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`THE JOURNAL OF THE EUROPEAN COLLEGE OF NEUROPSYCHOPHAFIMACOLOGY
`
`VOLUME 7, SUPPLEMENT 2 (1997)
`
`Abstracts of the
`
`Xth congress of the European College of
`Neuropsychopharmacoloy
`
`Vienna. Austria
`September 13-17, 1997
`
`VOLUME 7 (1997)
`
`ELSEVIER SCIENCE B.V.
`
`AMSTERDAM — LAUSANNE — NEW YORK - OXFORD — SHANNON — TOKYO
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`1 of 4
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`Alkermes, Ex. 1016
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`EUROPEAN NEUROPSYCHOPHARMACOLOGY
`
`The Journal of the European College of Neuropsychopharmacology
`
`Scope European Neuropsychopharrrracoiogy provides a medium for the prompt publication of articles in the field of
`neuropsychopharrnacology. Its scope encompasses clinical and basic research relevant to the efiects oi centrally acting
`agents in its broadest sense.
`
`J.M. van Flee (Utrecht. The Netherlands)
`
`M. Ackenheil (Munich. Germany)
`CM. Banki (Nagykallo. Hungary)
`P. Bech (Hillered. Denmark)
`FI.H. Belmaker (Beer Sheva, Israel)
`M. Bourin (Nantes. France)
`G.B. Cassano (Pisa. Italy)
`S.G. Dahl (Trornse. Norway)
`C.G. Gottfries (Hisings Backa. Sweden)
`P. Grof (Ottawa, Ont., Canada)
`F. Holsboer (Munich. Germany)
`S.Z. Langer (Paris. France)
`M. Linnoila (Bethesada, MD. USA)
`J.J. Lopez-lbor (Madrid, Spain)
`J. Maj (Krakow. Poland)
`
`Editors-in-Chief
`
`S.A. Montgomery (London. UK)
`Editoriai Board
`
`P. McGuf'fn (Cardiff. UK)
`H.Y. Meltzer (Cleveland, OH. USA)
`J. Mendlewicz (Brussels, Belgium)
`T.R. Norman (Heidelberg. Vic., Australia)
`R. Post (Bethesda, MD. USA)
`G. Racagni (Milan. Italy)
`G. Sedvall (Stockholm, Sweden)
`S.H. Snyder (Baltimore, MD, USA)
`H.M. van Praag (Maastricht. The Netherlands)
`H.G.M. Westenberg (Utrecht. The Netherlands)
`P.WiI|ner (London, UK)
`J.H. Woods (Ann Arbor, MI. USA)
`I. Yamashita (Sapporo. Japan)
`
`Types of paper Full-length Research Papers: detailing findings of original experimental or clinical research in any area of
`neuropsychopharmaoology: Short Communications: brief research reports or results that have reached a stage where they are
`ready for preliminary communication; Reviews on specialised topics. Letters to the Editor relating to material published in the
`joumal are also welcomed.
`
`Submissions Non-clinical manuscripts and related editorial correspondence should be addressed to: ENP Secretariat. P.O.
`Box 85410. 3508 AK Utrecht. The Netherlands.
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`Clinical manuscripts and related editorial correspondence should be addressed to: Professor Stuart A. Montgomery, European
`Neuropsychopharmacology. P.O. Box 8751, London W13 BWH. UK.
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`Alkermes, Ex. 1016
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`R2
`
`Psychotic disorders and antipsycltotics
`
`S22?
`
`P.2.110 The German postmarketing surveillance oi
`rlaperldone indally practice: Gender differences
`with regard to demographic and treatment data
`M. Albus. M. Linden. A. Klauder. M. Philipp. State Mental Hospital
`Ham: D 85540 Hoar: Germany
`
`Methods: In the context of a German postmarlteting surveillance on the
`long term use of risperidone in daily practice, gender differences with
`regard to demographic and treatment data during the first 3 months of
`risperidone administration investigated.
