`
`Robert E. Hales, M.D.
`Associate Professor of Psychiatry,
`Uniformed Services University of the Health Sciences,
`F, Edward Hébert School of Medicine
`Stuart C. Yudofsky, M.D.
`Professor and Chairman,
`Departmentof Psychiatry,
`The University of Chicago
`
`Edited by
`
`John A. Talbott, M.D.
`Professor and Chairman,
`Department of Psychiatry,
`University of Maryland School of Medicine
`
`American |
`Dsychiatric
`Press, Inc.
`
`THE AMERICAN PSYCHIATRIC PRESS
`TEXTBOOK OF
`
`PSYCHIATRY >
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`Note: The Editors and contributors have worked to ensure that all information in this book concerning
`drug dosages, schedules, and routes of administration is accurate as of the time of publication and consis-
`tent with standards set by the U.S. Food and Drug Administration 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 recommendthat readers follow the advice of a
`physician whois directly involved in their care or the care of a memberoftheir family.
`
`Books published by the American Psychiatric Press, Inc. represent the views and opinionsof the individual
`authors and do not necessarily reflect the policies and opinions of the Press or the American Psychiatric
`Association.
`
`The opinions or assertions contained herein are the private ones of Dr. Hales and are not to be construed
`as Official or reflecting the views of the Department of Defense, the Uniformed Services University of the
`Health Sciences, Walter Reed Army Medical Center, or the Department of the Army. This book was com-
`pleted in Dr. Hales’ private capacity. Neither government-financed time nor supplies were used in connec-
`tion with this project.
`
`Typeset by Harper Graphics
`Printed by RR Donnelley & Sons Company
`
`Copyright © 1988 American Psychiatric Press, Inc.
`ALL RIGHTS RESERVED
`Manufactured in the United States of America
`First Edition
`
`Library of Congress Cataloging-in-Publication Data
`
`The American Psychiatric Press textbook of psychiatry.
`
`Includes bibliographies and index.
`1. Psychiatry. I. Talbott, John A. Ii. Hales, Robert E. III. Yudofsky,
`Stuart C. [DNLM: 1. Mental Disorders. 2. Psychiatry. WM 100 A5112]
`RC454.A419
`1988
`616.89
`87-33655
`ISBN 0-88048-251-6
`
`j{i
`t
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`Chapter
`
`13
`
`Mood Disorders
`
`Robert M. A. Hirschfeld, m.p.
`Frederick K. Goodwin, M.D.
`
`MooD DISORDERS SPAN A WIDE SPECTRUM of con-
`ditions, ranging from reactions to loss and other
`negative life experiences to severe, recurrent, de-
`bilitating illnesses. On one end of the spectrum are
`the relatively normal states dominated by mood
`and cognitive disturbances. On the other end are
`the clinical syndromesin which these subtle symp-
`toms become entangled in a complex of physiolog-
`ical symptoms. Theillnesses covered in this chapter
`generally represent the more moderate to severe
`endof the spectrum:clinical depression and mania,
`comprising the mood disorders, and a variety of
`other conditions.
`A vast expanse separates depressive illness from
`normal depressed feelings and thoughts. At its
`worst, the illness pervades the person’s life, re-
`lentlessly changing day-to-day existence. Thoughts
`are distorted by self-disgust and hopeless despair,
`concentrationis difficult,and suicidal thoughts in-
`trude. Even when the torment subsides, mental
`processes remain slow: Memory dwindles and
`thinking disintegrates. Depressed people lack the
`energy to act, endure night after nightoffitful sleep,
`and take nointerest in life around them. They are
`in pain, a terrible, inescapable, and ultimately in-
`describable psychic and physical pain that may drive
`
`them to suicide. So intenseis their suffering that
`when some depressed individuals have gone on to
`develop terminal cancer, they found the pain of
`cancer easier to bear than the pain of depression.
