- Email: [email protected]
L on actual driving and memory
$432
P.6. Other topics
given a single oral dose of zaleplon 10 mg, triazolam 0.25 mg or placebo with and without a single dose of ethanol (0.75 g/kg) on 2 consecutive days. Administration of ethanol was staggered to ensure that peak concentrations of ethanol and each hypnotic drug occurred at the same time (ethanol given 60 min after triazolam or 30 min after zaleplon). Evaluation of psychomotor performance by objective tests (simple [SRT] and choice reaction time [CRT], DSST, symbol copying [SC], divided attention [DAT], body sway and auditory vigilance [AV]) and self-rating of sedation (Stanford Sleepiness Scale) were performed before drug intake and 2, 3.5, and 6 hours after triazolam dosing or 1.5, 3, and 5.5 hours after zaleplon dosing or 1, 2.5, and 5 hours after ethanol intake. The scores from the 2 consecutive test days of each period were averaged and compared by repeated measures analysis of variance in a 2 x 2 factorial model. Results: Ethanol produced significant impairment in DSST 1 hour after administration, in CRT 2.5 hours after administration, in SRT, body sway and AV 1 h to 2.5 hours after administration, in DAT 1 to 5 hours after administration and subjective sedation up to 6.5 hours after administration. Zaleplon produced significant impairment in DAT, body sway and subjective sedation 1.5 hours after administration, in DSST and symbol copying (SC), 1.5 to 3 hours after administration and in CRT 3 post-dose. Triazolam 0.25 mg produced significant impairment in body sway 2 hours after administration, in CRT and AV 2 to 3.5 hours after administration and in SRT, DSST, SC, DAT and subjective sedation 2 to 6 hours after administration. These impairments were of greater magnitude and longer duration than those produced by zaleplon. Zaleplon potentiated the deleterious effects of ethanol on DAT 3 hours after administration. Triazolam potentiated the deleterious effects of ethanol on body sway 6 hours after administration. Most of the deleterious effects were additive, with triazolam producing the greatest impairment. Conclusion: Triazolam with and without coadministration of ethanol produced the greatest impairment of psychomotor performance, vigilance, and complex functioning. Ethanol coadministration produced mainly additive effects with both hypnotics. Ethanol did not potentiate the moderate to strong impairment produced References by triazolam at the early observation time, but potentiation was [1] Mookhoek EJ, Huijgen J. Medicatiegebruik voor maagklachten bij pati~nten opgenomen op afdelingen voor langdurig verblijf in een observed on body sway at a later time point when the effects algemeen psychiatrisch ziekenhuis. Tijdschrift voor psychiatrie 1999; of triazolam was reduced. Zaleplon and ethanol potentiated each 41(6); 359-366. other's effects on DAT only, and the impairment produced by this [2] PenstonJG, PounderRE (1996), A survey of dyspepsiain Great Britain. combination was typically less than that observed after adminisAliment-Pharmacol-Ther.10; 83-89. [3] Talley NJ, Zinsmeister AR, Schleck CD, Melton LJ 3rd. Smoking, tration of triazolam alone. alcohol and analgesics in dyspepsia and among dyspepsia subgroups; lack of an association in a community.Gut 1994 May; 35(5), 619-624.
Method: A representative sample of patients hospitalised in the long-stay wards of a general psychiatric hospital were interviewed by using a structured questionnaire. The medical files of the patients were studied for data on psychiatric diagnoses and prescribed medication. Dyspepsia was defined as the presence of one or more of the following symptoms during the previous month: discomfort in the stomach or upper abdomen, pain in the stomach or upper abdomen, regurgitation, nausea, vomiting, feeling of fullness in stomach, loss of appetite. In order to identify possible determinants of dyspepsia we compared patients with ample expression of symptoms of the listing presented above (mild, severe or very severe complaints) with patients with no or little expression of symptoms (no or minor complaints). Results: The sample consisted of 110 patients. A total of 23 patients refused to participate. 8 patients were not able to participate. In total 79 (72%) patients completed the interview. Four out of five patients (N=63) reported one or more symptoms of dyspepsia: 54 (68%) symptoms of reflux-like dyspepsia, 23 (29%) symptoms of ulcer-like dyspepsia and 8 (10%) patients reported symptoms of non-specific dyspepsia. Significant positive associations were found for clozapine (OR=3,4), Laxantia (OR=4,4) and heavy smoking (OR=3,8). Significant negative associations were found for high potency antipsychotics (OR=0,14) and EPS drugs (OR=0,3). Conclusion: The prevalence of dyspepsia among patients hospitalised in long-stay wards of a general psychiatric hospital was found to be 80%. In general populations the prevalence ranges from 22 to 40%. 2,3 The higher prevalence of dyspepsia in our patients is mainly associated with a high prevalence of reflux-like dyspepsia. This could be explained by the many risk factors with regard to the gastro-oesophageal reflux disease these patients are confronted with. A clear relation was found between the presence of dyspeptic complaints and the use of laxantia, clozapine and heavy smoking. Within the survey population patients using high potency antipsychotics and Parkinson medication reported relative less dyspeptic complaints.