`Results: 886 schizophrenic patients (452 males and 432 females) were
`included in the study. More males were single compared to females.
`Although females were older than males with a longer duration of
`illness. they showed a higher level of psychosocial functioning. During
`pevions treatment females showed a higher rate of tardive dyskinesia,
`whereas male showed disturbed Kognition mor ofter. Druing treatment
`with risperidone the mean dosage of risperidone administeres was lower
`in females. however sigificantly only after 1 mondt (4.9 mg vs 4.6 mg}.
`The percentage of patients discontinuing treatment as well as medication
`compliance did not differ beween the genders. Minus symptomatology
`was higher in men throughout the whole treatment period. Symptom im-
`provement in plus and minus symptoms. in psychosocial functioning as
`well as in extrapyrarnidal side effects was significantly during the 3-month
`period. again without gender differences. As well, the therapeutic efficacy
`of risperidone was rated favorable in both groups.
`Conculsion: Risperidone treatment during a 3—mondt-period was ef-
`fichacious without differential effects on male and female schizophrenic
`patients.
`
`P.2.111
`
`D2 and 5 HT” receptor binding of different doses
`of quetlapine in schizophrenics. a pet study
`
`0. Gefvert ‘. 1.-M. Wieselgren 2. P. Hagstzrom ‘. M. aergsttom 3,
`T. Lundberg 1. 3. Langstroma. F.A. Wiesel 2. L.H. Lindstriim1.
`‘Psychiatric Research Unit Vd.trerd.r.' 2Ufi'erdtl:er Hospital, Uppsala;
`3Upp.rala University PET centre, Sweden
`Quetiapine ffseroquel‘). a dibenzothiazepine is a new anti-psychotic
`compound under development. in vitro data indicate that it has a similar
`receptor profile as that of clozapine. except for a much lower affinity for
`D4 and muscarinic cholinergic receptors.
`In 4
`Method: We undertook a study in 5 schizophrenic patients.
`patients the dose of quetiapine was titrated up to 750 mgiday in one
`week. The dose was maintained for 21 days. At day 29 two PET scans
`were then performed two hours after dosing (at steady state) at 09.00
`and 17.00. The ligand C“-raclopride was used to estimate D2 receptor
`binding in the striatum. and C‘ '-metylspiperone was used as ligand for 5
`HT2.i receptors in the frontal cortex. After the first two scans the dose of
`quetiapine was reduced to 450 mgfday and in 3 of these patients a further
`two PET scans were performed app. 8 days later at the steady state. The
`fourth patient had the dose of quetiapine further reduced to 300 mg»-‘day
`before having two more PET scans. In the remaining patient. who was
`being well-controlled after titration to 450 mg.-‘day. the dose was reduced
`to 300 mgfday and then to I50 mglday with two PET scans at the last two
`levels at steady state...
` Results:
`Dose of queliapine (mg)
`I50
`300
`450
`‘.50
`Number of patients in)
`i
`2
`3
`4
`D3 ('36 striatum)
`O
`0
`3]
`43
`5 trial to frontal cortex)
`3s
`5‘!
`74
`76
`
`Discussion: A consistent decrease of receptor blockade. on both D2
`and 5 l-lT2.s receptors. could be demonstrated with decreasing doses of
`quetiapine.
`The low values of D2 blockade at 150 mg and 300 mg are consistent
`with the clinical findings of these patients deteriorating after dose reduc~
`tion. They either had to discontinue quetiapine (n = 1) or increase the dose
`again to achieve symptom control (n = 1). However higher occupancy
`values can not be ruled out in other patients. at these dose levels. as the
`low ntunber of patients in this study will not take into the account the
`possibility of an inter individual variation of D; occupancy.
`
`These data confirm the Findings of our earlier study that quetiapine
`binds to both D3 and 5 HT» receptors. but with a higher level of
`occupancy and with a much more withstanding blockade of the serotonin
`receptors. From these data it is unlikely that quetiapine will cause BPS
`in the recommended dose range (150450 mg}. Thereby fulfilling one
`criterion of being an atypical neuroleptic. The laclt of EPS has been
`proposed to be related to a dopamine D2 occupancy of less then 75% and
`at the maximum recommended dose (750 mg) is well below this level.
