Clinical Geriatric Psychopharmacology

Transcription

1 Clinical Geriatric Psychopharmacology SECOND EDITION CARL SALZMAN, M.D. Director of Psychopharmacology Massachusetts Mental Health Center Associate Professor of Psychiatry Harvard Medical School Boston, Massachusetts with 19 Contributors WILLIAMS & WILKINS BALTIMORE HONG KONG LONDON MUNICH PHILADELPHIA SYDNEY TOKYO

2 CONTENTS Preface to the Second Edition..., Contributors vii xiii PART ONE THE ELDERLY, THEIR ILLNESSES, AND THEIR PHARMACOLOGIC TREATMENTS 1 1. INTRODUCTION: OLDER AMERICANS AND THEIR ILLNESS 3 BARRY D. LEBOWITZ, PH.D.; GENE D. COHEN, M.D., PH.D. Characteristics of the Elderly An Overview Complexities of Treating Mental Disorders in the Older Population 3 5 Prevalence of Mental Illness 5 Mental Health of the Elderly 6 Approaches to Treating the Elderly 7 When to Prescribe Drugs 8 The Nature of the Problem 8 Treatment Modalities 8 Treatment Providers 9 Treatment Settings: Home, Community, Institution Risk Versus Benefit Considerations i 9 10 Substance Abuse and and Psychotropic Drugs : 10 The Elderly and Their Caregivers 10 The Nonphysician Geriatic Care Provider 11 Clinicians' Misperceptions in Use of Prescriptions DRUG PRESCRIBING PATTERNS, RISKS, AND COMPLIANCE GUIDELINES 15 PETER P. LAMY PH.D., SC.D.; CARL SALZMAN, M.D.; JOYCE NEVIS-OLESEN Prescription Drug Use Patterns 16 Nonprescription Drug Use 17 Concerns about Psychotropic Drug Use 18 Psychotropic Prescribing Practices in Selected Settings 20 Hospital Inpatients 20 Use of Psychotropics in Nursing Homes 22 Common Side Effects of Psychotropic Drugs 22 Sedation 23 Confusion 23 Orthostatic Hypotension 23 Anticholinergic Reactions 23 Cardiac Side Effects 23 Extrapyramidal Symptoms 24 Polypharmacy, Drug Interactions, and Adverse Effects 24 Nutritional Status and Drug Effects 25

3 XVi CLINICAL GERIATRIC PSYCHOPHARMACOLOGY Guidelines for Psychotropic Drug Use: A Risk Approach Compliance with a Mutually Agreed-Upon Regimen Compliance 28 Types of Noncompliance 28 Techniques for Improving Compliance 29 The Patient-Doctor Relationship The Patient ; The Medications How to Achieve Better Compliance Conclusion. 32 PART TWO THE AGING PROCESS AND RESPONSE TO PSYCHOTROPIC DRUGS NEUROTRANSMISSION IN THE AGING CENTRAL NERVOUS SYSTEM 41 TREY SUNDERLAND, M.D. The Neurotransmission Process 41 The Effect of Age on Neurotransmitters 43 Norepinephrine 44 Dopamine 45 Serotonin 47 Acetylcholine 48 Benzodiazepine-GABA Receptor Complex 50 The Effect of Psychotropic Drugs on Neurotransmission 51 Age-Related Central Nervous System Alterations in Receptor Sensitivity and the Effects of Psychotropic Drugs PSYCHOTROPIC DRUGS AND THE AGING PROCESS: PHARMACOKINETICS AND PHARMACODYNAMICS 61 DARREL R. ABERNETHY, PH.D. Basic Pharmacokinetic Concepts and the Aging Process Absorption Effect of Aging 62 Clinical Implications 62 Distribution 62 Effect of Aging 62 Clinical Implications 62 Protein Binding Effect of Aging 63 Clinical Implications. 63 Hepatic Metabolism and Clearance Effect of Aging Clinical Implications 65 Renal Clearance 65 Effect of Aging 66 Clinical Implications 66 Steady-State Plasma Levels and Drug Accumulation 66 Effect of Aging 67 Clinical Implications 67 Pharmacodynamics and Aging 68 Pharmacokinetics of Specific Drug Groups 68 Sedative-Hypnotics 68 Anticonvulsants Antidepressants Lithium 71

