Alkermes, Ex. 1017
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`[E[MR2@lI9[E‘{M]
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`[N]EflUl}?@lP§Y7@Gfl@E9[H]l§3[:2£QflE3@@[l@@YF
`
`THE JOURNAL OF THE EUROPEAN COLLEGE
`OF llEUllOP8YCHOPH.I.IIAOOl.OGY
`
`VOLUME 11 SUPPLEMENT 3 (2001)
`
`Abstracts of the
`
`14th Congress of the European College of
`Neuropsychopharmacology
`
`Istanbul, Turkey
`October 13-17, 2001
`
`VOLUME 11, SUPPLEMENT 3 (2001)
`
`ELSEVIER SCIENCE B.V.fECNP
`
`AMSTERDAM — LONDON — NEW YOFIK - OXFORD — PARIS — SHANNON — TOKYO
`
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`EUROPEAN NEUROPSYCHOPHARMACOLDGY
`
`The Journal of the European College of Neuropsychopharmacoiogy
`
`Scope European Neuropsychopharmacoiogy provides a medium for the prompt publication of articles in the field of
`neuropsychopharmaooiogy. Its scope encompasses clinical and basic research relevant to the effects of centrally acting
`agents in its broadest sense.
`
`Editors-irr=Chief
`
`JM. van Flee (Utrecht. The Netherlands)
`
`S.A. Montgomery (London. UK)
`Editorial Board
`
`H. Akii (Ann Arbor. MI. USA)
`A.C. Altarnura (Milan. Italy)
`F. Artigas (Barcelona. Spain)
`I. Bitter (Budapest. Hungary)
`P. Blier (Gainesviile, FL. USA)
`0. Civeili (Irvine. CA. USA)
`G. Goodwin (Oxford. UK)
`T. Higuchi (Kanagawa. Japan)
`Ft.S. Kahn (Utrecht. The Netherlands)
`J.M. Kane (Glen Oaks. NY. USA)
`S. Kasper (Vienna, Austria)
`C. Kohier (Sodertalje. Sweden)
`G. Koob (La Jolla. CA. USA)
`M.H. Lader (London. UK)
`
`Y. Lecrubier (Paris, France)
`P. Linkowski (Bruxeiles, Belgium)
`D. Marazzitl (Pisa. Italy)
`C.B. Nemeroff (Atlanta. GA. USA)
`8.0. Ogren (Stockholm. Sweden)
`A.J. Flush (Dallas. TX. USA)
`A.F. Schatzberg (Stanford. CA. USA)
`C.A. Tamminga (Baltimore. MD. USA)
`J.W.G. Tiller (Parkv'rl|e. Vic.. Australia)
`J.L. Waddington (Dublin, ireiand)
`S. Yamawaki (Hiroshima, Japan)
`J. Zohar (Fiamat Gan. Israel)
`E.E. Zvartau (St. Petersburg. Russia)
`
`Types of paper Full-length Research Papers: detailing findings of original experimental or clinical research in any area
`of neuropsychopharmacologyz 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 iournal are also welcomed.
`
`Submissions Non-clinical manuscripts and related editorial correspondence should be addressed to: ENP Secretariat.
`R0. Box 85410, 3508 AK Utrecht, The Netherlands. Clinical manuscripts and related editorial correspondence should
`be addressed to: Professor Stuart A. Montgomery. European Neuropsychopharmacology. PO. Box 8751. London W13
`BWH, UK.
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`S132
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`S. f 3. Merritt
`
`rendering Lithium treatment more and
`supersensitivity mania,
`more ineffective (H. Himmelhorth, in J.C. Scares at S. Gershon.
`2000). Furtltcrrrtore. prior polypltanrraccutical course of treat-
`ment, especially antidepressants. contributes to Lithitun resistance.
`Withdrawal rebound can make Lithium ineffective or counterpro-
`ductive. Finally: "treatment with Lithium for less titan two years is
`either of negligible benefit or of actual harm to bipolar patients.
`A too short term treatment may be worse than useless. Three
`years is probably the minimum lertgth" (GM. Goodwin, 1994).
`Therefore. the prescription of Lithium in acute mood episodes is
`wamrnted. This decision must nonetheless be well thought over.
`taking into account a long-tenn strategy with the perspective
`of prolonged Lithium treatment. principally to stabilize mood
`oscillations. prevent or counteract ongoing cerebral damage, and
`prevent suicide.
`Indeed. on the long term. Lithium has many beneficial effects:
`against suicidal behaviour. viral
`infection. and more interest-
`ingly. against neurodegeneration [H.K. Manji er ul.. 2000). The
`t:r'eat:mettt's perspective is thereby broadened to neuroprotection.
`neurogenesis. and tttanagernent of pathological brain aging.
`There are several other drugs used to treat mania, with a more
`rapid eflicacy. These can represent an alternative choice. Again.
`the decision to use Litltiunt. alone or combined with other drugs in
`acute mood episodes. nurst take into account a long-temt strategy
`arid the long-term beneficial effects.
`
`References
`
`[I] Cede l.F.l.: Lithium salts in the treatment ofpsychotic excitement. Med.
`J. At.rst.. 36: 349-352. I9-$9.
`[2] El-.\-lallalth R.S.: Lithium: Actions and mechanisms. I vol.. American
`Psychiatric Press. London. I996.
`[J] Goodwin F.I(.. Jamison K.ll.: Manic-depressive illness. Oxford Univer-
`sity Press. New York. NY. I990.
