Pharmacotherapy of Depression

Pharmacotherapy of Depression

Preface

Contents

Biological Theories of Depression and Implications for Current and New Treatments

Introduction

Neuroendocrine Systems

Hypothalamic Pituitary Adrenal (HPA) Axis in Depression CRF

HPA Axis, Anxiety, and Stress

Limbic-Cortical-Striatal-Pallidal-Thalamic (LCSPT) Tract, Stress,and Depression

Hippocampus: Possible Pivotal Role Among LCSPT Tract Structures?

Neuronal Plasticity and Brain-Derived Neurotrophic Factor (BDNF)

How Strong Is the Case for a Major Role of Stress and the HPA Axisin Depression?

The Hypothalamus–Pituitary–Thyroid (HPT) Axis, Growth Hormone, Somatostatin, and Prolactin in Depression

Classic Neurotransmitters and the Monoamine Hypothesisof Depression

Serotonin

Norepinephrine

Dopamine

Other Neuromodulators: Cytokines, Substance P, Glutamate, g.-Aminobutyric Acid, and Enkephalins

Alterations in Physiological Function: Circardian Rhythms, Sleep, Pain Perception, and Appetite

Conclusion

References

Clinical Pharmacology and Therapeuticsof Antidepressants

Introduction

General Principles

Pharmacokinetics and Pharmacodynamics

Pharmacogenetics

Practical Aspects of Treatment

SSRIs

History

Pharmacokinetics

Dosages (Table 7)

Mechanism of Action

Drug Interactions/P450 Metabolism

Adverse Effects

Overview

Gastrointestinal

CNS

Suicidality

Serotonin Syndrome

Endocrine System

Hematologic

Sexual

SSRI Discontinuation/Withdrawal Syndrome

Safety

Safety in Overdose

Safety in Pregnancy and Lactation (See Also Chapter “Diagnosisand Treatment of Depression During Pregnancy and Lactation”)

