KAPLAN & §Anocr<’s
`
`
`
`COMPREHENSIVE
`
`T E X T B O O K O F
`PSYCHIATRY
`
`VOLUME I
`
`SEVENTH
`
`EDITION
`
`EDITORS
`
`Benjamin J. Sadock, M..
`
`Menas S. Gregory Professor of Psychiatry and
`Vice Chairman, Department of Psychiatry
`New York University School of Medicine
`Attending Psychiatrist, Tisch Hospital
`Attending Psychiatrist, Bellevue Hospital Center
`Consultant Psychiatrist, Lenox Hill Hospital
`New York, New York
`
`Virginia A. Sadock, M.D.
`
`Clinical Professor of Psychiatry
`Department of Psychiatry
`New York University School of Medicine
`Attending Psychiatrist, Tisch Hospital
`Attending Psychiatrist, Bellevue Hospital Center
`New York, New York
`
` éiié LIPPINCOTT WILLIAMS 5; WILKINS
`' A Wolters Kluwer Company
`Philadelphia - Baltimore - NewYork - London
`Buenos Aires - Hong Kong - Sydney - Tokyo
`
`\p\
`1 of211
`
`Alkermes, Ex. 1061
`
`1 of 211
`
`Alkermes, Ex. 1061
`
`

`
`
`
`.....-,.___...,.«.....m......._.a.....
`
`Acquisition: Editor: Charles W. Mitchell
`Developmental Editor: Kathleen Courtney Millet
`Production Editor: Jennifer D. Weir
`'
`Compositor: Maryland Composition, Inc.
`Printer: World Color
`
`Project Editor (New York): Justin A. Hollingsworth
`
`© 2000 by LIPPINCOTT WILLIAMS & WILKINS
`530 Walnut Street
`Philadelphia, PA 19106 USA
`LWW.com
`
`“Kaplan Sadock Psychiatry” with the pyramid logo is a trademark of Lippincott Williams & Wilkins.
`
`All rights reserved. This book is protected by copyright. No part of this book may be reproduced in any
`form or by any means, including photocopying, or utilized by any information storage and retrieval system
`without written permission from the copyright owner, except for brief quotations embodied in critical articles
`and reviews. Materials appearing in this book prepared by individuals as part of their official duties as U.S.
`government employees are not covered by the above—mentioned copyright.
`
`Printed in the USA
`
`
`Library of Congress Cataloging-in-Publication Data
`
`Kaplan & Sadock’s comprehensive textbook of psychiatry/VII / editors,
`Benjamin J. Sadock, Virginia A. Sadock.——7th ed.
`p.
`cm.
`Includes bibliographical references and index.
`ISBN 0-683-30128~4
`II. Sadock,
`1. Psychiatry.
`1. Sadock, Benjamin J.
`Virginia A.
`III. Title: Comprehensive textbook of psychiatry/VII.
`IV. Title: PsychiatryNII.
`[DNLM: 1. Mental Disorders. 2. Psychiatry. WM 100 K173 1999]
`RC454.C637 1999
`616.89—dc21
`DNLM/DLC
`for Library of Congress
`
`99-22698
`CIP
`
`
`Care has been taken to confirm the accuracy of the information presented and to describe generally
`accepted practices. However, the authors, editors, and publisher are not responsible for errors or omissions or
`for any consequences from application of the information in this book and make no warranty, expressed or
`implied, with respect to the currency, completeness, or accuracy of the contents of the publication.
`Application of this information in a particular situation remains the professional responsibility of the
`practitioner.
`The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set
`forth in this text are in accordance with current recommendations and practice at the time of publication.
`However, in view of ongoing research, changes in government regulations, and the constant flow of
`information relating to drug therapy and drug reactions, the reader is urged to check the package insert for
`each drug for any change in indications and dosage and for added warnings and precautions. This is
`pa.rticularly important when the recommended agent is a new or infrequently employed drug.