`Mania,
`in its mild or moderate form (hypo-
`mania),
`is the opposite of depression. Thoughts
`and associations come quickly and are unusually
`sharp andcreative. People who are going through
`this stage of mania are infused with a euphoric
`sense of well-being and omnipotence. They are more
`productive than usual, and more passionate too.
`Butrarely do these halcyon times last. Quick think-
`ing careens into racing thoughts. Ideas become
`jumbled. Sexuality and the general level of energy
`are increased and judgmentis impaired. Grandiose
`plans are formulated. Faced with the objections or
`resistance of others, the manic person becomeir-
`ritable, hostile, paranoid, assaultive, and, some-
`times, psychotic. The consequencesofall this manic
`energy can be terrible—lost loves, lost jobs, lost
`fortunes.
`This chapter begins with a brief description of
`the clinical features of the mood disorders. The
`history, epidemiology, clinical course, and sub-
`types for each condition—that is, major depres-
`sion, bipolar disorders, and schizoaffective dis-
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`order—are discussed, and problemsin differential
`diagnosis are considered. Next, biological and psy-
`chological theories of depression and mania are
`presented, along with evidence for their validity.
`The chapter concludes with a discussion of treat-
`ments for mood disorders, both somatic and psy-
`chotherapeutic.
`
`Clinical Features of Depression
`
`Viewed longitudinally, the natural history andclin-
`ical course of the mood disorders are quite varied.
`Some forms are episodic, others chronic. The
`symptom picture is frequently consistent across ep-
`isodes, but it may differ dramatically from one ep-
`isode to the next, or even change within an episode.
`The subjective experience of severe depression was
`described by one patient as follows:
`When I am my normalself I feel active, alive, able
`to enjoy things and to participate easily with other
`people; I eagerly seek them out. There is no ques-
`tion but that life and these experiences have great
`meaning to me. But when depressed it seems as
`though my friends require much more from me
`than I can ever possibly give, I seem a drain and
`burden on them; the guilt and resentmentare over-
`whelming. Everything I see, say, or do seems ex-
`traordinarily flat and pointless; there is no color,
`there is no point to anything. Things drag on and
`on, interminably. J am exhausted, dead inside. I
`wantto sleep, to escape somehow,butthere is al-
`waysthe thoughtthatif I really could sleep, I must
`always and again awake to the dullness and apathy
`ofit all. I doubt, completely, my ability to do any-
`thing well; my mind has slowed down and burned
`out... it’s virtually useless. The wretched thing
`works only well enough to torment me with a
`dreary litany of my inaccuracies and to haunt me
`with the total desperate hopelessnessof it all. What
`is the point of going onlikethis; it is crazy. (Good-
`win and Jamison in press)
`The patient whofirst presents to the physician
`may show involvementin severalclinical domains:
`affect (emotion), drive and other physical func-
`tions, somatic complaints, cognition, and behavior;
`a suicide attempt may have been made. The fol-
`lowing are frequent signs and symptomsfrom these
`domains.
`
`Affect—Although the most common emotion
`expressed in depression is sadness,clinical depres-
`sion can exist without sadness. A variety of other
`dysphorias may present themselves, including
`emptiness, “the blues,” ennui, and nervousness.
`Cognition—Cognitive processes are character-
`istically slowed, and cognitive contentreflects the
`
`low self-esteem thatis a hallmark of depression. A
`depressed person may describe himself as the worst
`person on the face of the earth or declare that ev-
`eryone would be better off if he were dead. De-
`pressed people often are very pessimistic, always
`expecting the worst. They typically experience ex-
`cessive guilt over minor incidents and may even
`have delusions of guilt. Their impaired judgment
`can further diminish their ability to cope with stress,
`and their difficulty concentrating can hinder al-
`ready-impaired cognitive performance.
`Behavior—Thesocial withdrawal characteris-
`tic of depression may be so extreme that patients
`may not get out of bed at all. Depressed patients
`frequently appearto be in slow motion,talking and
`moving slowly. Some, on the other hand, may have
`a difficult time keeping still, constantly wringing
`their hands and pacing thefloor.
