0, 4- } -v Psychotropic

NORMAN L. KELTNER, Ed D, RN Associate Professor, Graduate Program, University of Alabama School of Nursing, University of Alabama at Birmingham, Birmingham, Alabama

DAVID G. FOLKS, MD Professor of Psychiatry and Behavioral Neurobiology, University of Alabama School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama

Illustrated

St. Louis Baltimore Boston Chicago London Philadelphia Sydney Toronto Contents

PART ONE CLINICAL PSYCHOPHARMACOLOGY, 1 UNIT I Introduction to Psychotropic Use, 3 1 Psychiatric Care and Contemporary Treatment, 4 Benchmarks in Psychiatric Care, 4 Period of Enlightenment, 5 Period of Scientific Study, 5 Period of Psychotropic Drugs, 6 Period of Community Mental Health Care, 6 Remarks, 7

2 Review of Functional Neuroanatomy, 8 Richard A. Sugertnan Cleveland F. Kinney Supraspinal Motor Pathways, 18 Limbic Lobe, 23

3 Review of Neurotransmitters, 26 Richard A. Sugerman Synaptic Transmission, 26 Types of Synapses, 27 Membrane Receptors, 28 Mechanisms of Receptor Action, 28 Neurotransmission, 28 Neuron Excitation and Inhibition, 28 Defining Neurotransmitters, 29 Action and Synthesis of Neurotransmitters, 29 Cholinergic System, 29 Monoamine Systems, 32 Neuropeptides, 33 Amino Acid Transmitters, 34 Neurotransmitters and Neurochemistry of Behavior, 36

UNIT II Drugs Used in the Treatment of Mental Disorders, 41 4 Schizophrenia and Other Psychoses, 42 Historical Considerations, 42 DSM-III-R Terminology and Criteria, 44 Drugs, 45 History, 45 Classification Systems, 48 xiv Contents

Neurochemical Theory of Schizophrenia, 48 Pharmacologic Effects (Therapeutic Effects), 49 Psychiatric Symptoms Modified by Antipsychotic Drugs, 49 Other Uses and Effects, 50 Pharmacokinetics, 51 Side Effects, 53 Implications, 59 Chemical Class and Structure of Specific Drugs, 61 Remarks, 64

5 Mood Disorders, 67 Historical Considerations, 67 Scope of the Problem, 67 Diagnostic Considerations, 69 Major Depression, 69 Bipolar Disorder, 71 Suicide and Other Risks, 71 Diagnostic Dilemmas, 71 Treatment Considerations, 72 Depression, 72 Bipolar Disorder, 74 Other Mood Disorders, 75 Antidepressants, 75 Historical Considerations, 75 Neurochemical Theory of Effectiveness, 76 Tricyclic, Heterocyclic, and Non-MAOI Antidepressants, 80 Pharmacokinetics, 80 Side Effects, 81 Implications, 83 Specific Tricyclic Antidepressants, 85 Recently Developed Agents, 86 Implications, 87 Monoamine Oxidase Inhibitors, 89 Pharmacokinetics, 89 Side Effects, 89 Specific Interactions, 91 Implications, 93 Specific Monoamine Oxidase Inhibitors, 94 Treatment Issues and Caveats, 94 Antimanic and Mood-Stabilizing Drugs, 96 Lithium, 96 Pharmacokinetics, 96 Side Effects, 98 Implications, 100 Alternative Antimanic and Mood-Stabilizing Drugs, 102

6 Anxiety Disorders, 108 Historical Considerations, 108 Diagnostic Considerations, 111 Anticipatory Anxiety, 111 Posttraumatic Stress Disorder, 113 Contents xv

Mixed Anxiety-Depression, 113 Generalized Anxiety, 113 Nonpsychiatric Anxiety, 115 Treatment, 115 Anxiolytics, 118 , 118 Pharmacologic Effect, 118 Pharmacokinetics, 119 Side Effects, 122 Implications, 122 Buspirone, 125 Pharmacokinetics, 126 Implications, 126 Specific Anxiety Disorders and Mixed Syndromes, 127 Panic Disorder, 128 Treatment, 129 Phobic Disorders, 131 Treatment, 131 Obsessive-Compulsive Disorder, 133 Treatment, 133 Posttraumatic Stress Disorder, 135 Treatment, 135 Mixed Anxiety-Depression, 136 Treatment, 136

