NeuroPsychopharmacotherapy

Preface
Acknowledgments
Contents
About the Editors
Section Editors
Contributors
Part I: Basic Principles
Neurobiological Principles: Neurotransmitters
Neurotransmitters: More than Crossing the Synaptic Cleft
One Neuron: Two Messengers - Neurotransmission Beyond Dale´s Principle
Dopamine Neurons: A Versatile Model for Joint Neurotransmitter Release
Maintenance of Neuronal Network Activity: A Small Insight into Giant Domains
A New Frontier: Serotonylation of Histones - Neurotransmitter Activity Inside the Nucleus
Cross-References
References
Neurobiological Principles: Psycho-Neuro-Immuno-Endocrinology
Immunological Principles
Immunological Memory
Definition of Psycho-neuro-immunology
Methodological Aspects of Psycho-neuro-immunology
Interaction Between the Immune, Endocrine, and Central Nervous Systems
The Cytokine System
Stimulation of Cells in the CNS by Cytokines
Cytokine Production
Mode of Action
Kindling and Sensitization of the Immune Response: The Basis for a Stress-Induced Inflammatory Immune Response in Mental Illne...
Interaction of Cytokines and Neurotransmitters
Interleukin-1
Interleukin-2
Interleukin-6
TNF-α
Blood-Brain Barrier
Immune Genetics, the HLA System, and Schizophrenia
Cellular Immune System and Mental Disorders
Lymphocyte Population and Cytokine Production
Tryptophan-Kynurenine Metabolism in Mental Disorders
The Role of the Immune System in Cognition and Cognitive Disorders
Mental Disorders and Autoimmune Diseases
Treatment with Interferon-α and Depression
Schizophrenia and the Immune System
Disturbances of Neurotransmitters as a Result of Pre- or Postnatal Infections
Lymphocyte Status in Schizophrenic Disorders
Cytokines and Schizophrenia
CSF Diagnostic Procedures
Stimulation of Catecholamine Neurotransmitters
Anti-inflammatory Substances as a Therapeutic Approach in Schizophrenia
Anti-inflammatory Treatment in Schizophrenia
Other Immune-Related Substances in Schizophrenia
Depression and the Immune System
Interleukin-6 and Depressive Disorders
Major Depression and Cytokines
Cellular Immune System and Depressive Disorders
Anti-inflammatory Treatment of Depressive Disorders
Cyclooxygenase-2 (COX-2) Inhibition as an Example for an Anti-inflammatory Therapeutic Approach in Major Depression
Methodological Issues Regarding Anti-inflammatory Treatment in Major Depression
Anti-inflammatory Compounds Other than NSAIDs
Anti-IL-6 Complex as a Therapeutic Target in Major Depression
Other Immune-Related Substances in the Treatment of Major Depression
Immunological Effects of Psychopharmaceuticals
Antipsychotics
Antidepressants
Outlook
Cross-References
References
Pharmacokinetic and Pharmacodynamic Principles
Pharmacokinetics
Pharmacodynamics
``Dose-Response Curve´´: Concentration-Effect Relationships Explained
Difficulties Encountered in Clinical Trials Aimed at Demonstrating Concentration-Effect Curves
Why Single Center Trials Still Can Go Wrong
Variability of the Medication´s Concentration
Other Examples for Clear-Cut Concentration-Effect Relationships Obtained with Antipsychotics
Clear-Cut Concentration-Effect Relationships Obtained with Antidepressants
The Problem of the Placebo Responders
A Checklist to Improve Trials Investigating Concentration Effect Relationships
Cross-References
References
Pharmacovigilance
Introduction
Core Functions of Pharmacovigilance
How Pharmacovigilance Works
Pharmacovigilance in Different Countries
Adverse Drug Effects
Pharmacovigilance in Psychiatry
Prevention and Management of Adverse Drug Effects
Prevention of ADE
Pharmacogenetics
Therapeutic Drug Monitoring
Managing Adverse Drug Effects
References
Pharmacoeconomics
Introduction
Categories of Health Economic Evaluation
In Which Cases Is a Health Economic Evaluation Recommended?
Parameters of Health Economic Studies
Costs
Perspective
Time Horizon
Decision-Analytical Models and Procedures
Limitations
Institutions for Evaluating Cost-Effectiveness in Health Care
Health Technology Assessment and Cost-Effectiveness Thresholds
Pharmacoeconomic Evaluation of Drugs Prescribed for Brain Disorders
Supplement: Pharmacoeconomic Evaluations of Brain Disorders
References
Compliance and Psychoeducation
Compliance
Psychoeducation
References
Psychopathology: Rating Scales for the Assessment of Mental Status
Introduction
Assessment Aims
Characteristics of Instruments
Evaluation Criteria and Selection of Rating Scales
Selected Areas
Side Effects
Scales for Measuring Sexual Functioning
Scales for Measuring Extrapyramidal Motor Side Effects (EPS)
Other Domains
Ascertainment of Progression and Changes
Requirements for the Use of Interviews and Rating Scales
Examples of Practical Application
Conclusion and Perspectives
References
Xenobiotic Interactions in Psychopharmacotherapy: Classification and Handling
Introduction
Xenobiotic Interactions
Potentially Inadequate Medication (PIM), Potentially Inadequate Prescription (PIP)
Classification of Interactions
Pharmacodynamic Interactions
Pharmacokinetic Interactions
PD1 Interactions (So-Called ``Double Prescriptions´´)
PD2 Interactions
PD3 Interactions
PD4 Interactions
PK1 Interactions
PK2 Interactions
PK3 Interactions
PK3c Interactions: Prodrugs
Number of Potential Interactions
How to Handle Xenobiotic Interactions?
Data Bases to Check a Medication for Risk of Interaction
Drug Information Services (AID)
Therapeutic Drug Monitoring
The Clinical Pharmacological TDM Report
KONBEST
AMBEW
Cross-References
References
Randomized Controlled Trials and the Efficacy of Psychotropic Medications
Introduction
A Brief History of the Randomized Controlled Trial
The Role of Governmental Oversight of Medical Products
Key Characteristics of Modern Clinical Trial Designs
Protection of Human Subjects
Trial Design
Duration
Participant Selection
Confirmation of Diagnosis
Control Group
Randomization
Stratification
Blinding
Outcomes
Study Monitoring
Statistical Considerations of RCTs
Effect Size
P-value
Confidence Interval
Intention-to-Treat
Missing Data
Internal Validity
External Validity
Challenges to Detecting Efficacy of Drugs in RCTs
Placebo Response
Nonadherence to Treatment
Treatment Resistance
RCT Considerations for Specific Psychiatric Disorders
Major Depressive Disorder
Bipolar Disorder
Schizophrenia and Schizoaffective Disorder
Generalized Anxiety Disorder
Panic Disorder and Agoraphobia
Social Anxiety Disorder
Post-traumatic Stress Disorder
Obsessive-Compulsive Disorder
Attention-Deficit Hyperactivity Disorder
Eating Disorders
Substance Use Disorders
Nicotine
Alcohol
Opiates
Safety and Tolerability Assessment in RCTs
Criticism of Psychiatric Clinical Trials
``Me-too´´ Drugs
Summary
References
Adverse Drug Reactions, Intoxications and Interactions of Neuropsychotropic Medications
Abbreviations
Introduction
Adverse Drug Reactions and Intoxications: Definition, Prevalence, Severity
Information on ADRs on the Internet
ADRs Due to the Pharmacologic Target Profile of the Prescribed Medication
ADRs Due to Enantioselectivity
Enantiomer Nomenclature
ADRs Due to Chemical Structure
ADRs Due to Treatment Groups
Clinically Most Impressive Toxidromes
ADRs Due to Pharmacologic Target(s)
Clozapine ADRs and Clozapine Toxicity
Medications Not Covered in the Present Chapter
Further Reading
Pharmacovigilance
Optimization of Pharmacotherapy in Clinical Practice: An Example
Cross-References
References
TCM Substances in Neuropsychopharmacotherapy: Basic Aspects with a Focus on Depression
Introduction
Diet Decreases Incidence of Depression and Improves Symptoms: Meta-analyses and Clinical Intervention with Healthy Diet
Antidepressant Function of Herbal Medication
Antidepressant Phytochemicals: Structure, Activity, and Molecular Mechanism
Structure and Basic Properties of Phytochemicals for Antidepressant Activity
Diet and Phytochemicals Enhance 5-HT Level to Exert Antidepressant Activity
Phytochemicals Inhibit Type A Monoamine Oxidase
Phytochemicals Bind to NTF Receptors, Activate Signal Transduction, Induce NTF Expression, and Function as NTF-Mimics
Anti-Inflammatory Functions of Phytochemicals in Depression
Phytochemicals Modulate the HPA Axis
Phytochemicals Show Anxiolytic Functions
Novel Antidepressants Synthesized Based on Phytochemical Scaffold
Discussion
Financial and Competitive Interests Disclosure
Cross-References
References
TCM Substances in Neuropsychopharmacotherapy
Introduction
Medicinals of TCM
Ginkgo biloba L. ()
Radix et Rhizoma Ginseng/Ginseng ()
Stigma Croci ()
Gardeniae Fructus ()
Rhizoma Curcumae Longae ()
Radix et Rhizoma Glycyrrhizae ()
Radix Rehmanniae Raw (地)
Radix Rehmanniae Praeparata (地)
Bulbus Lilii ()
Hypericum perforatum/St.-John´s Wort (连/)
Formulae of TCM
Yueju Pill ()
Xiao Buxin Tang Decoction ()
Bulbus Lilii and Radix Rehmanniae Tang Decoction (地)
Conclusion
Cross-References
References
D-Serine: Basic Aspects with a Focus on Psychosis
Introduction
Evidence for NMDA Receptor Hypofunction in Schizophrenia
NMDA Receptor Antagonists
Anti-NMDA Receptor Antibodies
NMDA Receptor Hypofunction and Onset of Schizophrenia
NMDA Receptor System in Schizophrenia
Dopaminergic Transmission Under NMDA Receptor Hypofunction
NMDA Receptor Function Enhancement Therapy for Schizophrenia: Rationale for Application of D-Serine
Preclinical Studies
Clinical Studies
Issues and Improvement of NMDA Receptor Function Enhancement Therapy
Modulation of Brain D-Serine Signaling for Development of Next Generation Antipsychotics
Detection and Distribution of Endogenous D-Serine in Mammalian Brains
Biosynthesis of D-Serine
Storage of D-Serine
Extracellular D-Serine
Involvement of Neurons and Glia in Extracellular D-Serine Regulation
Regulatory Molecules for Extracellular D-Serine Signaling
D-Serine As an Endogenous Coagonist for the NMDA Receptor
Treatment of Schizophrenia by Modulating Extracellular D-Serine Signaling
Uptake of D-Serine
Degradation of D-Serine
D-Serine Action on GluD2 and GluN1/GluN3 Glutamate Receptors
D-Serine Systems in Schizophrenia
Conclusions
Cross-References
References
Amine Precursors in Depressive Disorders and the Blood-Brain Barrier
Introduction
Biogenic Amines and Depression
Serotonin Precursor
L-Tryptophan
5-Hydroxytryptophan
Dopamine Precursor
Histamine Precursor
Pathophysiology of Depression
Traumatic Brain Injury and Depression
Concussive Head Injury and Depression
Depression in Military
Depression in Alzheimer´s Disease
Depression in Parkinson´s Disease
Psychostimulant Abuse and Depression
Stress and Depression
Neurotrophins and Depression
BDNF and Serotonin Interaction in the CNS
Cytokines and Depression
Unifying Concepts of Depression
Monoamines and Neurotrophin Interaction
Monoamine and Cytokine Interaction
Blood-Brain Barrier Is the Gateway of Depression
Conclusion and Future Perspectives
References
The Endocannabinoid System in the Central Nervous System: Emphasis on the Role of the Mitochondrial Cannabinoid Receptor 1 (mt...
