Life-Threatening Effects of Antipsychotic Drugs

360 Pages·2016·5.296 MB·English

by  Peter Manu, Robert J. Flanagan, Kathlyn J. Ronaldson

Life-Threatening Effects
of Antipsychotic Drugs
Life-Threatening Effects
of Antipsychotic Drugs
Edited by
Peter Manu
HofstraNorthwell SchoolofMedicine, Hempstead,NY, UnitedStates;
SouthOaks Hospital,Amityville,NY, UnitedStates
Robert J. Flanagan
King’sCollege Hospital, London,United Kingdom
Kathlyn J. Ronaldson
Monash University, Melbourne, VIC, Australia
AMSTERDAM(cid:129)BOSTON(cid:129)HEIDELBERG(cid:129)LONDON
NEWYORK(cid:129)OXFORD(cid:129)PARIS(cid:129)SANDIEGO
SANFRANCISCO(cid:129)SINGAPORE(cid:129)SYDNEY(cid:129)TOKYO
AcademicPressisanimprintofElsevier
AcademicPressisanimprintofElsevier
125LondonWall,LondonEC2Y5AS,UnitedKingdom
525BStreet,Suite1800,SanDiego,CA92101-4495,UnitedStates
50HampshireStreet,5thFloor,Cambridge,MA02139,UnitedStates
TheBoulevard,LangfordLane,Kidlington,OxfordOX51GB,UnitedKingdom
Copyrightr2016ElsevierInc.Allrightsreserved.
Nopartofthispublicationmaybereproducedortransmittedinanyformorbyanymeans,electronic
ormechanical,includingphotocopying,recording,oranyinformationstorageandretrievalsystem,
withoutpermissioninwritingfromthepublisher.Detailsonhowtoseekpermission,furtherinformation
aboutthePublisher’spermissionspoliciesandourarrangementswithorganizationssuchasthe
CopyrightClearanceCenterandtheCopyrightLicensingAgency,canbefoundatourwebsite:
www.elsevier.com/permissions.
ThisbookandtheindividualcontributionscontainedinitareprotectedundercopyrightbythePublisher
(otherthanasmaybenotedherein).
Notices
Knowledgeandbestpracticeinthisfieldareconstantlychanging.Asnewresearchandexperience
broadenourunderstanding,changesinresearchmethods,professionalpractices,ormedicaltreatment
maybecomenecessary.
Practitionersandresearchersmustalwaysrelyontheirownexperienceandknowledgeinevaluating
andusinganyinformation,methods,compounds,orexperimentsdescribedherein.Inusingsuch
informationormethodstheyshouldbemindfuloftheirownsafetyandthesafetyofothers,including
partiesforwhomtheyhaveaprofessionalresponsibility.
Tothefullestextentofthelaw,neitherthePublishernortheauthors,contributors,oreditors,assume
anyliabilityforanyinjuryand/ordamagetopersonsorpropertyasamatterofproductsliability,
negligenceorotherwise,orfromanyuseoroperationofanymethods,products,instructions,orideas
containedinthematerialherein.
