Practitioner's Guide to Psychoactive Drugs for Children and Adolescents

information. This book aims to do this for practitioners, professionals in health, welfare, and education, and interested laypersons, including parents. This is no easy task, since the levels of technical knowledge vary from that of the special education teacher seeking information about the drugs that many such pupils will be receiving, to that of the modern young child and adolescent psychiatrist whose grasp of the difficult fields of pharmacokinetics (how drugs are absorbed, distributed, and eliminated) and neurotransmitter physiology (via which most psychoactive drugs work) is daunting to the editors, who grew up in the bucolic clinical-empirical era. Inevitably there are sections of the book that will prove too technical for any except the medically qualified, but considerable effort has been applied to make much of the text, especially that discussing the clinical uses and side effects of the drugs, comprehensible to anyone used to getting information by reading. We also take comfort in the fact that many of the major contributions in pediatric psychophar­ macology have been made by nonmedical professionals, notably psychologists, suggesting that an audience beyond the medically qualified is practicable. One other problem confronted us-whether to organize the book by psycho­ pathological symptoms (e.g., hyperactivity) and disorders (e.g., autism) or by drugs.

I. General Principles.- 1.Introduction: A Guide for Practitioners, Professionals, and Public.- I. Introduction.- A. Preamble.- B. Definitions.- C. The Multidisciplinary Team.- D. Child Psychiatry and Behavioral Pediatrics.- II. Historical Overview.- A. Foundations.- B. Current Trends and Future Directions.- III. Classification of Psychoactive Drugs.- A. Names of Drugs.- B. Look-Alike Drugs.- IV. Drug Evaluation.- V. Determinants of Prescribing.- A. Medical Knowledge.- B. Patient and Parent Factors.- C. Physician Factors.- D. Social Factors.- E. Economic Factors.- F. The Powerful Placebo.- VI. Principles of Drug Use.- A. First Do No Harm (Prima Non Nocere).- B. Know the Disorder and Use Drugs When Indicated.- C. Choose the Best Drug.- D. Understand the Drug and Its Properties.- E. Minimize Drug Use and Dosage.- F. Keep Things Simple.- G. Avoid Polypharmacy.- H. Don’t Be a Fiddler.- I. Don’t Follow Fads.- J. Take Particular Care with Children.- K. Establish a Therapeutic Alliance.- VII. Conclusion.- References.- 2. Pharmacology.- I. Introduction.- II. Fate of Drugs in the Body.- A. Passage of Drugs across Biological Membranes.- B. Routes of Drug Administration.- C. Distribution.- D. Elimination.- 1 Excretion.- 2 Biotransformation.- 3 Variability in Human Drug Biotransformation.- III. Pharmacokinetics.- A. Apparent Volume of Distribution.- 1 One-Compartment Model.- 2 Two-Compartment Model.- B. Elimination and Clearance.- 1 Flow-Limited Clearance.- 2 Capacity-Limited Clearance.- 3 Dosage, Clearance, and Half-Life.- C. Multiple Dosing and Steady-State Drug Concentrations.- D. Saturation Kinetics.- IV. Time Course of Pharmacological Effect.- A. Nonlinear Concentration-Response Curve.- B. Slow Equilibration with Site of Drug Action.- C. Presence of Active Metabolites.- D. Indirect or Slow Biochemical Response.- V. Pediatric Variations in Pharmacokinetics.- A. Absorption.- B. Distribution.- C. Biotransformation and Excretion.- D. Response.- VI. Mechanisms of Drug Action (Pharmacodynamics).- A. Enzymes.