Introduction
The Endocannabinoid System (ECS)
Historical Background of the ECS
Endocannabinoids
Synthesis and Degradation of Endocannabinoids
Receptors for Cannabinoids
CB1 Receptor (CB1R)
CB2 Receptor (CB2R)
Vanilloid Receptor (TRPV1)
Nuclear PPAR-γ Receptor
Other Receptors
The ECS and the Modulation of Functions in the CNS
Regulation of Mitochondrial Function
The Cannabinoid 1 Mitochondrial Receptor (mtCB1R)
Effects of Cannabinoids on Mitochondria
Conclusion
Cross-References
References
Experimental Psychopharmacology
Introduction
Use of Instrumental Techniques in Experimental Psychopharmacology
Use of Animal Models in Experimental Psychopharmacology: General Considerations
Overview of Animal Models Used in Experimental Psychopharmacology
Animal Models Used to Evaluate the Antidepressant Potential of Drugs
Animal Models Used to Evaluate the Anxiolytic Potential of Drugs
Animal Models Used to Evaluate Rewarding and Addictive Properties of Drugs
Animal Models Used to Evaluate the Antimanic Potential of Drugs
Animal Models Used to Evaluate the Antipsychotic Potential of Drugs
Animal Models Used to Evaluate the Effects of Drugs on Cognitive and Executive Functions
Animal Models Used to Evaluate New Drugs for the Treatment of Neurodegenerative Diseases
Towards Improved Behavioral Animal Models: The Example of Ultrasonic Vocalizations
Cross-References
References
Part II: General Aspects
Psychopharmacology: A Brief Overview of Its History
Introduction
The Ancient and Medieval Periods: Opium, Hellebore, and Chandra
The Nineteenth Century: First Attempts at Scientific Pharmacology, and the Need for Restraint
Tentative Explorations During the First Half of the Twentieth Century
Chlorpromazine and Reserpine: The Beginning of the 1950s Psychopharmacology Revolution
Haloperidol and Depot Antipsychotic Medications
After Haloperidol: The Atypical Antipsychotics
The Antidepressants
Mood Stabilizers
Anxiolytics and Minor Tranquilizers
Hypnotica
Psychostimulants
Nootropics (Cognitive Enhancers) and Anti-dementia Agents
Antiparkinsonian Drugs
Psychopharmacology and the Emergence of Modern Neurochemistry
Assessing the Effects of Modern Psychopharmacology
References
Historical Overview of Psychiatric Diagnostics in Japan
Introduction
Psychiatric Diagnostics Before DSM-III in Japan (Conventional Psychiatric Diagnostics)
Problems of Conventional Psychiatric Diagnostics
Turning Point of Psychiatric Diagnostics in Japan
Psychiatric Diagnostics After Introduction of DSM in Japan
Reaffirming the Basic Idea of DSM
Domestic Opinion About DSM-5
Major Depressive Disorder Versus Bereavement
Neurocognitive Disorder
Autism Spectrum Disorder
Toward Future Development of Psychiatric Diagnostics
Conclusion
References
Neuro-psychopharmacotherapy and the Differential Diagnostic Approaches in Europe
Introduction
Differential Diagnostic Approach to Establish the Diagnosis
Neuro-psychopharmacological Recommendations According to Treatment Phases
Treatment Resistance
Differential Diagnostic Approach According to Predominant Symptomatology and Subtypes
Differential Diagnostic Approach According to Special Circumstances
Summary and Discussion
References
Neuropsychopharmacotherapy and the Differential Diagnostic Approaches in China
Mental Health in China
Brief History
Prevalence of Mental Illness
Lack of Qualified Staff
Diagnostic Classification CCMD System in China
Brief History and Overview
CCMD-3
Diagnosis of Mental Disorders
Psychiatric Diagnosis Principles and Ideas
Principle of Diagnosis of Mental Disorders
Diagnostic Thinking of Mental Disorders
Basis of Disease
Onset and Course of Disease
Clinical Manifestation
Etiology and Inducement
Standardized and Diagnostic Mental Examination Tool
References
Ethical Issues in Neuropsychopharmacotherapy: US Perspective
Introduction
Autonomy
Beneficence and Nonmaleficence
Justice
Iatrogenic Properties and Trust
Nontherapeutic Use and Cosmetic Neuroenhancement
Socioenvironmental Determinants
Fluoxetine (Prozac)
Clinical Indications and Side Effects
Mechanism of Action of Fluoxetine
Additional Ethical Considerations with Fluoxetine
Modafinil (Provigil)
Clinical Indications and Side Effects
Mechanism of Action of Modafinil
Additional Ethical Considerations with Modafinil
Concluding Remarks
References
Ethics of Informed Consent: Coercive and Preventive Medication
The Normative Framework and Its Change Over Time
Informed Consent
Information
Capacity to Consent
Coercive Medication
Acute Conditions
Chronic Conditions
Preventive Medication
Primary Prevention of Schizophrenia
Primary Prevention of Dementia
Conclusion
Cross-References
References
Neuropsychopharmacotherapy: Aspects of Placebo Effects
Definition of Placebos and Areas of Use
Factors Involved in Drug and Placebo Responses
Influences of Attributes of Medication, Accompanying Information, and ``Ambiente´´ (Factors c and S)
Factor ``c´´ Effects
Factor ``S´´ Effects
Target Variables of Placebo Responses and Their Methods of Assessment (Factors R and m)
Functions and Symptoms Responding to Placebo (Factor R)
Methods of Assessment (Factor m)
Factors Associated with Patient/Participant Variables (Factors Pi and Pj and Their Interactions)
Considerations on General Placebo Response Rates in Psychiatric Drug Studies
Mechanisms Operating in Placebo Responses
Cognitive Functions
Expectancy
Learning
Additional Cognitive Mechanisms
Biological Mechanisms
The Opioid System
The Dopaminergic System
Use of Placebos for Therapy and the Role of Nocebo in Clinical Trials and Medical Practice
Nocebo Effects in Therapy
Cross-References
References
Neuropsychopharmacotherapy: International Regulations and Regulating Laws in Japan
Introduction
Single Convention on Narcotic Drugs, 1961
Convention on Psychotropic Substances, 1971
Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances, 1988
The Laws Regulating Drug Control in Japan
Control of Stimulant Drugs
Control of Narcotics and Other Psychotropics
Other Regulations for the Control of Cannabis and Opium
Some Specific Topics
Abuse of Etizolam
Regulation of Synthetic Cannabinoids in Japan
Cross-References
References
Health Economics for Neuropsychological Diseases in China
Introduction
A Broad View of Health Economics
General Classification of the Objects of Study
The Association Between Health Economics and Neurology
Economic Burden on Neurodegenerative Diseases
Parkinson´s Disease
Subjects and Methods
Calculation of Costs
Results
Characteristics of Patients
Neurological Care
Drugs Used and LED
Transportation and Non-neurological Care
Home Care
Loss of Production
Costs
Alzheimer´s Disease
Subjects and Methods
Data Collection Procedure
Calculation of Costs
Results
Characteristics of Patients
Discussion
References
Causal Inference Methods in Pharmacoepidemiology
Pharmacoepidemiology and Causal Inference
Common Study Designs in Pharmacoepidemiologic Studies
Cohort Study Design
New-User Design
Active Comparator Design
Case-Control Study Design
Within-Subjects Designs
Exposures in Pharmacoepidemiologic Studies
Confounding in Pharmacoepidemiologic Studies
Confounding Adjustment Methods in Pharmacoepidemiologic Studies
Potential Outcomes Framework and Causal Assumptions
Methods for Time-Fixed Confounding Adjustment
Methods for Complex Time-Varying Confounding Adjustment
Applications in Neuro-Psycho-Pharmacoepidemiology
Applicability of Causal Inference Methods in Pharmacoepidemiology
References
Neuropsychopharmacotherapy: Guidelines
Introduction
Guideline Developing Process
Existing Guidelines
Potential Benefits from Clinical Guidelines
Limitations of Clinical Guidelines
Review of the Important Guidelines
Guidelines for the Treatment of Schizophrenia (Displayed in Table 1)
The APA Practical Guideline for the Treatment of Patients with Schizophrenia
Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines for the Management of Schizophrenia and...
NICE Guideline Concerning Psychosis and Schizophrenia in Adults: Prevention and Management
The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia
The International College of Neuropsychopharmacology Schizophrenia Guideline
Canadian Network for Mood and Anxiety Treatments Clinical Guidelines for the Management of Patients with Schizophrenia (CANMAT)
British Association of Psychopharmacology
Guidelines for the Treatment of Major Depression (Displayed in Table 2)
NICE Guidelines for the Management of Depression in Adults
The APA Practical Guideline for the Treatment of Patients with Major Depressive Disorder
The Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical Guidelines for Management of Adults with Major Depressi...
Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines for Mood Disorders
The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Unipolar Depress...
British Association of Psychopharmacology
Guidelines for the Treatment of Bipolar Disorder (Displayed in Tables 3, 4, and 5)
British Association of Psychopharmacology
Canadian Network for Mood and Anxiety Treatments Guidelines for the Management of Patients with Bipolar Disorder (CANMAT)
The International College of Neuropsychopharmacology Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD)
National Institute for Health and Clinical Excellence Clinical Guideline for Bipolar Disorder
The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders
Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines for Mood Disorders
Conclusions
References
Neuropsychopharmacotherapy: Differential Dose Regimes in China
Prescription Patterns of Neuropsychopharmacotherapy in China
Brief Introduction
Antipsychotic Polypharmacy in China
Clozapine in China
Brief History
Prevalence of Clozapine Use in China
Product Information
Pattern of Utilization of Clozapine in China
References
Nutrition in Brain Aging: Its Relevance to Age-Associated Neurodegeneration
Introduction
The Molecular Mechanism of Brain Aging
Oxidative Stress and Aging
Oxidative Modification of Amino Acids and Proteins
Proteins Modified by Lipid Radicals
Oxidative Modified α-Synuclein (αSyn) in PD
Impaired Proteolysis Systems for Abnormal Proteins in Aging and PD
Mitochondrial Dysfunction in Aging and PD
How to Intervene the Brain Aging and Age-Associated Neurodegeneration?
Calorie Restriction (CR) and Small Natural Components
CR for Prolonged Healthy Lifespan
Small Natural Molecules Modulate Metabolism and Life Span Like CR
Metformin
Rapamycin
Polyphenols: Resveratrol and Flavonoids
Vitamins and Other Small Compounds in Aging
Can Dietary Habits Prevent Aging and Age-Associated Neurodegeneration?
The Low-Carbohydrate or Ketogenic Diet
The Mediterranean Diet (MedDiet)
Gut-Brain Axis in Aging and Neurodegeneration
Discussion and Conclusion
Cross-References
References
Ethnopharmacology and the Development of Psychoactive Drug: A Critical Overview
Natural Products, Ethnopharmacology, and Drug Development
Ethnopharmacology in the Context of Psychopharmacology
Lost in Translation
Like It or Not, You Do Want to See and Know How Homemade Medicines Are Made
The Magic Bullet Fairytale
Too Little About Too Many
Putting the Cart Before the Horse
Perspectives for a Translational Ethnopharmacology
Cross-References
References
Antidepressants: Molecular Aspects of SSRIs
Citalopram Versus S-Citalopram: Molecular Insights into Antidepressant Treatment
SSRI´s Mode of Action: Targeting the Serotonin Transporter
Citalopram Binding Properties Underlying the Antidepressant Response
Modulation of SERT Binding Sites
The Allosteric Binding Site
Modulation of Allosteric Binding Site
Effect of 5-HT on Citalopram Modulation of SERT
Citalopram-SERT Interaction at the Cellular Level: Regulation of SERT Cell Surface Exposure
Modulation of SERT Binding Sites
Effect of 5-HT on Citalopram Modulation of SERT
Kinase´s Modulation of SERT
Summary
Cross-References
References
Neurochemical Mobile: A Heuristic Tool for Understanding Dynamic Complexity and Treatment of Alcohol Withdrawal
Quest for Theoretical Modeling in Neuropsychiatry
Empiricism, ``Methodism,´´ and ``Dataism´´: How to Understand ``Complexity´´?
``Theoretical Neurobiology´´: Ways to the Big Picture?