BritishLibraryCataloguing-in-PublicationData
AcataloguerecordforthisbookisavailablefromtheBritishLibrary
LibraryofCongressCataloging-in-PublicationData
AcatalogrecordforthisbookisavailablefromtheLibraryofCongress
ISBN:978-0-12-803376-0
ForInformationonallAcademicPresspublications
visitourwebsiteathttps://www.elsevier.com/
Publisher:NikkiLevy
AcquisitionEditor:NikkiLevy
EditorialProjectManager:BarbaraMakinster
ProductionProjectManager:Julie-AnnStansfield
Designer:MatthewLimbert
TypesetbyMPSLimited,Chennai,India
List of Contributors
JamesF.Barrecchia ZuckerHillsideHospital,GlenOaks,NY,UnitedStates
DanCohen MentalHealthServicesNorth-HollandNorth,Heerhugowaard,
TheNetherlands; UniversityofGroningen,Groningen,TheNetherlands
AncaDan ColentinaHospital,Bucharest,Romania
Gheorghe-AndreiDan ColentinaHospital,Bucharest,Romania; CarolDavila
UniversityofMedicineandPharmacy,Bucharest,Romania
MarcDeHert UniversityPsychiatricCenterUniversityofLeuven,Kortenberg,
Belgium
MeganJ.Ehret FortBelvoirCommunityHospital,FortBelvoir,VA,UnitedStates
RobertJ.Flanagan King’sCollegeHospital,London,UnitedKingdom
WalterFro¨scher UlmUniversity,Ulm,Germany
JamesJ.Gugger JohnsHopkinsSchoolofMedicine,Baltimore,MD,UnitedStates
ChristopherHohman ZuckerHillsideHospital,GlenOaks,NY,UnitedStates
RichardI.G.Holt UniversityofSouthampton,Southampton,UnitedKingdom
JohnLally King’sCollegeLondon,London,UnitedKingdom
JulieLanganMartin UniversityofGlasgow,Glasgow,UnitedKingdom
PeterManu HofstraNorthwellSchoolofMedicine,Hempstead,NY,
UnitedStates; SouthOaksHospital,Amityville,NY,UnitedStates
DanielJ.Martin UniversityofGlasgow,Glasgow,UnitedKingdom
KatieF.M.Marwick UniversityofEdinburgh,Edinburgh,UnitedKingdom
AlexJ.Mitchell UniversityofLeicester,Leicester,UnitedKingdom
KathlynJ.Ronaldson MonashUniversity,Melbourne,VIC,Australia
KatherineSamaras GarvanInstituteofMedicalResearch,Sydney,NSW,Australia
MatisyahuShulman ZuckerHillsideHospital,GlenOaks,NY,UnitedStates
TilmanSteinert UlmUniversity,Ulm,Germany
BrendonStubbs King’sCollegeLondon,London,UnitedKingdom; MaudsleyNHS
FoundationTrust,London,UnitedKingdom
DavyVancampfort UniversityPsychiatricCenterUniversityofLeuven,Kortenberg,
Belgium
Jian-PingZhang HofstraNorthwellSchoolofMedicine,Hempstead,NY,
UnitedStates
xiii
Foreword
The Art and Science of Balance: Managing
the Efficacy and Safety of Antipsychotic Drugs
With the serendipitous discovery of chlorpromazine as the first “major
tranquillizer” over six decades ago, a new class of “antipsychotics” was born.
After predominant use for psychosis and agitation associated with different
psychiatric and medical conditions, antipsychotic medications became used
much more widely about two decades ago. This more widespread use of anti-
psychotics coincides with the development of a new “class” of antipsychotics,
the so-called “atypical” or second-generation antipsychotics that had less
of the neuromotor adverse effects of the so-called “typical” or first-generation
antipsychotics,butthatalsoaffectedmoreextra-dopaminergicneurotransmitter
targets. In fact, nowadays, antipsychotics are being used the most for nonpsy-
chotic conditions, including motor tics, stuttering, behavioral dysregulation
and impulsivity, nonpsychotic aggression, irritability, mania, depression,
anxiety,insomnia,obsessionsandcompulsions,eatingdisorders,etc.
It is clear that the heterogeneous class of medications that is still called
antipsychotics is efficacious for severe mental disorders and their various
symptoms that are often highly impairing. However, as with all medications,
these molecules can also have adverse effects. Clinically, efficacy and safety
need to be balanced. In the medical literature, adverse effects are often given
a second place to the exploration and description of efficacy. However, for
many psychiatrically ill patients, concerns about tolerability and safetytrump
efficacy considerations. Similarly, clinicians’ ability to effectively use medi-
cations is limited by their propensity to cause relevant side effects. Although
there are articles, chapters, and, even, books that focus on adverse effects,
the book Life-Threatening Effects of Antipsychotic Drugs is the first of its
kind.