`Some drugs and medical devices presented in this publication have Food and Drug Administration (FDA)
`clearance for limited use in restricted research settings. It is the responsibility of the physician or health care
`provider to ascertain the FDA status of each drug or device planned for use in their clinical practice.
`
`1098765432
`
`20f211
`
`Alkermes Ex. 1061
`
`
`
` ,.......,....._.....,..._._..,d-._,4...,_,.....
`
`
`
`
`
`2 of 211
`
`Alkermes, Ex. 1061
`
`

`
`
`
`Other Psychotic Disorders
`
`
`
`HlSt0l‘Y At the beginning of this century, patients with mental
`illness were grouped together as suffering from the common illness
`insanity. With the work of Emil Kraepelin, and Eugene Bleuler,
`distinct diagnostic groups began to emerge. Kraepelin was able to
`distinguish an unremitting, dementing illness in young patients that
`became known as schizophrenia, which he contrasted with an epi-
`sodic illness of affect now known as bipolar I disorder. However,
`there were patients who did not fit neatly into either category. Bleuler
`believed that the presence of any symptoms of schizophrenia even
`when there was an affective component was still schizophrenia. Pa-
`tients with mixed features of schizophrenia and affective (mood)
`disorder were first described by George Kirby and August Hoch in
`the early part of the century. In 1933, Jacob Kasanin introduced the
`term “schizoaffective psychosis” to describe a group of patients
`who had symptoms of both affective and schizophrenic illnesses.
`While he is credited with introducing the term, on subsequent review
`of these patients, all would now meet the diagnosis of a pure mood
`disorder. Nevertheless, the term schizoaffective disorder has sur-
`vived albeit in several different contexts.
`
`Comparative Nosology One of the difficulties in using a
`diagnosis that depends on not being another diagnosis is that both
`depend on changes in the other. Schizoaffective disorder is affected
`by any changes in the diagnostic criteria of schizophrenia, affective
`disorder, or both. As psychotic affective disorders and schizophrenia
`have been better distinguished, those who fall through the ‘ ‘diagnos-
`tic cracks” have become clearer. In the second edition of DSM
`(DSM-II) schizoaffective disorder was a subtype of schizophrenia
`and denoted patients who had any mood symptoms while meeting
`the criteria for schizophrenia. In contrast, the Research Diagnostic
`Criteria (RDC) for schizoaffective disorder allowed as few as one
`symptom of schizophrenia in a patient who met the criteria for a full
`affective disorder. The third edition of DSM (DSM-III), influenced
`
`by studies in the United States and Great Britain, narrowed the diag-
`nosis of schizophrenia and expanded the diagnosis of bipolar disor-
`der. It allowed symptoms of schizophrenia to coexist with a mood
`disorder as long as these schizophrenic symptoms did not remain
`when the mood disorder resolved. Moreover, mood-incongruent psy-
`
`chotic symptoms could now exist in bipolar disorder. Finally, schizo-
`affective disorder moved from its schizophrenia subtype place to
`stand alone as a “psychotic disorder not elsewhere classified.” The
`revised third edition of DSM (DSM-III-R) expanded this notion by
`inserting the criterion that a patient with schizoaffective disorder
`must meet the criteria for schizophrenia for at least 2 weeks indepen-
`dent of any mood syndrome.
`DSM-IV has retained most of the DSM-III-R criteria but has
`
`stricter diagnostic criteria for schizophrenia. Patients must meet the
`symptoms of schizophrenia for at least 1 month as opposed to the
`previous 1-week criterion. Schizoaffective disorder is now listed in
`the section “Schizophrenia and Other Psychotic Disorders.” The
`10th revision of International Statistical Classification of Diseases
`
`JOHN LAURIELLO, M.D., BRENDA R. ERICKSON, M.D., and
`SAMUEL J. KEITH, M.D.