4 CONTENTS XVii Neuroleptics 71 Using Pharmacokinetic Information in Prescribing Psychotropic Drugs 71 Absorption 71 Clearance 72 Protein Binding 72 PART THREE PSYCHOTROPIC DRUG TREATMENT OF THE ELDERLY TREATMENT OF DISORDERED BEHAVIOR. 79 JAMES B. LOHR, M.D.; DILIP V. JESTE, M.D.; M. JACKUELYN HARRIS, M.D.; CARL SALZMAN, M.D. Causes of Behavioral Symptoms 79 Dementia 79 Delirium, 80 Late-Onset Schizophrenia 81 Delusional Disorder 81 Early-Onset Schizophrenia 82 Primary Mood Disorder 82 General Principles for Treatment with Neuroleptics 82 Clinical Pharmacology 82 Absorption 83 Protein Binding 83 Volume of Distribution 83 Metabolism 83 Receptor-Site Alterations 83 Pretreatment Evaluation 83 Dosage and Administration 83 Side Effects 85 Sedation 85 Hypotension 85 Anticholinergic Reactions \ 86 Peripheral Symptoms \ 86 Central Nervous System Anticholinergic Manifestations 86 Cardiovascular Side Effects 86 Neuroleptic-Induced Movement Disorders 87 Extrapyramidal Reactions 87 Akathisia 87 Neuroleptic-Induced Parkinsonism 87 Acute Dystonic Reaction 88 Tardive Disorders 88 Clinical Appearance of Tardive Dyskinesia 88 Course 90 Risk Factors for Tardive Dyskinesia 90 Other Tardive Syndromes 91 Treatment of Tardive Dyskinesia 91 Neurologic Side Effects 91 Neuroleptic-Induced Catatonia : 91 Neuroleptic Malignant Syndrome 91 Grand Mai Seizures 92 Hypothermia and Hyperthermia 92 Miscellaneous Side Effects 92 Jaundice 92 Agranulocytosis 92 Weight Gain 92 Dermatoses 92 Ophthalmologic Side Effects 93

5 XViii CLINICAL GERIATRIC PSYCHOPHARMACOLOGY Syndrome of Inappropriate Secretion of Antidiuretic Hormone 93 Choice of Neuroleptics 93 Phenothiazines Chlorpromazine Thioridazine 96 Piperazines 96 Butyrophenones 97 Thioxanthenes 97 Dibenzoxazepines 97 Indolones Clozapine Treatment of Agitation with Non-Neuroleptic Drugs. 98 Propranolol 98 Trazodone, Buspirone, and Fluoxetine 98 Carbamazepine and Lithium 99 Difficult Clinical Situations Involving the Use of Neuroleptics 99 Tardive Dyskinesia, Parkinsonism, and the Elderly Patient 99 Agitation and Extrapyramidal Side Effects 99 L-Dopa-Induced Psychosis from Parkinson's Disease 100 Clinical Vignettes TREATMENT OF DEPRESSION: DIAGNOSTIC CONSIDERATIONS BALU KALAYAM, M.D.; CHARLES A. SHAMOIAN, M.D., PH.D. Syndromes of Depression Major Depressive Disorder " Delusional Depression 117 Masked Depression 118 Depression Associated with Organic Brain Dysfunction 118 Depression Associated with Dementia 118 Dementia Associated with Depression 119 Late-Onset Depression 120 Depression and Physical Illness 120 Depression as a Response to Physical Illness 121 Depression as a Part of Physical Illness (Secondary Depression) Depression Related to Medications Morbidity Accompanying Depression ; Suicide 124 Depression and Immunity 125 Assessment 125 Clinical Signs and Symptoms 126 Clinical Screening and Rating Instruments 126 Physical Examination and Laboratory Tests Differential Diagnosis TREATMENT OF DEPRESSION 137 GEORGE S. ALEXOPAOULOS, M.D. Description of Heterocyclic Antidepressants Clinical Pharmacology Absorption Protein Binding Hepatic Metabolism 138 Receptor Sensitivity 139 Side Effects 139 Orthostatic Hypotension 140 Sedation 140 Cardiac Toxicity 141 Anticholinergic Toxicity Peripheral Anticholinergic Side Effects

6 CONTENTS XiX Central Nervous System Anticholinergic Syndrome 143 Memory Disturbance 144 Dosage and Administration 144 Who Is a Candidate for Drug Treatment? 145 Choice of Heterocyclic Antidepressants 146 Secondary Amines 146 Desipramine 146 Nortriptyline 147 Protriptyline Maprotiline Amoxapine Tertiary Amines Amitriptyline 147 Imipramine 147 Doxepin Trimipramine Antidepressants with an Atypical Structure Trazodone Fluoxetine :' Bupropion 149 Monoamine Qxidase Inhibitors 149 Clinical Pharmacology 149 Absorption 150 Hepatic Metabolism 150 Side Effects 150 Orthostatic Hypotension. 150 Anticholinergic-Like Symptoms 151 Sedation 151 Hypertensive Crisis 151 Other Drug Interactions 151 Peripheral Neuropathy 151 Weight Gain 152 Inhibition of Orgasm 152 Exacerbation of Cognitive Dysfunction 152 Choice of Monoamine Oxidase Inhibitors \. 152 Phenelzine ): 152 Isocarboxazide ' 152 Tranylcypromine 152 Changing Antidepressants 152 Treatment with Central Nervous System Stimulants 153 Antidepressants and the Hypertensive Elderly Patient 153 Treatment for Delusional Depression 154 Electroconvulsive Therapy : Electroconvulsive Therapy Administration 155 Pretreatment Evaluation 155 General Anesthesia Anticholinergic Barbiturate Muscle Relaxation Oxygenation 156 The Electrical Stimulus Electrode Placement Risks of Electroconvulsive Therapy 157 Cardiovascular Complications 157 CNS Complications 157 Memory Loss 158 Other Complications Drug Interactions during Electroconvulsive Therapy Maintenance Treatment Clinical Vignettes

