`
`‘ERSHREGTATETROTORSSRNSTEMOCRTIO
`
`THE AMERICANPSYCHIATRIC PRESS
`PENMeRREST
`TEXTBOOKOF PSYCHIATRY
`
`
`
`THIRD EDITION
`
`
`
`
`
`EDITED BY
`
`ROBERT E. HALES, M.D., M.B.A.
`Professor and Chair, Department ofPsychiatry,
`University of California, Davis School of Medicine;
`Director, Behavioral Health Center, UC Davis Health System;
`Medical Director, Sacramento County Mental Health Services,
`Sacramento, California
`
`STUART C. YUDOFSKY,M.D.
`D. C.and Irene Ellwood Professor and Chairman,
`Departmentof Psychiatry and Behavioral Sciences,
`Baylor College of Medicine;
`Chief, Psychiatry Service,
`The Methodist Hospital,
`Houston, Texas
`
`JOHN A. TALBOTT, M.D.
`Professor and Chairman,
`Departmentof Psychiatry,
`University of Maryland School of Medicine,
`Baltimore, Maryland
`
`
`
`|asco lite
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`American
`sychiatric
`
`Washington, DC
`London, England
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`Note: Theauthors have worked to ensure thatall information in this book concerning drug dosages, schedules, and routes
`of administration is accurateas ofthe time of publication and consistent with standards set by the U.S. Food and Drug Ad-
`ministration and the general medical community. As medical research and practice advance, however, therapeutic standards
`may change. For this reason and because human and mechanical errors sometimes occur, we recommendthatreadersfol-
`low the advice of a physician whois directly involved in their care or in the care of a memberoftheir family.
`Bookspublished by the American Psychiatric Press, Inc., represent the views and opinionsofthe individual authors and do
`not necessarily representthe policies and opinionsof the Press or the American Psychiatric Association.
`Diagnostic criteria included in this textbook are reprinted, with permission, from the Diagnostic and Statistical Manual of
`Mental Disorders, 4th Edition. Copyright 1994, American Psychiatric Association.
`Copyright © 1999 American Psychiatric Press, Inc.
`
`ALL RIGHTS RESERVED
`
`Manufactured in the United States of America on acid-free paper
`Third Edition
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`99
`43 2
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`American Psychiatric Press, Inc.
`1400 K Street, N.W., Washington, DC 20005
`www.appl.org
`Library of Congress Cataloging-in-Publication Data
`The American Psychiatric Press textbook of psychiatry / edited by
`Robert E. Hales, Stuart C. Yudofsky, John A. Talbott. — 3rd ed.
`p.
`cm.
`Includes bibliographical references and index.
`ISBN 0-88048-819-0 (alk. paper)
`IL. Yudofsky, Stuart C.
`1. Psychiatry.
`I. Hales, Robert E.
`IIL. Talbott, John A.
`IV. Title: Textbook of psychiatry.
`[DNLM:
`1. Mental Disorders.
`2. Psychiatry. WM 100 A5112 1999]
`RC454.A197
`1999
`616.89—dc21
`DNLM/DLC
`for Library of Congress
`
`98-43411
`CIP
`
`British Library Cataloguing in Publication Data
`A CIPrecordis available from the British Library.
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`CHAPTER 13
`
`MOOD DISORDERS
`
`STEVEN L. DUBOVSKY, M.D.
`RANDALL BUZAN, M.D.
`
`One knows not whether there can be human compassionfor anemia ofthe soul. When thepitch oflife is dropped and
`thespirit is soput over and reversed that only is horrible which before was sweet and worldly andofthe day, the hu-
`man relation disappears.
`
`—Oliver Onions
`
` ood
`
`relatively |
`be
`can
`disorders
`Mistraightforward, or they can assume
`fa
`complex formsthat can bedifficult to treat. In this chap-
`ter, we review the epidemiology, diagnosis, comorbidity,
`and treatmentof the wide variety ofaffective syndromes
`that are encounteredin psychiatric practice.