`
`There are three disorders in addition to schizophrenia listed in
`the fourth edition of Diagnostic and Statistical Manual of Mental
`Disorders (DSM-IV) in the section “Schizophrenia and Other Psy-
`chotic Disorders.” The first, schizoaffective disorder, is a complex
`illness that has changed significantly over time. In its simplest defini-
`tion, it is presently conceived as an illness with coexisting, but inde-
`pendent, schizophrenic (psychotic) and mood components. Schizoaf-
`fective disorder is seen primarily as part of a schizophrenia spectrum
`rather than an equal hybrid of mood and schizophrenia disorders.
`Schizophreniform disorder is a diagnosis that assumes another will
`replace it after 6 months. Most cases of schizophreniform disorder
`progress to either schizophrenia or schizoaffective disorder, with
`some cases rediagnosed as a non—schizophrenia spectrum illness
`(i.e., schizotypal or schizoid personality disorders), while a few re-
`solve completely. Finally, the diagnosis brief psychotic disorder de-
`scribes an impairment in reality testing that lasts at least 1 day, but
`less than 1 month. All three disorders have a psychotic component,
`are often misunderstood, are incorrectly applied, and are not as well
`studied as schizophrenia, bipolarl disorder, or major depressive dis-
`order.
`
`SCHIZOAFFECTIVE DISORDER
`
`As the end of the century nears great strides have been made
`in clarifying the diagnostic criteria for many psychiatric illnesses.
`However, patients often do not fall neatly into set illness criteria.
`There are several approaches to dealing with such patients. One is
`to diagnose the patient with two distinct illnesses and treat those
`illnesses as separate problems. Another possibility is to consider that
`the patient has a primary illness and Symptoms of a second illness
`that are not as important and might even resolve when the primary
`illness is treated. A third approach considers that the patient suffers
`from a distinct blended illness with its own history, diagnosis, and
`treatment. This last approach best represents the current orthodoxy
`in the diagnosis and treatment of patients with the DSM-IV diagnosis
`of schizoaffective disorder. Unfortunately, this approach is not easily
`applied, often making the diagnosis confusing and convoluted.
`1232
`
`3of2‘|‘|
`
`Alkermes, Ex. 106,
`
`3 of 211
`
`Alkermes, Ex. 1061
`
`

`
`
`
`13.1
`
`Schizoaffective Disorder, Schizophreniform Disorder, and Brief Psychotic Disorder
`
`1233
`
`Table 13.1-1
`
`
`
`DSM-IV Diagnostic Criteria for
`Schizoaffective Disorder
` ——:———:—
`
`A. An uninterrupted period of illness during which, at some time,
`there is either a major depressive episode, a manic episode, or a
`mixed episode concurrent with symptoms that meet criterion A
`for schizophrenia.
`Note: The major depressive episode must include criterion
`A1: depressed mood.
`B. During the same period of illness, there have been delusions or
`’ hallucinations for at least 2 weeks in the absence of prominent
`mood symptoms.
`.
`.
`I
`I
`E
`C. Symptoms that meet criteria for a mood episode are present for
`
`
`I’ a substantial portion of the total duration ofthe active and residual ,
` I physiologill’
`“ iileiiaacisfoi
`,
`
`medication),
`"general ‘
`
`
`
`
`W
`
`Diagnostic and Clinical Features DSM-IV diagnostic cri-
`teria are provided in Table 13.1-l.
`
`These criteria are a product of several revisions that have sought
`to clarify several diagnoses including schizophrenia, bipolar disor-
`der, and major depressive disorder. It was hoped that improving these
`diagnoses would make schizoaffective disorder begin to stand out
`apart from them. However, the diagnostic criteria still leave much
`to interpretation. The diagnostician must accurately diagnose the af-
`fective illness, making sure it meets the criteria of either a manic or
`depressive episode but also determining the exact length of each
`episode (not always an easy or possible task). The length of each
`episode is critical for two reasons. First, to meet the B criterion
`(psychotic symptoms in the absence of the mood syndrome) one has
`to know when the affective episode ends and the psychosis continues.
