Table Of ContentThis publication and the symposium on which it was based
were sponsored by an educational grant
from the Janssen Research Foundation
Guidelines for Neuroleptic
Relapse Prevention
in Schizophrenia
Proceedings of a Consensus Conference
held April 19-20, 1989, in Bruges, Belgium
Edited by
Werner Kissling
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo Hong Kong
Barcelona Budapest
Dr. WERNER KISSLING
Psychiatrische Klinik und Poliklinik
der Thchnischen Universitlit Munchen
Ismaninger StraBe 22
W-8000 MUnchen 80, FRO
With 5 Figures
ISBN-13: 978-3-540-53985-8 e-ISBN-13: 978-3-642-86922-8
DOT: 10.1007/978-3-642-86922-8
Library of Congress Cataloging-in-Publication Data. Guidelines for neuroleptic relapse prevention in
schizophrenia: proceedings of a consensus conference held April 19-20, 1989, in Bruges, Belgium 1 edited by
Werner Kissling. Includes bibliographical references and index. ISBN 3-540-53985-9 (alk. paper). - ISBN
0-387-53985-9 (a1k. paper) 1. Schizophrenia - Relapse - Prevention - Congresses. 2. Antipsychotic drugs -
Congresses. 3. Schizophrenia - Chemotherapy - Congresses. I. Kissling, Werner. [DNLM: 1. Schizophrenia
- drug therapy - congresses. 2. Schizophrenia - prevention & control - congresses. 3. Tranquilizing Agents,
Major - therapeutic use - congresses. WM 203 G946 1989) RC514.G78 1991 616.89'82061 - dc20
DNLM/DLC for Library of Congress
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Preface
This volume is a summary of a consensus conference on guidelines for
neuroleptic relapse prevention that took place in Bruges, Belgium, in April
1989. The goal of this conference was to reach a consensus on all major aspects
of neuroleptic relapse prevention and to formulate precise and detailed treat
ment guidelines. The result of these efforts can be found in the last chapter
of this volume.
Literature reviews and an excerpt of the discussion between the experts were
included in this volume in order to enable the reader to better follow the chain
of reasoning which led to the guidelines presented here. The first section of the
book consists of a short statement by each of the participants describing the
current state of prophylactic treatment in his/her country.
I would like to express my heartfelt thanks to all those who attended the
consensus conference. Every participant provided a valuable contribution,
which ranged from his oral presentation to a literature review, most important
ly to active and disciplined participation in the two days of discussion. This
concerted effort made it possible for precise, detailed, and practically relevant
guidelines for neuroleptic relapse prevention to be formulated at the conclu
sion of the conference.
An especially important contribution was made by the chairman Professor
John M. Kane, without whom the entire enterprise could not have been under
taken. He moderated the entire discussion very competently, on the one hand
encouraging free discussion, while on the other hand gently but firmly guiding
the discussion back to the questions of practical relevance. He motivated us
to renounce vague, ineffectual, and convenient formulations and to take a
definite stand on the issue in question. The frequency with which his scientific
works were cited in the discussion, the reviews, and the formulation of the
guidelines indicates the extent to which Professor Kane's research has provided
the groundwork for these guidelines. He also made stylistic and contextual
revisions to the manuscript in conjunction with Dr. Marder, Dr. Barnes, and
Dr. Fleischhacker. Many thanks to all four colleagues.
Assisting in the tedious and time-consuming task of transforming the
several hundred pages of tape transcript into a readable short version was the
task of John Langerholc and Lois Woestman; their work, as well as the
editorial assistance of Margritta Aulehla, is gratefully acknowledged.
VI Preface
Last but not least, we are greatly obliged to the Janssen Research Founda
tion, and in particular to Dr. Paul Geerts, Dr. Ronald Kalmeijer, and Mrs. Ger
da Dyckmans for their generous organisatorial and financial assistance,
without which it would have been impossible to hold such a conference.
WERNER KISSLING
Contents
Introduction
W. Kissling ................................................... 1
Part I
Relapse Prevention in Different Countries:
The Current Situation
United States:
S. R. Marder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Austria:
W. W. Fleischhacker and U. Meise 13
United Kingdom:
T. R. E. Barnes and S. R. Hirsch 16
Sweden:
S. J. Dencker 24
B. Wistedt ................................................... 26
Federal Republic of Germany:
F. Muller-Spahn and H. Hippius 30
J. Thgeler .................................................... 34
United States:
J. M. Kane ................................................... 38
United Kingdom:
D. A. W. Johnson .............................................. 45
Switzerland:
B. Woggon ................................................... 49
Federal Republic of Germany:
W. Kissling ................................................... 50
VIII Contents
Partn
Reviews of the Literature
The Interaction of Drug and Family Therapy
in the Prevention of Relapse in Schizophrenia
M.1. Goldstein ............................................... 55
Predictors of Risk of Relapse in Schizophrenia
S. R. Marder .................................................. 67
Who Should Be Treated?