`
`EPIDEMIOLOGY
`
`Estimates of the incidence and prevalence of mooddisor-
`dersvary. In the UnitedStates, the lifetimerisk of a major
`depressive episodeis said to be around 6%, andthelifetime
`risk of any mooddisorderis said to be around 8% (Cassem
`1995; Kashani and Nair 1995). The prevalence of major
`
`depression ranges from 2.6% to 5.5% in men and from
`6.0% to 11.8% in women (Fava and Davidson 1996). The
`prevalence of dysthymia is 3%—-4% (Keller et al. 1996).
`Somereports suggest that as much as 48% of the United
`States population has had oneor morelifetime moodepi-
`sodes (Cassem 1995). Most studies have found unipolar
`depression in general to be twice as common in womenas
`in men (Reynoldset al. 1990). The meaningof the gender
`difference remainsto beclarified. Gender does not appear
`to affect the prevalence ofbipolar disorder (Reynoldsetal.
`1990). The incidence of major depressionis higher in sep-
`arated or divorced people than in marriedindividuals,es-
`pecially men, and in medically ill patients (Lehtinen and
`Joukamaa 1994; Reiger etal. 1988), and depressionis asso-
`ciated with greater use of general health services
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`THE AMERICAN PSYCHIATRIC PRESS TEXTBOOK OF PSYCHIATRY, THIRD EDITION
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`(Weissmanetal. 1988b). The prevalence ofmajor depres-
`sion in primary carepracticeis 4.8%—9.2 %, and the preva-
`lence ofall depressive disorders is 9%—-20%, which makes
`mooddisorders the most commonpsychiatric problemsin
`primary care (McDanielet al. 1995).
`Theeffects of culture andstress on the prevalence of
`depression wereillustrated by the Cross-National Collab-
`orative Group studyof 10 countries, which used the Diag-
`nostic Interview Schedule to make DSM-III (American
`Psychiatric Association 1980) diagnoses (Weissmanetal.
`1996). In this study, the lifetime rate for major depression
`varied from a low of 1.5 cases/100 adults in Taiwan to as
`many as 19.0/100 in Beirut, and the annualrate of depres-
`sion was as low as 0.8 cases/100 in Taiwan andas high as
`5.8/100 in New Zealand.
`The prevalence of bipolar disorder is generally re-
`ported as being between 1% and 2.5% (Akiskal 1995b;
`Angst 1995; Bebbington 1995; Kashani and Nair 1995);
`however, somestudies suggest rates for bipolar mooddis-
`orders of 3%-6.5% (Akiskal 1995b; Angst 1995):.Thefre-
`quencywith whichbipolar disorderisdiagnosed probably
`depends on howitis defined; broaderdefinitions produce
`significantly higher rates (Akiskal 1995b; Angst 1995).
`Most prevalence studies require the presence ofmaniafora
`bipolar diagnosis to be recorded,butthe bipolarII variant,
`which is characterized by episodes of hypomania but not
`mania, is more commonthanthebipolarI variant (Cassano
`et al. 1989; Simpson etal. 1993). Ifbipolar spectrum disor-
`ders (Akiskal 1995b), or subsyndromal and complex forms
`ofbipolar disorder(discussedlater in this chapter), are also
`considered, the incidence of bipolar mooddisorderis sub-
`stantially higher. Roughly 10%~15% ofpatients with a di-
`agnosis ofunipolar depression will eventually receive a re-
`vised diagnosis of bipolar disorder (Ollie et al. 1992).
`Whenconservative criteria are used, between 5% and
`15% of cases of adult depression are foundto be bipolar
`(Bebbington 1995; Geller et al. 1996). Akiskal’s group
`(Cassanoetal. 1989) found that one-third of patients with
`primary depression mettheir criteria for bipolar spectrum
`disorders. Therisk of bipolarity is higherin juvenile major
`depression—atleast 20% in adolescents and 32% in chil-
`dren ages less than 11 years (Geller et al. 1996). Thelife-
`timerate of bipolar disorderis relatively consistent across
`cultures, ranging from 0.3/100 in Taiwan to 1.5/100 in
`New Zealand (Weissmanetal. 1996).