•
• Study of the pharmacodynamic interaction between zaleplon and triazolam and ethanol on psychomotor performance in healthy subjects
A. Patat 1, C. Leistet 2, K. Goldberg 2, R. Mangano2, T. Roth 3. 1Wyeth Research, Paris, France; 2 Wyeth Research, Collegeville, PA, U.S.A.; 3Sleep Disorders and Research Center, Detroit, MI, U.S.A. Objective: To assess the potential pharmacodynamic interaction between equipotent doses of zaleplon (10 mg) or triazolam (0.25 mg) and ethanol. Methods: Eighteen healthy young male and female subjects aged 22 to 39 years participated in this randomized, double-blind, 6-period crossover, placebo-controlled study. Each subject was
Effects of ethanol at a blood alcohol concentration of 0.4 glL on actual driving and memory
V. Parks 1, C. Leister2, A. Patat 1, S. Troy2, A. Vermeeren3, E.R. Volkerts 4, J.C. Verster4. ! Wyeth Research, Department of Clinical Pharmacology, Paris, France; e Wyeth Research, Department of Clinical Pharmacology, Collegeville, PA, U.S.A.; 3Department of Psychology, Maastricht University, Maastricht, The Netherlands; 4 Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
Objective: The objective of this study was to assess the effects of a low dose of ethanol sufficient to raise blood alcohol concentrations (BAC) to approximately 0.5 g/L on actual driving and memory and look for gender differences.
P.6. Other topics Methods: Sixty healthy young female (30) and male (30) subjects (21~44 years) participated in two randomized, singleblind, 2-period crossover, placebo-controlled studies. Ethanol was administered in the afternoon to obtain and maintain a BAC of 0.5 g/L at the time of the pharmacodynamic assessment. This required that subjects drink an initial alcohol dose (pure ethanol 99.8% mixed with orange juice to a volume of 500 mL) of 0.43 and 0.36 g/kg, for men and women respectively. A second adjustable dose (pure ethanol 99.8% with orange juice to a volume of 250 mL) was administered before the driving test. Evaluation consisted of a divided attention task (DAT) and a memory test [word learning task (WLT) with measures of immediate (IFR) and delayed free recall (DFR) and recognition] and a 1-hour actual driving test. These results were obtained by pooling 2 studies [1,2]. Results: Mean BAC declined from 0.42 to 0.31 g/L during the DAT and WLT and from 0.41 to 0.23 g/L during the actual driving. Ethanol produced a significant impairment of actual driving (+1.4 cm increase in Standard Deviation of Lateral Position), of DAT (+69.8 msec increase in reaction time to peripheral stimuli) and in IFR (-0.6) and DFR (-1.2) of words. No changes occurred for word recognition, but recognition reaction time was significantly delayed (+28.5 msec). There was no significant gender effect on actual driving, DAT and memory performance. Conclusion: A dose of ethanol close to the legal limit of 0.5 g/L has significant deleterious effects on memory, particularly DFR, significantly prolonged reaction time and significantly impaired driving performance on an actual driving test.
References [1] A. Vermeeren et al. Differential residual effects of zaleplon and zopiclone on actual car driving: a comparison with a low dose of alcohol. Sleep 2002; 25 (2): 224-231. [2] E.R. Volkerts et al. The impact on car-driving performance of zaleplon or zolpidem administration during the night. Eur. Neuropsychopharmacol 2000; 10 (suppl 3): $395.