`Second, to meet criterion C the length of all mood episodes must be
`combined and compared with the total length of the illness. If the
`mood component is present for a substantial portion of the total
`illness, then that criterion is met. Calculating the total length of
`the episodes can be difficult, and it does not help that the term
`“substantial portion” is not defined. In practice, most clinicians
`look for the mood component to be 15 to 20 percent of the total
`illness. Patients who have one full manic episode lasting 2 months
`but who have suffered from symptoms of schizophrenia for 10
`years do not meet the criteria for schizoaffective disorder. Instead,
`the diagnosis would be a mood episode superimposed on schizo-
`phrenia. It is unclear whether the bipolar or depressive type speci-
`fiers are helpful, although they may direct treatment options. These
`subtypes are often confused with earlier subtypes (schizophrenic
`versus affective type) thought to have implications in course and
`prognosis. As with most psychiatric diagnoses, schizoaffective
`disorder should not be used if the symptoms are caused by sub-
`stance abuse or a secondary medical condition.
`The ICD-10 diagnostic criteria for schizoaffective disorder are
`listed in Table 13.1-2.
`
`and Related Problems (ICD-10) essentially describes the same disor-
`der. The ICD-l0 schizoaffective disorders describe single as well as
`recurrent episodes. Subtypes include manic, depressed, and mixed
`types. Mixed type includes a cyclic schizophrenia and a mixed
`schizophrenic-mood psychosis.
`
`Epidemiology There is no psychiatric epidemiological study of
`the incidence or prevalence of schizoaffective disorder in a general
`population. Even if there were such studies, older reports might not
`be useful, because the diagnosis (and therefore the incidence and
`prevalence) would have changed over time. Prevalence rates for con-
`secutive patients diagnosed in a psychiatric treatment setting are
`available. These numbers range from 2 to 29 percent, a potentially
`significant cohort requiring treatment. Several lines of evidence sup-
`port the idea that one might expect an increased prevalence of schizo-
`affective disorder in women. Women have a higher prevalence of
`major depressive disorder than men do, and women with schizophre-
`nia express more affective symptoms than men with schizophrenia
`do. In family studies of patients with schizoaffective disorder, rela-
`tives of females with schizoaffective disorder have a higher rate of
`schizophrenia and depressive disorders than do relatives of males
`with schizoaffective disorder.
`
`Etiology It is difficult to determine a cause of a disease that has
`changed so much over time. One might conjecture that the etiology
`of schizoaffective disorder as currently defined might be similar to
`the etiology of schizophrenia. Thus etiological theories of schizoaf-
`fective disorder would include some genetic and environmental caus-
`ation. Molecular genetic studies of schizoaffective disorder have
`lagged behind recent studies of the genetics of schizophrenia and
`bipolar I disorder. Available family studies have reported that families
`of schizoaffective probands have significantly higher rates of relatives
`with mood disorder than families of schizophrenia probands. Simi-
`larly, these schizoaffective probands have more psychotic symptoms
`than families of mood disorder probands. The results of these family
`studies have argued that schizoaffective disorder is a unique disorder,
`separate from schizophrenia and mood disorders.
`Possible environmental causes of schizoaffective disorder are
`similar to those of schizophrenia, including in utero insult (including
`malnutrition and viral causes) and obstetrical complications. One
`hypothesis considers schizophrenia to be a developmental and pro-
`gressing disorder that can be seen in the development of brain dysm-
`orphology. This includes less cortical gray matter and more fluid
`and fluid-filled spaces; however, no definitive study of patients with
`DSM-IV schizoaffective disorder has been done. One might assume
`that schizoaffective patients would have similar brain abnormalities,
`because the disorder mimics many aspects of schizophrenia.
`For nearly a half century the prevailing etiologic theory of schizo-
`phrenia was the dopamine hypothesis. In its simplest description it
`postulates that the underlying abnormality is excess dopamine in
`areas of the brain, leading to psychosis. Thus, successful treatment
`with antipsychotics is due to their dopamine-blocking properties.
`With the successful use of clozapine (Clozaril) and other serotonin-
`dopamine antagonists, the dopamine hypothesis has been amended.
`Currently, a critical balance between the neurotransmitters dopamine
`and serotonin is believed to be important for treating schizophrenia.