`In all industrialized countries in the world, the inci-
`dence of depression, mania, suicide, and psychotic mood
`disorders has been increasing in every generation born af-
`ter 1910 (Cross-National Collaborative Group 1992;
`Klerman 1988; Klermanet al. 1985). For unknown rea-
`sons, there was an abrupt jumpin therate of increase for
`
`people born after 1940—atrueincreasein the incidence of
`mooddisorders (cohorteffect) and nota function ofbetter
`recognition (Cross-National Collaborative Group 1992;
`Klerman 1988; Klermanetal. 1985). Not only are mood
`disorders becoming more common,but they are appearing
`at an earlier age (especially bipolar mooddisorders) (Lasch
`and Weissman 1990).
`Suicide is an obviouspublic health problem that com-
`plicates mood disorders more frequently than other condi-
`tions. The lifetime risk of suicide in mood disordersis
`10%-15% (Barklage 1991; Guze and Robbins 1970;
`Mueller and Leon 1996), and therisk of attempted suicide
`was increased 41-fold in depressed patients compared with
`those with other diagnoses in the Epidemiologic Catch-
`ment Area survey (Petronis et al. 1990). It is well known
`that womenattemptsuicide more frequently than men, but
`menare morelikely to succeed. In one study, however, the
`excess risk of completed suicide in men wasentirely ac-
`counted for by a higher prevalence of substance abusein
`men and a greaterlikelihood that women have primary re-
`sponsibility for children under age 18 (Youngetal. 1994).
`Therisk of suicideis high in maniaas well as in depression.
`Patients with mixed bipolar states characterized by a com-
`bination of depression,rage, and grandiosity may be more
`likely to involve others in a suicide attempt—for example,
`through gunfights with the police. As many as 4% ofpeople
`who commit suicide murder someoneelsefirst.
`Although manyclinicians agree on factors that in-
`crease therisk ofsuicide, formal attempts to predict suicide
`have been disappointing (Oxley and Van Meter1996). This
`is not surprising; suicideis such a rare event(in the United
`States, the rate is about 11/100,000) that a prohibitively
`large number ofpatients would have to be followed pro-
`spectively to demonstrate that a constellation of features
`predictedan increasedrisk. In addition, no consensusexists
`about how longto follow a depressed patient before a con-
`clusion can be madethat suicide will not occur. There may
`bea statistically significant association betweensuicide and
`traditionalrisk factors such as older age, recent loss, male
`sex, bipolar depression, psychosis, comorbid substance
`abuse,history of a suicide attempt(especially ifit was dan-
`gerous), and family history ofsuicide,butthis associationis
`notnecessarily helpful in predicting suicide in an individ-
`ual patient.
`Despite the demonstrated inability of mental health
`professionals to predict (or prevent) suicide in any system-
`atic manner (H.L. Miller et al. 1984), patients, families,
`and courts expect them to be able to do so. In an evaluation
`of immediate suicide risk, factors summarized in Table
`13-1 can be considered (Oxley and Van Meter 1996;
`Pokorny 1993; Youngetal. 1994). However, these factors
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`MOOD DISORDERS
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`TABLE 13-1. Factors suggesting an increasedrisk of
`suicide
`
`Demographic factors
`Male sex
`
`Recentloss
`
`Never married
`
`Older age
`Symptoms
`Severe depression
`Anxiety
`Hopelessness
`Psychosis, especially with commandhallucinations
`History
`History ofsuicide attempts, especially if multiple or severe
`attempts
`Family history of suicide
`Active substance abuse
`
`Suicidal thinking
`Presence of a specific plan
`Meansavailable to carry out the plan
`Absenceof factors that would keep the patient from
`completing the plan
`Rehearsalof the plan
`
`at best suggest increased immediaterisk. In addition,it is
`not known whetheronerisk factor is more important than
`another or howrisk factors may interact with each other
`(Oxley and Van Meter 1996). Given the currentstate of
`knowledge,it is probably impossible for anyoneto predict
`with any accuracythe long-term risk ofcompleted suicide.
`
`MOOD DISORDERSIN SPECIAL POPULATIONS
`
`Postpartum depression occurs in about 10% of mothers;
`risk factors include a history ofa mood disorder, unwanted
`pregnancy, unemployment of the mother,
`lack of
`breast-feeding, and the motheras head of the household
`J. Hopkinsetal. 1984; Warneretal. 1996). Postpartum
`depression increasesthe chanceof alcohol andillicit drug
`use in teenage mothers (Barnetet al. 1995). Thereis some
`evidence that depression ina motheradversely affects tem-
`perament(C. T. Beck 1996) and cognitive development
`(Hay and Kumar1995)in the infant. Depressed mothersof
`preschoolers have more negative perceptionsofandinter-
`actions with their children (Langet al. 1996).
