Pharmacotherapy of Depression (eBook)

Pharmacotherapy of Depression 3
Preface 5
Contents 7
Biological Theories of Depression and Implications for Current and New Treatments 13
Introduction 13
Neuroendocrine Systems 17
Hypothalamic Pituitary Adrenal (HPA) Axis in Depression CRF 17
HPA Axis, Anxiety, and Stress 18
Limbic-Cortical-Striatal-Pallidal-Thalamic (LCSPT) Tract, Stress,and Depression 18
Hippocampus: Possible Pivotal Role Among LCSPT Tract Structures? 20
Neuronal Plasticity and Brain-Derived Neurotrophic Factor (BDNF) 21
How Strong Is the Case for a Major Role of Stress and the HPA Axisin Depression? 21
The Hypothalamus–Pituitary–Thyroid (HPT) Axis, Growth Hormone, Somatostatin, and Prolactin in Depression 23
Classic Neurotransmitters and the Monoamine Hypothesisof Depression 25
Serotonin 26
Norepinephrine 27
Dopamine 28
Other Neuromodulators: Cytokines, Substance P, Glutamate, g.-Aminobutyric Acid, and Enkephalins 29
Alterations in Physiological Function: Circardian Rhythms, Sleep, Pain Perception, and Appetite 32
Conclusion 33
References 34
Clinical Pharmacology and Therapeuticsof Antidepressants 45
Introduction 45
General Principles 45
Pharmacokinetics and Pharmacodynamics 45
Pharmacogenetics 47
Practical Aspects of Treatment 49
SSRIs 58
History 58
Pharmacokinetics 58
Dosages (Table 7) 61
Mechanism of Action 62
Drug Interactions/P450 Metabolism 65
Adverse Effects 65
Overview 65
Gastrointestinal 67
CNS 67
Suicidality 68
Serotonin Syndrome 69
Endocrine System 69
Hematologic 70
Sexual 70
SSRI Discontinuation/Withdrawal Syndrome 72
Safety 72
Safety in Overdose 72
Safety in Pregnancy and Lactation (See Also Chapter “Diagnosisand Treatment of Depression During Pregnancy and Lactation”) 73
Efficacy 74
Cyclic Antidepressants 76
History 76
Pharmacology 76
Pharmacokinetics 77
Mechanism of Action 81
Adverse Effects 81
Cardiovascular: Orthostatic Hypotension 82
Cardiovascular: Conduction Effects 82
Sexual Dysfunction 83
Other Adverse Effects 84
Overdose 84
Clinical Use 85
Other Antidepressants 87
Bupropion 87
Venlafaxine 89
Duloxetine 91
Nefazodone and Trazodone 91
Mirtazapine 93
Overdose 94
The Role of Mixed Action Antidepressants in Therapeutics 95
Antidepressants Without United States FDA Approval 95
Reboxetine 95
Adverse Effects 96
Efficacy 96
Mifepristone 97
Substance P 97
Melantonergic Agents 98
Sigma Agonists 98
MAOIs 98
History 98
Pharmacology 99
Clinical Use 102
Adverse Effects 103
Hypertensive Crises 103
Drug–Drug Interactions 105
Overdose 105
Augmentation Strategies 106
Combinations of Antidepressants 106
Atypical Antipsychotic Augmentation of SSRI 107
Buspirone 108
Psychostimulants 108
Thyroid Hormone 109
Testosterone 110
Estrogen 110
Amantadine 112
Alternative and Non-Traditional Antidepressants 112
St John’s Wort 112
Adverse Effects 112
Drug–Drug Interactions 113
Efficacy 113
Conclusion 115
SAMe 115
Omega-3 Fatty Acids 116
Conclusion 117
References 118
Antidepressant Treatment of Geriatric Depression 137
Epidemiology 137
Phenomenology of Geriatric Depression 139
Diagnosis 140
Depression Subtypes and Comorbidity 142
Vascular Depression 142
Depression and Alzheimer’s disease 144
Depression and Cognitive Decline 145
Grief with Depression and Complicated Grief in the Elderly 146
Psychotic Depression 146
Suicidality 146
Depression with Concurrent Substance Abuse 147
Depression with Anxiety 148
Comorbidity Depression and Personality Disorders 148
Depression and Medical Illness 149
Treatment of Geriatric Depression 150
Pharmacological Treatment Issues 150
Physiology of Aging 152
Pharmacokinetics 152
Pharmacodynamics 155
Anticholinergic Adverse Effects 155
Cardiovascular Effects 156
Orthostatic Hypotension and Falls 157
Other Adverse Effects 158
Treatment of Major Depression 159
SSRIs 160
TCAs 166
Clinical Use of TCAs 169
Summary of Antidepressants in Geriatric Major Depression 170
Antidepressant Response in non-MDD Subtypes of Geriatric Depression 170
