PEDIATRIC PSYCHOPHARMACOLOGY FAST FACTS · 2008. 9. 9. · Anxiety Disorders Tic Disorders Substance Use Disorders Stimulant Use for Symptoms of ADHD in Special Populations Learning

PEDIATRICPSYCHOPHARMACOLOGY

FAST FACTS

Daniel F. Connor, M.D.Bruce M. Meltzer, M.D.

W. W. Norton & CompanyNew York • London

Contents

Preface xxv

PARTI: INTRODUCTION

1. Introduction to Pediatric Psychopharmacology 3A Brief History of the Field 4Epidemiological Trends in Pediatric Psychopharmacology 6Prescribing Algorithms 7Psychiatric Medication Use in Preschool Children 7Regulatory Issues in Pediatric Psychopharmacology 8

Off-Label Prescribing 8The Regulatory Process of Drug Development 9FDA Initiatives to Promote Pediatric Drug Development 10

Ethical Issues in Pediatric Psychopharmacology 12Developmental Pharmacology, Neurobiology, and Pediatric

Psychopharmacology 13

2. Basic Pharmacology 15Pharmacokinetics 15

Absorption 16Key Concepts 17Distribution 17Elimination 18Elimination Kinetics 18Elimination Half-Life 19Pediatric Variations in Pharmacokinetics 19

Cytochrome P450 Enzymes 20Summary 22

3. General Principles of Treatment 23Psychiatric Evaluation in Pediatric Psychopharmacology 24

Sources of Information 24

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Types of Information 25The Psychiatric Interview 26Mental Status Examination 26

Diagnostic Case Formulation 27Psychiatric Diagnosis, Target Symptoms, and Treatment Planning 30The Three Phases of Psychopharmacological Treatment 31Medication Initiation and Titration 32Clinical Management and the Evaluation of Outcome 33Compliance 34Medical Record Documentation 34Summary 36

PART II: THE MEDICATIONS

4. Stimulants 39Stimulant Drug Schedules 39Indications 40Efficacy in ADHD 40Efficacy in Narcolepsy 40Pharmacoepidemiology 41Currently Available Stimulants 41Pharmacology 42

Pharmacodynamics 42Pharmacokinetics 43

Stimulant Formulations and Dose 45Clinical Efficacy 45FDA Approval 45Pemoline 46

Stimulant Side Effects 46Stimulant Contraindications 50

Stimulant Drug-Drug Interactions 50Management of Stimulant Overdose 51

5. Antidepressants 53Selective Serotonin Reuptake Inhibitors 54

Fluoxetine 54Paroxetine 60Sertraline 63Citalopram 66Escitalopram 67Fluvoxamine 69SSRI Side Effects 71Drug-Drug Interactions 72Management of SSRI Overdose 72

Atypical Antidepressants 73Bupropion 73Trazodone 77

Contents

NefazodoneMirtazapine

Serotonin Norepinephrine Reuptake Inhibiting AntidepressantsVenlafaxineDuloxetine

Tricyclic AntidepressantsImipramineDesipramineAmitriptylineNortriptylineClomipramineTCA Drug-Drug Interactions

Monoamine Oxidase InhibitorsFuture Antidepressants in Pediatric Psychopharmacology?

MeclobemideReboxetine

Clinical Use of Antidepressants in Children and AdolescentsDuration of TreatmentMedical Monitoring for Increased SuicidalityLack of Response to Initial Antidepressant Treatment

6. Mood StabilizersLithium

PharmacologyIndicationsDosing and Duration of TreatmentContraindicationsSide EffectsDrug-Drug InteractionsManagement of OverdoseDrug Interference with Diagnostic Laboratory Testing

Divalproex SodiumPharmacologyIndicationsDosing and Duration of TreatmentContraindicationsSide EffectsDrug-Drug InteractionsManagement of OverdoseDrug Interference with Laboratory Testing

CarbamazepinePharmacologyIndicationsDosing and Duration of TreatmentContraindicationsSide EffectsDrug-Drug Interactions

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Management Of OverdoseDrug Interference with Laboratory Testing