`This study has been sponsored by Zeneca Pharmaceuticals. England.
`‘Seroque-l'
`is a trade mark and the property of Zeneca Ltd.
`
`R2.114 Aripiprazole, a new typical antipsychotic: Phase 2
`clinical trial result
`
`1.1.. Petrie ‘, A.R. Saba 1 . r.1>. McEvoy 2. lottura America
`Pharntaceuticois, CNS Research. Rochville. Maryland. USA. 2John
`Umsread Hospital‘. Duke University. Burner; NC 27509. USA
`
`A1-ipiprazole is a new atypical antipsychotic now starting world wide
`Phase III development by Otsulta Pharmaceuticals. Receptor pharma-
`cology showed that aripipazole is a postsynaptic dopamine receptor
`antagonist as well as presynaptic autorcceptor agonist. The latter action
`distinguishes aripiprazole from other currently available antipsychotic
`drugs. Aripirazole also demonstrated affinity for SHT; receptor. Alip-
`iprazole has a T-max of 3-5 hr with a half life of 50-80 hr. A positron
`emission tomography (PET) study showed that aripiprazole enters the
`brain and its binding to the D2 receptor
`increases with increasing
`doses.
`Recently completed double—blind Phase 11 studies were conducted in
`a total of 410 acutely relapsing hospitalised schizophrenic patients. In
`study 3]-93-202, aripiprazole was titrated up front 5 to 30 mg in 13
`days while in study 31-94~2DQ fixed doses of 2. 10. and 30 myday were
`administered. Both studies were of 4 weeks duration. and haloperidol was
`used as an active control.
`Based on the last observation carried forward (LOCI-‘} analysis. in both
`studies aripiprazole was superior to placebo in improving the BPRS-total.
`BPRS-score, CGl—sever'1ty. a.nd PANNS~total. Results of the fixed-dose
`study of 3l—94—20Q showed that all
`three aripiprazole doses (2, 10.
`and 30 mg;'day} showed clinical effect
`in improving the symptoms of
`acute psychiatric exacerbation of schizophrenia and the 30 mg dose was
`oonsinstently more effective than the lower two doses. The 30 mg dose
`demonstrated a unique early onset of efficacy from week I on all efiicacy
`variables including PANSS—negative score.
`Aripiprazole was well tolerated. Extrapyrarnidal symptoms (BPS) as
`measured by standard scales were comparable to the placebo treatment
`In the aripiprazole treatment groups there was no increase in prolactin
`level or in body weight.
`A favorable safety profile combined with data supporting efficacy in
`the treatment of the positive a.nd negative symptoms of schizophrenia.
`suggests that aripiprazole may represent an important advance in the
`management of psychotic disorders.
`
`P.2.115 Depressive symptoms In acute schizophrenia:
`Evaluation and outcome under new antlpsychotlcs
`
`MJ. Muller, O. Bertltert. Department of Psychiatry. University of Mainz,
`Germany
`
`Depressive symptoms occur frequently durirtg the course of psychotic
`disorders. Despite of their high clinical relevance,
`there is so far no
`commonly accepted guideline for evaluation and treatment of depressive
`symptomatology in more acute states of these disorders. However. recent
`studies with novel antipsychotics seem to yield promising results. Due
`to the complex nature of psychotic disorders. a substantial overlap of
`depressive and negative symptoms and the possible confounding with
`positive symptomatology and treatment-induced etttrapyrantidal side-
`effects (EPS) may account for difficulties in discriminating treatment
`outcome with respect to depressive symptoms.
`Based on recent factor—analytical models of schizophrenic symptoma-
`tology,
`the present approach focused on depressive symptoms. Using
`confin-natory factor analysis (CFA, LISREL 1.20}, a baseline model
`
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