The Brain as a Systemic Symptom Generator
Systems Pathology of the Brain
Systems Neurobiology and Addiction
The Basic Whole-Brain Macro-circuit Model
The View of Neurochemistry of the Circuitry: The Cellular and Subcellular Level
Clinical Foundations of a Systems Pathology of Addiction
Symptoms of Alcohol Withdrawal: Clinical Aspects
Quantification of Withdrawal Course: Assessment Scales
Treatment of Alcohol Withdrawal
Benzodiazepines
Clomethiazole
Clonidine
Physostigmine
Phenobarbital
Propofol
Anti-convulsants
Antipsychotics
Neurobiological Theory and Modeling of Addiction
Alcohol Effects on the Main Neurotransmitter Systems (NTMS)
The Basic Neurochemical Systems Model
The ``Neurochemical Matrix´´: A Heuristic Structure Model
The ``Neurochemical Mobile´´: A Metaphorical Process Model
Alcohol and the Neurochemical Mobile
Conclusion and Perspectives
Cross-References
References
Delusion and Dopamine: Neuronal Insights in Psychotropic Drug Therapy
Introduction
Delusions and Predictions
The Role of Dopamine in Delusion Formation
Moving Current Models Forward
Understanding Delusions
Delusional Infestation: Interface Between Hallucination and Delusion
Psychotropic Drug Therapy in Delusional Disorder
Conclusion
Cross-References
References
Hallucinogens as Therapeutic Agents: Past, Present, and Future
Introduction
History
Chemistry and Mechanism of Action
Pharmacokinetics
Clinical Studies
Indications
Adverse Effects and Toxicology
Combination Therapy
Conclusion
Cross-References
References
Lipid Metabolism Disturbances During Antipsychotic Treatment for Schizophrenia
Background
Lipid Metabolism and Schizophrenia
The Risk of Hyperlipidemia and Antipsychotics
Antipsychotic Drugs and Lipid Disturbances
Meta-analysis of Lipid Parameters Among Antipychotics
Effect of Smoking Status and Gender Differences on Lipid Parameters
Race/Ethnicity Differences in the Risk of Hyperlipidemia Among Schizophrenia
Hypotheses Regarding the Mechanisms for the Association Between Antipsychotics and Lipids
Guidelines and Interventions
References
Cannabinoid Drugs in Mental Health Disorders
Introduction
Search Strategy
Cannabinoids in Treatment of Mental Health Conditions
Anxiety Disorders / OCD
Post-Traumatic Stress Disorder (PTSD)
Psychotic Disorders
Tourette Syndrome
Dementia
Depression
Other Conditions
Cannabinoids in Treatment of Substance Use Disorders
Cannabis Use Disorder
Nicotine Dependence
Opioid Use Disorder
Alcohol Use Disorder
Discussion and Future Directions
Mental Health Conditions
Substance Use Disorders
Conclusion
Cross-References
References
Cognitive Enhancement and American Constitutional Law
Introduction
Government Safety Interests and Limits on a Constitutional Right to Cognitive Liberty
Tradition, Social Convention, and Limits on a Constitutional Right to Cognitive Liberty
Quasi-Constitutional Rights to Cognitive Liberty
Conclusion
Cross-References
References
Statutes
Articles, Book Chapters, and Books
Challenges of Parkinson´s Disease Care in Southeast Asia
Introduction
Geography of Southeast Asia and Regional Epidemiology of Parkinson´s Disease
Burden of Parkinson´s Disease in Southeast Asia
Diagnostic Delay and Misdiagnosis of Parkinson´s Disease in Southeast Asia
Knowledge Gaps of Parkinson´s Disease in Southeast Asia
Parkinson´s Disease Treatment: Availabilities and Accessibilities in Southeast Asia
Telehealth as a Solution for Specialist Parkinson´s Care in Southeast Asia
Conclusion
Cross-References
References
Neuropsychopharmacotherapy: Complementary Treatments
Introduction
Psychotherapies
Behavioral Activation Therapy
Cognitive Behavioral Therapy
Problem-Solving Therapies (PST)
Extended Problem-Solving Therapy
Brief Problem-Solving Therapy
Self-Examination Therapy
First-Wave Therapies
Second-Wave Therapies
Third-Wave Therapies
Acceptance and Commitment Therapy
Mindfulness-Based CBT
Cognitive Behavioral Analysis System of Psychotherapy
Dialectical Behavior Therapy
Interpersonal Psychotherapy
Psychodynamic Therapies
Non-directive Supportive Therapy
Life Review Therapy
Exposure Therapy
Eye Movement Desensitization and Reprocessing
The Dodo Bird Verdict
Common Factors Theory
Discussion
Problems with Meta-Analyses
Conclusions
Cross-References
References
Part III: Antidepressants
Antidepressants: Definition, Classification, Guidelines
History
Definition
Classification
New Classification
Indications
Guidelines
Cross-References
References
Antidepressants: Pharmacology and Biochemistry
Biochemical Mechanisms of Action
Effect on the Monoaminergic Synapse
Effects in the Entire Neuronal System
Reorganization Instead of Deficit Regulation
Effect by Inhibition of Reuptake
Effect on Receptors
Effect by Delayed Decomposition
Clinical Efficacy Profiles
Effect on the Noradrenergic System
Effect on the Serotonergic System
Effect on the Dopaminergic System
Effect on the Glutamatergic System
Adaptive Changes with Prolonged Use of Antidepressants
Neuroplasticity
Behavioural Pharmacological Effects of Antidepressants
Cross-references
References
Antidepressants: Indications, Contraindications, Interactions, and Side Effects
Introduction
Indications
Major Depressive Disorder
Anxiety Disorders, Obsessive-Compulsive Disorder, Trauma- and Stressor-Related Disorders
Other Approved Indications
Contraindications
Bipolar Disorder
Pregnancy and Breastfeeding
Liver and Kidney Impairment
Interactions
MAOIs
TCAs
SSRIs
SNRIs
Mirtazapine and Mianserin
Reboxetine
Bupropion
Agomelatine
Vortioxetine
Side Effects
Gastrointestinal System
Nausea, Vomiting, and Diarrhea
Xerostomia
Constipation
Drug-Induced Liver Injury
Genitourinary System
Sexual Dysfunction
Urinary Disturbances
Cardiovascular System
QTc Interval Prolongation and Arrhythmias
Blood Pressure Abnormalities
Heart Rate
Nervous System
Serotonin Syndrome
Seizures
Extrapyramidal Symptoms
Headache
Ophthalmic Effects
Weight Gain
Bleeding
Hyponatremia
Hyperhidrosis
Sleep Disturbances
Discontinuation Syndrome
Suicidality
SSRIs-Induced Emotional Indifference
Antidepressant-Induced Jitteriness
Conclusions
References
Antidepressants: Course and Duration of Therapy, Withdrawal Syndromes, and Resistance to Therapy
Course and Duration of Pharmacological Therapy
Acute Treatment Phase
Continuation Phase
Recurrence Prevention Phase
Withdrawal Syndromes
Acute Discontinuation Syndrome/Withdrawal Syndrome
Severe Cases of ADS
Persistent Post-discontinuation Syndromes and Rebound Phenomena
Basic Principles
Treatment and Prevention
Resistance to Therapy
Clinical Assessment of Resistance to Therapy
Cross-References
References
Tricyclics: Imipramine, Clomipramine, Trimipramine (Dibenzazepines)
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Pharmacodynamics/Mechanism of Action
Indications
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Toxicity
Combination Therapies, Interactions
Cross-References
References
Amitriptyline and Depressions
Chemistry, Developmental History, and Chemical Graphics
Pharmacology
Pharmacodynamics
Pharmacokinetics
Indication
Clinical Studies
Depression
Other Studies
Amitriptyline and Migraines
Amitriptyline and Pain: Recent Studies
Amitriptyline and Insomnia
Adverse Effects
Drug Interactions and Drug Combinations
References
Amoxapine and Depressions
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Nortriptyline and Maprotiline for Depressions
Chemistry and Developmental History
Pharmacology and Pharmacokinetics
Mechanism of Action
Indications
Clinical Studies
Side Effects, Adverse Reactions, and Toxicology
Combination Therapy: Interactions
Cross-References
References
Mianserine and Depressions
Chemistry, Developmental History
Pharmacology
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Trazodone and Depression
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects, Adverse Reactions, and Toxicology
Combination Therapy: Interactions
Cross-References
References
Serotonin Reuptake Inhibitors: Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, and Sertraline
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications
Clinical Studies
Side Effects, Adverse Reactions, and Toxicology
Combination Therapy: Interactions
Cross-References
References
Bupropion and Depressions
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Mirtazapine and Depressions
Chemistry and Developmental History
Pharmacology
Pharmacokinetics
Special Populations
Elderly
Renal Failure
Hepatic Failure
Pharmacodynamics: Mechanisms of Action
Indications
Clinical Studies
Mirtazapine Compared with Placebo and Amitriptyline
Other Antidepressants
Other Studies
General Anxiety Disorders
Pain
Side Effects and Adverse Effects
Drug Interactions and Combinations
Drug Interactions
Drug Combinations
References
Vilazodone and Depressions
Chemistry, Developmental History
Pharmacology
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs): Venlafaxine, Desvenlafaxine, Duloxetine, Milnacipran, Levomilnacipran
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Desvenlafaxine
Duloxetine
Milnacipran
Levomilnacipran
Side Effects, Adverse Reactions, Toxicology
Desvenlafaxine
Duloxetine
Milnacipran
Levomilnacipran
Pregnancy
Discontinuation Symptoms
Combination Therapy: Interactions
Cross-References
References
Monoamine Oxidase Inhibitors in Depressive Disorders
Introduction
Clinical Applications of MAOIs
Pharmacokinetics/Metabolism
Adverse Effects of MAOIs
Drug-Drug Interactions with MAOIs
Use of Drugs in Combination with MAOIs to Treat Depression
Pharmacological and Neurochemical Actions of MAOIs in Addition to Inhibition of MAO
Target Matching of MAOIs in Major Depressive Disorder (MDD)
Revitalization of Interest in MAOIs
Summary
References
Agomelatine and Depressions
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Depressive Disorders
Sleep Disorders, Insomnia
Other Studies
Long-Term Studies, Relapse Prevention
Side Effects, Adverse Reactions, and Toxicology
Combination Therapy - Interactions
Cross-References
References
Hypericum and Depression
Chemistry, Developmental History
Pharmacology
Clinical Studies
Side Effects/Adverse Effects and Toxicology
Combination Therapy: Interactions
Cross-References
References
Ginseng and Ginsenosides in Depression
Introduction
Pharmacology
Constituents of Ginseng and Phytochemical Classification of Ginsenoside
Pharmacological Activities in the Brain
Antidepressant Functions
Monoamine (Serotonin) and Type a Monoamine Oxidase Hypotheses
Effects on the HPA Axis
Effects on Deregulated Immune System
Effects on BDNF and Adult Neurogenesis in the Hippocampus
Pharmacokinetics of Ginseng and Ginsenosides
Side Effects/Adverse Reactions and Toxicology
Drug-Drug Interactions
Clinical Studies
Discussion
Financial and Competitive Interests Disclosure
Cross-References
References
Vortioxetine and Depressions
Chemistry, Developmental History (Fig. 1)
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications
Clinical Studies
Side Effects, Adverse Reactions
Combination Therapy: Interactions
References
Part IV: Mood Stabilizers
Mood Stabilizer: Definition
Description
References
Mood Stabilizers: Classification, Indications and Differential Indications
Classification
Lithium
Anti-convulsants
Antipsychotics
Indications
Differential Indications
Unipolar Depression/Major Depressive Disorder (MDD)
Schizoaffective Disorder
Borderline Personality Disorder
Cross-References
References
Mood Stabilizers: Pharmacology and Biochemistry
Introduction
Lithium
Anti-convulsants
Antipsychotics
References
Mood Stabilizers: Side Effects, Contraindications, and Interactions
Preliminary Pathophysiological Remarks
Important Generic Side Effects of Mood Stabilizers
Specific Side Effects
Contraindications
Interactions
Future Perspectives
Cross-References
References
Mood Stabilizers: Course and Duration of Therapy, Withdrawal Syndromes, and Resistance to Therapy
Introduction
Anti-convulsants
Lithium
Antipsychotics (AP)
Course and Duration of Treatment
Acute Treatment
Mood Stabilizers for Manic Symptoms
Mood Stabilizers for Depressive Symptoms
Mood Stabilizers for Mixed Symptoms/Mixed Features
Mood Stabilizers for Agitation
Maintenance Treatment
Withdrawal Syndromes
Anti-convulsants
Lithium
Antipsychotics
Resistance to Therapy
References
Mood Stabilizers: Lithium
Developmental History
Chemical Formula: Graphics
Physicochemical Properties
Pharmacology
Pharmacokinetics
Mechanisms of Action
Clinical Indications
Mood Stabilization in Bipolar Disorder
Comparison of Lithium with Other Mood-Stabilizing Drugs
Excellent Lithium Responders
Genetic Studies of Lithium Response
Lithium in the Treatment of Acute Episodes of Mood Disorders
Anti-suicidal Action in Mood Disorders
Antiviral and Immunomodulatory Action in Mood Disorders
Neuroprotective Action in Mood Disorders
Lithium in Dementia and Neurodegenerative Disorders
Side Effects/Adverse Reactions and Toxicology
The Long-Term Effects of Lithium on Kidney, Thyroid, and Parathyroid Function
Effect of Lithium on Neurocognitive Functions
Lithium in Pregnancy and the Postpartum Period
Lithium Intoxication
Lithium Interaction with Other Drugs
Combination Therapy
Conclusions
Cross-References
References
Mood Stabilizers: Carbamazepine
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Chemically Related Drugs: Oxcarbazepine and Eslicarbazepine
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Dose-Related Effects Related to Drug Mechanism of Action, and Toxic Effects
Not Necessarily Dose-Related Effects, Cutaneous Adverse Reactions
Teratogenic Effects
Combination Therapy - Interactions
Summary for Clinical Use in Psychiatric Indications
Cross-References
References
Mood Stabilizers: Lamotrigine
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications
Therapeutic Drug Monitoring
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Common Adverse Effects
Rare, Serious Adverse Effects - Severe Allergic, Immune System, or Skin Reactions
Other Rare, Serious Adverse Effects
Psychiatric Adverse Effects
Precautions
Combination Therapy - Interactions
Cross-References
References
Mood Stabilizers: Valproate
Chemistry and Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action (Pharmacodynamics)
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Mood Stabilizers: Olanzapin
Chemistry, Developmental History
Chemical Formula
Development and History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Acute Mania/Mixed Episodes
Agitation
Bipolar Depression
Maintenance Treatment
CANMAT/ISBD Guidelines
Additional Aspects
Side Effects/Adverse Reactions and Toxicology
Combination Therapy - Interactions
Combination Therapy
Interactions
References
Mood Stabilizers: Asenapine
Chemistry, Developmental History
Pharmacology
Indications (of Marketed Products)
Clinical Studies
Treatment of Mania
Treatment of Schizophrenia
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Mood Stabilizers: Quetiapine
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
References
Mood Stabilizers: Risperidone for Treating Bipolar Disorders in Adults
Introduction: The Chemistry and Developmental History of Risperidone for Treating Patients with Bipolar Disorders
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications
Clinical Studies
Overview
Acute Management of Agitation
Acute Manic Episodes
Acute Bipolar Depressive Episodes
Maintenance-Phase Treatment
Bipolar II Disorder
Rapid Cycling
Comorbid Substance Use Disorders
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Summary and Clinical Use
Control of Acute Agitation
Treatment of Acute Manic or Hypomanic Episodes
Treatment of Acute Bipolar Depression
Bipolar Maintenance Treatment
References
Guidelines on Mood Stabilizers
Introduction
Guidelines on Bipolar Disorder
Mood Stabilizers Sorted by Substance Class
Lithium
Acute Bipolar Depression
Acute Mania
Maintenance Treatment
Bipolar II Disorder
Mixed States
Rapid Cycling
Lithium in Pregnancy
Lithium in Breastfeeding Period
Conclusion
Anti-convulsants
Valproate
Acute Bipolar Depression
Acute Mania
Maintenance Treatment
Bipolar II Disorder
Mixed States
Rapid Cycling
Valproate in Pregnancy
Valproate in Breastfeeding Period
Conclusion
Carbamazepine and Oxcarbazepine
Acute Bipolar Depression
Acute Mania
Maintenance Treatment
Bipolar II Disorder
Mixed States
Rapid Cycling
Carbamazepine and Oxcarbazepine in Pregnancy
Carbamazepine and Oxcarbazepine in Breastfeeding Period
Conclusion
Lamotrigine
Acute Bipolar Depression
Acute Mania
Maintenance Treatment
Bipolar II Disorder
Mixed States
Rapid Cycling
Lamotrigine in Pregnancy
Lamotrigine in Breastfeeding Period
Conclusion
Gabapentin
Acute Bipolar Depression
Acute Mania
Maintenance Treatment
Gabapentin in Pregnancy
Gabapentin in Breastfeeding Period
Conclusion
Pregabalin
Acute Bipolar Depression
Acute Mania
Maintenance Treatment
Pregabalin in Pregnancy
Pregabalin in Breastfeeding Period
Conclusion
Topiramate
Acute Bipolar Depression
Acute Mania
Maintenance Treatment
Topiramate in Pregnancy
Topiramate in Breastfeeding Period
Conclusion
Second-Generation Antipsychotics
Quetiapine
Acute Bipolar Depression
Acute Mania
Maintenance Treatment
Bipolar II Disorder
Mixed States
Rapid Cycling
Quetiapine in Pregnancy
Quetiapine in Breastfeeding Period
Conclusion
Aripiprazole
Acute Bipolar Depression
Acute Mania
Maintenance Treatment
Bipolar II Disorder
Mixed States
Rapid Cycling
Aripiprazole in Pregnancy
Aripiprazole in Breastfeeding Period
Conclusion
Olanzapine
Acute Bipolar Depression
Acute Mania
Maintenance Treatment
Bipolar II Disorder
Mixed States
Effects on Rapid Cycling
Olanzapine in Pregnancy
Olanzapine in Breastfeeding Period
Conclusion
Risperidone and Paliperidone
Acute Bipolar Depression
Acute Mania
Maintenance Treatment
Bipolar II Disorder
Mixed States
Rapid Cycling
Risperidone and Paliperidone in Pregnancy
Risperidone and Paliperidone in Breastfeeding Period
Conclusion
Ziprasidone
Acute Bipolar Depression
Acute Mania
Maintenance Treatment
Bipolar II Disorder
Mixed States
Effects on Rapid Cycling
Ziprasidone in Pregnancy
Ziprasidone in Breastfeeding Period
Conclusion
Asenapine
Acute Bipolar Depression
Acute Mania
Maintenance Treatment
Bipolar II Disorder
Mixed States
Rapid Cycling
Asenapine in Pregnancy
Asenapine in Breastfeeding Period
Conclusion
Lurasidone
Acute Bipolar Depression
Acute Mania
Maintenance Treatment
Bipolar II Disorder
Mixed States
Rapid Cycling
Lurasidone in Pregnancy
Lurasidone in Breastfeeding Period
Conclusion
Cariprazine
Acute Bipolar Depression
Acute Mania
Maintenance Treatment
Bipolar II Disorder
Mixed States
Effects on Rapid Cycling
Cariprazine in Pregnancy
Cariprazine in Breastfeeding Period
Conclusion
Clozapine
Acute Bipolar Depression
Acute Mania
Maintenance Treatment
Bipolar II Disorder
Effects on Mixed States
Effects on Rapid Cycling
Clozapine in Pregnancy
Clozapine in Breastfeeding Period
Conclusion
General Conclusion and Recommendation
Acute Bipolar Depression
Acute Mania
Maintenance Treatment
Bipolar II Disorder
Effects on Mixed States
Effects on Rapid Cycling
Pregnancy
Breastfeeding Period
References
Part V: Antipsychotics/Neuroleptics
Antipsychotics/Neuroleptics: Definition, Classification, Indications and Differential Indications
Schizophrenia and Antipsychotics
Features of Schizophrenia
Etiology of Schizophrenia
Antipsychotics
Classification of Antipsychotics
First-Generation Antipsychotics
Second-Generation Antipsychotics
Variation of Antipsychotics
Dosing types
How to Use Antipsychotics for Schizophrenia
Wide Spread of Indications
Future of Antipsychotics
Cross-References
References
Antipsychotics/Neuroleptics: Pharmacology and Biochemistry
Introduction
Characteristics of the Dopaminergic System and First-Generation Antipsychotics
Characteristics of the Dopaminergic System and Second-Generation Antipsychotics
SDA
Rapid Dissociation of Dopamine D2 Receptors
Dopamine D2 Receptor Partial Agonist
Serotonin 5-HT1A Receptor Partial Agonist
Other Receptor Actions
Classification and Characteristics of Therapeutic Drugs
FGA
SGA
Cross-References
References
Antipsychotics/Neuroleptics: Course and Duration of Therapy, Withdrawal Symptoms, Resistance to Therapy, Side Effects, and Con...