Treatment of Dysthymia and Subsyndromal Depression 170
Treatment of Depression with Insomnia 171
Treatment of Depression Comorbid with Dementia 171
Treatment of Complicated Grief 172
Treatment of Post-Stroke Depression 173
Electroconvulsive Therapy 174
Psychosocial Treatments 175
Conclusions 176
References 176
Treatment of Psychotic Disorders 196
Introduction 196
Prevalence and Course of Depression in Schizophrenia 196
Functional Consequences of Depression in Schizophrenia 198
Differential Diagnosis of Depression in Schizophrenia 198
Treatment 199
Atypical Antipsychotics 199
Electroconvulsive Therapy 200
Augmentation of Antipsychotics 200
Efficacy 200
Safety 202
Conclusion 203
References 204
Treatment of Bipolar Depression 208
Introduction 208
Scope of Depression in Bipolar Illness 208
Potential Reasons for Understudy of This Phase of the Illness 210
Implications for Treatment Recommendations 210
Second Generation Antidepressants: Their Limitations Despite Preference Over TCAs 211
Bupropion 213
SSRIs 213
SNRIs 214
Mirtazapine 214
Pramipexole 214
Use of Antidepressant in Depression Breaking Through Ongoing Treatment with a Mood Stabilizer: Duration of Treatment 215
Mood Stabilizers in the Treatment of Bipolar Depression 216
Lithium 217
Carbamazepine (Tegretol, Equetro) 218
Valproate (VPA, Divalproex Sodium, or Depakote) 219
Lamotrigine (Lamictal) 220
Gabapentin and Pregabalin 223
Topiramate (Topamax) 224
Other Anticonvulsants 225
Oxcarbazepine (Trileptal) 225
Levetiracetam (Keppra) 225
Zonisamide (Zonegran) 226
Tiagabine (Gabitril) 226
Second Generation Atypical Antipsychotic Agents 227
Clozapine 227
Risperidone 228
Olanzapine 228
Quetiapine 229
Ziprasidone and Aripiprazole 229
Superior Effectiveness of Atypical vs. Typical Antipsychoticsin Bipolar Depression 230
Sequential Treatment Approaches 231
Acute Episode 231
Supraphysiologic Thyroid Hormone Augmentation 232
Omega-3-Fatty Acids (OFAs) 233
Inositol 233
Focus on Long-Term Prevention 234
Other Therapies Including ECT, rTMS, and VNS 234
A Critical Role for Psychoeducation and Targeted Psychotherapy 236
Rationale for Early Detection and Intervention 236
References 238
Substance Abuse and Depression 249
Introduction 249
Prevalence and Comorbidity 250
Functional Consequences of Comorbid Depressionand Substance Abuse 254
Clinical Evaluation and Differential Diagnosis 255
The Importance of an Adequate History 255
MDD vs. Substance-Induced Mood Disorder 255
Evaluation for Suicide Risk 256
Dysthymia 256
Depression After Prolonged Sobriety 256
Clinical Presentations 257
Alcohol Dependence 257
Depression and Acute Intoxication 257
Alcohol Dependence and Depression 257
Alcoholic Hypophoria 258
Pharmacotherapy of Depression in the Alcoholic 258
Clinical Pharmacology of Antidepressants in Alcoholism 258
Initiating Pharmacotherapy 260
Tricyclic Antidepressants (TCAs) 260
Serotonin Reuptake Inhibitors (SSRIs) 263
Nefazodone 266
Mood Stabilizing Antidepressants 266
Cocaine 268
Opiates 271
Sec24_6 271
Depression and Opiate Detoxification 274
Treatment Failures 274
Conclusion 275
References 275
Antidepressant Treatments in PTSD 285
Posttraumatic Stress Disorder (PTSD) 285
Acute Stress Disorder 285
Disorders of Extreme Stress or Complex PTSD 286
Epidemiology of Trauma and PTSD 286
Prevalence of Traumatic Events 286
Comorbid/Cooccurring Disorders 287
Neurobiology of PTSD 289
Pharmacotherapy for PTSD 292
Antidepressant Treatment 292
SSRI Antidepressants 292
Fluoxetine 292
Paroxetine 293
Sertraline 294
Citalopam/Escitalopram 295
Fluvoxamine 296
SNRI Antidepressants 296
Venlafaxine 296
Duloxetine 297
Novel Antidepressants 297
Nefazadone 297
Trazadone 297
Mirtazapine 297
Buproprion 298
Monoamine Oxidase Inhibitors (MOA-Is) 298
Tricyclic and Tetracyclic Antidepressants 299
Summary of Antidepressant Treatment of PTSD 299
Nonantidepressant Somatic Therapies 300
Anxiolytics/Hypnotics 300
Mood Stabilizers 301
Older Agents 301
Newer Agents 302
Antipsychotics 303
Risperidone 303