`At the same time it is accepted that there are abnormalities of seroto-
`nin and norepinephrine in mood disorders. These theories are particu-
`larly interesting when considering underlying causes of schizoaffec-
`tive disorder. Possibly this balance of dopamine and serotonin is
`particularly affected in schizoaffective disorder, leading to chronic
`psychosis and intermittent but substantial mood alterations.
`
`4of211
`
`Alkermes, Ex. 1061
`
`4 of 211
`
`Alkermes, Ex. 1061
`
`

`
`1234
`
`13. Other Psychotic Disorders
`
`Table 1 3.1-2
`
`
`lCD-10 Diagnostic Criteria for
`Schizoaffective Disorders—————
`
`G2.
`
`Note. This diagnosis depends upon an approximate ”balance” be-
`tween the number, severity, and duration of the schizophrenic and
`affective symptoms.
`G1. The disorder meets the criteria for one of the affective disorders
`of moderate or severe degree, as specified for each category.
`Symptoms from at least one of the groups listed below must be
`clearly present for most of the time during a period of at least
`2 weeks (these groups are almost the same as for schizophrenia):
`(1)
`thought echo,
`thought
`insertion or withdrawal,
`thought
`broadcasting (criterion Gl(1)a for paranoid,’ hebephrehic,
`or catatonic schizophrenia); ‘
`I
`"
`’
`vity, clearly referred I
`(2) delusions of control, influence, or passi
`A
`:
`to body or limb movements. or specific thou hts; action or
`
`
`
`‘
`
`(Haldol). A.D.’s manic symptoms resolved, but her belief that
`she was a rock star’s girlfriend remained. Since that first hospitali-
`zation she has lost custody of her son. She remains delusional ,
`about the child’s famous father, and in addition, she believes
`people are out to get her. She has had three distinct episodes of ~
`mania during which she needs little sleep and has racing thoughts
`, and pressured speech. She has been intermittently compliant with
`medications and is currently receiving haloperidol in a long-act- .»
`S. ingform. In the 10 yearslof her illness she has never been free ,
`of her delusions. Shefhas not beenable to work and receives
`.f¢s1¢ta!,.di.saléi1ity.i9§sis£anc§:..;
`T
`
`
`
`
`
`
`
`S S S SSTS if
`
`Differential Diagnosis The psychiatric differential diagnosis
`includes all the possibilities usually considered for mood disorders
`and for schizophrenia
`In any differential diagnosis of psychotic disorders a complete
`medical workup should be performed to rule out organic causes of
`the symptoms. A history of substance use with or without a positive
`toxicology screening test may indicate a substance-induced disorder.
`Preexisting medical conditions, their treatment, or both may cause
`psychotic and mood disorders. Any suspicion of a neurological ab-
`normality warrants consideration of a brain scan to rule out anatomi-
`cal pathology and an electroencephalogram (EEG) to determine any
`possible seizure disorders (e.g., temporal lobe epilepsy). Psychotic
`disorder due to seizure disorder is more common than that seen
`in the general population. It tends to be characterized by paranoia,
`hallucinations, and ideas of reference. Epileptic patients with psy-
`chosis are believed to have a better level of function than patients
`with schizophrenic spectrum disorders. Better control of the seizures
`can reduce the psychosis.
`The same hypothetical case is used in the 3 cases below with
`different outcomes to illustrate the diagnostic decision.
`
`Mrs. B. was a 32-year-old married woman with three children.
`She reported being relatively happy and free of illness until the
`birth of her third child. She had the usual “baby blues” that
`resolved after the first month. When her third child was 14 months
`old, she began to have trouble sleeping, and her husband noticed
`that she was sometimes irritable and at other times euphoric. She
`began to talk rapidly and call family members at all hours of the
`night. One night her husband received a phone call that his wife
`was in the county jail. She had secretly left the house, gone to a
`local bar, and instigated a fight with a female patron. The police
`_ thought she was acting wildly and suspected some sort of intoxi-
`cant. She was takento the local psychiatric clinic where a urine
`toxicology screen was negative. She was admitted to the hospital
`, and treated with the benzodiazepine, lorazepam_(Ativan), and
`the mood’ stabilizer lithium,"and after /2 weeks was completely
`_“asymptomatic._.