- B. Voltage-Gated Ion Channels.- C. Reuptake Mechanisms.- D. Receptors.- 1 Dose-Response Curve.- 2 Receptor Number and Distribution.- 3 Receptor Subtypes.- 4 Modeling of Drug-Receptor Interactions.- E. Mechanisms of Receptor Action.- 1 Ligand-Gated Ion Channels.- 2 G-Protein-Linked Receptors.- 3 Second and Third Messengers.- F. Speed of Response of Receptors.- G. Summary of Mechanisms of Receptor Activation.- References.- 3. Prevalence of Drug Therapy.- I. Introduction.- A. Research Objectives.- B. Scope of the Review.- II. Hyperactivity (Attention-Deficit Hyperactivity Disorder).- A. Early Studies.- B. Recent Surveys.- C. Special Education.- D. Socioeconomic Status.- E. Treatment Practices.- F. National Estimates of Treatment Prevalence.- III. Mental Retardation.- A. Institutional Settings.- B. Community-Based Facilities.- C. Public Schools.- D. National Estimates of Treatment Prevalence.- IV. Seizure Disorders.- A. Autism.- B. Mental Retardation.- C. Preschool-Aged Children.- V. Autism.- VI. Depression.- VII. Enuresis.- VIII. Tourette Syndrome.- IX. Other Disorders.- X. Summary.- References.- 4. Monitoring and Measuring Drug Effects. I. Physical Effects.- I. Introduction.- II. Baseline Physical Assessment.- A. Past Medical History.- B. Immunizations.- C. Hospitalizations.- D. Trauma.- E. Transfusions.- F. Current Medications.- G. Allergies.- H. Substance Use History.- I. Social History.- J. Family Medical History.- K. Family Psychiatric History.- III. Medical Review of Organ Systems.- A. General Health.- B. Eyes, Ears, Nose, and Throat.- C. Respiratory.- D. Cardiovascular.- E. Gastrointestinal.- E. Urinary Tract.- G. Genital and Reproductive Systems.- H. Musculoskeletal System.- I. Integument (Skin).- J. Endocrine System.- K. Central Nervous System.- IV. Psychiatric Review.- V. Physical and Neurological Exam.- VI. Baseline Biochemical Assessment of Blood and Urine.- VII. Speech and Language Assessment.- VIII. Monitoring Side Effects.- A. General Principles.- B. Types of Measures.- C. Formal Side Effect Rating Scales.- 1. Side Effects Rating Scales.- 2. Physical and Neurological Exam for Soft Signs.- D. Compliance with Medication.- IX. Laboratory Measures and Monitoring.- A. Electrocardiogram.- B. Dexamethasone Suppression Test.- C. Thyroid Function Tests.- D. Electroencephalography.- E. Catecholamine and Enzyme Assays.- F. Lumbar Punctures.- G. AIDS Screening.- H. Toxicology.- I. Genetic Studies.- J. Brain Imaging.- K. Routine Liver, Kidney, and Serum Measures.- X. Conclusions.- References.- 5. Monitoring and Measuring Drug Effects. II. Behavioral, Emotional, and Cognitive Effects.- I. Introduction.- II. Measurement.- A. Diagnosis.- 1 Unstructured.- 2 Structured.- 3 Semistructured.- 4 Symptom Checklists.- 5 Adolescents.- 6 Summary.- III. Rating Scales.- A. Some General Considerations.- B. “General-Purpose” Rating Scales.- 1 Clinical Global Impressions (CGI).- 2 Customized Scales.- 3 Child Behavior Checklist and Its Analogues.- 4 Revised Behavior Problem Checklist (RBPC).- C. Hyperactivity (ADHD).- 1 Teacher Rating Scales.- a. ADHD-Only Instruments.- b. Scales for ADHD plus Other Symptoms.- 2 Parent Rating Scales.- a. ADHD-Only Instruments.- b. Scales for ADHD plus Other Symptoms.- 3 Self-Rating Hyperactivity Scales.- 4 Situation-Specific Scales.- 5 Summary.- D. Oppositional, Conduct, and Aggressive Problems.- 1 Introduction.- 2 Informant Instruments.- a. The Conners Scales.- b. The Peer Conflict Scale.