`Physical functioning—Perhaps the most char-
`acteristic abnormalities associated with depression
`are disturbancesin regulation of basic bodily func-
`tion. These include problems with sleep, such as
`difficulty falling asleep and middle-of-the-night or
`early-morning awakening (sometimes two to three
`hoursprior to the individual’s normal wake-uptime).
`Changesin appetite are frequent, most often a loss
`of appetite and weight, but in some forms a sub-
`stantial increase in both; depressed patients often
`complain that food has no taste and holds no in-
`terest for them. Libido suffers and may be com-
`pletely lost. The ability to experience pleasure can
`also be so diminished that nothing is enjoyable.
`Neuroendocrine functioning is disturbed in
`some patients. Endocrine responses to such tests
`as insulin challenge are often abnormal. Many ab-
`normalities occur in the metabolism and presumed
`function of central neurotransmitters. Circadian and
`other body rhythmsare typically disturbed.
`Somatic functioning—Depression is often
`missed in primary care clinics because patients
`complain of somatic problems, such as constant
`fatigue, headaches, or gastrointestinal upsets, rather
`than depressed mood.
`Suicide—Approximately 15 percent of seri-
`ously depressed individuals may eventually kill
`themselves.
`
`Clinical Features of Hypomania and Mania
`
`Maniain its milder forms represents the opposite
`of depression. Severe mania is, however, quite dys-
`phoric and the simultaneous occurrence of depres-
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`MOOD DISORDERS
`ee
`
`sion and mania, called mixed states, is commonly
`associated with frank mania. This is how one pa-
`tient described it:
`
`The fast ideas become too fast and there are far too
`many.
`.
`. overwhelming confusion replacesclarity
`... you stop keeping up with it—memory goes.
`Infectious humor ceases to amuse—yourfriends be-
`comefrightened .
`.
`. everything is now against the
`grain... you areirritable, angry, frightened, un-
`controllable and trapped in the bleakest caves of the
`mind—caves you never knew were there. It will
`never end. Madnesscarvesits own reality. (Good-
`win and Jamison in press)
`
`Affect--The predominant mood is elevated,
`expansive, orirritable.
`Cognition—A hallmark of hypomaniais an ac-
`celeration of cognitive processes, progressing (in
`mania) to racing thoughts and flight of ideas. In
`conversation, the person jumps from onetopic to
`another in a seemingly random fashion without
`returning to the original topic and is also easily
`distracted. Inflated self-esteem can lead to gran-
`diose ideas and the belief that he or she is unique
`and in possession of special powers.
`Behavior—Very disturbed behavior is a hall-
`mark of mania. Increased psychomotoractivity is
`accompaniedby general restlessness. Patients tend
`to be very talkative and verbally intrusive, andtheir
`speech has a pressured quality. They will typically
`go on wild buying sprees, get involved in sexual
`indiscretions, pursue foolish business investments,
`and drive recklessly.
`Physical Functioning—Patients with mania
`usually needless sleep and, indeed, may not sleep
`at all for days at a time. Their increased activity
`level appears to be driven by boundless energy. A
`heightened sexual drive may lead to uncharacter-
`istic promiscuity. In the milder stages, the ability
`to experience pleasure is enhanced; appetite for
`food may becomevoracious. As in depression, ab-
`normalities occur in neuroendocrine functioning,
`body rhythms, and neurotransmitter metabolites.
`These abnormalities are sometimes reciprocal with
`those found in. depression, but sometimesare iden-
`tical.
`
`CL] DIAGNOSIS
`
`Modern approachesto diagnosis of depression be-
`gan with Emil Kraepelin, the German psychiatrist
`whopioneered classification of psychiatric disor-
`
`ders early in this century. Following a medical model,
`Kraepelin emphasized both longitudinal history and
`the pattern of current symptoms. He proposed that
`manic-depressiveillness constituted a genetic spec-
`trum of disorders, including what we nowcall bi-
`polar disorder, recurrent major depression,
`cyclothymia, and some patients with dysthymia.
