a) receiving nicotine and b) receiving it via inhalation of smoke. So we corducted an experiment in which instruction about receiving a nicotine or sham cigarette and the mode of application of nicotine by smoke inhalation or by buccal absorption from a tablet were systematically combined in order to assess the influence of expectations on changes in performance, emotional states, satisfaction from smoking, and salivary cortisol values (wh,ch have been shown to increase after smoking [211. Methods 96 female smokers (_> 10 cigarettes per day) were assigned to 6 groups of a 2 x 3 design comparing three modes of applica t~on of n~cotme (N)(N cigarette + placebo (P) tablet/sham cigarette + N tablet/sham cigarette + P tabletl combined with two modes of instruction (N cigarette/sham cigarette) So each subject believed to obtain nicotine, if given, by smoking. The tablet was merely introduced as a means for keepng the pH level constant. Subjects were asked to refrain from smoking for at least I/2 hour before starting the test. Two vigilance tasks from Cognitive Drug Research*), cdticai flicker fusion and subjective ratings on emotional states and the desire for smoking were obtained prior to and after smoking either the sham or the N cigarette, which was applied together with a tablet of magnesium hydrochloride covered with a spot of nicotine or tabasco (as a p!acebo) respectively. Saliva samples prior to and 5 + 15 minutes after smoking were obtained for analysis of free cortisol by RIA. Results." Analyses of covariance with respective baseline values and duration of smoking abstinence prior to the experiment as covariates revealed tqat reaction t~mes of the simple task were shorter u~der the condition of N c~garette applied w~th the concordant information about group assignment whereas with the application of nicotine via the tablet and with the olacebo condition both instructions (being assigned to a sham or nicotine condition) yielded identical reaction times. This, however, seems different for reactions to the complex task (longer reaction times for the N cigarette - N inst'uctlon condition and the reverse for the tablet application]. Furtqermore, overall instruction effects were wsible in subjective ratings on alertness and concentration thigher scores with the instruction of receiving tqe N cigarette}, whereas bodily symptoms of dizziness and nausea showed an interaction effect between instruction and mode of application. They occurred more often under the instruction of receiving a nicotine cigarette, if it was really applied, whereas these symptoms were less with the N tablet plus N instruction but highest in the condition of knowing to receive a snare cigarette when it was actually true The satisfaction by smoking as indicated by the desire for a second cigarette was least affected by ir structlon induced expectations but even smoking related saliva cortisol concentrations could be shown to be modified by expectations about renelwng mcotine or sham cigarettes. These results reveal that expectations can be reduced which produce symptoms like nicotine itself, and if there is a discrepancy between instruction and real nicotine effects this may also affect the subjective and objective responses. Results are discussed with respect to their relevance for nicotine dependence and withdrawal.
multicenter safety study of naltrexone IP-10-2~ Aadministration to individuals with alcoholism R S Crooo, D.F Labriola, J M Wroblewski, D W Nibbelink TheDuPon, Merck Pharmaceut/ca/ CompanF, f?O Box 8072t, Wi/rmngton, DE t9880-0721, USA The efficacy of naitrexone as ad uPctlve pharmacological treatment for a,co holism has been oemonstratea m two independent chnical trials (OMa lay et al., 1992; Volp~celh et el, 1992) m both studies, patients receiving natrexone drank on fewer says and were less likely to relapse to heavy onnk,ng than those receiving placebo The patient populations in these two studies consisted of indwiduals w~th alcohol dependence and no other s gPificant psychiatric disease or other drug use Tne patients in these studies receaved naitrexone 50 mg once daily as Dart of comprehensive treatment programs for alcohol dependence This communication descnbes a multlcenter open label Usage Study that has oeen conducted at 40 alcohol treatment programs in the ~n,ted States This study was performed to COllect additional information regard,rig the safety profile of naltrexone administration to individuals dunng early' recovery from aicohoiism. Patient selection criteria were designed to erlaole enroltmer~t of a representative population of individuals enteriPg alcohol treatment programs in the United States Comorbid psychiatric disease 9 r abuse of nomopioid drugs were not reasons for exclusion from the study Opioids were the only eoncomlta qr medications that prevented an indwidual from entering the study The study design permittea collection of safety data from 570 indlwduais w t h alcoholism who received naltrexone as adjunctive medication whde participating in a wide range of alcohol treatment programs. ~he charac tenstics of the study