- c. Child Behavior Checklist and Teacher Report Form.- d. The Revised Behavior Problem Checklist.- e. Inpatient Rating Scales.- 3 Self-Rating Scales.- a. The Youth Self Report.- b. Children’s Inventory of Anger.- 4 Conclusions.- E. Depression.- 1 Self-Rating Scales.- a. Children’s Depression Inventory (CDI).- b. Children’s Depression Scale (CDS).- c. Depressive Self-Rating Scale.- d. The Reynolds Scales.- e. Conclusion.- 2 Informant (Parent and Teacher) Scales.- a. Children’s Depression Inventory.- b. Children’s Depression Scale.- c. Bellevue Index of Depression (BID).- d. Emotional Disorders Rating Scale (EDRS).- e. Rating Scale of Dysphoria (RSD).- f. Conclusion.- 3 Interviews.- a. Children’s Depression Rating Scale — Revised.- b. Bellevue Index of Depression.- c. Other Interview Schedules.- 4 Other Instruments.- 5 Conclusions.- F. Bipolar (Manic-Depressive) Mood Disorder (Mania).- G. Anxiety Disorders.- 1 Self-Rating Scales.- a. Fear Survey Schedule for Children (FSSC-R).- b. Revised Children’s Manifest Anxiety Scale (RCMAS).- c. Childhood Anxiety Sensitivity Index (CASI) and Child Anxiety Frequency Checklist (CAFC).- d. State-Trait Anxiety Scale for Children.- 2 Specific Anxiety Disorders.- a. Obsessive-Compulsive Disorder (OCD).- b. Panic Disorder.- c. Separation Anxiety Disorder.- d. Phobic Disorders.- e. Posttraumatic Stress Disorder.- 3 Personality Scales.- 4 Behavior Rating Scales for Anxiety.- a. Louisville Behavior Check List.- b. Louisville Fear Survey for Children.- 5 Structured Interviews.- 6 Conclusions.- H. Other Disorders.- 1 Schizophrenia.- 2 Tic and Tourette Disorders.- I. Mental Retardation.- 1 The Aberrant Behavior Checklist (ABC).- 2 Behavior Problems Inventory (BPI).- 3 Emotional Disorders Rating Scale for Developmental Disabilities.- 4 Maladaptive Behavior Scale.- 5 Other Instruments.- J. Autism.- 1 The Children’s Psychiatric Rating Scale (CPRS).- 2 Aberrant Behavior Checklist.- 3 Conners Abbreviated Symptom Questionnaire.- 4 Timed Stereotypies Rating Scale.- 5 Ritvo-Freeman Real Life Rating Scale for Autism.- 6 Conclusion.- K. Preschool Rating Scales.- 1 Introduction.- 2 Child Behavior Checklist.- 3 The Preschool Behavior Questionnaire (PBQ).- 4 Other Preschool Instruments.- a. The Behavioural Screening Questionnaire (BSQ).- b. The Symptom Checklist.- c. Temperament Scales.- 5 Conclusion.- IV. Direct Observation.- A. General Considerations.- B. Types of Direct Observation Methods.- C. Some Illustrative Examples.- 1 Hyperactivity (ADHD).- 2 Conduct Disorder and Aggression Problems.- 3 Depression.- 4 Anxiety Disorders.- 5 Conclusion.- V. Performance, IQ, Achievement, and Automated Activity Measures.- A. Performance and Related Tests.- 1 Continuous Performance Task (CPT).- 2 Cancellation Tasks.- 3 Matching Familiar Figures (MFF) Task.- 4 Analogue Classroom Tests.- 5 Paired Associate Learning (PAL).- 6 Delay Task.- 7 Short Term Recognition Memory Task.- 8 Automated Measures of Activity Level.- B. Computer Testing.- 1 Advantages and Disadvantages.- 2 Current Status and Examples.- a. Gordon Diagnostic System.- b. Serial Recall: Assessment.- c. Test of Variables of Attention (TOVA).- d. The Fe Psy (“Iron Psych”) Test System.- C. IQ and Achievement Tests.- 1 IQ Tests.- 2 Achievement Tests.- a. General Considerations.- b. Some Specific Tests.- VI. Conclusions.- References.- 6. Medicolegal and Ethical Issues in the Pharmacologic Treatment of Children.- I. Introduction.- II. Obtaining Consent for Treatment.- A. The Doctrine of Informed Consent.