Antipsychotics/Neuroleptics
Classification of Antipsychotics
First Generation Antipsychotics (FGAs)
Phenothiazine Antipsychotics
With Alkylamino Side Chains
With Piperidine Side Chains
With Piperazine Side Chains
Butyrophenone Antipsychotics
Benzamide antipsychotics
Indole Derivatives
Other FGAs
Second Generation Antipsychotics (SGAs)
Serotonin-Dopamine Antagonists
Dibenzothiazepine
Multi-Acting-Receptor-Targeted-Antipsychotics
Partial Dopamine Agonists
Other SGAs
Course and Duration of Therapy
Antipsychotic Treatment in the Acute Phase of Schizophrenia
Antipsychotic Treatment in the Chronic Phase of Schizophrenia
Withdrawal Symptoms
Supersensitivity Psychosis
Treatment-Resistant Schizophrenia
Side Effects
Psychological Symptoms
Sedation
Cognitive Impairment
Paroxysmal Perceptual Alteration
Depression
Acute Extrapyramidal Symptoms
Parkinson´s Syndrome
Akathisia
Acute Dystonia
Late-Onset Extrapyramidal Symptoms
Tardive Dyskinesia
Tardive Dystonia
Seizures and Electroencephalography Abnormalities
Neuroleptic Malignant Syndrome
Autonomic Nervous System
Anticholinergic Side Effects
Antiadrenergic Side Effects
Cardiovascular System
Endocrine and Metabolic Systems
Increased Appetite and Weight Gain
Polydipsia, Water Intoxication and Syndrome of Inappropriate Antidiuretic Hormone Secretion
Respiratory Side Effects
Gastrointestinal Side Effects
Dermatological Side Effects
Ocular Side Effects
Hematological Side Effects
Increased Risk of Death
Contraindications
Cross-References
References
History of Antipsychotics
The Beginning of a New Era in Psychiatric Therapy: The Discovery of Chlorpromazine
Clozapine: The Slightly Different Antipsychotic
Notes on the Discovery of Antipsychotics and Their Effects
Pharmacotherapy and Its Relation to Social Psychiatry and Psychotherapy
From Revolution to Evolution: The Perspective of a Newer Drug History
Concluding Remarks
Cross-References
References
Piperazine Phenothiazines: Fluphenazine and Perphenazine
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects and Adverse Reactions
Combination Therapy: Interactions
Cross-References
References
Flupentixol in the Treatment of Psychosis
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Haloperidol in the Treatment of Psychosis
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications
Clinical Studies
Side Effects, Adverse Reactions
Combination Therapy: Interactions
Cross-References
References
Risperidone and Paliperone in the Treatment of Psychosis
Chemistry and Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects and Adverse Reactions
Cross-References
References
Low-Potency Antipsychotics: Levomepromazine, Melperon, and Pipamperone
Chemistry and Development History
Pharmacology
Pharmacokinetics
Levomepromazine
Melperone
Pipamperone
Mechanism of Action
Levomepromazine
Melperone
Pipamperone
Indications (of Marketed Products)
Levomepromazine
Melperone
Pipamperone
Clinical Studies
Levomepromazine
Melperone
Pipamperone
Side Effects/Adverse Reactions and Toxicology
Levomepromazine
Melperone
Pipamperone
Combination Therapy: Interactions
Cross-References
References
First-Generation Antipsychotics as a Bridge to Second-Generation Antipsychotics in the Japanese Pharmaceutical Industry: Mosap...
Mosapramine
Introduction
Chemistry, Developmental History
Pharmacology
Metabolic Sites and Pathways
Time to Peak, Half-Life Elimination (Single Dose)
Absorption
Distribution
Mechanism of Action
Indications (of Marketed Products)
Schizophrenia
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Toxicology
Contraindications
Combination Therapy: Interactions
Timiperone
Introduction
Chemistry, Developmental History
Pharmacology
Metabolic Sites and Pathways/ Metabolized in the liver
Time to Peak, Half-Life Elimination (Tablets)
Absorption
Distribution
Mechanism of Action
Indications (of Marketed Products)
Tablets
Injections
Clinical Studies
Oral Preparation (Tablet)
Injections
Side Effects/Adverse Reactions and Toxicology
Oral Preparation (Tablet)
Injections
Toxicology
Combination Therapy: Interactions
Zotepine
Introduction
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Distribution
Mechanism of Action
Indications (of Marketed Products)
Schizophrenia
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Serious Side Effects
Toxicology
Combination Therapy: Interactions
Adrenalin as Contraindication for Concomitant Use
Nemonapride
Introduction
Chemistry, Developmental History
Pharmacology
Metabolism and Metabolic Pathways
Excretion
Time to Peak (Single Oral Dose)
Time to Peak (Repeated Oral Administration)
Distribution and Blood-Brain Barrier Permeability (Rats and Dogs)
Mechanism of Action
Indications (of Marketed Products)
Schizophrenia
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Serious Side Effects
Toxicology
Contraindication
Careful Administration, Attention
Combination Therapy: Interactions
Cross-References
References
Clozapine in the Treatment of Psychosis
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects and Adverse Reactions
Combination Therapy: Interactions
Cross-References
References
Olanzapine in the Treatment of Psychosis
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects and Adverse Reactions
Combination Therapy: Interactions
Cross-References
References
Quetiapine in the Treatment of Psychosis
Chemistry and Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications
Clinical Studies
Side Effects, Adverse Reactions, Toxicology
Combination Therapy: Interactions
Cross-References
References
Asenapine in the Treatment of Psychosis
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (Of Marketed Products)
Clinical Studies for Psychosis
Side Effects/Adverse Reactions and Toxicology
Discontinuation
Somnolence
Extrapyramidal Adverse Events
Oral Hypoesthesia
Further Warnings Due to Adverse Events
Combination Therapy: Interactions
Cross-References
References
Ziprasidone, Zuclopenthixole, and Fluspirilene in the Treatment of Psychosis
Psychosis: Brief Introduction
Developmental History
Chemistry
Pharmacology
Mechanism of Action
Ziprasidone
Zuclopenthixole
Fluspirilene
Pharmacokinetics
Ziprasidone
Zuclopenthixole
Fluspirilene
Indications
Ziprasidone in the Treatment of Psychosis
Zuclopenthixole in the Treatment of Psychosis
Fluspirilene in the Treatment of Psychosis
Side Effects/Adverse Reactions and Toxicology
Ziprasidone
Zuclopenthixole
Fluspirilene
Combination Therapy: Interactions
Final Considerations
Cross-References
References
From Perospirone and Blonanserin to Lurasidone
Developmental History
Chemical Characteristics
Chemical Characteristics (Pharmaceutical Products Interview Form in Japan, Oct 2020)
Therapeutic Properties of Perospirone
Therapeutic/Pharmaceutical Properties of Blonanserin
Oral Agent
Transdermal Absorbent Tape Formulation
Therapeutic/Pharmaceutical Properties of Lurasidone
Pharmacology
Oral Agent
Transdermal Absorbent Tape Formulation
Perospirone
Pharmacokinetics
Metabolism
Time to Peak, Half-Life Elimination
Single Dose
Repeated Dose
Absorption
Distribution
Excretion
Oral Blonanserin
Metabolism
Time to Peak, Half-Life Elimination
Single Dose
Repeated Dose
Absorption
Distribution
Excretion
Blonanserin Transdermal Absorbent Tape Formulation
Metabolism
Time to Peak, Half-Life Elimination
Single Dose
Repeated Dose
Absorption
Lurasidone
Metabolism
Time to Peak, Half-Life Elimination
Single Dose
Repeated Dose
Absorption
Distribution
Excretion
Mechanism of Action
Perospirone
Site/Mechanism of Action
Results of Trials Supporting Therapeutic Efficacy
Blonanserin
Site/Mechanism of Action
Results of Trials Supporting Therapeutic Efficacy
Lurasidone
Site/Mechanism of Action
Results of Trials Supporting Therapeutic Efficacy
Indications of Marketed Products
Perospirone
Schizophrenia
Dosage and Administration
Blonanserin
Schizophrenia
Dosage and Administration
Oral Agent
Tape Preparation
Lurasidone
Schizophrenia
Dosage and Administration:
Countries Other than Japan/China
Japan/China
Bipolar Disorder
Dosage and Administration
Countries Other than Japan: Depressive Episodes Associated with Bipolar I Disorder (Bipolar Depression), as Monotherapy and as...