•
Impairment of autobiographical memory following bilateral maintenance electroconvulsive therapy
I. Amado-Boccara 1, P. Piolino 2, B. Millet 1, EJ. Bayle 1, M.O. Krebs 1, E Eustache 2. 1Seruice hospitalo-uniuersitaire de
Santb Mentale et Th~rapeutique - Hrpital Sainte Anne, Paris, France; 2University RenO Descartes, Paris V and EMI-INSERMUniuersity of Caen, France Electroconvulsive therapy (ECT) is of great efficacy to produce a rapid recovery from severe depressive pathology. In specific cases, ECT administered regularly in a maintenance follow-up has been used with substantial benefit to prevent recurrences in unipolar or bipolar depressive disorders. However, this form of treatment raises cognitive side effects, mainly on remote memory but investigations of the influence of ECT on autobiographical memory remain scarce and controversial. Objective: The aim of this study was to assess autobiographical memory in patients remitted from major depression and treated with monthly bilateral maintenance ECT (M-ECT). Methods: A semi structured interview (the Tempau Task) was assessed before the next M-ECT, three weeks after the last ECT for two patients and 6 or 12 months after the end of M-ECT treatment for two other patients. The Tempau Task consists in a cuedrecall procedure especially designed to explore the episodicity and the autonoetic consciousness of events recalled from each
$433
of five lifetime periods. A general cognitive evaluation was also performed with the Mattis Dementia Rating scale, and verbal and visual measures of learning and memory. Results: For the two patients assessed during M-ECT treatment, remote episodic autobiographical memories and autonoetic consciousness were severely affected across all time periods studied. Another patient tested six months after M-ECT exhibited a deficit of remote autobiographical memories which still persisted one year later, but restricted to one period of life corresponding to middle life. Performances of the fourth patient were comparable to the norms of his age 12 months after the end of M-ECT. All the patients showed a visuo-spatial memory deficit without cognitive decline. Conclusion: These findings corroborate the mnesic complaints of patients during and after M-ECT and highlight that the cumulative effects of M-ECT produce a global episodic retrograde amnesia during the treatment, followed by a consistent improvement at 12-month follow-up suggesting a transient pathology of memory.
•
Hypnotizability, pain threshold and dissociative experiences in patients with borderline personality disorder and self-mutilating behavior
C. Basoglu, M. Cetin, S. Ebrinc, B. Maden, H. Balibey, A.E Baykiz. Department of Psychiatry, GATA Haydarpasa
Teaching Hospital, Istanbul, Turkey Objective: There is a close relationship between hypnotizability and dissociative experiences. This association has been well documented. Recently, it has been demonstrated that both hypnotizability and dissociation were associated with pain threshold. Hypnotizability varies according to psychiatric diagnosis. There may be patients who are more or less hypnotizable. Self-mutilation (SM) occurs in 70-80% of patients who meet DSM-IV criteria for borderline personality disorder (BPD). Approximately 60% of these patients report that they do not feel pain during acts of SM such as cutting or burning their skin. This study aimed to investigate the association between pain threshold, hypnotizability and dissociative experiences in patients with BPD and self-mutilating behavior. Method: One hundred-three male consecutive outpatients with BPD and fifty-two healthy controls included in the study. All subjects were tried to screen with the The Dissociative Experiences Scale and Structured Clinical Interview for DSM-III-R Personality Disorder. Pain threshold were determined using a manual algometer. Hypnotizability of subjects was assessed by the eye roll sign of the Hypnotic Induction Profile. Results: BPD with reported self-mutilative behavior had significantly higher DES score (mean=35.70, SD=3.60) and pain threshold (mean=3.74, SD=1.36) compared with controls (mean=10.55, SD=9.49, t=l 1.93, p=.000) (mean=3.10, SD=1.09, t=2.98, p=.003) respectively. The subjects were scored and separated into four groups according to eye roll sign as Grade 1, 2, 3, 4. BPD (72=19.48, p=.000) patients significantly higher pain threshold than the controls in all Grades (X2=19.48, p=.000). Conclusions: Hypnotizability and dissociative experiences were associated with pain threshold. Highly hypnotizable subjects had higher pain thresholds than the low hypnotizable and higher dissociative experiences than the controls.