`Kraepelin differentiated manic-depressive ill-
`ness from dementia praecox (that is, schizophre-
`nia) because the group hecalled manic-depressive
`shared a periodic or episodic course, a relatively
`benign prognosis, and family history of similar dis-
`orders. Schizophrenia, by contrast, was marked by
`a chronic, deteriorating course and no family his-
`tory of manic-depressive illness. His views were
`codified in a series of textbooks that were very in-
`fluential throughout Europe. His approach formed
`the basis for the diagnostic system developed by
`the St. Louis group of Robins, Winokur, and Guze
`(Feighner 1972), which evolved into the Diagnostic
`and Statistical Manual of Mental Disorders (Third Edi-
`tion) (DSM-III; American Psychiatric Association
`1980).
`In the United States, psychiatry began this cen-
`tury quite unlike it did in Europe. Adolph Meyer,
`whoexerted great influence duringthe first half of
`the century, saw psychiatric disorders as primarily
`the outcomeof interactions between the individual
`and the environment. Although he acknowledged
`a role for genetics and other biological contribu-
`tions, his methods and teaching clearly empha-
`sized psychosocial factors. On the basis of careful
`life histories that he constructed of each patient,
`Meyerrelated importantlife experiences to the de-
`velopment and expression of illness.
`Meyer’s views contrasted with Kraepelin’s
`medical model, which posited that clinical phe-
`nomenain a given patient were understandable in
`terms of a given disease and its specific natural
`history and pathophysiology. This model had been
`very successfully used with general paresis sec-
`ondaryto central nervous system syphilis and with
`organic syndromes associated with vitamin defi-
`ciencies. However, until
`the advent of specific
`pharmacological treatments a half centurylater, it
`was not considered particularly useful as a basis
`for treatment approaches for the functional psy-
`choses.
`In 1957 Karl Leonhardt, another German psy-
`chiatrist, enlarged upon Kraepelin’s unitary con-
`cept of depression. He proposed that manic—
`depressiveillness be separated into “bipolar” (pa-
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`
`tients with a history of both mania and depression)
`and ‘‘monopolar’ (patients with a history of
`depressions only). His rationale was that the two
`groups appeared todiffer in family history of mania.
`This distinction has been widely accepted, partly
`because treatmentfor the two groupsis different.
`European usage of the term monopolar(or uni-
`polar) differs somewhat from the American usage.
`In Europeit generally refers to recurrent episodes
`of depression and thusreflects a longer course of
`illness; in the United States it usually refers simply
`to the absence of a history of mania and therefore
`is much moreinclusive and heterogeneous.
`Furtherdivisions in the bipolar group have been
`proposed. Receiving the most attentionis so-called
`bipolarI, which includes milder episodes of mania
`variously defined (for example, not requiring hos-
`pitalization) but excludes frank mania.
`The unipolar-bipolar distinction has been sup-
`ported by evidence from clinical trials (predomi-
`nantly the efficacy of lithium in bipolar disorder)
`and from genetic and family studies (bipolar dis-
`order is much more prevalent in the relatives of
`bipolar patients than in relatives of patients with
`other disorders). Therefore, this distinction serves
`as the basis for the classification of affective dis-
`orders in DSM-III-R. The two formsare related.
`Unipolar illness is very prevalent in bipolar pa-
`tients, although the converseis not true. However,
`recurrent (or cyclic) forms of unipolar illness often
`share manycharacteristics with bipolar disorders,
`such as younger age of onset, greater family load-
`ing of mania, and a pharmacological response to
`lithium.
`
`Approachesto the Subclassification
`of Depression
`
`Over the past half century, several systems have
`been proposedforclassifying depression, most of
`them dichotomousandbasedonetiologic assump-
`tions. In addition to the bipolar-unipolar distinc-
`tion,
`they include the endogenous-reactive,
`neurotic—psychotic, and primary-secondary dis-
`tinctions.