LamotriginePharmacologyIndicationsDosing and Duration of TreatmentContraindicationsSide EffectsDrug-Drug InteractionsManagement of OverdoseDrug Interference with Laboratory Testing

Medical Management of Pediatric Patients ReceivingMood Stabilizers

Newer Anticonvulsants with Potential Utility asMood-Stabilizing AgentsGabapentinOxcarbazepineTiagabineTopiramate

7. AntipsychoticsSecond-Generation Antipsychotics

PharmacologyIndicationsChoosing A Second-Generation AntipsychoticCommon Side EffectsDrug-Drug InteractionsManagement of Overdose

First-Generation AntipsychoticsChlorpromazineThioridazine HydrochlorideHaloperidolPimozideFluphenazine HydrochlorideMolindone HydrochlorideTrifluoperazine HydrochlorideSide EffectsManagement of Side Effects

8. Drugs to Treat Extrapyramidal Symptoms and SyndromesAnticholinergics

PharmacologyIndicationsPertinent StudiesChoosing an Anticholinergic for EPSContraindicationsSide Effects

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Drug-Drug InteractionsManagement of OverdoseDrug Interference with Laboratory Testing

Amantadine HydrochloridePharmacologyIndicationsPertinent StudiesDosing and Duration of TreatmentContraindicationsSide EffectsManagement of Side EffectsDrug-Drug InteractionsDrug Interference with Laboratory Testing

Bromocriptine and PergolidePharmacologyDosingSide Effects

Vitamin EPharmacologyDosingContraindicationsSide Effects

9. AnxiolyticsBenzodiazepines

PharmacologyIndicationsChoosing a BenzodiazepineDosing and Duration of TreatmentContraindicationsSide EffectsDrug-Drug InteractionsManagement of OverdoseDrug Interference with Laboratory Testing

BuspironePharmacologyIndicationsDosing and Duration of TreatmentContraindica tionsSide EffectsDrug-Drug InteractionsManagement of OverdoseDrug Interference with Laboratory Testing

Other DrugsAntihistaminesChloral HydrateNovel Benzodiazepine Receptor Aaonists

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xiv Pediatric Psychopharmacology: Fast Facts

10. Adrenergic Agents 213Clonidine 213

Pharmacology 213Indications 214Dosing and Duration of Treatment 215Contraindications 217Side Effects 217Drug-Drug Interactions 219Management of Overdose 219Drug Interference with Laboratory Testing 220

Guanfacine 220Pharmacology 220Indications 221Dosing and Duration of Treatment 221Contraindications 223Side Effects 223Drug-Drug Interactions 223Management of Overdose 223.Drag Interference with Laboratory Testing 223

Beta-Blockers 223Pharmacology 224Indications 225Dosing and Duration of Treatment 226Contraindictions 229Side £#ecte 229Drug-Drug Interactions 230Management of Drug Overdose 230

f Interference with Laboratory Testing 231

11. Other Medications 233Atomoxetine 233

Pharmacology 233Indications 234Dosing and Duration of Treatment 235Contraindications 237Side tfjQTecte 237Drug-Drug Interactions 237Management of Overdose 238Drugi Interference with Laboratory Testing 238

Modafinil 238Pharmacology 239Indications 239Dosing and Duration of Treatment 240Contraindications 240Side £#ecte 242Drug-Drug Interactions 242Management of Overdose 242Z>rw0 Interference with Laboratory Testing 242

Contents xv

Desmopressin Acetate 243Pharmacology 243Indications 243Dosing and Duration of Treatment 244Contraindications 244Side Effects 244Drug-Drug Interactions 244Management of Overdose 244Drug Interference with Laboratory Testing 245

Oxybutynin 245Pharmacology 245Indications 245Dosing and Duration of Treatment 246Side Effects 246Drug-Drug Interactions 246Management of Overdose 247Drug Interference with Laboratory Testing 247

Tolterodine 247Pharmacology 247Indications 248Dosing and Duration of Treatment 248Contraindications 248Side £jfjfecte 248Drug-Drug Interactions 249Management of Overdose 249/>ra</ Interference with Laboratory Testing 249

