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Published by
World Scientific Publishing Co. Pte. Ltd.
5 Toh Tuck Link, Singapore 596224
USA office: 27 Warren Street, Suite 401-402, Hackensack, NJ 07601
UK office: 57 Shelton Street, Covent Garden, London WC2H 9HE
British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library.
PHARMACOTHERAPY FOR DEPRESSION AND TREATMENT-RESISTANT
DEPRESSION
Copyright © 2010 by World Scientific Publishing Co. Pte. Ltd.
All rights reserved. This book, or parts thereof, may not be reproduced in any form or by any means,
electronic or mechanical, including photocopying, recording or any information storage and retrieval
system now known or to be invented, without written permission from the Publisher.
For photocopying of material in this volume, please pay a copying fee through the Copyright
Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, USA. In this case permission to
photocopy is not required from the publisher.
ISBN-13 978-981-4287-58-6
ISBN-10 981-4287-58-X
Typeset by Stallion Press
Email: [email protected]
Printed in Singapore.
XiaoLing - Pharmacotherapy for Depression.pm1d 8/2/2010, 6:21 PM
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IdedicatethisbooktomychildrenYanniandEllie.
George
IamextremelygratefultomywifeStefania
andoursonGiovanni
fortheirincrediblesupportofmywork.
Maurizio
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About the Authors
George I. Papakostas
GeorgeI.PapakostasisAssociateProfessorofPsychiatryatHarvard
MedicalSchoolandDirectorofTreatment-ResistantDepressionStu-
diesintheDepartmentofPsychiatryatMassachusettsGeneralHos-
pital in Boston, Massachusetts, USA. The focus of Dr. Papakostas’
researchincludesthepharmacotherapyofmajordepressivedisorder
includingtreatment-resistantdepression,thestudyofthe“placebo”
effectanditsrelevancetoclinicaltrialdesigninmajordepressivedis-
order,andthestudyofclinicalandbiologicpredictors,moderators,
and mediators of treatment outcome in major depressive disorder.
Dr. Papakostas has received numerous national and international
research awards from sources including the American College
of Neuropsychopharmacology, the Collegium Internationale Neu-
ropsychopharmacologium,theNewClinicalDrugEvaluationUnit
of the National Institute of Mental Health, the American Psychi-
atric Association, the World Federation of Societies of Biological
Psychiatry, the American Academy of Clinical Psychiatrists, the
InternationalCollegeofPsychosomaticMedicine,andtheAmerican
FoundationforSuicidePrevention.Heistheauthororco-authorof
over 150 clinical and scientific publications and book chapters, his
publications appearing in prominent journals, including the Amer-
ican Journal of Psychiatry, Biological Psychiatry, the Journal of Clinical
Psychiatry,andthe JournalofClinicalPsychopharmacology. Heisalso
ontheeditorialboardofthejournalPsychiatryResearch,andafield
editorforpsychopharmacologyfortheWorldJournalofBiologicalPsy-
chiatry.Dr.PapakostasisofteninvitedthroughouttheUnitedStates
vii
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viii PharmacotherapyforDepressionandTreatment-ResistantDepression
and abroad to lecture on a wide range of topics pertaining to the
treatmentofdepression.Todate,hehasdeliveredmorethan100lec-
turesatnationalorinternationalmeetingsinmorethan30countries.
Dr. Papakostas attended Medical School at the New York
University School of Medicine. He completed his residency in
adult psychiatry at Massachusetts General Hospital and McLean
Hospital, and a fellowship in Clinical Neuropsychopharmacology
atMassachusettsGeneralHospitalthatwasfundedbytheAmerican
CollegeofNeuropsychopharmacology.
Maurizio Fava
Dr.FavaobtainedhismedicaldegreefromtheUniversityofPadova
School of Medicine, USA, and completed a residency training in
endocrinologyatthesameuniversity.Aftercompletingaresidency
traininginpsychiatryattheMassachusettsGeneralHospital(MGH),
hehasbeenDirectoroftheMGHDepressionClinicalandResearch
Programsince1990atthesamehospital.UnderDr.Fava’sdirection,
the MGH Depression Clinical and Research Program has become
oneofthemosthighlyregardeddepressionprogramsinthecountry.
Dr.Favahasauthoredorco-authoredmorethan400originalarticles
publishedinmedicaljournalswithinternationalcirculation.Hehas
alsoeditedfivebooks,andpublishedmorethan50chaptersand500
abstracts. Dr. Fava is also a well-known national and international
speaker,andhasalsobeentherecipientofmanyhonorsandawards.
He is currently Executive Vice Chair for the MGH Department of
Psychiatry, Executive Director, MGH Clinical Trials Network and
Institute,andDirectoroftheMGHDepressionClinicalandResearch
Program,andProfessorofPsychiatryatHarvardMedicalSchool.
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Preface
Major depressive disorder (MDD) is a highly prevalent and, often,
chronic illness, which has been shown to result in considerable
patientsufferinganddistress,aswellassignificantdisability,mor-
bidity and mortality. Despite more than half a century of intensive
research, contemporary therapies for MDD demonstrate, at best,
modestoverallefficacy,mostoftenresultingineitheracompletelack
oforinsufficientsymptomimprovement.Inaddition,thetolerability
profile of all contemporary pharmacotherapies for MDD, although
greatlyimprovedsincetheirfirstappearanceinthemid-1950s,can
oftencontributetopoortreatmentadherence,aswellaspatientdis-
comfortanddisability.Furthermore,manypatientswhoexperience
robustantidepressanteffectsmaystillsufferarelapseorrecurrence
ofMDDshortlyafterthefulleradicationofsymptoms,anddespite
full compliance with their treatment. As a result, patients with
depressionoftendescribefeelingsasiftheyarecaughtinavicious
cycle, with only brief periods of complete symptom recovery that
arenotsufficientindurationtoallowforareturntothepre-morbid
leveloffunctioning.
When depression strikes, clinicians, patients, their families and
their loved ones are on the front line. Supporting them are those
working vigorously to enhance our ability to effectively treat
depression: those working in academic clinical care and research
centers, government sources including the National Institutes of
Health, the pharmaceutical industry, as well as private donors
and fundraisers. This book is intended as a review on the state
of our knowledge regarding pharmacologic treatments for depres-
sion. It is divided into four parts. The first three parts focus on
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