`Estimates of the prevalence of major depressionin el-
`derly people range from 2%—4% in community samples to
`12% ofmedically hospitalized patients to 16% ofgeriatric
`patients in long-term care (Blazer and Koenig 1996). Geri-
`
`atric depressionis associated with an increased likelihood
`ofcerebrovascular disease and enlarged ventricles and may
`be morelikelythan depression in youngerpatients to be ac-
`companied by prominent cognitive complaints (Soares and
`Mann 1997).
`Majordepressive disorder (MDD)is said to occur in as
`many as 18% ofpreadolescents, with no genderdifferences
`(Kashani and Nair 1995). However, mooddisordersareof-
`ten underdiagnosedin this population because manyclini-
`ciansstill do notbelieve that depression occursin children
`and because depression may be moredifficult to recognize
`in children thanin older patients. Amongadolescents, the
`prevalence ofMDDhasbeenreported to be 4.7% in 14- to
`16-year-olds (Kashani and Nair 1995). By this age, depres-
`sion is more commonin girls than in boys (Kashani and
`Nair 1995). In nonclinical samples, up to one-third of ado-
`lescents reported somedepressive symptoms (Kashani and
`Nair 1995). Major depression in adolescentsis associated
`with substance abuse andantisocial behavior, both ofwhich
`sometimes obscure the affective diagnosis (Kashani and
`Nair 1995). The lifetime prevalence of bipolar disorder
`was 0.6% in 150 adolescents who were notpsychiatrically
`referred (Kashani and Nair 1995). As discussedlaterin this
`chapter, manycasesofbipolar disorder in youngerpatients
`maybe overlooked because many depressedchildren and
`adolescents havenotyet hadtime to exhibit mania andbe-
`cause manic symptoms, when present, may be confused
`with behaviordisorders and attention-deficit disorder.
`
`ECONOMICS OF MOOD DISORDERS
`
`Depression produces more impairmentof physical func-
`tioning, role functioning, social functioning, and per-
`ceived currenthealth,is associated with more bodily pain,
`andcausespatients to spend more days in bed due to poor
`health than hypertension, diabetes, arthritis, and chronic
`pulmonary disease (Wells et al. 1989). In a study ofgeneral
`medical patients in a health maintenance organization,pa-
`tients with depressed moodor anhedoniaof2 weeks’ dura-
`tion but with an insufficient numberofadditional symp-
`toms to meetfull criteria for MDD still had 7.7 times as
`much impairmentofsocial, family, and work functioning
`as did patients without any depressive symptoms (Olfson
`1996). Thetotal cost of depressive disorders in the United
`States is generally estimated at $44 billion (Hall and Wise
`1995). This is equivalentto the total cost ofcoronary heart
`disease, a condition that is no more prevalent and less
`readily treatable than depression. Thedirectcostsoftreat-
`ing depression are about $12 billion, only $890 million of
`which is accounted for by the price of antidepressants
`(Hall and Wise 1995). Yet, tremendouseffort is being
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`expended by third-party reviewersto get physiciansto pre-
`scribe cheaper antidepressants. The morbidity cost of de-
`pressive disorders in the United States is around $24 bil-
`lion, and the mortality costs are $8 billion; these costs can
`be attributedin part to increasedaccidentrates, substance
`abuse, development ofsomaticillness, and increased use of
`medical hospitalization and outpatient treatment (Hall
`and Wise 1995).
`
`DIAGNOSIS
`
`Attempts to classify depression date back to at least the
`fourth century B.C., when Hippocrates coined the terms
`melancholia (black bile), and mania (to be mad). The inde-
`pendentdescriptions in 1854 by two French physicians,
`Falret and Baillarger, offolie circulaire and lafolie 4 double
`forme werethe first formal diagnoses ofalternating epi-
`sodes of mania and depressionas a single disorder (Sedler
`1983). At the beginning of the current century, Emil
`Kraepelin differentiated schizophrenia (dementia prae-
`cox) from “manic-depressive insanity”on the basis ofa de-
`teriorating course of the former and an episodic course of
`the latter (Akiskal 1996). Kraepelin (1921) believed that
`manic-depressive insanitywasa single illness thatincluded
`“periodic andcircular insanity,” mania, and melancholia.
