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P.3.18 Rivastigmine therapy for memory deficits in schizophrenia patients receiving electroconvulsive treatment
Clinical Neuropsychopharmacology Major Depression. It will be important to assess and compare the temporal efficacy and immunotropic effects of a spectrum of GABA-ergic and antianxiety drugs in patients with Major Depression. This finding may help identify the GABA-ergic mechanisms responsible for antidepressant activity. The study subjects were 35 male (mean age 33.1+3.2 years) and 15 female (35.1+1.6 years) patients who met DSM-III-R criteria for Major Depression. Nootrop (a cyclic derivate of GABA) was given as daily intramuscular injection of 1g/3g–5ml/15ml for 4–5 weeks (100–120 g treatment total dose) before antidepressant treatment in a placebocontrolled, randomized desigh (single doses randomized; repeated dose always last treatment). For single doses of Nootrop, there was a statistically significant dose related immunosuppression on leukocyte-pyruvate dehydrogenase activity, versus time curve 0–20 hours after Nootrop administration (% immunosuppression from placebo; 8, 16 and 20 for 3 g, 6 g and 9 g respectively). The initial Nootrop therapeutic dose (50–80 g) dependently elevated range of LPDG activity (more than 5 mmol/l/hour, 25% immunosuppression, 0.01
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characteristic cognitive side-effects most notably memory loss, which remains a common unpleasant and undesirable concern for patients and families. Unfortunately no pharmacological agent has been confirmed to lessen ECTinduced memory deficits. Rivastigmine is a selective CNS inhibitor of acetylcholinesterase used successfully in the management of Alzheimer’s Disease with reported benefits on cognition [1]. Acetylcholinesterase metabolizes the neurotransmitter acetylcholine which is intimately involved in human memory and cognition processes. By inhibiting acetylcholinesterase more acetylcholine becomes available to the patient for memory and cognitive functioning. Rivastigmine is characterized by selective binding and inactivation of acetylcholine receptor subtypes in specific regions of the brain. Its receptor selectivity enhances its therapeutic efficacy while minimizing peripheral adverse effects. In order to determine the advantageous effects, if any, of acetylcholinesterase agents in a subpopulation of schizophrenia patients with ECT induced memory deficits, this study examined the effects of rivastigmine on memory performance in patients treated with ECT. Method: Thirty patients with chronic treatment resistant schizophrenia disorder, diagnosed according to the criteria of the DSM-IV, were administered either rivastigmine or placebo in a prospective, randomized, double blind controlled trial. Doses were increased following the first week from 1.5 mg/day to 4.5 mg/day. Duration of drug administration was for at least 4 consecutive ECT sessions and for a maximum period of 4 weeks. Subjects were assessed with the cognitive subscale of the Alzheimer’s Disease assessment (ADAS-COG), Mini Mental State Examination, Positive and Negative Syndrome, Clinical global Impression and the Simpson Angus Rating Scales. Results: Pre-ECT measures showed no baseline differences between the subgroups. Over the course of the ECT trials, ADAS-COG scores of subjects receiving placebo increased indicating reduced cognitive performance, while subjects receiving rivastigmine improved their ADASCOG scores, thus indicating cognitive improvement (t=2.30, df=22, p=0.031). Conclusions: These findings, while preliminary, suggest the involvement of the acetylcholinergic system in the mediation of cognitive deficits following ECT-induced memory impairment. In addition, they indicate the possible beneficial effects of rivastigmine in lessening some of these treatment induced side effects. We hypothesize that cognitive impairment post ECT may be ameliorated to some extent by rivastigmine due to its enhancement of cholinergic activity, thus reversing the cognitive side effects. Further larger double blind studies of similar nature are mandated in order to further clarify the results of this study.