D.A. W. Johnson.............................................. 78
Dosage and Route of Administration of Neuroleptic Drugs
During Different Phases of a Schizophrenic Illness
J. M. Kane ................................................... 85
Duration of Neuroleptic Maintenance Treatment
W. Kissling ................................................... 94
Part III
General Discussion
General Discussion 115
Part IV
Guidelines for Neuroleptic Relapse Prevention in Schizophrenia
Towards a Consensus View
W. Kissling, J. M. Kane, T. R. E. Barnes, S. J. Dencker,
W. W. Fleischhacker, M. J. Goldstein, D. A. W. Johnson, S. R. Marder,
F. Muller-Spahn, J. Tegeler, B. Wistedt, and B. Woggon ............ 155
Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165
List of Contributors
BARNES, THOMAS R. E., Academic Unit, Horton Hospital, Long Grove
Road, Epsom, Surrey KT19 8PZ, United Kingdom
DENCKER, SVEN J., Berzeliigatan 26, 41253 G0teborg, Sweden
FLEISCHHACKER, WOLFGANG W., Klinik fUr Psychiatrie,
Universitiitsklinikum, AnichstraBe 35, 6020 Innsbruck, Austria
GOLDSTEIN, MICHAEL J., University of California, Los Angeles (UCLA),
Department of Psychology, 1285 Franz Hall, 405 Hilgard Avenue,
Los Angeles, CA 90024-1563, USA
HIPPIUS, HANNS, Psychiatrische Klinik der Universitiit Munchen,
NuBbaumstra13e 7, W-8000 Munchen 2, FRG
HIRSCH, STEPHEN R., Department of Psychiatry, Charing Cross
and Westminster Medical School, Fulham Palace Road, London W 6,
United Kingdom
JOHNSON, D.A. W., Department of Psychiatry, University Hospital of
South Manchester, Withington Hospital, West Didsbury, Manchester
M20 8LR, United Kingdom
KANE, JOHN M., Hillside Hospital, Division of Long Island Jewish
Medical Center, P.O. Box 38, Glen Oaks, NY 11004, USA
KISSLING, WERNER, Psychiatrische Klinik und Poliklinik
der Thchnischen Universitiit Munchen, Klinikum rechts der Isar,
Ismaninger Stra13e 22, W-8000 Munchen 80, FRG
MARDER, STEPHEN R., West Los Angeles Veterans Administration,
Medical Center, Brentwood Division, 11301 Wilshire Blvd., Los Angeles,
CA 90073, USA
MEISE, ULLRICH, Klinik fur Psychiatrie, Universitiitsklinikum,
Anichstra13e 35, 6020 Innsbruck, Austria
MULLER-SPAHN, E, Georg-August-Universitiit G()ttingen,
Klinik und Poliklinik fur Psychiatrie, Gerontopsychiatrie,
von-Siebold-Stra13e 5, W-3400 Gottingen, FRG
TEGELER, J., Rheinische Landesklinik, Psychiatrische Klinik der Universitiit,
Bergische Landstra13e 2, W-4000 Dusseldorf, FRG
WISTEDT, B., Danderyds Hospital, Department of Psychiatry,
Karolinska Institute, 18288 Danderyd 3, Sweden
WOGGON, B., Psychiatric University Hospital, Research Department,
Lenggstra13e 31, 8029 Zurich, Switzerland
Introduction
W. KISSLING
Can Half of All Schizophrenic Relapses be Avoided?
The current state of relapse prevention in schizophrenia is characterized by a
paradoxical situation. On the one hand, for almost 40 years now we have been
in possession of highly effective neuroleptic drugs, the prophylactic value of
which has been clearly proven in numerous controlled studies (Davis 1980;
Kane 1987). On the other hand, we are still confronted with the disconcerting
fact that under routine treatment conditions 500/0 of schizophrenic patients
suffer a relapse within one year of their most recent episode (Gaebel and Pietz
cker 1985) and that, on average, schizophrenic patients spend between 15%
and 20% of their time after their first illness in psychiatric hospitals due to
the frequent occurrence of relapses (Maurer and Biehl 1988; GmOr and
Tschopp 1988).