`Many of Kraepelin’s observations of the symptoms and
`course of mood disorders remain accurate, but manic-
`depressive (bipolar) disorder isnow known to be acomplex
`group ofdisorders that share features suchas a highrate of
`recurrence and alternations of moodstates but differ in
`other important respects.
`Inthe United States, the first edition ofDSM,Diagnos-
`tic and Statistical Manual: Mental Disorders (American Psy-
`chiatric Association 1952), reflected the influence of
`Adolph Meyer. Meyerbelieved that psychiatric disorders
`were reactionsto conflict or stress that were more specific
`to the individual than to theillness. Psychotic mooddisor-
`ders (e.g., psychotic depressive reaction) were diagnosed
`on the basis notof hallucinations and delusions butofse-
`verity and lack ofa precipitant (American Psychiatric Asso-
`ciation 1952). In DSM-II (American Psychiatric Associa-
`tion 1968), involutional melancholia and manic-depressive
`psychosis were added. The concept of a depressive reaction
`was maintained as depressive neurosis, which was considered
`a neurotic reaction to an internalconflict or external event.
`In the absenceofa precipitant, a diagnosis ofpsychotic de-
`pressive reaction was made for a single episode and
`manic-depressive psychosis for recurrent depressive epi-
`sodes, whether or not the patient mettraditional criteria
`
`for psychosis in use by mostclinicians. Alternating depres-
`sion and elation wascalled cyclothymia, which wasclassified
`with the personality disorders on the grounds that it was
`chronic and was not caused bya specific circumstance. In
`‘ subsequenteditions of DSM (discussedlater in this chap-
`ter), mood disorder diagnosesare based on symptom clus-
`ters rather than the presence or absenceofan identifiable
`precipitant, since the presence ofa precipitantdoes not de-
`monstrably affect the course or treatment response of
`mooddisorders.
`
`ENDOGENOUS AND REACTIVE DEPRESSION
`
`Thedifferentiation of depression according to whether a
`precipitant is present is derived from anearly distinction
`between endogenous(vital or melancholic) and reactive
`depression.In its original use by German descriptive psy-
`chiatrists, the term reactive referred to a depressed patient’s
`ability to react positively to interactions and events and
`thus implied the presence of milder symptomatology. As
`the term wastranslated into English, however, it came to
`mean depression that developedin reaction to someexter-
`nal stress, thus implyingan association between mild de-
`pression and depression in responseto stress. In DSM-U,
`this concept was conservedas neurotic depressive reaction. In
`later informal diagnostic schemes,milder formsofdepres-
`sion that are more responsiveto the environmentevolved
`into the conceptofhysteroid dysphoria, whichis a type ofde-
`pression with atypical symptoms that occursin a patient
`with interpersonalsensitivity and a characterological ten-
`dency to dramatize (Shea and Hirschfeld 1996). In
`DSM-III-R (American Psychiatric Association 1987) and
`DSM-IV (American Psychiatric Association 1994a), the
`term atypicaldepression (a modifier ofa major depressive ep-
`isode) is moreor less equivalent to bysteroid dysphoria and
`the modernderivative of neurotic depression.
`Atypical depressionis distinguished by moodreactiv-
`ity (i.e., the capacity to be cheered up temporarily by posi-
`tive interactions or events) as well as by severe fatigue
`(leaden paralysis), sensitivity to rejection, self-pity, a re-
`verse diurnal mood swing (depressionis worse later in the
`day), and reverse vegetative symptoms(e.g., increased in-
`stead of decreased appetite and sleep) (M. T. Tsuang and
`Faraone 1996). About 15% of depressive episodes have
`atypical features. Atypical symptoms are more commonin
`bipolar depression. As is discussed later, atypical depres-
`sion appears to respond better to monoamine oxidase
`inhibitor (MAOJ) antidepressants than to other antide-
`pressants.