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Clinical Neuropsychopharmacology
References [1] Rosler M, Anand R, Cicin-Sain A, Gauthier S, Agid Y, Dal-Bianco P, Stahelin HB, Hartman R, Gharabawi M. Efficacy and safety of Rivastigmine in patients with Alzheimer’s disease: international randomized controlled trial. BMJ 1999; 318: 633–8. P.3.19 A naturalistic study on quetiapine vs. other mood stabilizers in the treatment of bipolar disorder I and II G. Tacchini, S. Charitos, S. Fumagalli, O. Fusi, A.C. Altamura. CRT – Department of Psychiatry, University of Milano – Ospedale Sacco, Via G.B. Grassi, 74, 20157 Milano, Italy The literature on the use of quetiapine in the treatment of bipolar disorder I and II is quite limited and recent, and there are no naturalistic studies which compare the use of quetiapine vs. other mood stabilizers as lithium or valproate. The aim of the present study is to evaluate the efficacy and tolerability of quetiapine during an on-going follow-up period which presently reaches a maximum of 24 months. The present study is therefore conceived as a naturalistic, open label, and observational study, in which patients are recruited as soon as they are diagnosed as affected by a bipolar disorder, either they are still in acute phase or remitted; treatment is decided entirely by the clinician according to his/her judgment, and is only recorded by the research team. Patients stay in the study until next clinical relapse. 100 BD type I or II patients, according to DSM IV criterion, were recruited; to all of them the clinicians prescribed, at their own clinical judgment, quetiapine at a dosage between 400–800 mg (mean dose 593 mg±200 mg) or, alternatively, lithium (mean plasma level 0.76±0.15), valproate (mean dose 837 mg±300 mg) or quetiapine plus another stabilizer. Clinical assessments were carried out using the 21-item HAM-D, YMRS, BPRS, CGI and SAS at baseline and every 4 months during the follow-up which presently goes up to 24 months, with a mean of 14 months. An ECG and complete laboratory test assays, including complete blood count, hepatic function and thyroid function (TSH, fT3 and fT4) were performed at the baseline and at the end of the observation period. Endpoints were considered any relapses either depressive or manic. Results are analysed in terms of clinical improvements at the above mentioned scales, compliance, incidence and severity of side-effects, and variations of the blood parameters. The four treatment groups (i.e. quetiapine, lithium, valproate, and quetiapine plus another stabilizer)
have been compared by means of ANOVA for repeated measures and survival analysis. References [1] Altamura AC, Salvadori D, Madaro D, Santini A, Mundo E. Efficacy and tolerability of quetiapine in the treatment of bipolar disorder: preliminary evidence from a 12-month open-label study. J Affect Disord. 2003 Sep;76(1–3):267–71. [2] Kasper S, Stamenkovic M, Letmaier M, Schreinzer D. Atypical antipsychotics in mood disorders. Int Clin Psychopharmacol. 2002 Aug;17 Suppl 3:S1–10. [3] Sajatovic M, Brescan DW, Perez DE, DiGiovanni SK, Hattab H, Ray JB, Bingham CR. Quetiapine alone and added to a mood stabilizer for serious mood disorders. J Clin Psychiatry. 2001 Sep;62(9):728–32. P.3.20 Arrythmic markers affected by clozapine treatment in patients with schizophrenia: heart rate variability, late potentials and QT dispersion ¨ Kırımlı2 , O. ¨ Aslan2 , M.N. T¨um¨ukl¨u1 , K. Alptekin1 , O. 1 ¨ 2 1 B. Kıvırcık , O. Badak , A. T¨urk , B. Yemez1 , ¨ G¨oldeli2 , S. G¨uneri2 , Y. Akvardar1 , B. Akdeniz2 , O. 1 1 Z. Tunca . Department of Psychiatry and 2 Department ˙ of Cardiology, University of Dokuz Eyl¨ul, Izmir, Turkey Purpose: Clozapine is a well-known atypical antipsychotic agent which is very useful especially in patients with treatment-resistant schizophrenia, but there is still debate on its potential to cause arrythmia and sudden death [3]. Benign