population and the concomitant medications ~,sed during the study are representative of current treatment pract cos iq tqe United States The study population had a mean age of 3 8 9 years was 7z;% male, aqd 81% CaucaslaP Approximately 80% of the enrollee I-atlents received at least one conconHtant medication dudng the stJm, Tqe most frequently reported new-onset adverse chnical events were na.,3da headache, dizziness, and qer~,ousness (WHOART preferred terminoloqv The profiles of Adverse Climcal Events and liver function tests ooserveo dbring naltrexone administration in this study were similar to those seen during treatment of opioid dependent populations. The study results cor~ firm the value of a Usage Study as part of the development of adlur'.:t L~ ~'-edications for the treatmen: of c:hemlca dependencies
References [1 t Sutton. S R (I 991 ) Great expectations: Some suggestions for app/ying the balanced placebo design to nicotine and smoking British Journal of Addiction. 86. 659-662 [:1 Kirschbaum, C, Scherer, G 8 Stral&burger, C J (in press) Pituitary and adrenal hor mona responses to pharmacological, physical, and psychological stimulation in habitual smokers end nonsmokers Clinical Investigator *1 We are grateful to CDR for providing the tests and evaluations of the number detection and odd and even number tasks
400 References
References
Amit Z, Smith BR (i 992) Neurot'ansmnter systems ,egulat ng alcohol inta
C' Malley. S S , et al Naltrexone and Coping Skills Therapy for Alcohol Dependence A Controlled Study Arch Gen Psychiatry Vol 49, Nov 1992, p 881 887 Volpicelb J R , et al Naltrexone in the Treatment of Alcohol Dependence Arch Gen. Psych~atrv Vol 49, Nov 1992, p 876 880.
I
Experimentally induced expectations interfering IP" 10-24 I with nicotine effects induced by oral absorption and inhalation of smoke in nicotine dependent subjects
]
P-10-22 j Tianeptine in the treatment of alcohol dependence syndrome
P Netter, J. Hennig, T. Bbckling, R Olbrich. Department of Psycho/ogy,
N N Ivanets. State Research Center on Add/ctsons, 121921 Moscow
i./n/versi~ of GIessen, FRG
Russ/a
/~troduct/on In spite of the well established fact that reinforcing properties
AffectJve d~sorders are known t:) ~; ay an m]portant "die in trle clinical p~c ture of alcoholism Pathological c'av ng for alcohol is often unreal,zeal and manifested by depresswe s y m p t o m s Biological bases for neurochem~cal mechanisms of depressive states and alcoholism have much in common The goal of this work was to study, by the chnlco b~ochemicai m e t h o d the efficacy of a PeW antidepressant tlaneptme, in treating alcoholsm w~th chnical symptoms of depression and pathological craving for alcohol Tianeptine tablets (12.5 mg) were given to 35 alcohohc patients 3 braes a day over a period of 60 days The results showed high efficacy of tlaneptme depresswe symptorTs :~ sappeared, emotional state was normahzed and pathological crav nc tor alcoholdeactualized The estimates of the neurotransmittercontent rq the b~ooo plasma showed that the improvement of the clinical condition was accomoanied by the normalization of the serotonm and dooamlne concert Vat,on under the influence o; tlaneptlne The data obtained permit us :o recommend tlaneotlne as a drug that stabilizes remission and prevents early alcohohs~ relapse
of smoking do not only concern the content of nicotine but many additional nonpharmacologicat factors, it has not been tried to disentangle different reinforcing components of cigarettes in a systematic manner. In particular, effects of expectancy, widely investigated in alcohol and placebo research have not been analyzed for their interactions with the pharmacological action of mcotine [1]. The smoker's expectations concern the knowledge of a) receiving nicotine and b) receiving it via inhalation of smoke. So we corducted an experiment in which instruction about receiving a nicotine or sham cigarette and the mode of application of nicotine by smoke inhalation or by buccal absorption from a tablet were systematically combined in order to assess the influence of expectations on changes in performance, emotional states, satisfaction from smoking, and salivary cortisol values (wh,ch have been shown to increase after smoking [211. Methods 96 female smokers (_> 10 cigarettes per day) were assigned to 6 groups of a 2 x 3 design comparing three modes of applica t~on of n~cotme (N)(N cigarette + placebo (P) tablet/sham cigarette + N tablet/sham cigarette + P tabletl combined with two modes of instruction (N cigarette/sham cigarette) So each subject believed to obtain nicotine, if given, by smoking. The tablet was merely introduced as a means for keepng the pH level constant. Subjects were asked to refrain from smoking for at least I/2 hour before starting the test. Two vigilance tasks from Cognitive Drug Research*), cdticai flicker fusion and subjective ratings on emotional states and the desire for smoking were obtained prior to and after smoking either the sham or the N cigarette, which was applied together with a tablet of magnesium hydrochloride covered with a