7 Seizure Disorders, 139

Epilepsy, 139 Categories of Seizures, 139 Antiepileptic Drugs, 141 Hydantoins: Prototype Drug, Phenytoin, 143 Pharmacologic Effects, 144 Pharmacokinetics, 144 Side Effects, 150 Implications, 150 Related Hydantoins, 154 Long-Acting Barbiturates: Prototype Drug, Phenobarbital, 154 Pharmacologic Effects, 154 Pharmacokinetics, 155 Side Effects, 155 Implications, 156 Related Barbiturates, 157 Succinimides: Prototype Drug, Ethosuximide, 158 Pharmacologic Effects, 158 Pharmacokinetics, 158 Side Effects, 159 Implications, 159 Related Succinimides, 160 Oxazolidinediones: Prototype Drug, Trimethadione, 160 Pharmacologic Effects, 160 Pharmacokinetics, 160 Side Effects, 161 Implications, 161 xvi Contents

Related Oxazolidinedione, 162 Benzodiazepines: Prototype Drug, , 162 Related Benzodiazepines, 163 Other Antiepileptics, 163 Valproic Acid and Derivatives, 163 Pharmacologic Effects, 164 Pharmacokinetics, 164 Side Effects, 164 Implications, 164 Related Drugs, 166 Carbamazepine, 166 Pharmacologic Effect, 166 Pharmacokinetics, 166 Side Effects, 166 Implications, 167 Rarely Used Antiepileptics, 168 Phenacemide, 168 Acetazolamide, 168 Lidocaine, 168 Magnesium Sulfate, 168 Paraldehyde, 169 8 Sleep Disorders, 170 Historical Considerations, 170 Diagnostic Considerations, 171 Drugs Used to Treat Insomnia, 174 Neurochemical Effects of Hypnotics, 177 Benzodiazepines, 178 Pharmacologic Effects, 180 Pharmacokinetics, 181 Side Effects, 186 Implications, 186 Specific Benzodiazepines, 187 Treatment Considerations, 188 Other Drugs Used in the Treatment of Insomnia, 190 Discussion, 190 Other Sleep Disorders, 192 Hypersomnia, 192 Narcolepsy, 193 Sleep Apnea, 193 Parasomnias, 196 Periodic Leg Movements (Restless Leg Syndrome), 196 Comorbid Conditions, 196

9 Acute Psychoses and the Violent Patient, 200

Scope of the Problem, 200 The Clinical Approach, 200 Policies on Violence, 201 Diagnostic Considerations, 201 Assessment and Clinical Approach, 201 Contents xvii

Drug Treatment, 204 Short-Term Treatment, 204 Long-Term Treatment, 210 Implications and Treatment Issues, 212

10 Alcoholism and Other Substance Abuse Disorders, 215 Scope of the Problem, 215 Epidemiology, 215 Historical Perspective, 215 National Surveys, 216 Pregnancy Considerations, 216 Psychologic Considerations, 217 Genetic, Environmental, and Other Influences, 217 Genetic Influences, 217 Environmental Influences, 217 Psychiatric Influences, 218 Drug-Related Influences, 218 Endogenous Opiate Receptors, 219 Diagnostic Considerations, 219 American Psychiatric Association Considerations, 220 Defining Key Factors, 220 Comorbidity, 222 Drug Treatment, 222 Short-Term Treatment Objectives, 223 Long-Term Treatment Objectives, 223 Drugs Used in the Treatment of Alcoholism, 223 Drugs Used to Treat Narcotic () Dependence and Abuse, 225 Drugs Used to Treat Effects of Central Nervous System Stimulants, 227 Drugs Used to Treat Tobacco Dependence, 231 Drugs Used to Treat Cannabis (Marijuana) Dependence, 233 Drugs Used to Treat Abuse of Phencyclidine and Similar Agents, 234 Drugs Used to Treat Sedative-Hypnotic and Anxiolytic Abuse and Dependence, 234

UNIT III Drug Issues Related to Psychopharmacology, 241 11 Drugs Used for Electroconvulsive Therapy, 242 Historical Considerations, 242 Historical Perspective on the Negative View, 243 Modern Electroconvulsive Therapy, 243 Indications, 243 Contraindications, 246 Advantages, 246 Disadvantages, 246 How Electroconvulsive Therapy Works, 247 Drugs Used in Electroconvulsive Therapy, 247 Succinylcholine, 247 Pharmacokinetics and Interactions, 248 Methohexital, 248 Pharmacokinetics, 248 Side Effects, 248 Interactions, 249 xviii Contents