P.6. Other topics
given a single oral dose of zaleplon 10 mg, triazolam 0.25 mg or placebo with and without a single dose of ethanol (0.75 g/kg) on 2 consecutive days. Administration of ethanol was staggered to ensure that peak concentrations of ethanol and each hypnotic drug occurred at the same time (ethanol given 60 min after triazolam or 30 min after zaleplon). Evaluation of psychomotor performance by objective tests (simple [SRT] and choice reaction time [CRT], DSST, symbol copying [SC], divided attention [DAT], body sway and auditory vigilance [AV]) and self-rating of sedation (Stanford Sleepiness Scale) were performed before drug intake and 2, 3.5, and 6 hours after triazolam dosing or 1.5, 3, and 5.5 hours after zaleplon dosing or 1, 2.5, and 5 hours after ethanol intake. The scores from the 2 consecutive test days of each period were averaged and compared by repeated measures analysis of variance in a 2 x 2 factorial model. Results: Ethanol produced significant impairment in DSST 1 hour after administration, in CRT 2.5 hours after administration, in SRT, body sway and AV 1 h to 2.5 hours after administration, in DAT 1 to 5 hours after administration and subjective sedation up to 6.5 hours after administration. Zaleplon produced significant impairment in DAT, body sway and subjective sedation 1.5 hours after administration, in DSST and symbol copying (SC), 1.5 to 3 hours after administration and in CRT 3 post-dose. Triazolam 0.25 mg produced significant impairment in body sway 2 hours after administration, in CRT and AV 2 to 3.5 hours after administration and in SRT, DSST, SC, DAT and subjective sedation 2 to 6 hours after administration. These impairments were of greater magnitude and longer duration than those produced by zaleplon. Zaleplon potentiated the deleterious effects of ethanol on DAT 3 hours after administration. Triazolam potentiated the deleterious effects of ethanol on body sway 6 hours after administration. Most of the deleterious effects were additive, with triazolam producing the greatest impairment. Conclusion: Triazolam with and without coadministration of ethanol produced the greatest impairment of psychomotor performance, vigilance, and complex functioning. Ethanol coadministration produced mainly additive effects with both hypnotics. Ethanol did not potentiate the moderate to strong impairment produced References by triazolam at the early observation time, but potentiation was [1] Mookhoek EJ, Huijgen J. Medicatiegebruik voor maagklachten bij pati~nten opgenomen op afdelingen voor langdurig verblijf in een observed on body sway at a later time point when the effects algemeen psychiatrisch ziekenhuis. Tijdschrift voor psychiatrie 1999; of triazolam was reduced. Zaleplon and ethanol potentiated each 41(6); 359-366. other's effects on DAT only, and the impairment produced by this [2] PenstonJG, PounderRE (1996), A survey of dyspepsiain Great Britain. combination was typically less than that observed after adminisAliment-Pharmacol-Ther.10; 83-89. [3] Talley NJ, Zinsmeister AR, Schleck CD, Melton LJ 3rd. Smoking, tration of triazolam alone. alcohol and analgesics in dyspepsia and among dyspepsia subgroups; lack of an association in a community.Gut 1994 May; 35(5), 619-624.
Method: A representative sample of patients hospitalised in the long-stay wards of a general psychiatric hospital were interviewed by using a structured questionnaire. The medical files of the patients were studied for data on psychiatric diagnoses and prescribed medication. Dyspepsia was defined as the presence of one or more of the following symptoms during the previous month: discomfort in the stomach or upper abdomen, pain in the stomach or upper abdomen, regurgitation, nausea, vomiting, feeling of fullness in stomach, loss of appetite. In order to identify possible determinants of dyspepsia we compared patients with ample expression of symptoms of the listing presented above (mild, severe or very severe complaints) with patients with no or little expression of symptoms (no or minor complaints). Results: The sample consisted of 110 patients. A total of 23 patients refused to participate. 8 patients were not able to participate. In total 79 (72%) patients completed the interview. Four out of five patients (N=63) reported one or more symptoms of dyspepsia: 54 (68%) symptoms of reflux-like dyspepsia, 23 (29%) symptoms of ulcer-like dyspepsia and 8 (10%) patients reported symptoms of non-specific dyspepsia. Significant positive associations were found for clozapine (OR=3,4), Laxantia (OR=4,4) and heavy smoking (OR=3,8). Significant negative associations were found for high potency antipsychotics (OR=0,14) and EPS drugs (OR=0,3). Conclusion: The prevalence of dyspepsia among patients hospitalised in long-stay wards of a general psychiatric hospital was found to be 80%. In general populations the prevalence ranges from 22 to 40%. 2,3 The higher prevalence of dyspepsia in our patients is mainly associated with a high prevalence of reflux-like dyspepsia. This could be explained by the many risk factors with regard to the gastro-oesophageal reflux disease these patients are confronted with. A clear relation was found between the presence of dyspeptic complaints and the use of laxantia, clozapine and heavy smoking. Within the survey population patients using high potency antipsychotics and Parkinson medication reported relative less dyspeptic complaints.