spot of nicotine or tabasco (as a p!acebo) respectively. Saliva samples prior to and 5 + 15 minutes after smoking were obtained for analysis of free cortisol by RIA. Results." Analyses of covariance with respective baseline values and duration of smoking abstinence prior to the experiment as covariates revealed tqat reaction t~mes of the simple task were shorter u~der the condition of N c~garette applied w~th the concordant information about group assignment whereas with the application of nicotine via the tablet and with the olacebo condition both instructions (being assigned to a sham or nicotine condition) yielded identical reaction times. This, however, seems different for reactions to the complex task (longer reaction times for the N cigarette - N inst'uctlon condition and the reverse for the tablet application]. Furtqermore, overall instruction effects were wsible in subjective ratings on alertness and concentration thigher scores with the instruction of receiving tqe N cigarette}, whereas bodily symptoms of dizziness and nausea showed an interaction effect between instruction and mode of application. They occurred more often under the instruction of receiving a nicotine cigarette, if it was really applied, whereas these symptoms were less with the N tablet plus N instruction but highest in the condition of knowing to receive a snare cigarette when it was actually true The satisfaction by smoking as indicated by the desire for a second cigarette was least affected by ir structlon induced expectations but even smoking related saliva cortisol concentrations could be shown to be modified by expectations about renelwng mcotine or sham cigarettes. These results reveal that expectations can be reduced which produce symptoms like nicotine itself, and if there is a discrepancy between instruction and real nicotine effects this may also affect the subjective and objective responses. Results are discussed with respect to their relevance for nicotine dependence and withdrawal.
multicenter safety study of naltrexone IP-10-2~ Aadministration to individuals with alcoholism R S Crooo, D.F Labriola, J M Wroblewski, D W Nibbelink TheDuPon, Merck Pharmaceut/ca/ CompanF, f?O Box 8072t, Wi/rmngton, DE t9880-0721, USA The efficacy of naitrexone as ad uPctlve pharmacological treatment for a,co holism has been oemonstratea m two independent chnical trials (OMa lay et al., 1992; Volp~celh et el, 1992) m both studies, patients receiving natrexone drank on fewer says and were less likely to relapse to heavy onnk,ng than those receiving placebo The patient populations in these two studies consisted of indwiduals w~th alcohol dependence and no other s gPificant psychiatric disease or other drug use Tne patients in these studies receaved naitrexone 50 mg once daily as Dart of comprehensive treatment programs for alcohol dependence This communication descnbes a multlcenter open label Usage Study that has oeen conducted at 40 alcohol treatment programs in the ~n,ted States This study was performed to COllect additional information regard,rig the safety profile of naltrexone administration to individuals dunng early' recovery from aicohoiism. Patient selection criteria were designed to erlaole enroltmer~t of a representative population of individuals enteriPg alcohol treatment programs in the United States Comorbid psychiatric disease 9 r abuse of nomopioid drugs were not reasons for exclusion from the study Opioids were the only eoncomlta qr medications that prevented an indwidual from entering the study The study design permittea collection of safety data from 570 indlwduais w t h alcoholism who received naltrexone as adjunctive medication whde participating in a wide range of alcohol treatment programs. ~he charac tenstics of the study population and the concomitant medications ~,sed during the study are representative of current treatment pract cos iq tqe United States The study population had a mean age of 3 8 9 years was 7z;% male, aqd 81% CaucaslaP Approximately 80% of the enrollee I-atlents received at least one conconHtant medication dudng the stJm, Tqe most frequently reported new-onset adverse chnical events were na.,3da headache, dizziness, and qer~,ousness (WHOART preferred terminoloqv The profiles of Adverse Climcal Events and liver function tests ooserveo dbring naltrexone administration in this study were similar to those seen during treatment of opioid dependent populations. The study results cor~ firm the value of a Usage Study as part of the development of adlur'.:t L~ ~'-edications for the treatmen: of c:hemlca dependencies
References [1 t Sutton. S R (I 991 ) Great expectations: Some suggestions for app/ying the balanced placebo design to nicotine and smoking British Journal of Addiction. 86. 659-662 [:1 Kirschbaum, C, Scherer, G 8 Stral&burger, C J (in press) Pituitary and adrenal hor mona responses to pharmacological, physical, and psychological stimulation in habitual smokers end nonsmokers Clinical Investigator *1 We are grateful to CDR for providing the tests and evaluations of the number detection and odd and even number tasks