electrocardiographic abnormalities have also been detected due to clozapine treatment [2]. To explore the effect of clozapine on arrythmic markers, heart rate variability (HRV), QT dispersion and late potentials (LPs) were measured before and after 10 weeks’ treatment. LPs are associated with delayed activation of the myocardium and along with other tests of cardiac function might show increased risk of ventricular tachyarrhythmias and sudden cardiac death [1]. QT dispersion shows repolarization heterogeneity and is related with arrhythmias. HRV measures depend on the influence of sympathetic and parasympathetic activity on the sinus node. Although there are some studies on HRV and QT changes related with clozapine treatment, LP changes were never mentioned. Methods: 16 patients (5 men and 11 women) with DSM-IV schizophrenia were included in the study. Mean age was 36.44 years with a range of 20–56 years. Patients having a physical illness or a history of any cardiovascular or hematological illnesses were excluded. Echocardiograghic examination was performed on all of
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characteristic cognitive side-effects most notably memory loss, which remains a common unpleasant and undesirable concern for patients and families. Unfortunately no pharmacological agent has been confirmed to lessen ECTinduced memory deficits. Rivastigmine is a selective CNS inhibitor of acetylcholinesterase used successfully in the management of Alzheimer’s Disease with reported benefits on cognition [1]. Acetylcholinesterase metabolizes the neurotransmitter acetylcholine which is intimately involved in human memory and cognition processes. By inhibiting acetylcholinesterase more acetylcholine becomes available to the patient for memory and cognitive functioning. Rivastigmine is characterized by selective binding and inactivation of acetylcholine receptor subtypes in specific regions of the brain. Its receptor selectivity enhances its therapeutic efficacy while minimizing peripheral adverse effects. In order to determine the advantageous effects, if any, of acetylcholinesterase agents in a subpopulation of schizophrenia patients with ECT induced memory deficits, this study examined the effects of rivastigmine on memory performance in patients treated with ECT. Method: Thirty patients with chronic treatment resistant schizophrenia disorder, diagnosed according to the criteria of the DSM-IV, were administered either rivastigmine or placebo in a prospective, randomized, double blind controlled trial. Doses were increased following the first week from 1.5 mg/day to 4.5 mg/day. Duration of drug administration was for at least 4 consecutive ECT sessions and for a maximum period of 4 weeks. Subjects were assessed with the cognitive subscale of the Alzheimer’s Disease assessment (ADAS-COG), Mini Mental State Examination, Positive and Negative Syndrome, Clinical global Impression and the Simpson Angus Rating Scales. Results: Pre-ECT measures showed no baseline differences between the subgroups. Over the course of the ECT trials, ADAS-COG scores of subjects receiving placebo increased indicating reduced cognitive performance, while subjects receiving rivastigmine improved their ADASCOG scores, thus indicating cognitive improvement (t=2.30, df=22, p=0.031). Conclusions: These findings, while preliminary, suggest the involvement of the acetylcholinergic system in the mediation of cognitive deficits following ECT-induced memory impairment. In addition, they indicate the possible beneficial effects of rivastigmine in lessening some of these treatment induced side effects. We hypothesize that cognitive impairment post ECT may be ameliorated to some extent by rivastigmine due to its enhancement of cholinergic activity, thus reversing the cognitive side effects. Further larger double blind studies of similar nature are mandated in order to further clarify the results of this study.