Quetiapine 304
Olanzapine 305
Aripiprazole 305
Other Antipsychotics 305
Other Treatments 306
a2 Adrenoreceptor Agonists 306
a1 Adrenoreceptor Antagonists 306
Various Antagonists/Agonists 307
Prevention Medication 307
Repetitive Transcranial Magnetic Stimulation 308
Psychosocial Treatments 308
References 309
Diagnosis and Treatment of Depression During Pregnancy and Lactation 318
Depression and Pregnancy 318
The Risk of Being Depressed During Pregnancy 319
Risk Factors for Developing Depression During Pregnancy 321
The Risk to the Mother of Untreated Depression 322
Risk of Untreated Depression to the Fetusand to Pregnancy Outcome 324
The Effect of Untreated Depression on Pregnancy Outcome 324
The Risk of Pre-Term Labor/Delivery 324
Effect of Untreated Depression on the Course of Labor 325
The Impact of Untreated Depression on Fetal Development 326
The Impact of Stress and Anxiety on the Fetus 326
Effect of Stress on the Fetus 327
Effect of Depression or Stress on the Neonate 327
The Effect of Stress on Development 327
Fetal Programming and Its Relationship to Developmental Outcome 328
Prenatal Stress and Outcome: Animal Studies 328
Cortisol Stress and Fetal Programming 329
Treating Depression During Pregnancy 329
Pharmacologic Treatment of Depression During Pregnancy 330
The Risks and Benefits of Pharmacologic TreatmentDuring Pregnancy 330
Risk of Malformations 331
Risk of Spontaneous Abortion 334
Pre-term Birth and Fetal Growth Restriction (or Smallfor Gestational Age) 334
Impact of Antidepressants on the Neonate 335
Neonatal Adaptation 335
Persistent Pulmonary Hypertension 336
Non-SSRIs 337
Umbilical Cord Levels 337
Managing NAS 337
Developmental Risks 338
Prescribing Antidepressants During Pregnancy 339
Dosing Considerations During Pregnancy 339
Other Somatic Treatments 340
Electroconvulsive Therapy 340
Transcranial Magnetic Stimulation 341
Managing Mood Disorders in the Postpartum Period 342
Postpartum Blues and Postpartum Depression 342
Onset Prevalence and Risk Factors 342
Risk Posed by Postpartum Depression to Mother and Infant 344
Treating Postpartum Depression 344
Breast-Feeding 345
Choosing a Drug 348
Guidelines to Consider in Deciding on Continuing Medication (These Guidelines Are Adapted from di Scalea (244)) 349
Conclusion 350
References 352
Antidepressant Treatment of Pediatric Depression 364
Introduction 364
Epidemiology 365
Diagnosis and Course 365
Research on Antidepressants in Child and Adolescent Depression 367
Fluoxetine 367
Sertraline 368
Paroxetine 369
Venlafaxine 370
Citalopram, Escitalopram 371
Other Second-Generation Antidepressants 371
Discussion: Application of Antidepressant Researchto Clinical Practice 372
The Current Safety Controversy on Child and Adolescent Depression Treatment 374
Advisories, Warnings, and Regulations on Youth Suicideand Antidepressants 374
Evidence of Possible Antidepressant-Related Suicidal Ideationand Behavior 375
Effect of FDA Warning on Antidepressant Prescribingand Suicide Rates 376
Discussion: The Current Antidepressant-Suicide Controversyand Clinical Practice 377
Recommendations for Clinical Practice with Childrenand Adolescents with Major Depression 378
Treatment Guidelines 379
References 379
Managing Depression in Primary Care 384
Introduction 384
Epidemiology 384
Diagnostic Screening in Primary Care 385
Overview 385
Screening Tools for Primary Care 386
Risk Factors as a Screening Consideration 387
Assessment and Differential Diagnosis 388
Bipolar Disorder 391
Risk Assessment 391
Symptom Severity Assessment 394
Management of Depression 396
Maximizing Treatment Outcomes 397
Treatment Approaches 398
Treatment Goals 400
Conclusion 401
References 402
Treatment of Depression in the Medically Ill 407
Introduction 407
Diabetes 408
Ischemic Heart Disease 409
Post-stroke 412
Dementia (See Also, Chapter “Antidepressant Treatmentof Geriatric Depression”) 415
Parkinson’s Disease 416
Conclusions 418
References 418
Index 423