Japan: Improvement of Depressive Symptoms in Bipolar Disorder
Clinical Studies
Phase III Validation Trial of Perospirone
Haloperidol-Controlled, Double-Blind Controlled Trial (Murasaki et al. 1997)
Mosapramine-Controlled, Double-Blind Controlled Trial (Kudo et al. 1997)
Phase III Validation Trial of Oral Blonanserin
Haloperidol-Controlled, Double-Blind Controlled Trial (Murasaki 2007)
Risperidone-Controlled, Double-Blind Controlled Trial (Miura 2008)
Phase III Validation Study of a Blonanserin Transdermal Absorbent Tape Formulation
Placebo-Controlled, Double-Blind Controlled Trial (Iwata et al. 2020)
Phase III Trial of Lurasidone (Schizophrenia)
Placebo-Controlled, Double-Blind Controlled Trial (1) (Higuchi et al. 2019a)
A Placebo-Controlled, Double-Blind Controlled Trial (2) (Higuchi et al. 2019b)
A Placebo-Controlled, Double-Blind Controlled Trial (3) (Iyo in submission)
Placebo-Controlled, Double-Blind Controlled Trial (International 1) (Nasrallah et al. 2013)
Placebo-Controlled, Double-Blind Controlled Trial (International 2) (Meltzer 2011)
Placebo-Controlled, Double-Blind Controlled Trial (International 3) (Loebel et al. 2013)
Phase III Trial of Lurasidone (Depressive Symptoms in Bipolar Disorder)
Placebo-Controlled, Double-Blind Controlled Trial (Kato et al. 2020)
Placebo-Controlled, Double-Blind Controlled Trial (International 1) (Loebel et al. 2014b)
Placebo-Controlled, Double-Blind Controlled Trial (International 2) (Loebel et al. 2014a)
Placebo-Controlled, Double-Blind Controlled Trial (International 3) (Suppes et al. 2016)
Side Effects/Adverse Reactions and Toxicology
Side Effects
Perospirone
Blonanserin (Oral)
Blonanserin (Transdermal Tape)
Lurasidone
Information Based on the Common Clinical Use of the Three Drugs
Toxicology
Information from Non-Clinical Trials Common to the Three Drugs
Perospirone
Blonanserin
Lurasidone
Contraindications
Common to Three Drugs
Lurasidone
Careful Administration, Attention
Perospirone
Blonanserin
Common Oral and Transdermal Tape Formulations
Transdermal Tape Preparation Only
Lurasidone
Common Improvement of Depressive Symptoms in Schizophrenia and Bipolar Disorder
``Improvement of Depressive Symptoms in Bipolar Disorder´´ Only
Combination Therapy: Interactions
Common to Three Drugs
Blonanserin (Common to Oral Drug and Transdermal Tape)
Lurasidone
Cross-References
References
Amisulpride and Sulpiride in the Treatment of Psychosis
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects, Adverse Reactions
Combination Therapy: Interactions
Cross-References
References
Cariprazine in the Treatment of Psychosis
Chemistry, Developmental History
Pharmacology
Indications (of Marketed Products)
Clinical Studies
Schizophrenic Disorders
Manic Episodes in Bipolar Disorder
Depressive Episodes in Bipolar Disorder
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
D-Serine in the Treatment of Psychosis
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy - Interactions
Cross-References
References
The Dopamine D2 Receptor Partial Agonist Antipsychotics, Aripiprazole, and Brexpiprazole
Chemistry and Developmental History
Pharmacology
Definitions of First-, Second-, and Third-Generation Antipsychotics
Novelty of Pharmacological Activities
Explanation of Clinical Effectiveness of Aripiprazole Based on Its Pharmacological Properties
Very Low Risk of Increasing Blood Prolactin Levels
Low Risk for Extrapyramidal Symptoms
Low Risk for Body Weight Gain
Low Sedative Effects
Whether Aripiprazole Can Be Regarded as a Third-Generation Antipsychotic
Possible Low Risk of Aripiprazole for Dopamine Supersensitivity Psychosis
Pharmacology of Brexpiprazole and Aripiprazole
Receptor Binding Affinity
Partial Agonist Activity at 5-HT1A Receptors
Antagonist Activity at 5-HT2A Receptors
Partial Agonist Activity at D2/D3 Receptors
Evaluation of D2 Receptor Antagonist Activity Using Anti-apomorphine Effects
Inhibitory Effect on Conditioned Avoidance Response
Cataleptogenic Effect
Effect on Prolactin
Postsynaptic Dopamine D2 Receptor Sensitizing Effect
Ameliorating Effect on Cognitive Deficit
Indications (of Marketed Products)
Clinical Studies
Clinical Trials of Aripiprazole in Schizophrenia
Efficacy and Safety of Aripiprazole and Haloperidol as an Active Control
Efficacy and Safety of Aripiprazole and Risperidone as an Active Control
Effectiveness of Aripiprazole in Comparison with Olanzapine
Effectiveness of Aripiprazole in Comparison with Risperidone, Olanzapine, and Quetiapine
Relapse Prevention Study of Aripiprazole
Clinical Trials of Aripiprazole in Bipolar Mania
Clinical Trials of Aripiprazole in the Adjunctive Treatment of Major Depressive Disorder
Clinical Trials of Aripiprazole for Irritability Associated with Autistic Disorders
Clinical Trials of Aripiprazole in Tourette´s Disorder
Clinical Trials of the Aripiprazole Once-Monthly Long-Acting Injection (AOM) in Schizophrenia
Clinical Trials of the AOM as a Maintenance Treatment of Bipolar I Disorder
Clinical Trials of Brexpiprazole in Schizophrenia
Clinical Trials of Brexpiprazole in the Adjunctive Treatment of Major Depressive Disorder
Side Effects/Adverse Reactions
Aripiprazole
Brexpiprazole
Combination Therapy: Interactions
Conclusions
Cross-References
References
Evidence-Based Treatment with Antipsychotics in Schizophrenia: S3-Guideline and Current References
Introduction
General Therapeutic Recommendations
Therapeutic Goal
Shared Decision-Making
Application Forms
Choice of Drug
Response
Side Effects
Contraindications
Switching Antipsychotics
Therapeutic Procedure for Treatment with Antipsychotics
Monotherapy
Dose
Therapeutic Drug Monitoring
Acute Therapy
Negative Symptoms
Maintenance Treatment
Relapse Prevention after Acute Therapy
Relapse Therapy
Reduction of Medication Dose
Treatment Resistance
High-Dose Therapy
Cross-References
References
Part VI: Tranquilizers/Anxiolytics
Tranquilizers/Anxiolytics: Definition, Indications, Contraindications, and Treatment
Introduction
Mechanisms of Action and Pharmacokinetic Aspects
Benzodiazepines
Gabapentin/Pregabalin
Buspirone/Tandospirone
Lavender Oil
Antidepressants
D-cycloserine Augmentation
Overview, Indications, and Contraindications
Benzodiazepines
Gabapentin/Pregabalin
Buspirone/Tandospirone
Lavender Oil
Antidepressants
D-cycloserine Augmentation
Antipsychotics
Novel Anxiolytic Agents
Treatment Resistance and Limitations of Anxiolytic Treatment
Other Drugs and Substances
Other Medical and Mental Health Conditions
Cross-References
References
Tranquilizers/Anxiolytics: Pharmacology and Biochemistry of Anxiolytic Drugs Acting via GABAergic Mechanisms
Introduction
Barbiturates
Benzodiazepines
GABAA Receptors
Agonists, Inverse Agonists and Partial Agonists
Subtypes of GABAA Receptor
Barbiturate Interactions with GABA Receptor Subtypes
How Are the Anxiolytic Properties of Benzodiazepines Mediated?
Drugs Acting at Subtypes of GABAA Receptor
Where in the Brain Do GABAA Receptors Exert Their Anxiolytic Effects?
Does the Development of Dependence on, or Abuse of Benzodiazepines Depend Upon Particular Subtypes?
GABAA Receptor Subunit Chromosomal Localization
Pharmacokinetic Properties
Anxiolytic Drugs Acting at Other Sites
The GABApentinoids
Serotonergic Drugs
Cross-References
References
Tranquilizer/Anxiolytics: Antidepressants
Chemistry, Developmental History
Developmental History
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
Tricyclic Antidepressants (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Other Antidepressants
Pharmacology
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Generalized Anxiety Disorder (GAD)
Social Anxiety Disorder (SAD)
SSRIs
SNRIs
MAOIs
Other Antidepressants
Panic Disorder (PD)
Specific Phobia
Separation Anxiety Disorder in Adults and Selective Mutism
Side Effects/Adverse Reactions and Toxicology
SSRIs/SNRIs
TCAs
MAOIs
Other Antidepressants
Combination Therapy: Interactions
Cross-References
References
Tranquilizer/Anxiolytics: Pregabalin
Chemistry and Developmental History
Chemical Formula
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Generalized Anxiety Disorder
Adjunctive Therapy for Generalized Anxiety Disorder
Elderly Population with Generalized Anxiety Disorder
Social Anxiety Disorder
Obsessive-Compulsive Disorder
Post-traumatic Stress Disorder
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Tranquilizer/Anxiolytics: Gabapentin
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications
Indications (of Marketed Products)
Off-label Use of Gabapentin
Clinical Studies in Marketed Indications
Side Effects/Adverse Reactions and Toxicology
Pregnancy and Breast Feeding
Toxicity in Overdose
Abuse/Dependency Potential
Combination Therapy - Interactions
Cross-References
References
Tranquilizer/Anxiolytics: Buspirone
Chemistry, Developmental History
Pharmacology
Indications (Of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
References
Tranquilizer/Anxiolytics: Tandospirone
Chemistry: Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indication (of Marketed Products)
Clinical Studies
Anxiety
Depression with Anxiety
Behavioral and Psychological Symptoms of Dementia (BPSD)
Anorexia Nervosa
Somatic Diseases
Gastrointestinal Disorders
Ataxia (Spinocerebellar Degeneration)
Other Disorders
Combination Therapy, Augmentation, and Interactions
Mood Disorder with Anxiety
Cognitive Impairment in Schizophrenia
Movement Disorder
Side Effects and Adverse Reactions
Memory Impairment
Effect on Blood Pressure
Driving Performance Impairment
Gynecomastia
Conclusion
Cross-References
References
Tranquilizer/Anxiolytics: Mexazolam
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
References
Tranquilizer/Anxiolytics: Benzodiazepines (Short-Acting) - Etizolam
Chemistry, Developmental History
Pharmacology
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Tranquilizer/Anxiolytics: Benzodiazepines (Intermediate-Acting) - Alprazolam, Bromazepam, Clonazepam, Lorazepam
Chemistry, Developmental History
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Alprazolam
Lexicomp Risk Category
References
Tranquilizer/Anxiolytics: Benzodiazepines (Long-Acting) - Chlordiazepoxide, Clorazepate, Diazepam, Ethyl Loflazepate, Flutopra...
Chemistry, Developmental History
Chemical Formula (Graphic)
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications of Market Products
Clinical Studies
Side Effects/Adverse Reactions and Toxicity
Combination Therapy-Interactions
References
Tranquilizer/Anxiolytics: Lavender Oil
Chemistry, Developmental History
History
Chemistry
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (Of Marketed Products)
Clinical Studies
Clinical Use
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Anxiolytics: Misuse, Dependence, and Withdrawal Syndromes
Introduction
Benzodiazepines
Benzodiazepine Misuse
Benzodiazepine Withdrawal
Benzodiazepine Use Disorders
Benzodiazepines: Summary
Gabapentinoids
Gabapentinoid Misuse and Dependence
Gabapentinoid Withdrawal
Gabapentinoids: Summary
Azapirones
Azapirone Misuse and Dependence
Azapirone Withdrawal
Azapirones: Summary
Cross-References
References
Augmentation of Psychotherapy with D-Cycloserine in Patients with Anxiety Disorders
Introduction
DCS, Learning and Memory
DCS and Fear Extinction
Experimental Evidence on DCS Augmentation of Exposure Therapy
Moderators of the Efficacy of DCS Augmentation
Future Directions in DCS Augmentation Research
Practical Implications
Cross-References
References
Part VII: Hypnotics
Hypnotics: Definition, Classifications, Indications, and Differential Indications
Definition
Classifications
Hypnotics in the Classical Meaning
Benzodiazepines
Z-Drugs (Nonbenzodiazepines/Benzodiazepine-Receptoragonists)
Chloralhydrate
Melatonin and Melatoninagonists
Psychotropic Drugs with a Sedative Effect Profile
Sedative Antidepressants
Sedative Antipsychotics
Other Substances Used for Sleep Disorders
Antihistamines
Clomethiazol
L-Tryptophan
Orexinreceptorantagonists
Phytopharmaceuticals
Indications
International Classifications of Sleep Disorders
Guidelines/Recommendations
Differential Indications
Insomnia in the Aged People
Insomnia in Children and Adolescents
Insomnia in Pregnancy and Lactation
Cross-References
References
Hypnotics: Pharmacology
Pharmacokinetics
GABAergic Drugs
Benzodiazepine Receptor Agonists: Brotizolam, Flunitrazepam, Flurazepam, Lormetazepam, Midazolam, Nitrazepam, Oxazepam, Temaze...
Z-drugs
Barbiturates
Phenobarbital
Primidone
Clomethiazole
Chloral Hydrate
Valerian
Anti-serotonergic Drugs: Antidepressants
Trazodone
Noradrenergic Drugs
Mirtazapine
Antidopaminergic Drugs: Antipsychotics
Quetiapine
Olanzapine
Pipamperone/Floropipamide
Melperone
Chlorprothixene
Prothipendyl
Antihistaminergic Drugs
Diphenhydramine
Doxylamine
Promethazine
Hydroxyzine
Doxepin (Low Dose)
Trimipramine
Amitriptyline
Antiorexinergic Drugs: Orexin Receptor Antagonists
Suvorexant
Lemborexant
Melatonergic Drugs: Melatonin and Melatonin Agonists
Melatonin
Ramelteon
Tasimelteon
Agomelatine
Precursors
Tryptophan
Mechanism of Action
GABAergic Drugs
Benzodiazepine Receptor Agonists: Flurazepam, Lormetazepam Midazolam, Oxazepam, Temazepam, Triazolam
Z-drugs
Barbiturates
Clomethiazole
Chloral Hydrate
Valerian
Anti-serotonergic Drugs: Antidepressants
Trazodone
Noradrenergic Drugs
Mirtazapine
Antidopaminergic Drugs: Antipsychotics
Quetiapine
Olanzapine
Pipamperone/Carpiperone/Floropipamide
Melperone
Chlorprothixene
Prothipendyl
Antihistaminergic Drugs
Diphenhydramine
Doxylamine
Promethazine
Hydroxyzine
Doxepin (Low Dose)
Trimipramine
Amitriptyline
Antiorexinergic Drugs: Orexin Receptor Antagonists
Suvorexant
Lemborexant
Melatonergic Drugs: Melatonin and Melatonin Agonists
Melatonin
Ramelteon
Tasimelteon
Agomelatine
Precursors
Tryptophan
Cross-References
References
Hypnotics: Course and Duration of Therapy, Side Effects, Contraindications, Interactions, Withdrawal Syndromes, and Resistance...