`In contrast to reactive depression, the term endogenous
`depression referred in the Germanliterature to depression
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`MOOD DISORDERS
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`that was unresponsive to the environment andin the Amer-
`ican literature to depression with greater severity, more
`considerable guilt and loss of interest, typical vegetative
`symptomssuch as decreased appetite andsleep, and other
`physical symptomssuchas difficulty concentrating,early
`morning awakening,and a diurnal mood swing(depression
`is worse in the morning) (M. T. Tsuang and Faraone
`1996). In DSM-IV,the melancholicfeatures specifier retains
`mostof the features of endogenousdepression; recent re-
`search suggests that “lack of reactivity” and “distinct qual-
`ity ofdepressed mood”predictthe full syndrome most con-
`‘ sistently (K. S. Kendler 1997). However, melancholic
`depression can appearin response to an obvious precipi-
`tant. Endogenous depression has a better response to
`tricyclic antidepressants than doesreactive depression and
`has a lower rate of response to psychotherapy and placebo
`(M. T. Tsuang and Faraone 1996).
`Recent work has confirmed that the melancholic sub-
`type ofmajor depressionis a more severe form ofmajor de-
`pression that is associated with more depressive episodes,
`more symptoms, more impairment, more help-seeking,
`and more comorbidity with anxiety disorders and nicotine
`dependence but that is not qualitatively different from
`nonmelancholic major depression (K. S. Kendler 1997). In
`twins, the presence of MDD with melancholicfeatures in
`one twin increasedthe risk ofmajor depression but notnec-
`essarily melancholia in the other twin (K. S. Kendler
`1997). Twin studies do not suggest an environmentalinflu-
`ence onliability to melancholia in depressedpatients (K.S.
`Kendler 1997). It is also now appreciated that melancholic
`and atypical depression are not necessarily mutually
`exclusive.
`
`DIAGNOSIS AND DSM-IV
`
`The term affect usually refers to the outward and change-
`able manifestation of a person’s emotional tone, whereas
`mood is a more enduring emotionalorientation that colors
`the person’s psychology (American Psychiatric Associa-
`tion 1984a). However, the change from affective disorders in
`DSM-III to mood disorders in DSM-IV does not imply a
`reconceptualization of what these disorders primarily in-
`volve(i.e., dysregulation of mood or dysregulation ofaf-
`fect); the two termsare used interchangeablyin DSM-IV.
`DSM-IV distinguishes between mood episodes and
`mood disorders (Fava and Davidson 1996; First et al.
`1996). An episodeis a period lasting at least 2 weeks during
`which there are enough symptomsforfull criteria to be met
`for the disorder. The criteria for a major depressive episode
`are summarized in ‘Table 13-2. Patients with or without a
`history of mania may have a major depressive episodeif
`
`TABLE 13-2. DSM-IV criteria for a major
`depressive episode
`
`A.
`
`Five (or more) ofthe following symptoms have been
`present during the same 2-week period and represent a
`change from previous functioning;at least oneof the
`symptomsis either (1) depressed moodor(2) loss of
`interest or pleasure.
`Note: Donot include symptomsthat are clearly due to a gen-
`eral medical condition, or mood-incongruentdelusionsor hal-
`Iucinations.
`(1) depressed mood mostofthe day, nearly every day, as
`indicated by either subjective report(e.g., feels sad or
`empty) or observation madeby others (e.g., appears
`tearful). Note: In children and adolescents, can be
`irritable mood.
`
`(3)
`
`(2) markedly diminished interest or pleasure in all, or
`almostall, activities most of the day, nearly every day
`(as indicated byeither subjective account or
`observation madebyothers)
`significant weight loss when notdieting or weight
`gain (e.g., a change of more than 5% of body weight
`in a month), or decrease orincrease in appetite
`nearly every day. Note: In children, consider failure
`to make expected weight gains.