`The endogenous-reactive dichotomyis partic-
`ularly important becauseofits etiologic and treat-
`ment implications. Endogeneity was first used in
`psychiatry in 1929 by the English psychiatrist Rob-
`ert D. Gillespie, who applied the term to disorders
`that apparently arose from internal causes and ap-
`peared to be unresponsive to environmental stim-
`
`uli. As its usage evolved, the endogenous concept
`took on further meanings and implications,
`including depressions occurring in the absence of
`precipitating stress, depressions occurring in older
`people with stable, nonneurotic premorbid per-
`sonalities, depressions that are very severe, de-
`pressions with psychotic symptomatology, and
`depressions characterized by a particular symptom
`complex.
`These latter three usages were descriptive and
`“etiology free” and presaged contemporary usage,
`in which endogenous, endogenomorphic, and melan-
`cholic all refer to a cluster of vegetative symptoms
`(such as early morning awakening,loss of appetite,
`loss of sexual drive), morning worsening of mood,
`excessive guilt, psychomotor agitation or with-
`drawal, pervasivelack of pleasure, and loss of reac-
`tivity to the environment. Such disorders are
`generally presumed to involve biological predis-
`position and to require somatic intervention; their
`onset may or may not have been precipitated by
`stress, but once the depression is underway, the
`patient is no longer reactive to the environment.
`Initially, the term reactive depression was applied
`to depressive episodes that follow and appear to
`result from psychosocial stress (such as divorce or
`death of a loved one), and it was the presence or
`absence of such events that formed the basis for
`this dichotomousclassification. Recent data make
`it clear that the nature of the depressive symptoms
`and the degree of functional impairment are in-
`dependentof the presence or absence of precipi-
`tating events, and,like endogenous, the term reactive
`has descriptive meaning only.
`The existence of endogenous and nonendog-
`enous symptom clusters has been confirmed by
`several factor-analytic investigations (Mendels and
`Cochrane 1968), but studies of family history, pre-
`morbid personality, and biological factors have not
`supported the utility of the distinction. Patients
`with endogenous depression do tend to respond
`better to antidepressant medication than do pa-
`tients with nonendogenous depression.
`In contrastto the ‘““endogenomorphic” depres-
`sion, Klein andhis associates have described (Klein
`1974; Liebowitz and Klein 1979) hysteroid dysphoria,
`which is characterized by reactive mood and ex-
`treme fatigue and associated with atypical vege-
`tative symptoms—hypersomnia with initial in-
`somnia, evening worsening, and hyperphagia.
`Klein has proposed thatrejection sensitivity—ex-
`treme sensitivity to interpersonal rejection—plays
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`MOOD DISORDERS
`
`
`a role in precipitating hysteroid dysphoria and that
`such depressions are responsive to monoamineox-
`idase inhibitors.
`In England the notion that depression can be
`described as a point on a single dimension of se-
`verity has been very popular. One end of this di-
`mension has been called neurotic and the other
`psychotic. A serious problem with this approachis
`the lack of agreement on the meaning of the terms
`(Klermanetal. 1979b). Psychotic depressions are typ-
`ically described as severe, incapacitating, and ac-
`companied almost invariably by endogenous
`symptomatology (in fact the two terms werefre-
`quently used interchangeably) and in some cases
`by delusions andhallucinations. Neurotic can refer
`to depressions that are milder, nonendogenous,
`and nonpsychotic and that may occur following
`psychosocial stress. Neurotic depressions are gen-
`erally viewed as characterological in nature, arising
`in individuals with a long-standing history of in-
`terpersonal conflicts, low self-esteem, and char-
`acter pathology.