`‘
`e,
`I
`,
`V
`., U l;.
`.
`5 Q‘
`’
`'l
`
`. f;He,r.difig ., is i5, bip.o1arsI}diS9rd9r;.mani9;tYP.s=: ..
`
`S
`
`. S
`
`.l
`
`Ms. A.D. was a 29-year-old white unmarried woman, with a
`10-year history of schizoaffective disorder bipolar type. She was
`first hospitalized after child protection took her son away for
`alleged child abuse. When the patient was interviewed at that
`time, she was described as dressed like a “gypsy” with heavy,
`makeup and pressured speech. She told the treatment team her 1
`son had been abused by his father, a well-known rock star. During V.
`.F11i§.Fi1?.1‘? .sh.¢.Was.stabi1iz¢d.9rz.1it1¢i9rh. Esk_a.1ith).afihalopefidol.s.
`
`T
`
`Discussion The patient suffered from an elevated and eu-
`phoric mood alone. She did not exhibit any symptoms of schizophre-
`nia and was appropriately treated with a benzodiazepine, lorazepam,
`to calm her and long-term treatment with a mood stabilizer, lithium.
`This patient might have future episodes with hallucinations, delu-
`sions, or both. These psychotic symptoms may or may not be con-
`gruent with her mood state (e.g., a patient who is depressed and has
`the delusion of being a terrible person who has committed a crime
`and deserves to suffer and be punished). However, the psychotic
`symptom might also be very incongruent with the mood. The critical
`
`5 of211
`
`Alkermes, Ex. 1061
`
`5 of 211
`
`Alkermes, Ex. 1061
`
`

`
`
`
`
`
`
`
`
`
`13.1
`
`Schizoaffective Disorder, Schizophreniform Disorder, and Brief ‘Psychotic Disorder
`
`1235
`
`pletely asymptomatic after 2 weeks of treatment. A year later her
`husband brought her back to the psychiatric hospital. He reported
`she had been doing well and was compliant with her medication,
`which was now lithium carbonate alone. Her mood has been
`
`unremarkable, but in the last month she again began to say that
`someone had stolen her social security benefits. On interview she
`was calm and cooperative although a little guarded. She reluc-
`tantly admitted that the man’s voice had returned recently. Risper-
`idone wasadded back to her regimen, and after 2 weeks she
`returned to her usual self.
`
`I Her diagnosis isschizoaffective disorder, bipolar type. M
`
`Discussion The third case (above) displayed symptoms of
`both a mania and a delusion. She was appropriately treated with an
`antipsychotic agent and a mood stabilizer. If the vignette had ended
`there, one might conclude that she had a manic episode with psy-
`chotic features. However, she had an exacerbation a year later. This
`time her mood was totally normal but her delusions and hallucina-
`tions returned. She is restarted on the antipsychotic since it appears
`the mood stabilizer alone was insufficient. It was very appropriate
`in this circumstance to first taper the patient off the antipsychotic
`and try the patient on a mood stabilizer alone, aware of the long-
`term risks of antipsychotics. However, having had the delusional
`episode while on the mood stabilizer most likely portends a need
`for intermittent or maintenance antipsychotic treatment.
`These 3 women, while having historical details in common, illus-
`trate the differences between a pure mood disorder, schizophrenia,
`and schizoaffective disorder.