Naltrexone 249Pharmacology 250Indications 250Contraindications 251Side tffifecte 251Drug-Drug Interactions 253Management of Overdose 253

12. Herbal and Alternative Medicines 255Regulatory Issues 255St. John's Wort 256

Pharmacology 256Indications 257Dosing and Duration of Treatment 257Contraindications 258Side £#ecte 258Drug-Drug Interactions 259

Melatonin 259Pharmacology 260Indications 260Dosing and Duration of Treatment 262Contraindications 262

xvi Pediatric Psychopharmacology: Fast Facts

Side Effects 262Drug-Drug Interactions 262

Essential Fatty Acids 262Secretin 263Kava 263Valerian 264Conclusions 264

13. Electroconvulsive Therapy in Adolescents 265Evidence of Effectiveness 266Indications for ECT in Adolescents 267Predictors of Response 268Contraindications 268Assessment of the Adolescent for ECT 268Description and Administration 269Adverse Effects 270Legal Considerations 271Informed Consent and Assent 272Transcranial Magnetic Stimulation 272

PART III: THE DISORDERS AND THEIR TREATMENT

14. Attention-Deflcit/Hyperactivity Disorder 275Diagnostic Features 275Prevalence 276Etiology 277Course of Illness 277

Comorbidity in ADHD 278Assessment 279Treatment Options 279

Psychosocial Interventions 279Medication Interventions 281

Stimulants in ADHD 282Indications 282Choosing A Stimulant 284Stimulant Treatment 284Stimulant Nonresponders 286Stimulant Side Effects 287

Nonstimulants in ADHD 289Bupropion 292Atomoxetine 292Clonidine and Guanfacine 293Modafinil 295Tricyclic Antidepressants 295

Clinical Management of ADHD with ComorbidPsychiatric Disorders 295Oppositional Defiant Disorder/Conduct Disorder 296

Contents

DepressionBipolar DisorderAnxiety DisordersTic DisordersSubstance Use Disorders

Stimulant Use for Symptoms of ADHD in Special PopulationsLearning DisabilitiesPersons with Developmental DelayPreschool ChildrenChildren with Seizure Disorders

Summary: An Algorithm for the Treatment of ADHD

15. Tic Disorders and Tourette's DisorderDiagnostic FeaturesPrevalenceComorbidityCourse of Illness and OutcomeAssessmentTreatmentPharmacotherapy

Typical NeurolepticsAtypical AntipsychoticsPergolideAlpha-Adrenergic Agonists: Clonidine and GuanfacineOther Tic-Suppressing Agents

Pharmacological Treatment of ADHD in Patients withTic Disorders or Tourette's disorderStimulants and Tic DisorderNonstimulant Medication Alternatives for Combined

ADHD and Tic DisorderCombined Pharmacotherapy

Pharmacological Treatment of OCD in Patients withTic Disorders or Tourette's disorder

Pediatric Autoimmune Neuropsychiatric DisordersAssociated with Streptococcas

16. Conduct Disorder, Oppositional Defiant Disorder,and Impulsive AggressionOppositional Defiant Disorder

PrevalenceEtiologyCourse of Illness

Conduct DisorderPrevalenceEtiologyCourse of Illness

Comorbidity in ODD and CD

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xviii Pediatric Psychopharmacology: Fast Facts

Psychopharmacological Treatment of ODD and CDImpulsive AggressionTreatment of Excessive, Maladaptive Aggression

Psychosocial TreatmentsEducational InterventionsPsychopharmacological TreatmentsMeasuring Treatment Response

A Clinical Approach to the Aggressive Child or Adolescent

17. Mood DisordersDepressive Disorders

Diagnostic Features and Subtypes of Mood DisordersPrevalenceComorbidityCourse of IllnessAssessmentCultural Factors Affecting AssessmentTreatment of Depression

Bipolar DisordersDescription and Diagnostic FeaturesComorbidityPrevalenceCourse of IllnessAssessment

Treatment of Pediatric Bipolar IllnessPsychosocial TherapiesPsychopharmacologyChoosing a MedicationDuration of Treatment

Pediatric Bipolar Illness Medication Treatment AlgorithmAcute TreatmentMaintenance TreatmentTreatment ofComorbid ADHD

