Managing Treatment-Resistant Depression

Road to Novel Therapeutics

1st Edition - March 31, 2022
Editors: Joao Quevedo, Patricio Riva-Posse, William V. Bobo
Language: English
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 2 4 0 6 7 - 0
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 2 4 0 6 8 - 7

Managing Treatment-Resistant Depression: Road to Novel Therapeutics defines TRD for readers, discussing the clinical and epidemiological predictors, economic burden and neurob… Read more

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Managing Treatment-Resistant Depression: Road to Novel Therapeutics defines TRD for readers, discussing the clinical and epidemiological predictors, economic burden and neurobiological factors. In addition, staging methods for treatment resistance are fully covered in this book, including serotonin specific reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, other classes of antidepressants, including tricyclic antidepressants and monoamine oxidase inhibitors, augmentation strategies, and newer antidepressant treatments like ketamine and esketamine. In addition, evidence supporting the use of psychotherapies and neuromodulation strategies are also reviewed. Written by top experts in the field, this book is the first of its kind to review all methods of treatment for TRD.

Cover
Title page
Table of Contents
Copyright
Contributors
Chapter 1: Defining treatment-resistant depression, difficult-to-treat depression, and staging treatment intensity
Abstract
Introduction
Treatment-resistant depression
Difficult-to-treat depression
Conclusions
References
Chapter 2: Clinical and epidemiological predictors of treatment-resistant depression
Abstract
Introduction
Clinical predictors
Epidemiological predictors
Discussion
References
Chapter 3: The economic burden of treatment-resistant depression: Cost-of-illness perspective
Abstract
Introduction
Economic burden from a cost-of-illness perspective
The cost of treatment-resistant depression
Discussion
Conclusion
References
Chapter 4: The neurobiology of treatment-resistant depression
Abstract
Introduction
Why do people get depressed?
How do antidepressant treatments work?
Why do antidepressants fail?
Why is ketamine different?
Conclusions
References
Chapter 5: Modeling treatment-resistant depression in the preclinical setting
Abstract
Introduction
Common mechanisms of antidepressant response in depression
Studying antidepressant response in preclinical models
Animal models
Rodent animal models
Other animal models of depression
Cellular models
Induced pluripotent stem cells
Cocultured cellular models
High-throughput peripheral blood mononuclear cell assays
Multiscale reverse translation modeling of TRD
Conclusions
References
Chapter 6: Treatment algorithms for treatment-resistant depression
Abstract
Introduction
Early treatment algorithms: GAP, TMAP, and STAR*D
Subsequent treatment algorithms: 2015–20
The benefits of treatment algorithms
Cost efficacy of algorithms
Algorithm development
Implementing algorithms in clinical practice
The future of algorithms
Conclusion
References
Chapter 7: Tools to aid precision treatments to prevent or manage treatment-resistant depression (TRD): Pharmacogenomics, machine learning, and artificial intelligence
Abstract
Introduction
Brief history of pharmacogenomic tests and algorithms for clinical use
Evidence for pharmacogenomic testing in clinical practice
PGx economic studies
Algorithms for medication guidance
Machine learning for medication guidance
AI for medication guidance
Genome-wide association studies and polygenic risk scores (PRS) for diagnosis and medication guidance
A note on black box algorithms
Future directions for PGx and algorithm testing
References
Further reading
Chapter 8: Tricyclic antidepressants for treatment-resistant depression
Abstract
Introduction
Pharmacological properties
Indications
Clinical studies in people with treatment-resistant depression
Adverse effects and toxicology
Drug interactions
Clinical use
Summary
Additional resources
References
Chapter 9: Monoamine oxidase inhibitors for treatment-resistant depression
Abstract
Introduction
Pharmacological properties
Indications
Clinical studies in people with treatment-resistant depression
Adverse effects and toxicology
Interactions
Clinical use
Summary
Additional resources
References
Chapter 10: Switching antidepressants in patients with treatment-resistant depression
Abstract
Introduction
Switching antidepressant and TRD definition
Switching within the same class or switching across classes?
Is switching better than continuation of the same antidepressant?
Practical and clinical issues in switching antidepressants
Choice of second step antidepressant
Conclusions
References
Chapter 11: Adjunctive strategies for treatment-resistant depression
Abstract
Overview
General principles of adjunctive therapy
Preferred options for adjunctive therapy
Other options for adjunctive therapy
Notable failures, disappointments, and near misses
Summary
References
Chapter 12: Combining antidepressants to address treatment-resistant depression
Abstract
Charles B. Nemeroff, M.D., Ph.D.
Julie Farrington, M.D.
Sussann Kotara, M.D.
Brief overview of antidepressants
References
Chapter 13: Ketamine/esketamine for treatment-resistant depression
Abstract
Introduction
History
Efficacy
Safety
Implementation
Conclusion
References
Chapter 14: Psychedelic agents for treatment-resistant depression
Abstract
Acknowledgments
Introduction
Chemistry
Pharmacokinetics
Mechanisms of action
Clinical studies
Adverse effects and toxicology
Drug interactions
Summary and future directions
References
Chapter 15: Inflammation and treatment resistance: Mechanisms and treatment implications
Abstract
Introduction
Foundation for the hypothesis of inflammation’s role in depression
Clinical predictors of treatment resistance and inflammation
Mechanisms by which inflammation affects antidepressant treatment response
Impact of inflammation on neurocircuits
Therapeutic targets addressing TRD and inflammation
Future directions
References
Chapter 16: Opioid agents for treatment-resistant depression
Abstract
Introduction
Opioid agents and their potential in treatment-resistant depression
Opioid agents: Mechanisms of action, pharmacokinetics and clinical studies
Summary and future directions
References
Chapter 17: Transcranial magnetic stimulation for treatment-resistant depression
Abstract
Introduction
Historical overview
Proposed mechanisms: How does TMS work?
Parameters, response and remission rates, and durability
Effect on treatment-resistant bipolar depression
Potential biomarkers
Optimal stimulation parameters
Future directions and perspectives
References
Chapter 18: tDCS for treatment-resistant depression
Abstract
Introduction
History and development
Mechanisms of action
Clinical efficacy of tDCS for TRD patients
Adverse effects
Adverse effects in depression trials