S60
Clinical Neuropsychopharmacology
References [1] Rosler M, Anand R, Cicin-Sain A, Gauthier S, Agid Y, Dal-Bianco P, Stahelin HB, Hartman R, Gharabawi M. Efficacy and safety of Rivastigmine in patients with Alzheimer’s disease: international randomized controlled trial. BMJ 1999; 318: 633–8. P.3.19 A naturalistic study on quetiapine vs. other mood stabilizers in the treatment of bipolar disorder I and II G. Tacchini, S. Charitos, S. Fumagalli, O. Fusi, A.C. Altamura. CRT – Department of Psychiatry, University of Milano – Ospedale Sacco, Via G.B. Grassi, 74, 20157 Milano, Italy The literature on the use of quetiapine in the treatment of bipolar disorder I and II is quite limited and recent, and there are no naturalistic studies which compare the use of quetiapine vs. other mood stabilizers as lithium or valproate. The aim of the present study is to evaluate the efficacy and tolerability of quetiapine during an on-going follow-up period which presently reaches a maximum of 24 months. The present study is therefore conceived as a naturalistic, open label, and observational study, in which patients are recruited as soon as they are diagnosed as affected by a bipolar disorder, either they are still in acute phase or remitted; treatment is decided entirely by the clinician according to his/her judgment, and is only recorded by the research team. Patients stay in the study until next clinical relapse. 100 BD type I or II patients, according to DSM IV criterion, were recruited; to all of them the clinicians prescribed, at their own clinical judgment, quetiapine at a dosage between 400–800 mg (mean dose 593 mg±200 mg) or, alternatively, lithium (mean plasma level 0.76±0.15), valproate (mean dose 837 mg±300 mg) or quetiapine plus another stabilizer. Clinical assessments were carried out using the 21-item HAM-D, YMRS, BPRS, CGI and SAS at baseline and every 4 months during the follow-up which presently goes up to 24 months, with a mean of 14 months. An ECG and complete laboratory test assays, including complete blood count, hepatic function and thyroid function (TSH, fT3 and fT4) were performed at the baseline and at the end of the observation period. Endpoints were considered any relapses either depressive or manic. Results are analysed in terms of clinical improvements at the above mentioned scales, compliance, incidence and severity of side-effects, and variations of the blood parameters. The four treatment groups (i.e. quetiapine, lithium, valproate, and quetiapine plus another stabilizer)
have been compared by means of ANOVA for repeated measures and survival analysis. References [1] Altamura AC, Salvadori D, Madaro D, Santini A, Mundo E. Efficacy and tolerability of quetiapine in the treatment of bipolar disorder: preliminary evidence from a 12-month open-label study. J Affect Disord. 2003 Sep;76(1–3):267–71. [2] Kasper S, Stamenkovic M, Letmaier M, Schreinzer D. Atypical antipsychotics in mood disorders. Int Clin Psychopharmacol. 2002 Aug;17 Suppl 3:S1–10. [3] Sajatovic M, Brescan DW, Perez DE, DiGiovanni SK, Hattab H, Ray JB, Bingham CR. Quetiapine alone and added to a mood stabilizer for serious mood disorders. J Clin Psychiatry. 2001 Sep;62(9):728–32. P.3.20 Arrythmic markers affected by clozapine treatment in patients with schizophrenia: heart rate variability, late potentials and QT dispersion ¨ Kırımlı2 , O. ¨ Aslan2 , M.N. T¨um¨ukl¨u1 , K. Alptekin1 , O. 1 ¨ 2 1 B. Kıvırcık , O. Badak , A. T¨urk , B. Yemez1 , ¨ G¨oldeli2 , S. G¨uneri2 , Y. Akvardar1 , B. Akdeniz2 , O. 1 1 Z. Tunca . Department of Psychiatry and 2 Department ˙ of Cardiology, University of Dokuz Eyl¨ul, Izmir, Turkey Purpose: Clozapine is a well-known atypical antipsychotic agent which is very useful especially in patients with treatment-resistant schizophrenia, but there is still debate on its potential to cause arrythmia and sudden death [3]. Benign electrocardiographic abnormalities have also been detected due to clozapine treatment [2]. To explore the effect of clozapine on arrythmic markers, heart rate variability (HRV), QT dispersion and late potentials (LPs) were measured before and after 10 weeks’ treatment. LPs are associated with delayed activation of the myocardium and along with other tests of cardiac function might show increased risk of ventricular tachyarrhythmias and sudden cardiac death [1]. QT dispersion shows repolarization heterogeneity and is related with arrhythmias. HRV measures depend on the influence of sympathetic and parasympathetic activity on the sinus node. Although there are some studies on HRV and QT changes related with clozapine treatment, LP changes were never mentioned. Methods: 16 patients (5 men and 11 women) with DSM-IV schizophrenia were included in the study. Mean age was 36.44 years with a range of 20–56 years. Patients having a physical illness or a history of any cardiovascular or hematological illnesses were excluded. Echocardiograghic examination was performed on all of