`
`Course and Prognosis Considering the uncertainty and
`evolving diagnosis of schizoaffective disorder, determining the long-
`term course and prognosis is difficult. Given the definition of the
`diagnosis, one might expect patients with schizoaffective disorder
`to have either a course similar to an episodic mood disorder, a chronic
`schizophrenic course, or some intermediate outcome. It has been
`presumed that an increasing presence of schizophrenic symptoms
`predicted worse prognosis. Studies using RDC criteria showed that
`after 1 year patients with schizoaffective disorder had different out-
`comes depending on whether their predominant symptoms were af-
`fective (better prognosis) or schizophrenic (worse prognosis). With
`the narrower definition of DSM-III-R and DSM-IV, all patients had
`to have an independent schizophrenic component to meet the diagno-
`sis of schizoaffective disorder. One study that followed patients diag-
`nosed with DSM-III-R schizoaffective disorder for 8 years found
`that the outcomes of these patients more closely resembled schizo-
`phrenia than a mood disorder with psychotic features.
`
`Treatment There are several extensive reviews of the treatment
`of schizoaffective disorder, but critical evaluation of the results of
`these studies is not easy. Because the operational definition of schizo-
`affective disorder has shifted over the last 30 years, comparing or
`pooling studies is impossible. The efficacy and selection of treatment
`for a patient under the broader (more mood disorder inclusive) DSM-
`II criteria may differ from that of the patient diagnosed with the
`narrower DSM-III-R criteria. However, there are some general rec-
`ommendations for treatment. The principle rule is to treat the pa-
`tient’s symptoms, not the diagnostic label.
`
`Mood Stabilizers Mood stabilizers are a mainstay of treat-
`
`ment for bipolar disorders and would be expected to be important
`in the treatment of patients with schizoaffective disorder. Few studies
`have examined the efficacy of mood stabilizers in schizoaffective
`
`6of2‘|‘|
`
`Alkermes, Ex. 1061
`
`distinction for this patient was that the psychotic symptom existed
`only during the mood episode. Conceptually,
`the psychosis was
`fueled by the mood. Correct the mood and there is no fuel for the
`psychosis and it also disappears.
`Mrs. S. was a 32-year-old married woman with three children.
`She reports that she has been relatively happy and free of illness
`until the birth of her third child. She had the usual “baby blues”
`that resolved after the first month. When her third child was 14
`
`months old she began to have trouble sleeping and her husband
`noticed that she was becoming increasingly isolated and not able
`to take care of her children. One night her husband received a
`phone call that his wife was in the county jail. She had secretly
`left the house, gone to a local bar and instigated a fight with a
`female patron. The police thought she was acting wildly and
`suspected some sort of intoxicant. She was taken to the local
`psychiatric clinic where a urine toxicology screen was negative.
`At that time she told the staff that she was sure someone was
`using her social security number and consuming the benefits she
`, would need when she was older. She had gone to the bar because
`
`a man’s voice had told her that the person who was using her
`benefits was there. This voice had been talking to her for over a
`‘year and often commented on her looks and actions. The patient
`1‘. was admitted to the hospital, treated with the antipsychoticrisper-
`idone (Risperdal), and after 2 weeks of treatment was completely
`asymptomatic.
`V
`¥1¢r.£1iagn9$is. is..S¢hizophr9nia: .Par.anoid type-
`
`r
`
`‘
`
`
`
`Discussion The patient’s primary symptoms were delusions
`and hallucinations without any accompanying mood abnormality.
`They were of sufficient severity and duration to give her a diagnosis
`of the paranoid type of schizophrenia, and she was appropriately
`treated with an antipsychotic agent. Patients suffering from schizo-
`phrenia often have both depressive and euphoric symptoms. A com—
`mon mistake is assuming that a schizophrenic patient presenting with
`a full range of affect is a patient with schizoaffective disorder. The
`presence of euphoria or demoralization alone does not meet the crite-
`ria for diagnosis of schizoaffective disorder. Patients must both meet
`the appropriate criteria for the affective disorder and have the affec-
`tive disorder for a substantial portion of their chronic illness. That
`said, a patient with schizophrenia suffering from subsyndromal de-
`moralization or disinhibited behavior might benefit from an antide-
`pressant or mood stabilizer, respectively.