7 XX CLINICAL GERIATRIC PSYCHOPHARMACOLOGY 8. TREATMENT OF MANIA 175 BENJAMIN LIPTZIN, M.D. Diagnosis of Mania in the Elderly 175 Treatment with Lithium Pretreatment Evaluation 176 Clinical Pharmacology of Lithium in the Elderly Absorption Protein Binding Distribution Metabolism Excretion Side Effects Confusion Ataxia Cardiovascular Toxicity 178 Renal Toxicity 178 Gastrointestinal Disturbances 178 Tremor 178 Thyroid Toxicity 179 Psoriasis Dosage and Administration Maintenance Treatment 180 Lithium and Diet Lithium and Hyponatremia-Producing Drugs Alternatives to Lithium 180 Treatment with Neuroleptics 181 Treatment with Anticonvulsants 181 Carbamazepine 181 Other Anticonvulsants 182 Calcium Channel Blockers 182 Treatment with Electroconvulsive Therapy Clinical Vignettes TREATMENT OF ANXIETY 189 CARL SALZMAN, M.D. Characteristics of Late-Life Anxiety 189 Differential Diagnosis 190 Physical Illness 190 Drugs 190 Depression 190 Panic Disorder 191 Obsessive-Compulsive Disorder Delirium and Dementia Diagnostic Evaluation 191 Treatment of Anxiety States with Benzodiazepines Sources of Prescribing Information Clinical Pharmacology of Benzodiazepines 196 Absorption 196 Protein Binding 196 Volume of Distribution 196 Metabolism Pharmacodynamics of Benzodiazepines Age Comorbidity Polypharmacy 197 Compliance Selection of Benzodiazepines

8 CONTENTS XXi Short Half-Life Benzodiazepines Oxazepam Lorazepam Alprazolam Long Half-Life Benzodiazepines 199 Chlordiazepoxide 199 Diazepam 199 Prazepam and Clorazepate 199 Halazepam 199 Clonazepam 199 Side Effects Sedation Cerebellar Toxicity 200 Psychomotor Impairment 200 Cognitive Impairment 200 Prescribing Guidelines for Benzodiazepines 201 Treatment of Anxiety with Nonbenzodiazepine Medications 202 Barbiturates and Meprobamate 202 Buspirone 203 P-Blockers 203 Antidepressants Antihistamines Neuroleptics 204 Treatment of Panic Anxiety, Phobias, and Obsessive-Compulsive Disorders... Benzodiazepines Antidepressants Conclusion Clinical Vignettes THE IMPACT OF AGE ON SLEEP AND SLEEP DISORDERS 213 J. CHRISTIAN GILLIN, M.D.; SONIA ANCOLI-ISRAEL, PH.D. The Neurobiology and Chronobiology of Normal Sleep Normal Age-Related Changes in Sleep and Wakefulness Napping Behaviors and Excessive Daytime Sleepiness \ 217 Formal Evaluation of Sleep Disorders Types of Sleep Disorders \ Dyssomnias: Intrinsic Sleep Disorders 221 Psychophysiologic Insomnia 221 Narcolepsy 221 Obstructive Sleep Apnea 221 Central Sleep Apnea.. Periodic Limb Movement Disorder Restless Legs Syndrome Dyssomnias: Extrinsic Sleep Disorders Environmental Sleep Disorder Altitude Insomnia Hypnotic-Dependent Sleep Disorder Stimulant-Dependent Sleep Disorder Alcohol-Dependent Sleep Disorder Dyssomnias: Orcadian Rhythm Sleep Disturbances Time Zone Change (Jet Lag) Syndrome Shift-Work Sleep Disorder 223 Delayed Sleep Phase Syndrome 223 Advanced Sleep Phase Syndrome Non-24-Hour Sleep-Wake Syndrome Parasomnias 223 Sleep Starts Nocturnal Leg Cramps

