HANDBOOK OF PSYCHIATRIC DRUGS - PART 1 pdf

Lieberman and Allan Tasman 2006 John Wiley & Sons, Ltd... Library of Congress Cataloging in Publication Data Lieberman, Jeffrey A., 1948– Handbook of psychiatric drugs / Jeffrey A.. Drug

HANDBOOK OF PSYCHIATRIC

DRUGS

Handbook of Psychiatric Drugs Jeffrey A Lieberman and Allan Tasman

2006 John Wiley & Sons, Ltd ISBN: 0-470-02821-1

Institute, New York, USA

Allan Tasman

Professor and Chair Department of Psychiatry and Behavioral Sciences University of Louisville School of Medicine, Louisville,

Kentucky, USA

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Library of Congress Cataloging in Publication Data

Lieberman, Jeffrey A., 1948–

Handbook of psychiatric drugs / Jeffrey A Lieberman, Allan Tasman.

Includes bibliographical references and index.

ISBN-13: 978-0-470-02821-6 (pbk : alk paper)

ISBN-10: 0-470-02821-1 (pbk : alk paper)

RM315.L54 2006

British Library Cataloguing in Publication Data

A catalogue record for this book is available from the British Library

ISBN-13 978-0-470-02821-6

ISBN-10 0-470-02821-1

Typeset in 9.5/11.5pt Times by Integra Software Services Pvt Ltd, Pondicherry, India Printed and bound in Great Britain by Clays Ltd, Bungay, Suffolk NR35 1ED This book is printed on acid-free paper responsibly manufactured from sustainable forestry in which at least two trees are planted for each one used for paper

To our patients for their courage and for their assistance inthe search for treatments for mental illness.

To my family in gratitude for their love, support and

patience Jeffrey Lieberman

With love and thanks to my family, and especially my fatherGoodman Tasman, for your inspiration and support

Allan Tasman

Drug Selection for the Treatment of Major

Depression With Psychotic Features 19Drug Selection for the Treatment of Delusional

Acute Extrapyramidal Side Effects (Dystonia,

Tardive Dyskinesia and Other Tardive

Drug Interactions and Antipsychotic Agents 36Antipsychotic Medications and Pregnancy 38

Obsessive–Compulsive Disorder (OCD) 50

Social Phobias and Posttraumatic Stress

Drug Selection and Initiation of Treatment for

Special Considerations in the Selection of an

Response, or Acute Treatment, Period 63

Treatment of Partially Responsive and

Continuation and Maintenance Periods, and

Other Second-Generation Antidepressants 79

Withdrawal from Sedative–Hypnotics 230

Management of Withdrawal in Patients with

Medications for Alcohol Dependence 238Medications for Cocaine Dependence 241

Drug Treatments for Nicotine Dependence 247Pharmacotherapies for Substance Abusers with

Pharmacotherapy for Specific Psychiatric

Drug Interactions in Chemical Dependency 251

There is little question that this is the most exciting time

in history to be involved in the treatment of patients withpsychiatric disorders The explosive growth in our knowledgebase in all areas of the field, particularly in neuroscience,has revolutionized both our understanding of the nature ofpsychiatric illnesses and our ability to provide effective treat-ments As molecular genetics and pharmacology, neurochem-istry, and new drug discovery techniques continue to advance,physicians are faced with the need to assimilate an ever-changing body of knowledge In particular, the change in phar-macotherapy for psychiatric illnesses continues at a dizzyingpace

We have been very gratified by the extremely positive

inter-national response to our major textbook, Psychiatry, Second

Edition (Tasman, A, Kay, J, Lieberman, JA, Wiley, 2003).

We believe, however, that busy clinicians need a quick ence guide to the most up-to-date information on prescribing

refer-medications for psychiatric illnesses This book, the

Hand-book of Psychiatric Drugs, is based on the outstanding

chap-ters on pharmacotherapy in Psychiatry, Second Edition The

material has been condensed, updated to just months beforepublication, and organized by specific classes of medications

To enhance the daily utility of this handbook, we chose aformat that emphasized ease of use, and ensured that eachchapter follows a specific template of topics, including thepharmacology, mechanism of action and pharmacokinetics,indications and methods of prescribing, side effects and druginteractions, and descriptions of each specific drug within theclass We have aimed to include prescription medications incommon use anywhere in the world Further, each chapter wasthen reviewed by highly respected psychiatrists with pharma-cotherapy expertise in that particular class of medication

We feel confident that you will find this book to be one ofyour most useful sources of information regarding your dailyclinical practice.