While the title could sound alarmist, the clear intention of this impressive
volume is not to warn against the use of antipsychotics. The deliberation
about the use, choice of agent, and duration of treatment is a clinical
decision. Rather, the book’s seven sections populated by 16 chapters and
written by experts in the respective areas, aim to thoroughly educate about
the possibility and nature of severe and potentially life-threatening adverse
effects of antipsychotics. The book and its chapters tell clinicians that these
xv
xvi Foreword
adverse effects, although fortunately generally rare, do exist and that clini-
cians need to be equipped to identify and deal with them in order to provide
optimal care. Detailed knowledge about the serious adverse events covered
in this book should not lead clinicians to stop using antipsychotics when
they are needed, but should rather lead to a more informed and judicious use
of antipsychotics. Clinicians should not be intimidated by the described
potentially life-threatening adverse effects, but rather be as educated as
possible about how to prevent, identify, and manage them. Patients’ and
families’ participation in shared decision making also needs to be informed
by such knowledgeas appropriate.
Anydrugeffectresultsfromaninteractionbetweenthepharmacodynamic
and pharmacokinetic properties of the medication, the clinician prescribing
the medication in a certain way, the individual patient receiving the medica-
tion, and specific circumstances at the time. Most individual risk can be
anticipated, monitored, and managed. However, there are also idiosyncratic
reactions, interactions with other medications and unpredictable outcomes.
Thebestwaytodealwiththeunknownistoeducateoneselfasmuchasposs-
ible about the known around it. In this spirit, Life-Threatening Effects of
Antipsychotic Drugs will help clinicians to be less surprised and caught off
guard, feel equipped about what and when to ask and to monitor in order to
catchsignsofdevelopingadverseeffectsearly,howtomanageadverseevents
appropriately, and when to refer to other specialists as needed. Having read
or consulted this authoritative book will help clinicians optimize the benefit-
to-risk ratio for their patients who require acute or ongoing antipsychotic
treatment.
Clearly, despite the scholarship and clinical wisdom contained in
each chapter of Life-Threatening Effects of Antipsychotic Drugs, a lot more
needs to be learned. Additional research is needed to identify patient level
risk factors and to help identify potentially life-threatening adverse effects
before they become so serious that they cannot be managed well anymore.
Other treatment strategies that can effectively counter potentially serious
adverse effects need to be identified, so that they are not life-threatening.
Medications need to be developed devoid of the described risks. While
there will hopefully be additional knowledge added over the next years to
come, Life-Threatening Effects of Antipsychotic Drugs summarizes what we
know todate,providingclinicianswith toolstoimprovetheir careofpatients
treatedwith antipsychotics.
ChristophU. Correll and John M. Kane
Preface
Medical deteriorations can have major adverse consequences for psychiatric
patients. They interrupt behavioral interventions and may require the discon-
tinuation of psychotropic drug treatment. When they occur in a psychiatric
hospital ward, such deteriorations prolong the length of stay and can add
considerable expense to the episode of mental illness. They may also prove
fatal even when the conditions are rapidly diagnosed and treated. Most of
the time, the life-threatening somatic disorders encountered in psychiatric
practice are due to exacerbations of established conditions, such as coronary
artery disease, chronic obstructive pulmonary disease, or liver cirrhosis.
However, some of the cases represent adverse effects of psychotropic drugs.
In this category, the greatest concern is represented by the antipsychotic
drugs, molecules that bind to numerous receptors in the brain and elsewhere
and may lead tomany organ-specific orsystemic complications.