•
• Study of the pharmacodynamic interaction between zaleplon and triazolam and ethanol on psychomotor performance in healthy subjects
A. Patat 1, C. Leistet 2, K. Goldberg 2, R. Mangano2, T. Roth 3. 1Wyeth Research, Paris, France; 2 Wyeth Research, Collegeville, PA, U.S.A.; 3Sleep Disorders and Research Center, Detroit, MI, U.S.A. Objective: To assess the potential pharmacodynamic interaction between equipotent doses of zaleplon (10 mg) or triazolam (0.25 mg) and ethanol. Methods: Eighteen healthy young male and female subjects aged 22 to 39 years participated in this randomized, double-blind, 6-period crossover, placebo-controlled study. Each subject was
Effects of ethanol at a blood alcohol concentration of 0.4 glL on actual driving and memory
V. Parks 1, C. Leister2, A. Patat 1, S. Troy2, A. Vermeeren3, E.R. Volkerts 4, J.C. Verster4. ! Wyeth Research, Department of Clinical Pharmacology, Paris, France; e Wyeth Research, Department of Clinical Pharmacology, Collegeville, PA, U.S.A.; 3Department of Psychology, Maastricht University, Maastricht, The Netherlands; 4 Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands
Objective: The objective of this study was to assess the effects of a low dose of ethanol sufficient to raise blood alcohol concentrations (BAC) to approximately 0.5 g/L on actual driving and memory and look for gender differences.
P.6. Other topics Methods: Sixty healthy young female (30) and male (30) subjects (21~44 years) participated in two randomized, singleblind, 2-period crossover, placebo-controlled studies. Ethanol was administered in the afternoon to obtain and maintain a BAC of 0.5 g/L at the time of the pharmacodynamic assessment. This required that subjects drink an initial alcohol dose (pure ethanol 99.8% mixed with orange juice to a volume of 500 mL) of 0.43 and 0.36 g/kg, for men and women respectively. A second adjustable dose (pure ethanol 99.8% with orange juice to a volume of 250 mL) was administered before the driving test. Evaluation consisted of a divided attention task (DAT) and a memory test [word learning task (WLT) with measures of immediate (IFR) and delayed free recall (DFR) and recognition] and a 1-hour actual driving test. These results were obtained by pooling 2 studies [1,2]. Results: Mean BAC declined from 0.42 to 0.31 g/L during the DAT and WLT and from 0.41 to 0.23 g/L during the actual driving. Ethanol produced a significant impairment of actual driving (+1.4 cm increase in Standard Deviation of Lateral Position), of DAT (+69.8 msec increase in reaction time to peripheral stimuli) and in IFR (-0.6) and DFR (-1.2) of words. No changes occurred for word recognition, but recognition reaction time was significantly delayed (+28.5 msec). There was no significant gender effect on actual driving, DAT and memory performance. Conclusion: A dose of ethanol close to the legal limit of 0.5 g/L has significant deleterious effects on memory, particularly DFR, significantly prolonged reaction time and significantly impaired driving performance on an actual driving test.
References [1] A. Vermeeren et al. Differential residual effects of zaleplon and zopiclone on actual car driving: a comparison with a low dose of alcohol. Sleep 2002; 25 (2): 224-231. [2] E.R. Volkerts et al. The impact on car-driving performance of zaleplon or zolpidem administration during the night. Eur. Neuropsychopharmacol 2000; 10 (suppl 3): $395.