`[4] Goodwin GM: The recurrence of mania after [itltium withdroltctl:
`implications for the use of lithium in the treatment of bipolar affective
`disorder. Br. J. Psyeltiarn. I64: t46—lS2. I994.
`[5] Manji H.K. B-trvvden CL. Belmalter R H.: Bipolar medications. I voI..
`Arrrerican Psychiatric Press. 2000.
`[6] Soares .l.C. Gerslton S: Bipolar disorders: Basic mechanism and thera-
`peutic implications. Marcel Dekter. inc. New York. Basel.
`II] Vieta E.. Gasto C; Trastotnos bipolares. I vo|.. Springer Verlag lberica.
`Barcelona. I997.
`
`lithium with the original antipsychotic. chlor-
`mood stabiliser.
`prontazine, which showed an advantage to chlorpromazine in
`highly active rrranic patients (4). This data accords with clinical
`experience and indeed with audits of clinical practice internation-
`ally. which all illustrate the widespread. perhaps universal use of
`antipsychotic drugs. often at quite high doses. Severe mania may
`demand the actions that only antipsychotics can produce.
`A greater challenge comes from the development of the atypical
`antipsychotics and the realisation that lower doses of the classical
`drugs are preferable in the treatment of schizophrenia because
`of the severity of adverse elfects. We remain a little uncertain
`whether the central action that is sought in acute treatment of
`mania is primarily the chemical straightjacltet of antipsychotie
`overdose. The classical antipsycltotics certainly reduce demands
`on staff (4) by controlling behaviour. The atypical antipsychotics
`will not have the saute side effect burden. Will they prove to be
`as useful as the older drugs? How we balance the interests of staff
`and patients. suggests the need for new approaches to assessing
`outcome in ueatrnent trials. and more emphasis on the patient
`experience.
`The new trials we already have are interesting because they
`suggest
`that atypicals can produce antimanic clfects that are
`certainly superior to placebo and probably additive to the action
`of so-called mood stabilisers like divalproex and lithium. This
`is already suggested by studies of risperidonc and olartzapine.
`Indeed combination treatments are extremely common in practice
`and may allow the balance between eflicacy and side effects to be
`optimised in acute and long term trcauttcnt.
`There is the further issue of whether atypical antipsychotics
`are tltemselt-cs ‘mood stabilising‘. and whether the meaning of
`that term is in need of re-statement. Certainly clozapine has a
`reputation and sonic evidence to support a potent action in the
`rapid cycling states where mood instability is a defining feature.
`We are at a stage of rapid and incremental growth in available
`information because of the efforts of companies to identify the
`actions of their still new compounds. The greater challenge is
`to integrate the increasingly wide range of choices into coherent
`clinical plaming and humane treatment of a diflicult condition.
`These are challenges primarily for clinicians. not for industry. and
`canortlybeaddrrrtsedbythegrowthofthettittlctdturc within
`everyday practice.
`
`Typical and atypical antlpaychotlcs In the
`treatment of mania
`
`References
`
`GM. Goodwin. University Department of Psyclriany. The
`llirrrrefard Hospital. aphid OX3 7.1!, UK
`
`For many years. antipsychotics have been the cornerstone of
`treatment for acute mania in Europe. It provoked surprise. and not
`a little consternation. therefore, that in influential US guidelines.
`antipsychotics were defined to be ad_'r‘rrncrr‘ce. not first line. in
`the management ofmania. The first line drugswere declaredto
`be mood stabilisers (I). The term mood stabilizer is imprecisely
`defined but carries a reassuring ring. It is bestowed on lithium for
`the good reason that there exists clear evidence that it prevents re-
`currence and relapse in the long term. The term is conferred upon
`the anticortvulsants on the basis of much less convincing evidence.
`Although divalproerr certainly has equal efiicacy to lithium in the
`ueatment of acute mania (2). in long term mairttenance the results
`were inconclusive (3).
`The basis for the distinction between mood stabiliscrs and
`
`adjunctive treatments was always opinion, rather than evidence.
`There is an excellent controlled comparison of the gold standard
`
`[I] Frances. A.. Docherty. 1.2 and Knhtl. DA. The Expert Consensus
`Guideline series: ueaunem ofbipolar disorder. [996 J. Clin. Psyehiatr.
`5? {Suppl IZA). 1-88.
`[2] Bowden CL. Brugger AM. Srrrann AC, et al. Elficacy of divalproert
`vs lithium and placebo in the treatment of mania. I994 Journal of the
`American Medical Association. 27]: 9l8—92-I.
`[J] Bowden CL. Calabrese. JR. McEItt:ry. SL. et II. A randontised. placebo-
`controllerl l2-month trial of‘ Divalproett and lithium in treatments of
`outpatients with bipolar l disorder. 2000 Arch. Gen. Psychiatry 57.
`481-489
`[4] Prion-RF. Calfey-EM lr. Klert-Cl Cornparisorr oflithitmr carbonate and
`chlorpromazine in the ueatmerrt ofnunia. I912. Arch Gen Psychiatry.
`26: lot6—l53
`
`Treatment of mlrratl episodes
`
`G5. Sachs. Harvard Ripalar Research Program. USA
`
`Mixed episodes challenge clinicians and researchers to assess and
`treat a condition defined by frequent fluctuation of signs and
`symptoms. Terms such as Bipolar Disorderartrl Manic-Depressive
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