9 XXii CLINICAL GERIATRIC PSYCHOPHARMACOLOGY Sleep-Related Painful Erections 223 Sleep Behavior Disorder 223 Sleep-Related Abnormal Swallowing Syndrome 223 Medical/Psychiatric Sleep Disorders Associated with Mental Disorders 223 Sleep Disorders Associated with Psychoses 223 Sleep Disturbance with Depression 223 Sleep Disturbances with Anxiety Disorders 224 Sleep Disturbances Associated with Alcoholism Medical/Psychiatric Sleep Disorders Associated with Neurologic Disorders Cerebral Degenerative Disorders 224 Dementias Parkinson's Disease Fatal Familial Insomnia 225 Medical/Psychiatric Sleep Disorders Associated with Other Medical Disorders..225 Nocturnal Cardiac Ischemia 225 Chronic Obstructive Pulmonary Disease 225 Sleep-Related Gastroesophageal Reflux 225 Fibrositis Syndrome (Fibromyalgia) Special Issues and Sleep-Wake Patterns in the Elderly Conclusion 226 Clinical Vignettes TREATMENT OF INSOMNIA IN THE ELDERLY 235 QUENTIN R. REGESTEIN, M.D. Nonpharmacologic Treatment of Insomnia Treatment of Underlying Illness Sleep Chart 235 Regular Rising Times 236 Restriction of In-Bed Times 236 Avoidance of Irregular Naps 236 Exercise Hot Baths Relaxation Techniques Bladder Training Other Measures Drugs That Can Disrupt Sleep \ Caffeine 238 Nicotine 238 Alcohol 238 Nonprescription Drugs 238 Prescription Drugs 238 Pharmacologic Treatment of Insomnia 239 Benzodiazepines and Insomnia 240 Side Effects of Benzodiazepine Hypnotics in Elderly Patients 240 Selecting a Benzodiazepine Hypnotic Pharmacologic Properties of Benzodiazepines Intermediate and Short Half-Life Benzodiazepines 241 Long Half-Life Benzodiazepines 242 Other Drugs to Assist Sleep 243 Alcohol 243 Barbiturates 243 Chloral Hydrate 244 Other Hypnotics 244 L-Tryptophan 244 Antihistamines 244 Aspirin Neuroleptics and Antidepressants Which Hypnotic to Choose? 245 Clinical Vignettes 246

10 CONTENTS XXIII 12. MEMORY DYSFUNCTION AND DEMENTIA: DIAGNOSTIC CONSIDERATIONS 255 BARRY REISBERG, M.D. Age-Associated Memory Impairment 255 Mild Neurocognitive Disorder. 257 Alzheimer's Disease 261 Mild Alzheimer's Disease Moderate Alzheimer's Disease Moderately Severe Alzheimer's Disease Severe Alzheimer's Disease Diagnostic Use of Functional Stages 269 Alzheimer's Disease and Other Dementias: Differential Diagnosis 270 Alzheimer's Disease and Geriatric Depression: Differential Diagnosis 271 Alzheimer's Disease and Geriatric Anxiety: Differential Diagnosis 275 Conclusion NEUROBIOLOGY AND TREATMENT OF DEMENTIA 277 PIERRE N. TARIOT, M.D. Neurobiology of Alzheimer's Disease Neuropathology of Alzheimer's Disease Molecular Pathology of Alzheimer's Disease 278 Plaque Proteins 278 Tangle Proteins 278 Neurotransmitter Physiology in Alzheimer's Disease 279 Acetylcholine 279 Monoamines 279 Serotonin 279 Amino Acids 279 Peptides 280 Etiologic Hypotheses 280 Genetic 280 Toxic Factors Infectious Agents : Altered Neuroplasticity Summary of Neurobiologic Research ' Experimental Therapeutic Strategies in Alzheimer's Dementia 283 Therapies for Symptom Relief 283 Therapy Affecting the Circulatory System 283 Restitutive Therapies Acetylcholine Cholinergic Precursors 283 Cholinesterase Inhibitors 284 Cholinergic Receptor Studies 284 Monoamines Indoleamines GABA 286 Peptides 286 Summary of Restitutive Strategies 286 Metabolic Enhancement 286 Ergot Alkaloids 286 Nootropics 287 Neuronal Growth/Plasticity 287 Transplant. 288 Therapy of Neuropathologic Changes 288 Metabolic/Hormonal 288 Experimental Strategies for Other Dementias Multi-Infarct Dementia Parkinson's Disease 288

11 XXiV CLINICAL GERIATRIC PSYCHOPHARMACOLOGY Huntington's Disease Human Immunodeficiency Virus-Associated Dementia Conclusion 289 APPENDIX: PSYCHOTROPIC DRUG DOSAGES AND DRUG INTERACTIONS 301 ERIC WATSKY, M.D.; CARL SALZMAN, M.D. INDEX 333