This paradoxical situation is not only a professional challenge but it also
calls for our empathy, because it is associated with a great deal of suffering
for both patients and their families. In order to improve the quality of our
work and to reduce patients' unnecessary suffering, it is our duty not to simply
ascertain the fact that the situation is paradoxical but rather to investigate the
reasons for the high relapse rate and to discuss all possibilities for improve
ment. This introduction will deal in more detail with both the possible causes
and remedies of the unsatisfactory situation in neuroleptic relapse prevention.
Both aspects were also the subject of the consensus conference, the results of
which are presented in this volume.
When neuroleptic drugs were introduced into psychiatry almost 40 years ago,
they caused a revolution in the treatment of schizophrenic patients. The in
troduction of this new, very efficient form of treatment greatly reduced the dura
tion of acute schizophrenic episodes, and thereby the duration of great suffering
for the afflicted patients and their families. The sharp drop in the mean length
of the hospital stay that occurred simultaneously with the introduction of
neuroleptic drugs is certainly to a great extent causally connected to the in
troduction of this more efffective form of treatment. Even sociotherapy, which
also contributes to a reduction in the length of hospital stays, would have been
inconceivable without concurrent neuroleptic treatment.
After numerous controlled studies had shown that neuroleptic drugs were
effective not only in acute treatment, but also in reducing the high relapse rate
in schizophrenia from 80% to 20%, many psychiatrists were led to hope that
Guidelines for Neuroleptic Relapse Prevention
in Schizophrenia (Ed. by W. Kissling)
© Springer-Verlag Berlin Heidelberg 1991
2 w. Kissling
a drastic improvement in the prognosis of schizophrenia was imminent, and
that this disease would soon appear much less dreadful.
Unfortunately these hopes have not yet been realized. In practice, the
course of schizophrenia under routine treatment conditions has turned out to
be far less favorable, and the actual relapse rates lie drastically higher than
would be expected from the results of controlled studies. For example, in spite
of the availability of a highly effective relapse prevention treatment, a quarter
of a million people in West Germany must be treated each year for
schizophrenia (Pietzcker 1987), in most cases due to a relapse. On average,
under routine treatment conditions, first episode patients must be readmitted
twice during the 5 year period following their first episode (Maurer and Biehl
1988) and only 16070 of schizophrenic patients remain relapsefree for 5 years
(Gmur and Tschopp 1988; Shepherd et al. 1989). A third of all the beds in
psychiatric wards are occupied by schizophrenic patients; furthermore, each
fifth new admission to a psychiatric clinic is due to schizophrenia. The im
measurably great human suffering and the immense (but measurable) costs in
curred due to schizophrenic illness (in West Germany more than 7 billion
dollars each year) emphasize the impact of this problem. Although most of
these data were gathered in West Germany, it is to be presumed that these
figures will not differ significantly in other countries in view of the similar
treatment conditions and uniform prevalence of schizophrenia.
Why then do so many patients suffer a relapse in spite of the existence of
a highly efficient relapse prevention therapy? As is always the case in the
medical field - and especially so in psychiatry - there is unfortunately not
one single cause, but several. In the following I would like to investigate these
causes in somewhat more detail.
The discrepancy between the unsatisfactorily high actual relapse rates and
those ideally possible is linked, on the one hand, to the fact that there is nor
mally somewhat less therapeutic and organizational effort expended under
routine treatment conditions than in clinical studies. Questions of patient
selection might possibly playa role here to some extent as well, although the
published patient characteristics of many relapse prevention studies do not
deviate significantly from the distribution found under routine treatment con
ditions. Such methodological reasons can thus only account for a minor part
of this discrepancy.
The major reason for the high relapse rates under routine treatment condi
tions is the patients' high noncompliance with the neuroleptic relapse preven
tion plan proposed to them. Only about 40%-50% of the schizophrenic pa
tients for whom a neuroleptic relapse prevention is in fact indicated actually
go through with it (Kane 1985; Kissling 1988). For first episode patients this
noncompliance rate is even as high as 75070 (Gaebel and Pietzcker 1983).
Aside from illness-related factors, this high noncompliance could also be
due to the fact that schizophrenic patients are not well-enough informed about
their illness and above all are not given sufficient support nor motivation to
undergo prophylactic treatment. When we have a look at the extent to which
campaigns propagating prophylactic treatment for coronary heart diseases