•
Impairment of autobiographical memory following bilateral maintenance electroconvulsive therapy
I. Amado-Boccara 1, P. Piolino 2, B. Millet 1, EJ. Bayle 1, M.O. Krebs 1, E Eustache 2. 1Seruice hospitalo-uniuersitaire de
Santb Mentale et Th~rapeutique - Hrpital Sainte Anne, Paris, France; 2University RenO Descartes, Paris V and EMI-INSERMUniuersity of Caen, France Electroconvulsive therapy (ECT) is of great efficacy to produce a rapid recovery from severe depressive pathology. In specific cases, ECT administered regularly in a maintenance follow-up has been used with substantial benefit to prevent recurrences in unipolar or bipolar depressive disorders. However, this form of treatment raises cognitive side effects, mainly on remote memory but investigations of the influence of ECT on autobiographical memory remain scarce and controversial. Objective: The aim of this study was to assess autobiographical memory in patients remitted from major depression and treated with monthly bilateral maintenance ECT (M-ECT). Methods: A semi structured interview (the Tempau Task) was assessed before the next M-ECT, three weeks after the last ECT for two patients and 6 or 12 months after the end of M-ECT treatment for two other patients. The Tempau Task consists in a cuedrecall procedure especially designed to explore the episodicity and the autonoetic consciousness of events recalled from each
$433
of five lifetime periods. A general cognitive evaluation was also performed with the Mattis Dementia Rating scale, and verbal and visual measures of learning and memory. Results: For the two patients assessed during M-ECT treatment, remote episodic autobiographical memories and autonoetic consciousness were severely affected across all time periods studied. Another patient tested six months after M-ECT exhibited a deficit of remote autobiographical memories which still persisted one year later, but restricted to one period of life corresponding to middle life. Performances of the fourth patient were comparable to the norms of his age 12 months after the end of M-ECT. All the patients showed a visuo-spatial memory deficit without cognitive decline. Conclusion: These findings corroborate the mnesic complaints of patients during and after M-ECT and highlight that the cumulative effects of M-ECT produce a global episodic retrograde amnesia during the treatment, followed by a consistent improvement at 12-month follow-up suggesting a transient pathology of memory.
•
Hypnotizability, pain threshold and dissociative experiences in patients with borderline personality disorder and self-mutilating behavior
C. Basoglu, M. Cetin, S. Ebrinc, B. Maden, H. Balibey, A.E Baykiz. Department of Psychiatry, GATA Haydarpasa
Teaching Hospital, Istanbul, Turkey Objective: There is a close relationship between hypnotizability and dissociative experiences. This association has been well documented. Recently, it has been demonstrated that both hypnotizability and dissociation were associated with pain threshold. Hypnotizability varies according to psychiatric diagnosis. There may be patients who are more or less hypnotizable. Self-mutilation (SM) occurs in 70-80% of patients who meet DSM-IV criteria for borderline personality disorder (BPD). Approximately 60% of these patients report that they do not feel pain during acts of SM such as cutting or burning their skin. This study aimed to investigate the association between pain threshold, hypnotizability and dissociative experiences in patients with BPD and self-mutilating behavior. Method: One hundred-three male consecutive outpatients with BPD and fifty-two healthy controls included in the study. All subjects were tried to screen with the The Dissociative Experiences Scale and Structured Clinical Interview for DSM-III-R Personality Disorder. Pain threshold were determined using a manual algometer. Hypnotizability of subjects was assessed by the eye roll sign of the Hypnotic Induction Profile. Results: BPD with reported self-mutilative behavior had significantly higher DES score (mean=35.70, SD=3.60) and pain threshold (mean=3.74, SD=1.36) compared with controls (mean=10.55, SD=9.49, t=l 1.93, p=.000) (mean=3.10, SD=1.09, t=2.98, p=.003) respectively. The subjects were scored and separated into four groups according to eye roll sign as Grade 1, 2, 3, 4. BPD (72=19.48, p=.000) patients significantly higher pain threshold than the controls in all Grades (X2=19.48, p=.000). Conclusions: Hypnotizability and dissociative experiences were associated with pain threshold. Highly hypnotizable subjects had higher pain thresholds than the low hypnotizable and higher dissociative experiences than the controls.