`Mrs. S.A. was a 32-year-old married woman with three chil-
`dren. She reports that she has been relatively happy and free of
`illness until the birth of her third child. She had the usual “baby
`blues” that resolved after the first month. When her third child
`was 14 months old she began to have trouble sleeping and her
`husband noticed that she was becoming increasingly irritable,
`euphoric, isolated and not able to take care of her children. One
`night her husband received a phone call that his wife was in the
`county jail. She had secretly left the house, gone to a local bar
`* and instigated a fight with a female patron. The police thought
`she was acting wildly and suspected some sort of intoxicant. She
`was taken to the local psychiatric clinic where a urine toxicology
`screen was negative. At that time she told the staff that she was
`sure there was someone using her social security number and
`-‘consuming the benefits she would need when she was older. She
`also described herself as being one of the 10 smartest people in ,
`the world and was 'sure,that,t the treatment team did not understand
`Zher because of their incompetence and she asked to be seen by ;
`.the head of the hospital. The patientwas treated with the antipsy- —'
`.¢h9ti¢..[rispi9ti£19h¢ .=_1i1<1.th¢Lir299si,.stabi1iz¢r.1itIziut11.and.Was. C9111-.
`,
`
`
`
`6 of 211
`
`Alkermes, Ex. 1061
`
`

`
`1236
`
`13. Other Psychotic Disorders
`
`disorder, in contrast to the extensive studies of lithium, valproate
`(Depakote), and to a lesser extent carbamazepine (Tegretol) in bipo-
`lar I disorder. A recent study that compared lithium with carbamaze-
`pine showed superiority for carbamazepine for schizoaffective disor-
`der, depressive type, but no difference in the two agents for the
`bipolar type. In practice however, these medications are used exten-
`sively alone, in combination with each other, or with an antipsychotic
`agent. In manic episodes, schizoaffective patients should be treated
`aggresively with dosages of a mood stabilizer in the middle to high
`therapeutic blood concentration range. As the patient enters a mainte-
`nance phase the dosage can be reduced to low to middle range to
`avoid adverse effects and potential effects on organ systems (e.g.,
`thyroid and kidney) and to improve ease of use and compliance.
`Laboratory monitoring of plasma drug concentrations and periodic
`screening of thyroid, kidney, and hematological functioning should
`be performed. As in all cases of intractable mania, the use of electro-
`convulsive therapy (ECT) should be considered.
`Psychosis or akathisia must be distinguished from a manic epi-
`sode. For a psychotic agitation, an antipsychotic agent (often with
`a benzodiazepine) is indicated. In akathisia, numerous studies have
`shown that reducing the antipsychotic agent dosage or using benzodi-
`azepine or a ,8-adrenergic receptor antagonist are helpful.
`
`Antidepressants By definition manyschizoaffective patients
`suffer from major depressive episodes. Treatment with antidepres-
`sants mirrors treatment of bipolar depression. Care should be taken
`not to precipitate a cycle of rapid switches from depression to mania
`with the antidepressant. The choice of antidepressant should take
`into account previous antidepressant successes or failures. Selective
`serotonin reuptake inhibitors (e.g., fluoxetine [Prozac] and sertraline
`[Zoloft]) are often used as first-line agents because they have less
`effect on cardiac status and have a favorable overdose profile. How-
`ever, agitated or insomniac patients may benefit from a tricyclic
`antidepressant. As in all cases of depression, use of ECT should be
`considered.
`
`It is very important to try to distinguish psychosis, akinetic syn-
`dromes, and primary negative symptoms from depression. Again,
`psychosis should be adequately treated with an antipsychotic agent.
`Suspected akinetic treatment can be improved by lowering the dosage
`of antipsychotic agent, treating with an anticholinergic agent, or
`switching to a serotonin-dopamine antagonist like clozapine (Clo-
`zaril), risperidone, olanzapine (Zyprexa), or quetiapine (Seroquel).
`Negative symptoms are often difficult to tease out. While there are
`no definitive studies, these symptoms may improve with the use of
`serotonin-dopamine antagonists.
`
`Antipsychotic Agents As mentioned above, antipsychotic
`agent