`
`DSM-HI-R Mood Disorders
`
`Mood disorders in DSM-III-R (renamed from
`affective disorders in DSM-III are divided into two
`major categories, depressive (unipolar) disorders
`and bipolar disorders (see Figure 1). The clinical
`descriptionsthat follow are organized according to
`these categories, as is the discussion of epide-
`miology, clinical course, and subtypes. Brief de-
`scriptionsof seasonal affective disorder and schizo-
`affective disorder are also included.
`
`Depressive Disorders
`
`Major Depression
`
`Clinical Description Major depression is a broad
`diagnostic category that subsumes disorders pre-
`viously and variously categorized as psychotic
`depression, involutional depression, and recurrent
`unipolar affective illness, and some (more severe)
`cases of psychoneurotic depressive reaction. The
`criteria for major depression are listed in Table 1.
`Major depression can be subclassified as recurrent
`or single episode and as melancholic and/or psy-
`chotic.
`
`MOOD DISORDERS
`
`Bipolar Disorders
`
`Depressive Disorders
`
`Bipolar |
`
`Cyclothymia
`
`Major Depression
`
`Dysthymia
`
`Figure 1. DSM-III-R mooddisorders.
`
`Course The “natural” course of depressionis dif-
`ferent for patients treated with today’s antidepres-
`sant and mood-stabilizing medications than it was
`for patients in the predrug era. Studies donein the
`two periodsreflect that change, but comparisons
`between the older and the more recent literature
`must be done cautiously because of substantial
`methodological differences. Many of the predrug
`studies included only hospitalized patients, and
`they usually did not distinguish between bipolar
`- and unipolar patients. This selection process would
`necessarily bias toward the more severely ill pa-
`tients.
`Long-term follow-up studiesin the predrug era
`found that ‘untreated’ unipolar depression was
`recurrent about half the time, although method-
`ological limitations probably resulted in substantial
`underestimation (Zis and Goodwin 1979). Thus,
`the studies with the fewest methodological short-
`comings found recurrence rates for major depres-
`sive illness in the 75- to 80-percent range (Zis and
`Goodwin 1979). Another review noted that 15 per-
`cent of patients with major depression died by sui-
`cide (Robins and Guze 1970).
`With treatment, the average duration of an ep-
`isode of major depression can be reduced to four
`to six months (Keller 1984). Follow-up studies in-
`dicate that in actual clinical practice the average
`duration is longer, often lasting more than a year
`from the time the patient first presents for treat-
`ment; this evidence suggests that adequate care is
`not often provided.
`Two-thirds of patients with major depression
`withouta history of dysthymia will recover within
`one year of presenting for treatment, and nearly
`80 percent will recover within two years (Keller
`1984). This means that one in five patients with
`major depression will stay depressed through two
`years.
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`
`TABLE 1. DSM-III-R CRITERIA FOR A MAJOR
`DEPRESSIVE EPISODE
`
`A. Atleast five of the following symptoms have been
`present during the same two-week period and
`represent a change from previous functioning; at
`least one of the symptoms waseither (1) depressed
`mood or(2) loss of interest or pleasure.
`
`(1), Depressed mood(or can beirritable mood in
`children or adolescents) most of the day, nearly
`every day as indicated either by subjective
`account or observation by others.
`(2) Markedly diminished interest or pleasurein all
`or almostall activities most of the day, nearly
`every day (as indicated either by subjective
`account or observation by others of apathy
`most of the time)
`(3) Significant weight loss or weight gain when not
`dieting (e.g., more than 5% of body weight in a
`month) or decrease or increase in appetite
`nearly every day
`(4) Insomnia or hypersomnia nearly every day
`(5) Psychomotor agitation or retardation nearly
`every day (observable by others, not merely
`subjective feelings of restlessness or being
`slowed down)
`(6) Fatigue or loss of energy nearly every day
`(7) Feelings of worthlessness or excessive or
`inappropriate guilt (which may be delusional)
`nearly every day (not merely self-reproach or
`guilt for being sick)
`(8) Diminished ability to think or concentrate, or
`indecisiveness, nearly every day (either by
`subjective account or observed by others)
`(9) Recurrent thoughts of death (notjust fear of
`dying), recurrent suicidal ideation without a
`specific plan, or a suicide attempt or a specific
`plan for committing suicide
`
`B.