- B. Elements of Informed Consent.- 1 Information.- 2 Voluntariness.- 3 Competency.- C. Exceptions to the Requirements of Informed Consent.- D. Special Consent Issues with Children and Adolescents.- 1 Parental Authority.- 2 The Authority of Children.- 3 Developmental Aspects of Competency.- 4 Assent.- E. Consent Procedures in Practice.- F. Documenting Informed Consent.- III. The Right to Refuse Treatment.- IV. Consent to Treatment and the Custody Problem.- V. Confidentiality.- VI. Risk Management in the Treatment of Children and Adolescents.- VII. Conclusions.- References.- 7. Disorders, Symptoms, and Their Pharmacotherapy.- I. Introduction.- II. Disruptive Behavior Disorders.- A. Attention-Deficit Hyperactivity Disorder.- 1 Diagnostic Features and Pharmacotherapy.- a. Stimulants.- b. Tricyclic Antidepressants.- c. Neuroleptics (Antipsychotics).- d. Other Drugs.- 2 Potential Biochemical Correlates.- B. Conduct Disorders.- 1 Diagnostic Features and Pharmacotherapy.- 2 Potential Biochemical Correlates.- C. Oppositional Defiant Disorder.- III. Mood Disorders.- A. Major Depressive Disorder (MDD).- 1 Diagnostic Features and Pharmacotherapy.- 2 Potential Biochemical Correlates.- B. Bipolar Disorder.- 1 Diagnostic Features and Pharmacotherapy.- 2 Potential Biochemical Correlates.- I. Schizophrenic Disorders.- A. Diagnostic Features and Pharmacotherapy.- B. Potential Biochemical Correlates.- V. Developmental Disorders.- A. Mental Retardation.- 1 Diagnostic Features and Pharmacotherapy.- 2 Potential Biochemical Correlates.- B. Specific Developmental Disorders.- C. Pervasive Developmental Disorder.- 1 Diagnostic Features and Pharmacotherapy.- 2 Potential Biochemical Correlates.- VI. Eating Disorders.- A. Anorexia Nervosa.- B. Bulimia Nervosa.- 1 Diagnostic Features and Pharmacotherapy.- 2 Potential Biochemical Correlates.- C. Pica.- D. Rumination Disorder of Infancy.- VII. Gender Identity Disorder.- VIII. Anxiety Disorders.- A. Overanxious Disorder.- B. Separation Anxiety Disorder.- C. School Phobia.- D. Avoidant Disorder.- E. Posttraumatic Stress Disorder (PTSD).- F. Obsessive-Compulsive Disorder (OCD).- 1 Diagnostic Features and Pharmacotherapy.- 2 Potential Biochemical Correlates.- IX. Tic Disorders.- A. Simple Tics.- B. Tourette Syndrome.- 1 Diagnostic Features and Pharmacotherapy.- 2 Potential Biochemical Correlates.- X. Psychoactive Substance Abuse and Dependence Disorders.- XI. Sleep Disorders.- XII. Elimination Disorders.- A. Enuresis.- 1 Diagnostic Features and Pharmacotherapy.- 2 Potential Biochemical Correlates.- B. Encopresis.- XIII. Dimensional Considerations.- A. Aggression.- 1 Clinical Features and Pharmacotherapy.- 2 Potential Biochemical Correlates.- B. Attention.- XI. Summary.- References.- II. Specific Drugs.- 8. Stimulants.- I. Pharmacological Aspects of Stimulant Medication: Definition and Nomenclature.- A. Pharmacology.- B. Pharmacokinetics.- II. Clinical Effects: Short-Term.- A. General Clinical Effects.- B. Physical Effects.- C. Effects on Behavior and Emotion.- D. Effects on Cognition, Learning, and Academic Performance.- E. Effects on Social Systems.- F. Dose Effects on Behavior and Learning.- III. Clinical Effects: Long-Term.- IV. Predicting the Clinical Response to Stimulants.- V. Side Effects and Toxicity.- A. Lethal Dose.- B. Short-Term Side Effects.- 1 Usual Side Effects.- 2 Tics.- 3 “Behavioral Rebound”.- 4 Cognitive Toxicity.- 5 Behavioral Toxicity.- 6 Idiosyncratic Side Effects.- 7 Summary of Short-Term Side Effects.