Summary and future directions
Conclusions
References
Further reading
Chapter 19: ECT for treatment-resistant depression
Abstract
Introduction
ECT basics
History and development
Mechanisms of action
Clinical studies
Direct comparison to other treatments
Bipolar depression
Depression with psychotic features
Suicidality
Special populations
Maintenance ECT (M-ECT)
Safety and adverse effects of ECT
Future directions
Summary
References
Chapter 20: MST for treatment-resistant depression
Abstract
Introduction
History and development
Clinical studies
Adverse effects and interactions
Mechanism of action
Other indications
Conclusion
References
Chapter 21: VNS for treatment-resistant depression
Abstract
History
The VNS device and its mechanism of action
Indications
Clinical studies
Adverse effects
Interactions
Transcutaneous vagus nerve stimulation
Conclusion
References
Chapter 22: Deep brain stimulation for treatment-resistant depression
Abstract
Introduction
Targets for DBS in treatment-resistant depression
Conclusions
References
Chapter 23: Other neurosurgical interventions for treatment-resistant depression
Abstract
Acknowledgments
Introduction
PCS: The over simplification of the functional neuroanatomy of mood regulation may lead to missed opportunities in treatment development
Psychiatric neurosurgery
Future directions
References
Chapter 24: Treatment-resistant psychotic depression
Abstract
Introduction
Evidence-based treatment of psychotic depression
Options to consider for treatment-resistant psychotic depression
Summary
References
Chapter 25: Evidence-based psychotherapy for treatment-resistant depression
Abstract
Introduction
Effectiveness of psychotherapy for depression
Effectiveness of psychotherapy for TRD
Psychotherapy methods for TRD
Conclusion
References
Chapter 26: Treatment-resistant bipolar depression
Abstract
Introduction
Variables associated with treatment resistance in bipolar depression
Management of treatment-resistant bipolar depression
Interventions for treatment-resistant bipolar depression
Conclusions
References
Chapter 27: Treatment-resistant depression in children and adolescents
Abstract
Introduction
Depression in youth
Treatment-resistant depression studies
Antidepressant studies for acute treatment
Psychotherapy studies for acute treatment
Complementary alternative medicine
Combination treatment
Factors associated with treatment nonresponse
Conclusion
References
Chapter 28: Treatment-resistant depression in geriatrics
Abstract
Introduction
Epidemiology
Pathophysiology
Clinical presentation
Current treatment options
Future directions
References
Chapter 29: Identification and management of anxious depression in patients with treatment-resistant depression
Abstract
Part I: Identification
Part II: Management
Part III: Clinical summary
References
Part I references
Psychopharmacology references
Ketamine references
ECT references
TMS references
Psychotherapy references
Psychedelics references
VNS references
DBS references
Clinical summary references
Chapter 30: Managing treatment-resistant depression with comorbid personality disorders
Abstract
Personality disorders in DSM-5
The relationship between personality disorders and depression
Assessment of comorbid personality and depressive disorders
The impact of personality disorders on functioning and treatment outcome in patients with MDD
Borderline personality disorder and depression
Narcissistic personality disorder and depression
Alternative, personality-derived models of TRD
Clinical summary
Appendix
References
Chapter 31: Managing treatment-resistant depression with comorbid substance use disorders
Abstract
Introduction
Alcohol use disorder and major depressive disorder
Opioid use disorder and major depressive disorder
Stimulant (cocaine and methamphetamine) use disorder and major depressive disorder
Summary of the chapter: Practical considerations
References
Chapter 32: Managing treatment-resistant depression in the setting of chronic pain
Abstract
Definition and measurement of chronic pain disorders
The McGill Pain Questionnaire and the Brief Pain Inventory
Summary of recommendations for assessment practices in comorbid pain and depression scenarios
How common is depression in pain patients?
How common is pain in depression patients?
What is the impact of pain and depression comorbidity, in terms of outcomes either for depression or for pain?
Approaches to treatment of comorbid pain and depression
Medication treatment of comorbid pain and depression
Overall results from antidepressants
Key antidepressants for special consideration
Conclusion
References
Chapter 33: Inhaled gases for treatment-resistant major depression
Abstract
Acknowledgment
Introduction
Nitrous oxide
Isoflurane
Xenon
The use of inhalants in complimentary medicine: Aromatherapy
References
Chapter 34: Drugs under investigation for treatment-resistant depression
Abstract
Medications targeting the hypothalamic–pituitary–adrenal (HPA) axis
Medication targeting the melatonergic system
Medications targeting the glutamatergic system
Atypical antipsychotics
Other drugs
Conclusions
References
Chapter 35: Chronotherapeutics for treatment-resistant depression
Abstract
Introduction
Light therapy
Sleep deprivation therapy and combined chronotherapies
Conclusions
References
Chapter 36: Managing treatment resistant depression in primary care settings
Abstract
Scope of problem
Challenges of managing TRD in primary care settings
Collaborative care for management of depression in primary care (Fig. 36.1)
Components of collaborative care for depression
Advancing treatment in primary care settings
Clinical summary (Table 36.1)
References
Chapter 37: Treatment-resistant depression in pregnancy, the postpartum period, and transition to menopause
Abstract
Introduction
Unipolar peripartum depression
Pharmacologic treatment of unipolar peripartum depression
Peripartum bipolar depression
Depression during the transition to menopause
References
Chapter 38: Lifestyle interventions for treatment-resistant depression
Abstract
Introduction
Diet and nutrition
Probiotics
Mindfulness
Mindful movement
Exercise
Acupuncture
Common mechanisms of action of lifestyle modifications
References
Chapter 39: Managing the risk of suicide in people with treatment-resistant depression
Abstract
Introduction
Terms and definitions
Suicide prevalence
Suicide risk factors
Alternative methods for suicide prediction
Suicide risk in TRD
Treatment of suicide in TRD
Conclusions and future directions
References
Chapter 40: Maintaining motivation and preserving the therapeutic alliance as tools to overcome treatment-resistant depression
Abstract
Understanding the therapeutic Alliance
Relationship between therapeutic alliance and treatment outcome
Techniques to improve therapeutic alliance and enhance motivation
Therapeutic alliance in telehealth and other technology-based interventions
Clinical summary
Disclaimers
References
Index