Introduction
Course and Duration of Therapy
Evaluation
Treatment in a Nutshell
Recommendations for the Management of Insomnia
Benzodiazepine and Z-Compounds
Sedative Antidepressants
Agomelatine
Mirtazapine
Trazodone
Low-Dose Doxepin
Melatonin Agonists
Pregabalin
Suvorexant
Miscellaneous
Side Effects and Contraindications
Adverse Effects: Benzodiazepines and Related Compounds
Safety Profile Beyond Benzodiazepines
Anti-H1 Action
Anticholinergic Action
Acute Toxicity
Alphalytic Action
Pregabalin
Suvorexant
Melatonin and Agonists
Contraindications
Pregnancy
Elderly
Contraindication Beyond Benzodiazepines
Anti-H1
Anticholinergic
Alpha-Blockers (Trazodone, Mirtazapine)
Interactions
Pharmacological Interactions
Pharmacokinetic Interactions
Pharmacodynamic Interactions
Specific Interactions
Resistance to Therapy and Withdrawal Syndrome
Monitoring the Response to Therapy
Response Assessment
Poor Response to Therapy
Reduction of Drugs
Addiction and Tolerance
Cross-References
References
Hypnotics: Guidelines and Current References
Introduction
Approaches to Treat Insomnia
Guidelines for the Pharmacological Treatment of Insomnia
General Recommendations
Hypnotics for Treating Insomnia
Benzodiazepines and Benzodiazepine Receptor Agonists (``Z-Drugs´´)
Orexin Receptor Agonists
Suvorexant
Lemborexant
Daridorexant
Melatonergic Drugs
Prolonged-Release Melatonin
Ramelteon
Agomelatine
Antidepressants
Antipsychotics
Anti-convulsants
Antihistamines
Phytotherapeutics
Other Drugs
Drugs for Treating Insomnia in Special Populations
Women: Effects of Menopause and Pregnancy
Elderly Patients
Adults with Intellectual Disabilities
Patients Suffering from Neurological Diseases
Conclusions
Internet
Cross-References
References
Somnologics
Anti-insomnics
Somnics
Phytopharmaceuticals
Valerian
Hops
Cannabis
Oats
St. John´s Wort
Chamomile
Kava
Lavender
Lemon Balm
Passion Flowers
Other Natural Remedies for the Promotion of Sleep
Critical Risk-Benefit Assessment of Phytotherapeutic Somnics
Benzodiazepines and Benzodiazepine Receptor-Agonists
Anxiolytic and Mood-Stabilizing Benzodiazepines
Antidepressants (Table 1)
Antihistamines
Antipsychotics
Amino Acids
Other Somnics
Alcohol
Chronotherapeutics
Melatonin
Ramelteon
Tasimelteon
5-Hydroxytryptophan
Antivigilantics
Orexin Antagonists
Antihypersomnics
Vigilantics
Modafinil
Pitolisant
Norepinephrine-Dopamine Reuptake Inhibitors
Solriamfetol
Methylphenidate
Central Sympathomimetics
Anticataplectics
Pitolisant
Sodium Oxybate
Conclusion
References
Part VIII: Psychostimulants
Stimulants: Definition, Pharmacology, Indications, Side Effects, and Treatment Strategies
Definition, Classification, and List of Products
Pharmacology and Pharmacokinetics
Enantiomers
Metabolism
Formulations
Methylphenidate
Amphetamines
Treatment Strategies and Indications
Monitoring and Maintenance
Augmentation Strategies
Guanfacine
Atomoxetine
Second Generation Antipsychotics
Concern for Diversion
Comorbidities
Mood Disorders
Developmental Disorders
Physical Conditions
Substance Use Disorders
Modafanil
Treatment Strategies and Dosages
Side Effects
Stimulant Side Effects, Contraindications, Interactions
Cardiac Adverse Events
Height and Weight
Psychiatric
Substance Use Disorder
Tic Disorders
Pregnancy
Risk for Substance Use Disorders
Dependence, Tolerance, and Withdrawal
Withdrawal
Drug-Drug Interactions
Cross-References
References
Psychostimulants: Primary and Secondary Indications
Psychostimulants
Chemistry, Developmental History
Methylphenidate
Amphetamines
Dexamphetamine
Mixed Amphetamine Salts (MAS)
Lisdexamfetamine
Modafinil
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Primary Indications
Secondary Indications
Clinical Studies
Side Effects/Adverse Reactions
Methylphenidate and the Amphetamines (Including Lisdexamfetamine)
Modafinil
Toxicology
Combination Therapy and Drug Interactions
Cross-References
References
Efficacy of Amphetamines, Methylphenidate, and Modafinil in the Treatment of Mental Disorders
Introduction
Efficacy of Amphetamine Derivatives in Children, Adolescents, and Adults with ADHD
Efficacy of Methylphenidate in Children, Adolescents, and Adults with ADHD
Efficacy of Modafinil in the Treatment of Neuropsychiatric Disorders
Conclusions
Cross-References
References
International Comparison of ADHD Clinical Practice Guidelines: Comparing NICE, UMHS, and CADDRA Guidelines to Consider the Lat...
Introduction
Target Guidelines
Scope and Treatment Goal Setting
Diagnosis
Treatment
Side Effects of Drug Therapy
Termination of Treatment
Conclusion
Cross-References
References
Part IX: Agents for Treatment of Withdrawal and Dependency
Pharmacology of Alcohol and Alcohol Use Disorder
Introduction
Behavioral Pharmacology of Alcohol
Acute Effects in Animals
Chronic Effects in Animals
Acute Effects in Humans
Chronic Effects in Humans
Behavioral Changes
Changes in the Brain
Neurobiological Mechanisms Underlying Alcohol Action
Gamma-Aminobutyric Acid (GABA)
Glutamate
Dopamine
Serotonin
Endogenous Opioids
Others
Neurobiological Changes Related to Alcohol Dependence
Glutamate
Dopamine
Opioid System
Oxidative Stress
Others
Physical Damages Related to Alcohol Dependence
Liver
Cardiovascular System
Factors Relevant to Alcohol Dependence
Enzymes Related to Alcohol Metabolism
Dopamine D3 Receptor
From Genotype to Phenotype
Conclusion
References
Disulfiram and Cyanamide
Chemistry and Developmental History
Chemical Formula (Graphic)
Developmental History
Pharmacology
Indications (of Marketed Products)
Disulfiram
Cyanamide
Clinical Studies
Disulfiram
Implantation: Surreptitious Use of Disulfiram
Side Effects/Adverse Reactions and Toxicology
Precautions for Co-administration
Combination Therapy: Interactions
References
Topiramate, Naltrexone, and Acamprosate in the Treatment of Alcohol Use Disorders
Chemistry, Developmental History
Chemical Formula
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Nalmefene in the Treatment of Alcohol Use Disorders
Chemistry: Developmental History
Pharmacology
Indication (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Recommendations from Current German, British, American, and Australian Guidelines on Alcohol Treatment
Introduction
Acute and Short Treatments
Detoxification and Withdrawal
Pharmacological Withdrawal Treatment
Rehabilitation and Post-acute Therapy
Pharmacological Rehabilitation Treatment
Cross-References
References
Nicotine Replacement Therapy
Chemistry and Developmental History of Nicotine
Pharmacology of Nicotine
Pharmacokinetics
Mechanism of Action
Indications of Nicotine: Nicotine Replacement Therapy (NRT)
Clinical Studies
Side Effects of NRT (Adverse Reactions and Toxicology)
Combination Therapy and Interactions
References
Agents for Treatment of Withdrawal and Dependency: Varenicline
Chemistry and Developmental History
Development of Varenicline
Neuropsychiatric Safety History
Cardiovascular Safety History
Summary
Pharmacology
Pharmacokinetics
Absorption
Distribution
Metabolism
Elimination
Drug Interactions
Mechanism of Action
Full Agonists to nAChRs
Antagonists to nAChRs
Partial Agonist to nAChRs
Indication (Market Products)
Clinical Studies
FDA Approval for Varenicline
Limitations
Pooled and Meta-analyses
Summary
Neuropsychiatric Safety
Neuropsychiatric Safety in Specific Subgroups
Neurodevelopmental Disorders
Alcohol Abuse and Dependence
Schizophrenia and Bipolar Affective Disorder
Psychotic, Anxiety, and Mood Disorders
Anxiety Disorders
Cardiovascular Safety History
EAGLES
Side Effects/Adverse Reactions and Toxicology
Mild to Moderate Side Effects
Nausea
Insomnia
Other Adverse Effects
Severe Side Effects
Neuropsychiatric Adverse Events
History of Psychiatric Illness
Nicotine Withdrawal
Seizures
Interaction with Alcohol
Driving or Operating Machinery
Cardiovascular Events
Abnormal Sleep-Related Events
Serious Skin Reactions
Pregnancy and Lactation
Others
Combination Therapy
Cross-References
References
Part X: Anti-dementia Medications
Anti-dementia Medications: Classification, Indications, and Differential Indications
Dementia: Definition and Background
Indications
Acetylcholinesterase Inhibitors: Mechanisms and Efficacy
Memantine: Mechanisms and Efficacy
Anti-dementia Drugs for Non-AD Dementias
Ginkgo biloba
Differential Indications
Future Perspectives
Cross-References
References
Anti-dementia Medications: Pharmacology and Biochemistry
Anti-dementia Drugs Within the Changing Field of Etiopathology for Dementia Disorders
Anti-dementia Drugs Presently Available
Acetylcholine Esterase Inhibitors
Memantine
Anti-amyloid Drugs
Drugs Which Improve Mitochondrial Function
Concluding Remark
References
Anti-dementia Medications: Course and Duration of Therapy and Withdrawal Syndromes
Introduction
Course of Duration
Withdrawal Effects
Conclusion
References
Anti-dementia Medications: Specific Agents
Treatment of the Central Symptoms of Dementia
Alzheimer´s Disease
Cholinesterase Inhibitors
Donepezil
Rivastigmine
Galantamine
Huperzine-A
Excitatory Amino Acid Receptor Antagonists
Vascular Cognitive Impairment and Dementia
Preventive Medications
Hypertensive Disease
Glucose Metabolism Disorders and Diabetes
Abnormal Lipid Metabolism
Antithrombotic Therapy
Oral Antiplatelet Drugs
Anticoagulant Therapy of Atrial Fibrillation
Other Cardioembolic Anticoagulant Therapy
Treatment Medications
Donepezil
Rivastigmine
Galantamine
Huperzine-A
Brain Circulation Promoter
Brain Protective Agents
Parkinson´s Disease with Dementia and Dementia with Lewy Bodies
Therapy of Cognitive Dysfunction
Cholinesterase Inhibitors
Excitatory Amino Acid Receptor Antagonists
Treatment of Motor Symptoms
Frontotemporal Dementia
Treatment of Cognitive Impairment
Cholinesterase Inhibitors
Donepezil
Rivastigmine
Galantamine
Eserine
Excitatory Amino Acid Receptor Antagonists
The Treatment of Behavioral and Psychological Symptoms of Dementia
The Behavioral and Psychological Symptoms of Dementia and the Treatment
Overview
Treatment
Cognition-Promotion Drugs
Antipsychotics
Antidepressants
Mood Stabilizers
Others
Sleep Disorders in Patients with Dementia and Pharmacotherapy
Overview
Treatment
Herbal Medicine for Dementia
References
Acetylcholinesterase inhibitors (Galantamine, Rivastigmine, and Donepezil)
Chemistry and Developmental History
Chemical Formula (Graphic)
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Meta-analysis
Side Effects/Adverse Reactions and Toxicology
Combination Therapy - Interactions
Cross-References
References
Memantine for Treatment of Dementia
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Clinical Findings
Conclusion
Key Points
Cross-References
References
Nootropics (Piracetam, Pyritinol, Co-dergocrine, Meclophenoxat, Pentoxifylline, Nimodipine)
Introduction
Piracetam
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Pyritinol
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Co-dergocrine
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Meclophenoxate
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Pentoxifylline
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Nimodipine
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Conclusions
Cross-References
References
Anti-dementia Medications and Anti-Alzheimer´s Disease Drugs: Side Effects, Contraindications, and Interactions
Introduction
Anti-dementia Drugs
Reversible Acetylcholinesterase Inhibitors (AChE-I)
Galantamine and Donepezil
Side Effects
Contraindications
Interactions
Memantine
Ginkgo biloba
Contraindications
Nootropic Drugs (ND)
Piracetam (Example)
Co-Medication
Outlook on the Current State of Recombinant Monoclonal Antibodies Against Beta-Amyloid
Cross-References
References
Complementary Medications (Statins, Nicergoline, Naftidrofuryl) in Dementia
Statins
Nicergoline
Naftidrofuryl
Other Pharmacological Agents
Conclusion
Cross-References
References
Novel Pharmaceutical Approaches in Dementia
Dementia
Approved Drugs for Clinical Use for Dementia
NMDA Receptor Modulators Under Clinical Trials
New Drug Targets
Repurposing Existing Drugs for Dementia
Novel Pharmaceuticals and Search for Novel Targets and Approaches
Kynurenine Pathways and Kynurenic Acid
Future Perspectives
Cross-References
References
Part XI: Parkinsonian Drugs
Definition and Classification of Parkinsonian Drugs
Introduction
Dopaminergic Drugs
Levodopa