Efficacy

Cyclic Antidepressants

History

Pharmacology

Pharmacokinetics

Mechanism of Action

Adverse Effects

Cardiovascular: Orthostatic Hypotension

Cardiovascular: Conduction Effects

Sexual Dysfunction

Other Adverse Effects

Overdose

Clinical Use

Other Antidepressants

Bupropion

Venlafaxine

Duloxetine

Nefazodone and Trazodone

Mirtazapine

Overdose

The Role of Mixed Action Antidepressants in Therapeutics

Antidepressants Without United States FDA Approval

Reboxetine

Adverse Effects

Efficacy

Mifepristone

Substance P

Melantonergic Agents

Sigma Agonists

MAOIs

History

Pharmacology

Clinical Use

Adverse Effects

Hypertensive Crises

Drug–Drug Interactions

Overdose

Augmentation Strategies

Combinations of Antidepressants

Atypical Antipsychotic Augmentation of SSRI

Buspirone

Psychostimulants

Thyroid Hormone

Testosterone

Estrogen

Amantadine

Alternative and Non-Traditional Antidepressants

St John’s Wort

Adverse Effects

Drug–Drug Interactions

Efficacy

Conclusion

SAMe

Omega-3 Fatty Acids

Conclusion

References

Antidepressant Treatment of Geriatric Depression

Epidemiology

Phenomenology of Geriatric Depression

Diagnosis

Depression Subtypes and Comorbidity

Vascular Depression

Depression and Alzheimer’s disease

Depression and Cognitive Decline

Grief with Depression and Complicated Grief in the Elderly

Psychotic Depression

Suicidality

Depression with Concurrent Substance Abuse

Depression with Anxiety

Comorbidity Depression and Personality Disorders

Depression and Medical Illness

Treatment of Geriatric Depression

Pharmacological Treatment Issues

Physiology of Aging

Pharmacokinetics

Pharmacodynamics

Anticholinergic Adverse Effects

Cardiovascular Effects

Orthostatic Hypotension and Falls

Other Adverse Effects

Treatment of Major Depression

SSRIs

TCAs

Clinical Use of TCAs

Summary of Antidepressants in Geriatric Major Depression

Antidepressant Response in non-MDD Subtypes of Geriatric Depression

Treatment of Dysthymia and Subsyndromal Depression

Treatment of Depression with Insomnia

Treatment of Depression Comorbid with Dementia

Treatment of Complicated Grief

Treatment of Post-Stroke Depression

Electroconvulsive Therapy

Psychosocial Treatments

Conclusions

References

Treatment of Psychotic Disorders

Introduction

Prevalence and Course of Depression in Schizophrenia

Functional Consequences of Depression in Schizophrenia

Differential Diagnosis of Depression in Schizophrenia

Treatment

Atypical Antipsychotics

Electroconvulsive Therapy

Augmentation of Antipsychotics

Efficacy

Safety

Conclusion

References

Treatment of Bipolar Depression

Introduction

Scope of Depression in Bipolar Illness

Potential Reasons for Understudy of This Phase of the Illness

Implications for Treatment Recommendations

Second Generation Antidepressants: Their Limitations Despite Preference Over TCAs

Bupropion

SSRIs

SNRIs

Mirtazapine

Pramipexole

Use of Antidepressant in Depression Breaking Through Ongoing Treatment with a Mood Stabilizer: Duration of Treatment

Mood Stabilizers in the Treatment of Bipolar Depression

Lithium

Carbamazepine (Tegretol, Equetro)

Valproate (VPA, Divalproex Sodium, or Depakote)

Lamotrigine (Lamictal)

Gabapentin and Pregabalin

Topiramate (Topamax)

Other Anticonvulsants

Oxcarbazepine (Trileptal)

Levetiracetam (Keppra)

Zonisamide (Zonegran)

Tiagabine (Gabitril)

Second Generation Atypical Antipsychotic Agents

Clozapine

Risperidone

Olanzapine

Quetiapine

Ziprasidone and Aripiprazole

Superior Effectiveness of Atypical vs. Typical Antipsychoticsin Bipolar Depression

Sequential Treatment Approaches

Acute Episode

Supraphysiologic Thyroid Hormone Augmentation

Omega-3-Fatty Acids (OFAs)

Inositol

Focus on Long-Term Prevention

Other Therapies Including ECT, rTMS, and VNS

A Critical Role for Psychoeducation and Targeted Psychotherapy

Rationale for Early Detection and Intervention

References

Substance Abuse and Depression

Introduction

Prevalence and Comorbidity

Functional Consequences of Comorbid Depressionand Substance Abuse

Clinical Evaluation and Differential Diagnosis

The Importance of an Adequate History

MDD vs. Substance-Induced Mood Disorder

Evaluation for Suicide Risk

Dysthymia

Depression After Prolonged Sobriety

Clinical Presentations

Alcohol Dependence

Depression and Acute Intoxication

Alcohol Dependence and Depression

Alcoholic Hypophoria

Pharmacotherapy of Depression in the Alcoholic

Clinical Pharmacology of Antidepressants in Alcoholism

Initiating Pharmacotherapy

Tricyclic Antidepressants (TCAs)

Serotonin Reuptake Inhibitors (SSRIs)

Nefazodone

Mood Stabilizing Antidepressants

Cocaine

Opiates

Sec24_6

Depression and Opiate Detoxification

Treatment Failures

Conclusion

References

Antidepressant Treatments in PTSD

Posttraumatic Stress Disorder (PTSD)

Acute Stress Disorder

Disorders of Extreme Stress or Complex PTSD

Epidemiology of Trauma and PTSD

Prevalence of Traumatic Events

Comorbid/Cooccurring Disorders

Neurobiology of PTSD

Pharmacotherapy for PTSD

Antidepressant Treatment

SSRI Antidepressants

Fluoxetine

Paroxetine

Sertraline

Citalopam/Escitalopram

Fluvoxamine

SNRI Antidepressants

Venlafaxine

Duloxetine

Novel Antidepressants

Nefazadone

Trazadone

Mirtazapine

Buproprion

Monoamine Oxidase Inhibitors (MOA-Is)