`insomnia or hypersomnia nearly every day
`(4)
`(5) psychomotoragitationor retardation nearly
`every day (observable by others, not merely
`subjective feelings of restlessness or being slowed
`down)
`fatigueorloss of energy nearly every day
`feelings of worthlessness or excessive or
`inappropriate guilt (which may be delusional)
`nearly every day (not merely self-reproach or
`guilt about being sick)
`(8) diminished ability to think or concentrate, or
`indecisiveness, nearly every day (either subjective
`account or as observed by others)
`recurrent thoughts of death (not just fear of dying),
`recurrentsuicidal ideation without a specific plan, or
`a suicide attemptor a specific plan for committing
`suicide
`
`(6)
`(7)
`
`(9)
`
`The symptomsdo not meetcriteria for a mixed
`episode.
`‘The symptomscause clinically significant distress or
`impairmentin social, occupational, or other important
`areas of functioning.
`‘The symptomsare not dueto the direct physiological
`effects of a substance (e.g., a drug of abuse, a
`medication) or a general medical condition(e.g.,
`hypothyroidism).
`‘The symptomsare not better accounted for by Bereave-
`ment, i.e., after the loss of a loved one, the symptoms
`persist for longer than 2 monthsorare characterized by
`marked functional impairment, morbid preoccupation
`with worthlessness, suicidal ideation, psychotic
`symptoms, or psychomotorretardation.
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`TABLE 13-4. DSM-IV atypical features specifiersevo
`they fulfill these criteria, but major depressive disorder
`(MDD)refers to one or moreepisodes ofmajor depression
`With atypical features (can be applied when these features
`in the absence of mania or hypomania (i.e., unipolar de-
`predominate during the most recent 2 weeks of a major de-
`pression). A major depressive episode may be modified by
`pressive episode in major depressive disorderor in bipolar I or
`bipolar II disorder when the major depressive episode is the
`additionalspecifiers for melancholic features (Table 13-3)
`mostrecent type of mood episode, or whenthese features pre-
`and/or atypical features (Table 13-4).
`dominate during the mostrecent2 years of dysthymic disor-
`Theinterpretation ofstudies of mooddisordersis fa-
`der)
`cilitated by familiarity with several commonterms (Fava
`A. Moodreactivity (i.e., mood brightens in responseto
`and Davidson 1996; First et al. 1996). In most treatment
`actual or potential positive events)
`studies, response is defined as at least 50% improvement,
`Two(or more) ofthe following features:
`whereas partial response is 25%—50% improvement and
`(1)
`significant weight gain or increase in appetite
`nonresponse is < 25% improvement. Accordingtothis ter-
`minology, patients whoarestill half as symptomatic as at
`(2) hypersomnia
`the beginningof treatmentwill be considered responders
`(3)
`leaden paralysis (i.e., heavy, leaden feelings in arms
`at the end ofa treatment study. Thisis notatrivial point,
`or legs)
`given that moststudies consider improvement rather than
`(4)
`long-standingpattern ofinterpersonalrejection
`sensitivity (not limited to episodes of mood
`remission as the end point. Remission is definedasthe state
`disturbance) thatresults in significant social or
`of having few or no symptoms of a mooddisorder for at
`occupational impairment
`least 8 weeks. Recovery, the period after remission,is pres-
`C. Criteria are not met for with melancholic features or
`ent if no symptoms have been present for more than 8
`with catatonic features during the sameepisode.
`weeks, and the term implies that the disorderis quiescent.
`RT
`A relapse is a return of symptomsduring the period of re-
`mission, andthe term implies continuation ofthe original
`episode; whereas recurrenceis a later return of symptoms
`(during recovery), and this term implies development ofa
`
`B.
`
`TABLE 13-2. DSM-IV melancholic features
`specifieree
`With melancholic features (can be applied to the currentor
`most recent major depressive episode in major depressive dis-
`order and to a major depressive episode in bipolar I or bipolar
`II disorder onlyif it is the most recent type of mood episode)
`A. Either ofthe following, occurring during the most
`severe period ofthe current episode:
`(1)
`loss of pleasure in all, or almostall, activities
`(2)
`lack ofreactivity to usually pleasurable stimuli (does
`notfeel muchbetter, even temporarily, when
`something good happens)
`B. Three (or more)ofthe following:
`(1) distinct quality of depressed mood(i.e., the
`depressed moodis experiencedasdistinctly different
`from the kind offeeling experienced after the death
`of a loved one)
`(2) depression regularly worse in the morning
`(3)
`early morning awakening(atleast 2 hours before
`usual time of awakening)
`(4) marked psychomotorretardation or agitation
`(5)
`significant anorexia or weight loss
`(6)
`excessive or inappropriate guilt
`
`a
`
`new episode. Thesedistinctionscanbedifficult to make in
`clinical practice. For example, mild residual symptoms of
`an initial episode may be overlooked or maybeattributed
`to character pathology after improvementofthe more dra-
`matic manifestations of an episode; this may lead to the
`conclusion that a return of more severe symptoms repre-
`sents a new episoderatherthan an exacerbationofthe orig-
`inal episode.