18. Psychotic DisordersDevelopmental ConsiderationsPrevalenceComorbidityAssessmentEarly-Onset Schizophrenia

PrevalenceCourse and PrognosisAssessment

Treatment OptionsPsychopharmacological TreatmentsPsychosocial Treatments

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Contents xix

19. Extrapyramidal Syndromes and CentralSerotonin Syndrome 401Acute Dystonic Reactions 401Parkinsonism 402Akathisia 403Tardive and Other Neuroleptic-Related Dyskinesias 403

Assessment of Neuroleptic-Induced Dyskinesias 405Etiology of Neuroleptic-Induced Dyskinesias 405Treatment of Neuroleptic-Induced Dyskinesias 406

Neuroleptic Malignant Syndrome 407Central Serotonin Syndrome 408

20. Anxiety Disorders 411Prevalence and Epidemiology 412Comorbidity 413Assessment 413Separation Anxiety Disorder 414Panic Disorder With and Without Agoraphobia 416Generalized Anxiety Disorder 417Social Phobia 418Treatment Options for Anxiety Disorders 419

Psychosocial Therapies 420Psychopharmacology in Pediatric Anxiety Disorders 420

21. Obsessive-Compulsive Disorder 427Prevalence 427Comorbidity 428Course of Illness and outcome 429Assessment 429Treatment 430

Cognitive-Behavioral Therapy 432Psychopharmacology 432

Pediatric Autoimmune Neuropsychiatric DisordersAssociated with Streptococcas 438

22. Posttraumatic Stress Disorder 439Prevalence 440Comorbidity 441Course of Illness and Outcome 442Assessment 443Treatment Options 443

Psychosocial Interventions 445Psychopharmacology 446

23. Mental Retardation, Autism, and Other PervasiveDevelopmental Disorders 455Mental Retardation 455

Diagnostic Features 455

xx Pediatric Psychopharmacology: Fast Facts

Prevalence and EpidemiologyComorbidityCourse of Condition and OutcomeAssessmentPsychoeducational TreatmentPsychopharmacological Treatment

Childhood Autism and the Pervasive Developmental DisordersDiagnostic FeaturesPrevalenceComorbidityCourse and OutcomeAssessmentTreatment

24. Eating DisordersDiagnostic Criteria

Anorexia NervosaBulimia NervosaBinge Eating Disorder

PrevalenceCourse of Illness

Anorexia NervosaBulimia NervosaBinge Eating Disorder

ComorbidityAssessmentMultidisclplinary Treatment

Anorexia NervosaBulimia Nervosa

Psychopharmacological TreatmentAdjunctive Medications in Anorexia NervosaAdjunctive Medications in Bulimia Nervosa

25. Sleep DisordersNormal Sleep ArchitectureDifficulties Falling Asleep or Night WakingUnusual Arousal Events During Sleep (Parasomnias)

Night Terrors, Sleepwalking, and Sleep TalkingNightmaresNocturnal Enuresis

Excessive Daytime SleepinessDisturbed Nocturnal SleepSleep-Disordered Breathing and Sleep ApneaNarcolepsy

Sleep Problems Associated with Psychiatric ConditionsAttention-Deficit/Hyperactivity DisorderDepressionBipolar Disorder

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Contents xxi

Anxiety Disorders 501Psychotic Disorders 502Developmental Delay 502

Sleep Problems Associated with Medical andNeurological Disorders 502

26. Other Important Topics in Pediatric Psychopharmacology 503Combined Pharmacotherapy 503

Reasons for Rational Combined Pharmacotherapy 503Prevalence of Combined Pharmacotherapy 504Controlled Studies of Combined Pharmacotherapy 504Combined Pharmacotherapy in the Clinical Setting 505

Psychopharmacology and the Suicidal Patient 507Epidemiology 507Etiology 507Assessment of the Suicidal Child or Adolescent 508Treatment of the Suicidal Child or Adolescent 510

An Approach to Pediatric Psychopharmacology inConflicted Family Situations 511

Psychopharmacology and The Substance-Abusing Youngster 512General Treatment Considerations in Youth with