Tricyclic and Tetracyclic Antidepressants

Summary of Antidepressant Treatment of PTSD

Nonantidepressant Somatic Therapies

Anxiolytics/Hypnotics

Mood Stabilizers

Older Agents

Newer Agents

Antipsychotics

Risperidone

Quetiapine

Olanzapine

Aripiprazole

Other Antipsychotics

Other Treatments

a2 Adrenoreceptor Agonists

a1 Adrenoreceptor Antagonists

Various Antagonists/Agonists

Prevention Medication

Repetitive Transcranial Magnetic Stimulation

Psychosocial Treatments

References

Diagnosis and Treatment of Depression During Pregnancy and Lactation

Depression and Pregnancy

The Risk of Being Depressed During Pregnancy

Risk Factors for Developing Depression During Pregnancy

The Risk to the Mother of Untreated Depression

Risk of Untreated Depression to the Fetusand to Pregnancy Outcome

The Effect of Untreated Depression on Pregnancy Outcome

The Risk of Pre-Term Labor/Delivery

Effect of Untreated Depression on the Course of Labor

The Impact of Untreated Depression on Fetal Development

The Impact of Stress and Anxiety on the Fetus

Effect of Stress on the Fetus

Effect of Depression or Stress on the Neonate

The Effect of Stress on Development

Fetal Programming and Its Relationship to Developmental Outcome

Prenatal Stress and Outcome: Animal Studies

Cortisol Stress and Fetal Programming

Treating Depression During Pregnancy

Pharmacologic Treatment of Depression During Pregnancy

The Risks and Benefits of Pharmacologic TreatmentDuring Pregnancy

Risk of Malformations

Risk of Spontaneous Abortion

Pre-term Birth and Fetal Growth Restriction (or Smallfor Gestational Age)

Impact of Antidepressants on the Neonate

Neonatal Adaptation

Persistent Pulmonary Hypertension

Non-SSRIs

Umbilical Cord Levels

Managing NAS

Developmental Risks

Prescribing Antidepressants During Pregnancy

Dosing Considerations During Pregnancy

Other Somatic Treatments

Electroconvulsive Therapy

Transcranial Magnetic Stimulation

Managing Mood Disorders in the Postpartum Period

Postpartum Blues and Postpartum Depression

Onset Prevalence and Risk Factors

Risk Posed by Postpartum Depression to Mother and Infant

Treating Postpartum Depression

Breast-Feeding

Choosing a Drug

Guidelines to Consider in Deciding on Continuing Medication (These Guidelines Are Adapted from di Scalea (244))

Conclusion

References

Antidepressant Treatment of Pediatric Depression

Introduction

Epidemiology

Diagnosis and Course

Research on Antidepressants in Child and Adolescent Depression

Fluoxetine

Sertraline

Paroxetine

Venlafaxine

Citalopram, Escitalopram

Other Second-Generation Antidepressants

Discussion: Application of Antidepressant Researchto Clinical Practice

The Current Safety Controversy on Child and Adolescent Depression Treatment

Advisories, Warnings, and Regulations on Youth Suicideand Antidepressants

Evidence of Possible Antidepressant-Related Suicidal Ideationand Behavior

Effect of FDA Warning on Antidepressant Prescribingand Suicide Rates

Discussion: The Current Antidepressant-Suicide Controversyand Clinical Practice

Recommendations for Clinical Practice with Childrenand Adolescents with Major Depression

Treatment Guidelines

References

Managing Depression in Primary Care

Introduction

Epidemiology

Diagnostic Screening in Primary Care

Overview

Screening Tools for Primary Care

Risk Factors as a Screening Consideration

Assessment and Differential Diagnosis

Bipolar Disorder

Risk Assessment

Symptom Severity Assessment

Management of Depression

Maximizing Treatment Outcomes

Treatment Approaches

Treatment Goals

Conclusion

References

Treatment of Depression in the Medically Ill

Introduction

Diabetes

Ischemic Heart Disease

Post-stroke

Dementia (See Also, Chapter “Antidepressant Treatmentof Geriatric Depression”)

Parkinson’s Disease

Conclusions

References

Index