The deaths occurring in persons taking antipsychotic drugs belong to
four categories: homicides or suicides; natural deaths not-related to the
antipsychotic treatment; overdoses; and adverse effects of medications taken
in therapeutic doses. The mechanisms of deaths produced by adverse effects
of antipsychotic drugs prescribed, administered and taken in therapeutic
dosages are relatively well understood. The antipsychotic-induced delay in
myocardial repolarization may lead to a polymorphic ventricular arrhythmia,
torsades de pointes, which can degenerate into ventricular fibrillation
and produce sudden cardiac death. Pump failure and cardiogenic shock may
complicate the left ventricular dysfunction of antipsychotic-induced myocar-
ditis. Gas exchange failure and low cardiac output explain the death of
patients who developed massive pulmonary thromboembolism, a multifact-
orial condition to which antipsychotics may contribute directly by creating a
hypercoagulable state, and indirectly through decreased mobility, morbid
obesity, and inflammatory changes. Patients with drug-induced agranulocyto-
sis, severe gastrointestinal hypomotility, or pancreatitis are at risk of dying
from septic shock or from multiple organ failure. Multiple organ failure may
also complicate neuroleptic malignant syndrome, rhabdomyolysis, and heat
stroke. Postictal arousal failure followed by respiratory arrest is sometimes
seen in patients who had a drug-induced seizure. Asphyxia is the mode of
death in patients with airway obstruction produced by neuroleptic-related
xvii
xviii Preface
oropharyngeal dysphagia. Finally, in patients with severe drug-induced
kidneyorliver failure,death may be the outcome ofcatastrophic bleeding.
The scientific assessment of these potentially fatal drug effects is limited
by the lack or prospective, long-term controlled trials and by suboptimal
postmortem investigations. Without exception, all of the large-scale epidemi-
ologicalstudiesonfatalityratespresented inthisbookhavereliedonclinical
assessments, rather than on complete forensic evaluation that included a
careful autopsy and accurate toxicological measurements. Therefore, the
prevention of these medical deteriorations has remained the subject of
debate, as has the risk of recurrent complications once the antipsychotic drug
therapy is restarted.
This book represents the first attempt to describe in detail what is known
about life-threatening adverse effects of antipsychotic drugs. Edited by a
multidisciplinaryteam,thechaptersdescribingtheseadverseeffectsarebased
on the best available evidence, presented in a sequence that will allow the
readers to learn the epidemiology, pathobiology, clinical features, and
principles of management and prevention of these complications in
psychiatricsettings.Additionalchaptershighlightthebenefitsofantipsychotic
drugs and propose models for risk(cid:1)benefit analyses by frontline clinicians.
Theworkisnotintendedtoreplaceprintandelectronicresourcesrequiredfor
the practice of psychopharmacology, but to offer a sensible framework for
dealing with complications that may have devastating consequences on
patients,theirfamilies,andtheirphysicians.
Peter Manu, Robert J. Flanagan and Kathlyn J. Ronaldson
Editors
Acknowledgments
This book owes its existence to the hard work, talent, and dedication of our
contributors, scientists and clinicians from Australia, Belgium, Germany,
Great Britain, Ireland, the Netherlands, Romania, and the United States. As
the Editors of their work, we extend our thanks and deep appreciation to all
for their investment of time together with their insight, knowledge, and
discernment. We are also grateful to John Kane and Christoph Correll for
their advice during the planning of the book and for providing an illuminat-
ing Foreword toit.
Kathlyn Ronaldson is grateful to Professor John McNeil, Head,
Department of Epidemiology and Preventive Medicine, Monash University
for enabling her access to the resources of the University to complete the
workof writing chapters and editing thisbook.
We acknowledge the valuable suggestions made by the Elsevier’s
reviewers of our book proposal and the grace and patience with which
Julie-Ann Stansfield and her team have worked with us during the produc-
tion of thisbook.
xix
Symbols and Conventions
We have used either Syste`me Internationale (SI) symbols for quantities such
as g (gram), m (meter), s (second), or symbols accepted for use with SI such
as L (liter), min (minute), h (hour), d (day), mo (month), yr (year). We have
adopted the superscript notation for use with symbols, e.g., mgL21, as this
expresses rates, e.g., min21, and complex units, e.g., mgkg21day21, clearly
and unambiguously.
For more information on SI, see Flanagan, R.J., 1995. Leading article:
SI units—common sense not dogma is needed. Br. J. Clin. Pharmacol. 39,
589(cid:1)594.
xxi