`
`(1) It cannot be established that an organic factor
`initiated and maintained the disturbance
`(2) The disturbance is not a normal reaction to the
`death of a loved one (uncomplicated
`bereavement) (Note: Morbid preoccupation
`with worthlessness, suicidal ideation, marked
`functional impairment or psychomotor
`retardation, or prolonged duration suggest
`bereavement complicated by Major
`Depression.)
`
`C. At no time during the disturbance have there been
`delusions or hallucinations for as long as two
`weeks in the absence of prominent mood
`symptoms(that is, before the mood symptoms
`developed or after they have remitted)
`D. Not superimposed on either schizophrenia,
`schizophreniform disorder, delusional disorder, or
`psychotic disorder NOS.
`Copyright 1987 American Psychiatric Association. Used with
`permission.
`
`Amongthese recoveredpatients, one-thirdwill
`relapse within one year and as manyas 75 percent
`will relapse within five years. In fact, once hospi-
`talized for an episode of major depression, only 15
`percent of patients will have no recurrence of the
`disorder. Thesestatistics indicate that depression
`is a highly recurrent and pernicious disorder and
`supportthe belief that inadequate attentionis given
`to prophylactic treatment, even in university treat-
`mentsettings (see Figure 2).
`The phenomenonofdouble depression is partic-
`ularly ominous for prognosis. Double depression,
`which can occur in one-quarter of moderately to
`severely depressed samples of patients with major
`depression, refers to the superimposition of a ma-
`jor depressive episode on an underlying chronic
`depression, as depicted in Figure 3 (Keller etal.
`1983). Full recovery from double depression (that
`is, remission of both acute and chronic symptom-
`atology) is only half as likely as from depression
`alone (39 percent recovered after two years, com-
`pared with 79 percent for depression alone). Re-
`lapse is also twice as frequent among those with
`double depression who dorecover.
`An overwhelming majority of suicides are com-
`mitted by persons whohave psychiatric disorders,
`60 to 80 percent of them diagnosed as depressed.
`It has been estimated that the ultimaterisk of sui-
`cide in primary affective disorders is 15 percent,
`with the five years following onset of the disorder
`representing the period of greatest risk. This rate
`is 30 times the risk for the general population (Ro-
`bins and Guze 1970).
`
`Chronic
`Course
`
`20%
`
`Full
`
`Recovery
`40%
`
`Episodic
`Course
`40%
`
`Figure 2. Clinical course of depression.
`
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`8 of 41
`
`Alkermes, Ex. 1062
`
`
`
`409
`
`
`
`Severity
`
`
`Major Depression Superimposed
`on a Chronic Minor Depression
`
`\
`\
`\
`
`7
`
`7
`
`on
`
`\
`
`\
`
`Major Depression Only
`
`owN
`
`Years
`Figure 3. Double depression.
`
` MOOD DISORDERS
`
`Symptom
`
`Major risk factors for suicide among depressed
`patients include
`
`1.
`
`a diagnosis of chronic depression or a depres-
`sion severe enough to have required hospital-
`ization,
`2. ahistory of previous suicide attempts,
`3.
`a family history of suicide, and
`4. achangein status from inpatient to outpatient.
`
`As is the case in the general population, persons
`at highest risk for suicide are unemployed males
`whoare unmarried orlive alone (Roy 1982).
`
`Epidemiology Epidemiological information on
`nonbipolar andbipolar depressionsis summarized
`in Table 2 (Myers et al. 1984; Weissman and Boyd
`1982). The overall six-month prevalence for all af-
`fective disorders is about eight percent in women
`and four percent in men. The highest prevalences
`for both sexes tend to be in the young and middle
`
`adult years, with a drop-off in frequency after age
`65. In any six-month period four percent ofall
`women and twopercent of all men could be di-
`agnosed as having major depression; similar pro-
`portions could be diagnosed as having dysthymia.