`
`UNIPOLAR AND BIPOLAR MOOD DISORDERS
`
`Oneofthe most importantdistinctions between mooddis-
`ordersis the distinction between unipolar and bipolarcat-
`egories (Leonhard 1987a, 1987b). Unipolar mooddisor-
`ders are characterized by depressive symptoms in the
`absence ofa history of a pathologically elevated mood.In
`bipolar mooddisorders, depression alternatesoris mixed
`with mania or hypomania. Patients who haveonly hadre-
`current mania (“unipolar mania”) are given the diagnosis
`of bipolar mooddisorderon the assumption that they will
`eventually develop an episodeofdepression (M.T. Tsuang
`and Faraone 1996). DSM-IV criteria for a manic episode
`are summarized in Table 13-5. Hypomania, a milder form
`of pathologically elevated mood that can be presentfor a
`shorter period beforeit is diagnosed,is described in Table
`13-6. Although most people think ofelation as a defining
`characteristic of mania and hypomania, manypatients ex-
`perience onlyirritability, anxiety, or a dysphoric sense of
`
`8 of 89
`
`Alkermes, Ex. 1064
`
`8 of 89
`
`Alkermes, Ex. 1064
`
`

`

`MOOD DISORDERS
`A85
`
`TABLE 13-5. DSM-IV criteria for a manic episode
`
`A. A distinct period of abnormally and persistently elevated,
`expansive,orirritable mood,lasting at least 1 week (or
`any duration if hospitalization is necessary).
`B. During the period of mood disturbance, three (or more)
`of the following symptomshavepersisted (four if the
`moodis only irritable) and have been present to a
`significant degree:
`(1)
`inflated self-esteem or grandiosity
`(2) decreased need for sleep (e.g., feels rested after only
`3 hoursof sleep)
`(3) more talkative than usual or pressure to keep talking
`(4)
`flight of ideas or subjective experience that thoughts
`are racing
`(5) distractibility (i-e., attention too easily drawn to
`unimportantorirrelevant external stimuli)
`increase in goal-directedactivity (either socially, at
`workor school, or sexually) or psychomotor
`agitation
`excessive involvementin pleasurableactivities that
`have a high potential for painful consequences(e.g.,
`engaging in unrestrained buying sprees, sexual in-
`discretions, or foolish business investments)
`C. The symptoms do not meetcriteria for a mixed episode.
`D. The mooddisturbanceis sufficiently severe to cause
`marked impairment in occupational functioningor in
`usual social activities or relationships with others, or to
`necessitate hospitalization to prevent harm to self or
`others, or there are psychotic features.
`E. The symptomsare not due to the direct physiological
`effects of a substance (e.g., a drug of abuse, a medication,
`or other treatment) or a general medical condition(e.g.,
`hyperthyroidism).
`
`(6)
`
`(7)
`
`TABLE 13-6. DSM-IV criteria for a hypomanic
`episode
`
`A. A distinct period ofpersistently elevated, expansive, or
`irritable mood,lasting throughoutat least 4 days, thatis
`clearly different from the usual nondepressed mood.
`B. During the period of mood disturbance, three (or more)
`of the following symptomshave persisted (four if the
`moodis only irritable) and have been present to a
`significant degree:
`(1)
`inflated self-esteem or grandiosity
`(2) decreased need forsleep (e.g., feels rested after only
`3 hoursof sleep)
`(3) more talkative than usual or pressure to keep talking
`(4)
`flight of ideas or subjective experience that thoughts
`are raci