Atropine, 249 Pharmacokinetics, 249 Side Effects, 249 Interactions, 249

12 Drugs of Abuse, 251 Alcohol, 257 Etiologic Theories, 257 Pharmacokinetics, 258 Physiologic Effects, 260 Related Issues, 261 Other Central Nervous System Depressants, 264 Barbiturates, 264 Pharmacokinetics, 265 Physiologic Effects, 265 Related Issues, 265 Inhalants, 266 Narcotics (), 266 Pharmacokinetics, 266 Physiologic Effects, 266 Related Issues, 267 Specific Drugs, 268 Stimulants, 269 Cocaine, 269 Pharmacokinetics, 269 Physiologic Effects, 270 Amphetamines, 270 Pharmacokinetics, 271 Physiologic Effects, 271 Related Issues, 271 Hallucinogens, 272 Mescaline and Related Synthetic Substances, 272 Pharmacokinetics, 272 Physiologic Effects, 272 Psilocybin, Psilocin, 273 Pharmacokinetics, 273 Physiologic Effects, 273 Marijuana, 273 Pharmacokinetics, 273 Physiologic Effects, 273 Lysergic Acid Diethylamide, 274 Pharmacokinetics, 274 Physiologic Effects, 274 Phencyclidine, 274 Pharmacokinetics, 274 Physiologic Effects, 274 Related Issues, 275 Remarks, 275 Screening Tests, 276 Contents xix

13 Drugs Used to Stimulate the Central Nervous System, 278

Cerebral Stimulants, 278 Amphetamines, 278 Pharmacologic Effect, 279 Pharmacokinetics, 280 Side Effects, 281 Implications, 282 Other Prescription Central Nervous System Stimulants, 284 Methylphenidate, 284 Pharmacokinetics, 285 Side Effects, 285 Implications, 285 Pemoline, 286 Other Stimulants: Caffeine and Amphetamine-Like Anorectics, 286 Caffeine, 286 Phenylpropanolamine, 287 Treatment Considerations, 290 Treatment of Depression, 290 Treatment of Depressed Medically 111 Patients, 290 Use as a Challenge Test for Predicting a Response to Antidepressants, 291 Use in Elderly Persons, 291 Caffeine Augmentation of Electroconvulsive Therapy, 291 Treatment of Schizophrenia, 291 Miscellaneous Uses, 291

14 Drugs Used to Treat Extrapyramidal Side Effects, 293 Review of Parkinsonism, 293 Drugs Used to Treat Parkinsonism, 296 Anticholinergic Antiparkinson Agents, 299 Pharmacologic Effects, 299 Pharmacokinetics, 299 Side Effects, 299 Implications, 300 Patient Education, 301 Related Anticholinergic Antiparkinson Drugs, 302 Benztropine, 302 ; Biperiden, 302 Procydidine, 302 , 303 Issues in Antiparkinson Drug Administration, 303 Other Agents, 305 Benzodiazepines: Treatment of EPSEs, 305 Beta-Adrenergic Antagonists: Treatment of EPSEs, 305 Clonidine: Treatment of EPSEs, 305 and Verapamil: Treatment of Tardive Dyskinesia, 305 Dantrolene: Treatment of Neuroleptic Malignant Syndrome, 305 xx Contents

UNIT IV Developmental Issues Related to Psychotropic Drugs, 307

15 Psychopharmacology for Children, 308 Scope of the Problem, 308 General Principles, 308 Common Syndromes, 311 Attention Deficit Hyperactivity Disorder, 311 Psychotic Disorders, 313 Depression and Mania, 317 Other Syndromes, 320 Miscellaneous Agents Used in the Treatment of Childhood Emotional Problems, 321 Remarks, 322

16 Psychopharmacology for Adolescents, 324 Scope of the Problem, 324 General Principles of Adolescent Psychopharmacology, 324 Strategies for Effective Administration, 324 Other Issues of Administration, 325 Common Syndromes, 325 Attention Deficit Hyperactivity Disorder, 325 Psychotic Disorders, 328 Depression and Mania, 329 Other Disorders, 334 Other Drugs Used to Treat Mental Disorders, 335 Remarks, 335

17 Psychopharmacology for Elderly Persons, 338 Scope of the Problem, 338 General Factors Pertinent to Psychotropic Drug Therapy, 339 Pharmacokinetics, 341 Pharmacodynamics, 344 Drug Reactions, 345 Compliance, 345 Psychiatric Disturbances Prevalent in Late Life, 346 Mood Disorders, 346 Psychotic Disorders, 348 Anxiety Disorders and Acute Insomnia, 349 Mixed Anxiety-Depression, 350 Agitation and Aggression, 351 Delirium, "Sundowning," and Confusion Associated with Dementia, 352 Remarks, 355

PART TWO PSYCHOTROPIC DRUG PROFILES, 359

Appendix, 459 General Index, 461 Disorders Index, 480 Drug Index, 485