Psychiatric Disorder and SUDs 512

APPENDICES 515

Appendix 1: Pediatric PsychopharmacologySummary Table: Evidence of Efficacy by Drug and Disorder inChildren and Adolescents < 18 Years Old 517

Appendix 2: Pharmacodynamics of PsychiatricMedications Commonly Used in Children and Adolescents 521

Pharmacodynamics of Antidepressants 522Pharmacodynamics of Atypical Antipsychotics 522Pharmacodynamics of Anticonvulsants 522Pharmacodynamics of Stimulants 526

Appendix 3: Pediatric Psychopharmacology andthe Cardiovascular System 529

The ECG 529Reading the ECG 530ECG Parameters 531Psychiatric Medications and the ECG 532

Pulse and Blood Pressure 533

Appendix 4: Practical Tools for the Clinical childand Adolescent Psychopharmacologist 537

Growth Curves: Boys 538Growth Curves: Girls 539Parent's Questionnaire 540

xxii Pediatric Psychopharmacology: Fast Facts

Patient Medication Log 546Medication Side Effects Rating ScalesAntipsychotic Side Effects Profile 548Atomoxetine Side Effects Profile 550Antidepressant Side Effects Profile 551Benzodiazepine Side Effects Profile 553Buspirone Side Effects Profile 554Carbamazepine Side Effects Profile 555Clonidine/Guanfacine Side Effects Profile 556Lamotrigine Side Effects Profile 557Lithium Side Effects Profile 558Monoamine Oxidase Inhibitor Side Effects Profile 560Modafinil Side Effects Profile 562Oxcarbazepine Side Effects Profile 563Stimulant Side Effects Profile 564Topiramate Side Effects Profile 565Valproic Acid/Divalproex Side Effects Profile 566Abnormal Involuntary Movement Scale (AIMS) 568Clinical Global Impressions (CGI) 573Global Assessment Children's Scale (CGAS) 574Disorder Rating ScalesBrief Psychiatric Rating Scale for Children (BPRS-C) 576Pediatric Symptom Checklist (PSC) 578The SNAP-IV Teacher and Parent Rating Scale 580Abbreviated Parent Questionnaire 585Children's Depression Rating Scale—Revised (CDRS-R) 586Yale-Brown Obsessive Compulsive Scale (Y-BOCS) 596Children's Aggression Scale—Parent Version 599Overt Aggression Scale 601The Nisonger Child Behavior Rating Form: Parent Version 602The Nisonger Child Behavior Rating Form: Teacher Version 605Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire

(PQ-LES-Q) 609

Appendix 5: Parent Support Resources 611General Mental Health Resources for Children and Adolescents 611Attention-Deficit/Hyperactivity Disorder 612Bipolar Disorder 612Depression 612Independent Herbal and Alternative Medication Internet Sites 612Learning Disabilities 612Mental Retardation 613Obsessive-Compulsive Disorder 613Tic Disorders and Tourette's Disorder 613

Bibliography gj5Introduction to Pediatric Psychopharmacology 615Basic Pharmacology 616

Contents xxiii

General Principles of Treatment 617Stimulants 617Antidepressants 619Mood Stabilizers 622Antipsychotics 625Drugs to Treat Extrapyramidal Symptoms and Syndromes 626Anxiolytics 628Adrenergic Agents 630Other Medications 631Herbal and Alternative Medicines 633Electroconvulsive Therapy in Adolescents 635Attention-Deficit Hyperactivity Disorder 636Tic Disorders and Tourette's disorder 639Conduct Disorder, Oppositional Defiant Disorder, and Impulsive

Aggression 642Mood Disorders 644Psychotic Disorders 651Extrapyramidal Syndromes and Central Serotonin Syndrome 653Anxiety Disorders 655Obsessive-Compulsive Disorder 657Posttraumatic Stress Disorder 659Mental Retardation, Autism, and other Pervasive Developmental

Disorders 660Eating Disorders 664Sleep Disorders 666Other Important Topics in Pediatric Psychopharmacology 667Pediatric Psychopharmacology and the Cardiovascular System 669

Index 671