Jeffrey A Lieberman, M.D

New York, NY

Allan Tasman, M.D

Louisville, KY

We would like to gratefully acknowledge the authors of those

chapters in Psychiatry Second Edition from which material in

this book was adapted

Robert J Boland Antidepressants

W Wolfgang Fleischhacker Antipsychotic Drugs

Marlene P Freeman Mood Stabilizers

Alan J Gelenberg Mood Stabilizers

Laurence L Greenhill Stimulants

Jeffrey Halperin Stimulants

Martin B Keller Antidepressants

Rachel E Maddux Anxiolytic Drugs

Stephen R Marder Antipsychotic Drugs

Seiya Miyamoto Antipsychotic Drugs

Scott E Moseman Mood Stabilizers

Mark H Rapaport Anxiolytic Drugs

Lon S Schneider Cognitive Enhancers and

Treatments for Alzheimer’sDisease

Richard I Shader Sedative–Hypnotic Agents

Douglas A Songer Sedative–Hypnotic AgentsPierre N Tariot Cognitive Enhancers and

Treatments for Alzheimer’sDisease

We also acknowledge Jeffrey Selzer, author of the chapter

‘Drugs for Treating Substance Abuse in Psychiatric Drugs’

We would also like to thank our colleagues from the College ofPhysicians and Surgeons of Columbia University, New York,who contributed to the final editing process:

Notice

This book discusses new research, treatments, and drug apies in the field of psychiatry Readers are advised to checkthe product information currently provided by the manufac-turer of each drug to be administered to verify the recom-mended dose, the method and duration of administration, andthe contraindications It is the responsibility of the treatingphysician, relying on experience and knowledge of the patient,

ther-to determine dosages and the best treatment for the patient.Neither the publisher nor the editors assume any responsibilityfor any injury and/or damage to persons or property

The Publisher

1 ANTIPSYCHOTIC DRUGS

INTRODUCTION

Information about antipsychotic drugs and developments inthe treatment of psychosis is rapidly expanding The advent ofnewer second-generation antipsychotics in the wake of clozapinerepresents the first significant advances in the pharmacologictreatment of schizophrenia and related psychotic disorders,and second-generation antipsychotics have become first-choiceagents for acute and maintenance therapy for these illnesses.There is growing evidence that most of the new medi-cations can offer advantages over conventional neuroleptics;these include fewer extrapyramidal symptoms, lower risk oftardive dyskinesia, reduced cognitive impairment, and possibleimprovement in negative symptoms Treatment successes havecontributed to the increased use of newer antipsychotic agentsand have also allowed psychiatrists to expand clinical expec-tations In addition, these second-generation drugs are beingused increasingly for various conditions beyond schizophrenia,

as happened with the conventional antipsychotics

PHARMACOLOGY

The first-generation antipsychotic agents are equally tive in the treatment of psychotic symptoms of schizophrenia,although they vary in potency and their propensity to inducevarious side effects All have a high affinity for dopamine

effec-Handbook of Psychiatric Drugs Jeffrey A Lieberman and Allan Tasman

2006 John Wiley & Sons, Ltd ISBN: 0-470-02821-1

D2 receptors In addition, all produce extra-pyramidal toms (EPS), including parkinsonism, dystonia, akathisia, areassociated with a substantial risk of tardive dyskinesia (TD),and increase serum prolactin concentration in the usual clin-ical dose range First-generation agents are usually classi-fied into three groups: phenothiazines, butyrophenones (e.g.,haloperidol), and others (e.g., thiothixene, molindone, andloxapine), based on their structure

symp-Second-generation antipsychotic drugs are characterized bythe following criteria:

• few or no EPS; significant reduction in tardive dyskinesialiability compared to first-generation antipsychotics

• expanded spectrum of therapeutic efficacy

• less prolactin elevation

There is a continuum of typical and atypical effects in atypicaldrugs rather than several dichotomous groups