`Nonbipolar major depression is more common
`than bipolar disorder and, unlike bipolar disorder,
`is disproportionately found in womenby a factor
`of approximately twoto one. Noclear relationship
`exists between the syndrome of major depression
`and social class or race. Age at onset for major
`depression ranges from the 20s to the 50s, a later
`and wider range than is true for bipolar disorder,
`which ranges from late adolescence to the 30s, with
`a peak in the 20s.If recent indications that rates of
`major depression are increasing among the young
`and decreasing among the elderly are borne out,
`the difference in age of onset between bipolar and
`nonbipolar disorders will narrow.
`Several risk factors for major depression have
`been reported, although noneis either necessary
`or sufficient for its development (Hirschfeld and
`
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`9 of 41
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`410 THE AMERICAN PSYCHIATRIC PRESS TEXTBOOK OF PSYCHIATRYSSSoroeeeeeeeeaNaePE
`
`
`
`TABLE 2. EPIDEMIOLOGY OF MAJOR
`DEPRESSIVE AND BIPOLAR DISORDERS
`
`Mid to late 30s
`
`Social class
`
`Norelationship
`
`Race
`Family History
`% Major
`depression
`in relatives
`% Bipolar
`depression
`in relatives
`
`Norelationship
`
`17%
`
`2-3%
`
`1:1.2
`
`Late teens to
`early 20s
`Slight increase in
`upperclasses
`Norelationship
`
`15%
`
`8%
`
`Melancholia is a DSM-III-R reformulation of en-
`dogenous depression without etiologic implica-
`tions (see Table 3). The symptoms most char-
`Risk Factor Major Depression_Bipolar Disorder
`
`acteristic of melancholia are lack of reactivity and
`Lifetime
`Female 5-9%
`-6-.9%
`psychomotor change. Depressive delusions, while
`prevalence
`Male 2-4%
`relatively uncommon,arealso highly discriminat-
`Male/Female
`1:2
`ing. On the other hand, symptoms such as sleep
`ratio |
`and appetite disturbances andloss of interest, while
`Age at onset
`typical of melancholic depressions, are frequently
`found in nonmelancholic depressions as well.
`Psychotic features in DSM-III-R is a distinct im-
`provementoverearlier use of the term, since now
`its meaning is confined to those patients with de-
`lusions, hallucinations, or depressive stupor, rather
`than being simply a confusing synonym for “se-
`. vere” (see Table 4). Psychotic features are further
`categorized as mood congruent or mood incon-
`gruent.
`To receive a diagnosis of mood-congruent psy-
`chotic depression, a patient must evidence depressive
`stuporor delusions and/orhallucinations with mood-
`congruent content (for example,
`themes of per-
`sonal inadequacy, guilt, punishment, nihilism, and
`so on). To receive a diagnosis of psychotic depression
`with mood-incongruent features, a patient must evi-
`
`a T
`
`ABLE 3. DSM-III-R DIAGNOSTIC CRITERIA FOR
`MELANCHOLIC TYPE OF MAJOR
`DEPRESSIVE EPISODE
`
`Specify melancholic if current episode is melancholic
`type, eg., at least five of the following:
`(1) Loss of interest or pleasure in all or almostall
`activities
`(2) Lack of reactivity to usually pleasurable stimuli
`(does not feel much better, even temporarily,
`when something good happens)
`(3) Depression regularly worse in the morning
`(4) Early morning awakening (at least two hours
`before usual time of awakening)
`(5) Psychomotor retardation or agitation (not merely
`subjective complaints)
`(6) Significant anorexia or weightloss (e.g., more
`than 5% of body weight in a month)
`(7) Nosignificant personality disturbance before first
`major depressive episode
`(8) One or more previous major depressive episodes
`followed by complete or nearly complete
`recovery
`(9) Prior good responseto specific and a