- C. Long-Term Side Effects.- 1 Drug Dependence and Abuse.- 2 Height and Weight Suppression.- 3 Cardiovascular Effects.- VI. Clinical Indications and Usage.- A. Standard Indications.- B. Probable Indications.- C. Usage.- 1 When to Use Medication.- 2 Initial Medical Workup.- 3 Prescribing and Titrating.- D. Monitoring Response to Medication.- 1 Assessing Initial Response to Medication.- 2 Maintenance on Medication.- a. Assessing Progress.- b. When the Effect Appears to Diminish.- c. Side Effects.- d. Reassessment.- E. Discontinuing Medication.- VII. Contraindications and Drug Interactions.- VIII. Summary.- IX. Conclusion.- References.- 9. Antidysthymic Drugs (Antidepressants and Antimanics).- I. Introduction.- II. Diagnosis and Epidemiology of Depression in Children and Adolescents.- III. Antidepressants.- A. Types.- B. Heterocyclic Antidepressants.- 1 Definition, Classes, Generic and Trade Names.- 2 Cellular Actions.- 3 Pharmacokinetics.- 4 Behavioral and Emotional Effects.- 5 Cognitive and Learning Effects.- 6 Physiological Side Effects.- 7 Adverse Effects.- 8 Clinical Indications.- a. Mood Disorders.- b. Attention-Deficit Hyperactivity Disorder (ADHD).- c. Enuresis.- d. Anxiety Disorders.- 9 Contraindications and Drug Interactions.- C. Monoamine Oxidase Inhibitors.- 1 Definitions and Classes.- 2 Pharmacology.- 3 Clinical Effects.- 4 Clinical Indications.- a. Affective Disorders.- b. Attention-Deficit Disorders.- 5 Side Effects and Drug Interactions.- 6 Contraindications.- D. Summary of Antidepressant Treatment of Children and Adolescents.- IV. Antimanics.- A. Introduction.- 1 Epidemiology of Mania.- 2 Antimanic Drugs.- B. Lithium.- 1 Definition.- 2 Cellular Actions.- 3 Pharmacokinetics.- 4 Behavioral and Emotional Effects.- 5 Cognitive and Learning Effects.- 6 Adverse Effects.- 7 Clinical Indications and Usage.- a. General Diagnostic Considerations.- b. Medical Workup.- c. Treatment in Bipolar Disorders.- d. Effects on Aggressive Behavior.- e. Attention-Deficit Hyperactivity Disorder.- f. Unipolar Major Depression.- g. Dosage.- h. Contraindications and Drug Interactions.- C. Carbamazepine.- 1 Pharmacology.- 2 Clinical Effects.- a. Behavioral Effects.- b. Pharmacokinetics, Dosage, and Blood Levels.- 3 Clinical Indications.- 4 Side Effects.- D Valproate.- 1 Pharmacology.- 2 Clinical Effects.- 3 Clinical Indications.- 4 Side Effects.- E. Clonazepam.- 1 Pharmacology.- 2 Clinical Effects.- 3 Clinical Indications.- 4 Side Effects.- F. Summary of Antimanics in Child and Adolescent Disorders 262 References.- 10. Antipsychotics (Neuroleptics).- I. Definition, Classes, Individual Drugs, Generic and Trade Names.- II. Pharmacology and Pharmacokinetics.- A. Cellular Effects.- B. Pharmacokinetics.- 1 Oral Administration.- 2 Parenteral Administration.- 3 Depot Preparations.- 4 Therapeutic Effect.- 5 Blood Levels.- 6 Pharmacokinetics in Children.- C. System Effects.- D. Interactions.- III. Clinical Indications and Usage.- A. Indications.- 1 Dosage.- 2 Pretreatment Screening.- B. Schizophrenia.- C. Psychotic Depression and Bipolar Disorder.- 1 Psychotic Depression.- 2 Bipolar Disorder (i.e., Manic or Manic and Depressive Episodes).- D. Conduct Disorder and Conduct Problems.- E. Autism and Other Pervasive Developmental Disorders (PDD).- F. Tourette Syndrome.- G. Mental Retardation Associated with Disruptive Behavior or Psychiatric Disorder.- 1 Short-Term Efficacy.- 2 Effects on Cognition.- H. Attention-Deficit Hyperactivity D...