Chemistry

Antipsychotic drugs bind to numerous neurotransmitterreceptor subtypes, including those of dopamine, norepinephrine,epinephrine, acetylcholine, serotonin, and histamine They act

to antagonize the endogenous ligands at these receptors Boththerapeutic and extrapyramidal side effects can be attributed tothe antagonism of dopamine at D2receptors, with actions at theother neuroreceptors associated with various other side effects.The typical antipsychotics have been described as being ofhigh (e.g., haloperidol), low (e.g., chlorpromazine), and mid(e.g., loxapine) potency on the basis of their degree ofaffinity for D2 receptors and their therapeutic dose range.Atypical antipsychotics are characterized by generally loweraffinities for D2 receptors and relatively greater affinitiesfor serotonin (5-hydroxytryptamine) 5-HT2A receptors inparticular, but also for noradrenergic receptors (1 and

2, muscarinic acetylcholine receptors, histamine, and otherdopamine (DA) subtype receptors Aripiprazole is currentlythe only antipsychotic that acts as a partial agonist at D2and5-HT1A receptors as well as an antagonist at the 5-HT2A and

D2 receptors, and these properties are believed to accountfor its therapeutic effects It has no appreciable activity at

muscarinic receptors and modest affinity for alpha-1 adrenergicand histamine H1receptors.

Mechanism of Action

The therapeutic actions of antipsychotic drugs are generallyattributed to antagonism of DA receptors, particularly the D2subtype Atypical antipsychotics, with their lower D2receptoraffinities and broader spectrum of pharmacologic properties,also antagonize 5-HT2A receptors, giving possible therapeuticadvantages and a superior motor side effect profile At this point

it is unclear what clinical effects 5-HT2A antagonism confers,other than mitigating the adverse effect of striatal D2 antag-onism, and propensity to cause EPS The low EPS liability

of aripiprazole is at least in part related to its partial agonistactivity at the D2receptor Its D2antagonist activity is broadlycomparable with that of haloperidol and chlorpromazine, but itclearly has weaker cataleptogenic activity Furthermore, chronictreatment with aripiprazole is associated with much less upregu-lation of striatal D2receptors compared with haloperidol.What has been established is that as a consequence of theirdifferent pharmacologic profile, the atypical drugs have a muchwider separation of the dose-response curves of therapeuticantipsychotic action and extrapyramidal side effects

Pharmacokinetics

Antipsychotic agents are rapidly absorbed from the testinal tract and undergo extensive first pass metabolism.They are highly lipophilic, which results in ready transportacross the blood-brain barrier Antipsychotics are metabolized

gastroin-by the cytochrome P450 enzyme system The isozyme systemspredominantly involved are CYP2D6, CYP1A2, CYP3A4, andCYP2C19, and medications that inhibit or compete for thesesubstrates can increase antipsychotic blood levels After under-going various degrees of metabolism, antipsychotic drugs andtheir metabolites are glucuronidated in the liver and excreted

by the kidney in the urine or in feces

The average plasma half-life of the antipsychotics as afamily is approximately 20 to 24 hours, allowing for once-daily dosing Aripiprazole and its active metabolite dehydro-aripiprazole have exceptionally long half-lives of 75 and 94

hours respectively and steady state concentrations are achievedafter 14 days Some drugs have shorter half-lives (e.g., queti-apine: 6 to 12 hours; ziprasidone: 4 to 10 hours), which suggeststwice-daily administration However, with repeated dosingthe pharmacodynamic effects may extend beyond the periodsuggested by pharmacokinetic parameters, allowing the consol-idation of dosing to once daily

Among the second-generation antipsychotics, olanzapine(5–10 mg initial dose) and ziprasidone (10–20 mg initial dose)are available in a parenteral form for acute use in agitatedpatients, giving the benefits of a more rapid onset of actionand the ability to bypass the extensive first-pass metabolismthat these agents undergo

Several of the antipsychotic drugs (three in the UnitedStates: haloperidol and fluphenazine decanoate, and Risperi-done – Risperdal Consta) are available in long-acting injectablepreparations for intramuscular administration This allows forless fluctuation in plasma level compared to oral formula-tions, bypasses first-pass metabolism, and can improve patientcompliance

Recommended dosages for second-generation chotic agents are shown in Table 1-1

antipsy-INDICATIONS FOR USE OF ANTIPSYCHOTIC DRUGS

Antipsychotic agents are effective for treating nearly everymedical and psychiatric condition where psychotic symptoms

or aggression are present They are currently used routinely inthe management of psychosis and/or agitation associated with:

• Schizophrenia and Schizoaffective Disorder

• Acute manic and mixed episodes of bipolar disorder

• Major depression with psychosis