Levodopa/Carbidopa (Sinemet) and Levodopa/Benserazide (Levodopa + Dopa Decarboxylase Inhibitor(DCI))
Wearing Off and Dyskinesia
Long-Acting Levodopa-DCI (Dopa Decarboxylase Inhibitor)
Levodopa/Carbidopa Intestinal Infusion
Dopamine Agonists
Ergot Dopamine Agonists
Non-ergot Dopamine Agonist
Dopamine Dysregulation Syndrome and Impulse Control Disorders
Sudden Onset of Sleep
Truncal Deformities (Camptocormia, Head Drop, Pisa Syndrome)
Injectable Dopamine Agonist
Monoamine Oxidase B Inhibitors
Selegiline
Rasagiline
Safinamide
Catechol-O-Methyltransferase Inhibitor
Entacapone
Tolcapone
Opicapone
Zonisamide
Non-dopaminergic Drugs
Anticholinergic Agent
NMDA Receptor Antagonist
Adenosine A2A Receptor Antagonist
L-DOPS
Cross-References
References
Clinical Aspects of the Pharmacology and Biochemistry of Drugs for the Treatment of Motor Symptoms of Parkinson´s Disease
General Principles
Anticholinergic Compounds
Glutamate (N-Methyl-D-Aspartate) NMDA Antagonists
Adenosine Antagonism
Antagonizing Adenosine Receptors
Dopamine Supplementation
Levodopa
Excurs: Clinical Presentation of Levodopa-Related Fluctuations of Movement
The Importance of Levodopa Brain Delivery
Levodopa: Modes of Oral Applications
3-OMD
Oral Levodopa Therapy and Physiological Continuous Dopaminergic Stimulation
Strategies to Reduce Motor Complications
Excurs: Past and Current Developments of Levodopa Formulations
MAO-B-Inhibitors
Dopamine Agonists
Levodopa, Dopamine Agonists, and Placebo
Conclusion
References
Parkinsonian Drugs: Indications
Introduction
Anticholinergics
Levodopa
Dopamine Agonists (DAs)
Amantadine and Budipine
Selegiline and Rasagiline
Safinamide (See Also Chapter ``Safinamide for Treating Parkinson´s Disease´´)
COMT Inhibitors
Therapy Recommendations
References
Treatment of Parkinson´s Disease: Early, Late, and Combined
Introduction
Early Versus Late Treatment
Early Monotherapy
Off-Related Symptoms
Dyskinesia
Tremor
Gait and Postural Symptoms
Non-motor Symptoms
Gastrointestinal and Bladder Dysfunction
Drooling
Pain
Cognitive Signs and Symptoms
Dementia
Psychosis/Hallucinations
Depression
Clinical Management
Cross-References
References
Guidelines
Course and Duration of Therapy with Parkinsonian Drugs and Withdrawal Syndromes
Introduction
Natural Progression of Pathological Features in Patients with PD
Natural Progression of Motor Symptoms in PD
Pathophysiology in the Basal Ganglia
Influence of Therapeutic Intervention in the Prognosis of Patients with PD
Dopamine Replacement Therapy
Effects of AADC Inhibitors on l-DOPA
Continuous Infusion Therapy with l-DOPA
Motor Complications Following l-DOPA Treatment
Motor Fluctuations Associated with l-DOPA Treatment
Dyskinesia Associated with l-DOPA Treatment
Mechanism of LID
Autonomic Dysregulation Induced by l-DOPA
Effects of l-DOPA Withdrawal
Neuroleptic Malignant Syndrome
COMT Inhibitors
Monoamine Oxidase (MAO)-B Inhibitors
Selegiline
Rasagiline
Safinamide
Serotonin Syndrome
Dopaminergic Agonists
Bromocriptine
Pergolide
Cabergoline
Lisuride
Adverse Events of Ergot-Derived DA Agonists
Pramipexole
Ropinirole
Rotigotine
Apomorphine
Impulsive Control Disorder (ICD)
Dopaminergic Agonist Withdrawal Syndrome (DAWS)
Amantadine
Anticholinergics
Initial Treatment for Patients with Early PD
Natural Progression of Non-motor Symptoms in Patients with PD
Autonomic Dysfunction
Dementia
Visual Hallucinations
Olfactory Dysfunction
Rapid Eye Movement (REM) Sleep Behavior Disorder
Milestones in Patients with Late-Stage PD
Treatment of PD in the Future
References
Drugs in the Treatment of Dystonia, Multisystem Atrophy, and Non-Parkinson Tremor
Introduction
Pharmacotherapy for Dystonia
Dopa-Responsive Dystonia
Botulinum Neurotoxin (BoNT)
Efficacy and Safety of BoNT Therapy for Cervical Dystonia
Efficacy and Safety of BoNT - Therapy for Blepharospasm
Efficacy and Safety of BoNT - Therapy for Oromandibular Dystonia
Efficacy and Safety of BoNT - Therapy for Spasmodic Dysphonia
Efficacy and Safety of BoNT - Therapy for Writer´s Cramp and Muscle Cramp
Efficacy and Safety of BoNT - Therapy for Segmental, Axial, and Generalized Dystonia
Oral Systemic Pharmacotherapy
Anticholinergics
Focal Dystonia
Segmental and Generalized Dystonia
Further Oral Medications
Focal Dystonia
Segmental and Generalized Dystonia
Drug Therapy of Multiple System Atrophy (MSA)
Therapy of Essential Tremors
Primary Orthostatic Tremor
Holmes Tremor and Thalamus Tremor
References
Side Effects, Contraindications, and Drug-Drug Interactions in the Use of Antiparkinsonian Drugs
Introduction
Common SEs of Antiparkinsonian Drugs
Neuropsychiatric SEs
Gastrointestinal SEs
Cardiovascular SEs
Dopamine Dysregulation Syndrome (DDS) and Impulse Control Disorders (ICDs)
Specific SEs for Antiparkinsonian Drugs
Levodopa (L-dopa)
Side Effects
Contraindications
Interactions
Dopamine Agonists (DAs)
Side Effects
Contraindications
Interactions
Monoamine B Oxidase (MAOB) Inhibitors
Side Effects
Contraindications
Interactions
Catechol-O-Ethyl Transferase (COMT) Inhibitors
Side Effects
Contraindications
Interactions
Amantadine
Side Effects
Contraindications
Interactions
Anticholinergics
Side Effects
Contraindications
Interactions
Zonisamide
Side Effect
Contraindications
Interactions
Adenosine A2A Receptor Antagonists
Side Effects
Contraindications
Interactions
References
Parkinsonian Toxins: From MPTP to Endogenous Neurotoxins
Introduction
Exogenous Neurotoxins Prepare Classical Animal and Cellular Models of PD
MPTP, the Only Neurotoxin to Induce Parkinsonism in Humans
6-Hydroxydopamine (6-OHDA), the Oldest and Popular Neurotoxin to Prepare a PD Animal Model
Rotenone, a Mitochondrial Neurotoxin
Search for Endogenous Dopaminergic Neurotoxins
Dopamine-Derived DHTIQ: Enzymatic Synthesis and the Enantio-Specific Toxicity
Phenylethylamine-Derived TIQ Derivatives
Indoleamine-Derived Neurotoxins β-carbolines
Environmental PD-Related Neurotoxins
Pesticides: Paraquat, Maneb
Metals: Are They Occupational Risk Factors for Idiopathic PD?
Discussion
References
Guidelines for the Use of Parkinsonian Drugs (in USA)
Introduction
Parkinsonian Drugs
Levodopa
Dosing
Side Effects
Levodopa-Related Complications
New Formulations of Carbidopa-Levodopa
Extended-Release Carbidopa-Levodopa
Carbidopa-Levodopa Intestinal Gel
Levodopa Powder
Dopamine Agonists
Pramipexole
Ropinirole
Rotigotine
Apomorphine
Side Effects of Dopamine Agonists (DA)
MAO-B Inhibitors
Rasagiline
Selegiline
Safinamide
Side Effects of MAO-B Inhibitors
COMT Inhibitors
Entacapone
Tolcapone
Opicapone
Side Effects of COMT Inhibitors
Anticholinergics
Dosing
Side Effects
NMDA Receptor Antagonist
Amantadine
Dosing
Side Effects
Adenosine A2A Receptor Antagonist
Istradefylline
Dosing
Side Effects
Strategies for Medication Dosing in PD
Early PD
Late PD
Conclusions
Cross-References
References
Guidelines for the Use of Parkinsonian Drugs in Canada
Introduction
Drugs for Disease Modification in Parkinson´s Disease
Drugs for Motor Symptoms of Parkinson´s Disease
Monotherapy
Adjunct for Fluctuations
Adjunct for Dyskinesia
Drugs for the Non-motor Symptoms of Parkinson´s Disease
Neuropsychiatric Issues
Sleep
Autonomic Symptoms
Pain/Sensory Symptoms
Conclusions
References
German Guidelines for the Use of Parkinsonian Drugs
Introduction
Grades of Recommendation
Therapy
Goals of Therapy
Drug Treatment
Levodopa
Levodopa Oral Preparations
Levodopa Infusion Therapy (Duodopa-or Lecigon-Pump)
Dopamine Agonists (DA)
COMT Inhibitors
MAO-B Inhibitors
Safinamide
Amantadine
Anticholinergics
Implementation of Therapy
Indications for Drug Therapy and Selection
Therapy Initiation with a Non-ergot DA
Therapy Initiation with Levodopa
Therapy Initiation with Levodopa Independent of Disease Onset
Combination Therapy
Insufficient Symptomatic Control after Initial Adjustment with MAO-B Inhibitors
Insufficient Effectivity of a Monotherapy with DA or Intolerability before Attaining a Sufficient Dose
Therapy After Fluctuations in Effectivity and Dyskinesia Appear
Fluctuations
Definition of Motor Fluctuations
Wearing off/End-of-Dose Akinesia
Therapy for Motor Fluctuations
Wearing-off/End-of-Dose Akinesia
Paroxysmal ``On-Off´´ Fluctuations
Freezing
Dyskinesias
Definition of Dyskinesias
Therapy of Dyskinesia
Off-Dystonia
Biphasic Dyskinesia
Pharmacotherapy of Tremor
Problematic Aspects of the Guidelines
Cross-References
References
Parkinsonian Drugs: Guidelines for Japan
Anti-Parkinson Disease Drugs That Are Permitted in Japan by the Department of Health, Labor and Welfare
The Guidelines for the Treatment of Parkinson´s Disease in Japan
Principles of the Guidelines
Clinical Efficacy and Safety of Anti-PD Drugs
Clinical Efficacy and Safety of the Surgical Treatment
General Discussion on the Treatment of PD
Treatment of Motor Disturbances
Non-drug Treatment of Motor Disturbance
Treatment of Non-motor Symptoms
Future Treatment and Others
References
Guidelines for Therapeutic Management of Parkinson´s Disease in China
Introduction
Principles of Treatment of PD
Integrated Therapy
Multiple-Disciplinary Treatment Modality
Long-Term Management
Pharmacological Therapies
The Principle of Medication for PD
Pharmacological Treatment for Early-Stage PD
Disease-Modifying Therapy for Early-Stage PD
Symptomatic Treatment of Early-Stage PD
Pharmacological Treatment for Middle to Advanced-Stage PD
Treatment of Postural Balance Disorders
Treatment of Motor Complications
Treatment of Non-Motor Symptoms
Treatment of Sleep Disorders
Treatment of Sensory Disturbances
Treatment of Autonomic Dysfunction
Treatment of Mental and Cognitive Disorders
Surgical Treatment
Traditional Chinese Medicine
Rehabilitation and Exercise Therapies
Psychological Intervention
Nursing and Caring
Artificial Intelligence and Mobile Technology
Telemedicine
Wearable Devices
Smart Phone Applications
Virtual Reality Technology
Conclusions
Cross-References
References
Parkinsonian Drugs in China
Introduction
Dopamine Replacement Therapy for PD
COMT Inhibitor
Monoamine Oxidase-B (MAO-B) Inhibitor
Dopamine Agonist
Principles of Drug Selection Criteria in China
Current Neuroprotective Therapy for PD
The Role of Neurotrophic Factors in the Treatment of PD
Gene Target Therapy in PD
Traditional Chinese Medicine for PD
References
Levodopa Therapy for the Treatment of Parkinson´s Disease
Chemistry, Developmental History
Chemical Formula (Graphic) (See Fig. 1)
Pharmacology
Mechanism of Action
Pharmacokinetics
Indications (of Marketed Products) and Side Effects/Adverse Effects: Clinical Studies
References
Levodopa/Carbidopa Intestinal Gel in Parkinson´s Disease
Chemistry, Developmental History
Chemical Formula (Graphic) (See Fig.1a, b)
Pharmacology: Mechanism of Action and Pharmacokinetics
Indications (of Marketed Products) and Side Effects/Adverse Effects: Clinical Studies
Combination Therapy
Cross-References
References
Monoamine Oxidase Inhibitor (MAO-I)-Mediated Neuroprotection for Treating Parkinson´s Disease
Introduction
DA Synthesis and Metabolism in the Brain
MAO-A and MAO-B in the Human Brain in Relation to PD
Clinical Studies on MAO-B Inhibitor (MAO-B-I) in PD
Molecular Mechanisms of Possible Neuroprotection of DA Neurons by MAO-B Inhibitors (MAO-B-Is)
Mechanism of sPD Hypothesized from Causative Proteins of fPD
Mechanism Based on Catecholaldehyde Hypothesis
Neurotoxin Hypothesis and Neuroprotection by MAO-B-Is
Neuroprotective Mechanism of MAO-I that May Not Be Related to MAO Inhibition
MAO-B Inhibitors (MAO-B-I) and Pro-inflammatory Cytokines from Activated Microglia in Neuroinflammation in PD
Conclusions
Conflict of Interest
Cross-References
References
Selegiline for Treating Parkinson´s Disease
Introduction
History
Pharmacokinetics
Pharmacodynamics
Selegiline in Long-Term Trials
DATATOP
SIN-DEP-PAR
Swedish Parkinson Study Group
Norwegian-Danish Study
SELEDO Trial
Conclusion
Cross-References
References
Safinamide for Treating Parkinson´s Disease
Chemistry
Pharmacodynamics
Pharmacokinetics
Pharmacokinetic Studies in Humans
Pharmacokinetic Interactions
Pharmacodynamic Interactions
Safety and Tolerability
Pivotal Clinical Trials with Safinamide in Levodopa-/DDC-Treated Patients
Cross-References
References
From Anti-Parkinson´s Drug Rasagiline to Novel Multitarget Iron Chelators with Acetylcholinesterase and Monoamine Oxidase Inhi...