Joao Quevedo

Dr. João Luciano de Quevedo, MD, PhD, is a Professor of Psychiatry at the McGovern Medical School, the University of Texas Health Science Center at Houston, where he is the Vice-Chair for Faculty Development and Outreach, Director of the Translational Psychiatry Program, and Director of the Treatment-Resistant Depression Clinic. Before moving to Houston, he was a Dean at the University of Southern Santa Catarina Medical School, Criciúma, SC, Brazil, where he is still an Adjunct Professor of Psychiatry. He is also Editor-in-Chief of the Brazilian Journal of Psychiatry and Director of the Continuous Medical Education Program in Psychiatry (PROPSIQ) of the Brazilian Psychiatric Association. Dr. Quevedo’s research interest is neurobiology of psychiatric disorders, particularly mood disorders, and he is a specialist in both unipolar and bipolar treatment–resistant depression. He is author of nearly 600 publications and 10 scientific books.

Affiliations and expertise

Professor of Psychiatry at the McGovern Medical School, The University of Texas Health Science Center at Houston, TX, USA

Patricio Riva-Posse

Dr. Patricio Riva-Posse, MD is an Assistant Professor in the Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine. After completing his training in Neurology and in Psychiatry, he has focused his clinical and research work in the field of treatment resistant mood disorders. He is the Director of the Treatment Resistant Depression Clinic, and Director of Neuromodulation Services. He conducts research in invasive and non-invasive neuromodulation as well as novel pharmacological approaches. He is an investigator in NIH-funded project studying subcallosal cingulate deep brain stimulation. Born in Argentina, he earned his Medical Doctor degree from the Universidad de Buenos Aires.

Affiliations and expertise

Emory University, Atlanta, GA, USA

William V. Bobo

Dr. William V. Bobo, M.D., M.P.H., is Professor of Psychiatry at the Mayo Clinic Alix School of Medicine and Chair, Department of Psychiatry & Psychology at Mayo Florida, where he also serves as the Medical Director for Leadership Development. His clinical and research interests are focused on the treatment of patients with refractory mood disorders and on examining and predicting the clinical effects — both beneficial and harmful--of medications used to treat people with severe mood disorders. He lives with his wife in Jacksonville, Florida.

Affiliations and expertise

Mayo Clinic, Jacksonville, FL, USA