Introduction
The Multifunctional Iron-Chelating Compounds HLA20 and M30
Design Strategy
Targeting Multiple AD Etiologies with HLA20 and M30
Metal Accumulation, OS and MAO Activity
Regulation of APP and Aβ formation
Neuroprotection, Neurorescue, and Neurogenesis Effects
Activation of the Hypoxia-Inducible Factor (HIF)-1α Signaling Pathway
Selective AChE Inhibitors with Site-Activated Chelating and Neuroprotective/Neurogenesis Properties
Design Strategy
In Vitro Pharmacological Profile
Selective AChE-MAO-A and -B Inhibitors with Site-Activated Chelating and Neuroprotective/Neurogenesis Properties
Design Strategy
In Vitro Pharmacological Profile
Design Strategy for Activity-Dependent Neuroprotective Protein (ADNP) Analogs
Conclusions
References
Bromocriptine for Treating Parkinson´s Disease
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Toxicology
Conclusion
Cross-References
References
Lisuride: An 8-Alpha-Ergoline with Ergot Antagonistic Properties
Introduction
Chemistry and Developmental History
Pharmacology
Pharmacokinetics
Biochemistry and Mode of Action (MoA)
Receptor Binding
Biochemistry
Neurophysiology
Indications and Clinical Applications
Clinical Pharmacology
Applications in Clinical Endocrinology
Clinical Studies
Parkinson´s Disease and Related Disorders
Oral Application
Side Effects/Adverse Reactions and Toxicology
Parenteral Application
Subcutaneous Lisuride: Continuous Dopaminergic Stimulation
Other Motor Disturbances
Migraine
Toxicology
Conclusion
Combination Therapy: Interactions
Cross-References
References
Pergolide in the Treatment of Parkinson´s Disease
Chemistry and Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Monotherapy
Adjunctive Therapy
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Combination Therapy
Interactions
Cross-Reference
References
Cabergoline in the Treatment of Parkinson´s Disease
Chemistry and Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (Marketed Products)
Clinical Studies
Monotherapy
Adjunctive therapy
Side Effects/Adverse Reactions and Toxicology
Combination Therapy - Interactions
Combination Therapy
Interactions
Cross-References
References
Apomorphine for the Treatment of Parkinson´s Disease
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications
Bolus Injections
Continuous Apomorphine Infusion
The Apomorphine Strip
Contraindications for Apomorphine Use
Clinical Studies
Bolus Injections
Infusion
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Key Points
References
Pramipexole for Treating Parkinson´s Disease
Chemistry, Developmental History
Chemical Formula
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Ropinirole in the Treatment of Parkinson´s Disease
Chemistry: Developmental History
Chemical Formula
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Future Direction
Cross-References
References
Rotigotine for Treating Parkinson´s Disease
Introduction
Basic Data
Pharmacology of Rotigotine
Transdermal Patch
Available Dosages
Special, Product-Specific Advice
Advantages of Transdermal Application
Present Status in Research
Effects on Motor Symptoms in Early and Late Stage of PD
Comparison with Other Substances (See above)
RTG and Quality of Sleep
Rotigotine in Patients with Dysphagia
Rotigotine and ICD
RTG in Pain
RTG in Freezing of Gait
Rotigotine in RLS (Chapter ``Definition and Classification of Parkinsonian Drugs´´)
Future
Summary
References
Entacapone/Tolcapone/Opicapone for Treating Parkinson´s Disease
History and Pharmacology
Mode of Action of COMT Inhibition
Entacapone
Chemistry, Pharmacokinetics and Pharmacodynamics
Clinical Efficacy
Safety and Tolerability
Regulatory Affairs
Stalevo
Tolcapone
Chemistry, Pharmacodynamics, Pharmacokinetics
Clinical Efficacy
Safety Concerns with Tolcapone: The Liver Problem
Tolcapone or Entacapone in Clinical Practice
Opicapone
Chemistry
Pharmacokinetics
Opicapone in Healthy Subjects
Opicapone in PD Patients
Conclusion: Future Advantages of Opicapone in Clinical Practice
References
Amantadine for Treating Parkinson´s Disease
Introduction
Pharmacology
Clinical Efficacy
Side Effects
New Drugs
Conclusion
References
Trihexyphenidyl, Biperiden, and Other Anticholinergics in the Treatment of Parkinson´s Disease
Chemistry, Developmental History
Chemical Formula
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Survey Review
Monotherapy
Adjunctive Therapy
Side Effects/Adverse Reactions and Toxicology
Combination Therapy - Interactions
References
Mazaticol for Treating Parkinson
Chemistry, Developmental History
Development History
Chemical Characteristics (Pharmaceutical Products Interview form in Japan 2015)
Chemical Formula
Pharmacology
Pharmacokinetics
Metabolism
Excretion
Time to Peak
Half-Life Elimination
Distribution
Blood-Brain Barrier Permeability
Mechanism of Action
Anti-acetylcholine Activity
Anti-Tremorine-Induced Tremor Activity
Anti-Physostigmine-Induced Death Activity
Effect on Haloperidol-Induced Parkinsonism
Activity to a Dopaminergic Neuron
Mydriatic Activity
Anti-Pilocarpine-Induced Salivation Activity
Effects on Gastric Motility in Cats and on Ileum Motility in Rabbits
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Side Effects
Toxicology
Contraindications
Careful Administration
Attention
Combination Therapy: Interactions
Cross-References
References
Piroheptine for Treating Parkinson
Chemistry, Developmental History
Development History
Chemical Characteristics
Chemical Formula
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy - Interactions
Cross-References
References
Droxidopa for the Treatment of Parkinson´s Disease
Chemistry, Developmental History
* Chemical Formula (Graphic)
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (For Marketed Products)
Clinical Studies
Droxidopa for nOH
Droxidopa for Motor Symptoms
Long-Term Efficacy and Durability of Droxidopa
Graphic
Side Effects/Adverse Events and Toxicology
Combination Therapy and Interactions
Cross-References
References
Istradefylline for Treating Parkinson´s Disease
Introduction
The Adenosine System and Adenosine A2A Receptors
Nonclinical Studies for Istradefylline
Studies in Experimental PD Models
Mode of Action of A2A Receptor Antagonists
Clinical Trials
Future Aspects
Physiology of Adenosine A2A Receptors
Potential Clinical Aspects of A2A Antagonist
Conclusions
References
Zonisamide for Treating Parkinson´s Disease
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Dopaminergic Mechanisms
Non-dopaminergic Mechanisms
Neuroprotective Effects
Effects on Cortical Plasticity
Indications
Clinical Studies
Side Effects
Combination Therapy: Interactions
Cross-References
References
Part XII: Anti-convulsant Agents
Anti-convulsant Agents: Definition and Indication
Definition
Indication
Cross-References
References
Anti-convulsant Agents: Pharmacology and Biochemistry
Introduction
From Potassium Bromide to Cenobamate
Preclinical and Clinical Profile of Antiseizure Drugs
Mechanisms of Action of Antiseizure Drugs
Are some Antiseizure Drugs Also Antiepileptogenic?
Pharmacokinetics of Antiseizure Drugs
Tolerability and Safety of Antiseizure Drugs
Conclusions and Outlook
Cross-References
References
Anti-convulsant Agents: Beginning and Duration of Therapy, Withdrawal, and Resistance - Children
Introduction
Initiation of Therapy
Duration of Therapy
Combination of Drugs
Withdrawal of Therapy
Patients Who Are Resistant to Antiepileptic Drugs
Therapeutical Aspects in Certain Conditions
Genetic Epilepsies
Febrile Convulsions
Adverse Reactions
Summary
References
Anti-convulsant Agents: Principal Considerations on Effectiveness, Side Effects, and Interactions
Introduction
Choosing an AED
Effectiveness of AEDs
Side Effects
Drug Interactions
Comorbidities
Stopping AEDs
Cross-References
References
Anti-convulsant Agents: Beginning, Maintenance, Pharmacoresistance, Duration of Therapy, and Withdrawal - Adults
Initiation of Pharmacological Therapy
To Be Spoilt for Choice: Which Anti-convulsant Is the Best for the Individual Patient?
The Maintenance of Anti-convulsive Therapy
Pharmacoresistance and the Step to Non-pharmacological Therapy
Ending Pharmacological Therapy
Cross-References
References
Anti-convulsant Drugs: Differential Indications - Neuropathic Pain and Migraine
Neuropathic Pain
Neuropathic Pain: Pathophysiology
Peripheral Sensitization: Molecular Mechanisms Targeted by Anti-Convulsants
Central Sensitization: Molecular Mechanisms Targeted by Anti-convulsants
Anti-convulsant Therapy in Neuropathic Pain
Calcium Channel Modulators
Sodium Channel Blockers
Topical Therapy
A Look Ahead: Effective Treatment with Anti-convulsants in Specific Subgroups of Patients
Migraine
Migraine: Pathophysiology
Anti-convulsant Therapy in Migraine Prophylaxis
Summary
References
Anti-convulsant Agents: Acute Drug Therapy Outside Status Epilepticus
Introduction
What Is an Acute Seizure?
Which Patients Should Be Treated and Why?
Which Is the Optimal Treatment?
Specific Causes of Acute Seizures and Their Treatment
Traumatic Brain Injury and Intracranial Hemorrhage
Acute Cerebrovascular Event (Ischemic/Hemorrhagic)
Sinus Venous Thrombosis
Cerebral Infection
Hypoxic-Ischemic Brain Injury
Autoimmune Encephalitis
Posterior Reversible Encephalopathy Syndrome (PRES)
Eclampsia
Metabolic Disturbances
Electrolyte Disturbances
Alcohol Withdrawal
Intoxication
References
Anti-convulsant Drugs and Cognition
The Relevance of Cognitive Side Effects
Cognitive Effects of Antiepileptic Drugs
General Risk Factors
Cognitive Profiles of Different Antiepileptic Drugs
Reversible Versus Lasting Effects
Cognitive Monitoring of Antiepileptic Pharmacotherapies
Indication
Assessment
Measures
Strategies to Encounter Cognitive Side Effects
Conclusion
Cross-References
References
Anti-convulsant Agents: Potassium Bromide
Chemistry, Developmental History
Chemical Formula (Graphic): KBr
Pharmacology
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Anti-convulsant Agents: Phenobarbital and Primidone
Chemistry, Developmental History
The Chemistry of Barbiturates
Developmental History
Pharmacology
Pharmacokinetics
Therapeutic Drug Monitoring for Phenobarbital and Primidone
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Conclusion
References
Anti-convulsant Agents: Ethosuximide and Methsuximide
Chemistry
Clinical Formula (Graphic)
Pharmacology
Pharmacokinetic
Mechanism of Action
Indications
Clinical Studies
Side-Effects and Adverse Reactions
Combination Therapies and Interactions
References
Anti-convulsant Agents: Phenytoin and Fosphenytoin
Introduction
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications
Clinical Studies
Phenytoin
Fosphenytoin
Side Effects
Phenytoin
Fosphenytoin
Combination Therapy: Interactions
Cross-References
References
Anti-convulsant Agents: Valproic Acid
Chemistry, Developmental History
Pharmacology
Indications
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
References
Anti-convulsant Agents: Carbamazepine, Oxcarbazepine, and Eslicarbazepine Acetate
Chemistry and Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications and Clinical Use
Evidence from Clinical Studies
Side Effects/Adverse Reactions
Dose-Related Side Effects
Idiosyncratic Adverse Events
Endocrine and Metabolic Adverse Events
Teratogenicity
Interactions
Cross-References
References
Anti-convulsant Agents: Vigabatrin
Chemistry, Developmental History
History
Pharmacology
Pharmacokinetics
Dosing
Pregnancy and Lactation
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
VGB for Infantile Spasms
Clinical Efficacy (Table 1)
Vigabatrin for Refractory Focal Epilepsy
Vigabatrin Monotherapy
Side Effects/Adverse Reactions and Toxicology
Vigabatrin and Visual Field Loss
Pathophysiology
Incidence of Visual Field Loss
Confounding Factors for Visual Field Loss
Visual Field Testing
Vigabatrin-Associated Brain Abnormalities on MRI
References
Anti-convulsant Agents: Lamotrigine
Chemistry: Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Side Effects/Adverse Reactions
Toxicology
Teratogenicity
Combination Therapy: Interactions
Drug-Drug Interactions
Interactions with Other AED
Interactions with Psychotropic, Oral Contraceptives (OC), and Other Drugs
Drug-Laboratory Interactions
Drug-Lifestyle Interactions
Cross-References
References
Anti-convulsant Agents: Gabapentin and Pregabalin
Chemistry and Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Anti-convulsant Agents: Levetiracetam and Brivaracetam
Chemistry: Developmental History
Pharmacology and Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Anti-convulsant Agents: Topiramate
Chemistry, Development History
Pharmacology
Pharmacokinetics
Mechanisms of Action
Indications (of Marketed Products)
Clinical Studies
Topiramate As Monotherapy
Topiramate As Add-On in Focal Epilepsies
Topiramate in Epilepsies with Generalized Seizures
Topiramate in Epileptic Encephalopathies
Topiramate Extended Release TPM XR
Topiramate Dosing
Side Effects/Adverse Reactions and Toxicology
Safety of Topiramate
Teratogenicity
Combination Therapy - Interactions
Discussion
Conclusion
References
Anti-convulsant Agents: Sulthiame
Chemistry and Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Anti-convulsant Agents: Zonisamide
Chemistry and Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Anti-convulsant Agents: Rufinamide
Chemistry, Developmental History
Chemical Formula
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications
Clinical Studies
Side Effects/Adverse Reaction and Toxicology
Combination Therapy: Interactions
Cross-References
References
Anti-convulsant Agents: Stiripentol
Chemistry and Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indication
Clinical Studies (See Table 1)
Randomized Controlled Trials
Long-Term Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
References
Anti-convulsant Agents: Felbamate
Chemistry, Developmental History
Chemical Formula (Graphic)
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications
Clinical Studies
Adjunctive Therapy for Focal Seizures
Outpatient Withdrawal to Monotherapy in Patients with Focal Seizures
Trials in Patients Undergoing Evaluation for Epilepsy Surgery
Adjunctive Therapy in Lennox-Gastaut Syndrome
Open Label Studies of Felbamate Use
Side Effects/Adverse Reactions and Toxicology
Combination Therapy - Interactions
Practical Clinical Use
Summary - Clinical Use of Felbamate
References
Anti-convulsant agents: Cortisone and Adrenocorticotropic Hormone (ACTH)
Chemistry, Developmental History
Chemical Formula
Pharmacology, Pharmacokinetics, and Mechanisms of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Conclusion
Cross-References
References
Anti-convulsant Agents: Everolimus
Chemistry: Developmental History
Pharmacology
Pharmacokinetics
mTOR: Mechanism of Action
Indications (of Marketed Products)
mTOR Inhibitors for Neurologic Symptoms in Tuberous Sclerosis Complex (TSC)
Clinical Studies
mTOR Inhibitors: Cognition and Behavior
Dosing
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Conclusion
References
Anti-convulsant Agents: Benzodiazepines (Clobazam, Clonazepam, Diazepam, Lorazepam, Midazolam)
Chemistry, Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy - Interactions
Cross-References
References
Anti-convulsant Agents: Lacosamide and Perampanel
Lacosamide
Chemistry and Developmental history
Pharmacology
Mechanisms of Action
Pharmacokinetics
Indications and Dosage
Clinical Studies
Adjunctive Therapy in Partial Seizures
Monotherapy in Partial Seizures
Adjunctive Therapy in Generalized Seizures
In Status Epilepticus
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Fertility, Pregnancy, and Lactation
Perampanel
Chemistry and Developmental History
Pharmacology
Mechanisms of Action
Pharmacokinetics
Indications
Clinical Studies
For the Treatment in Partial-Onset Seizures
For the Treatment of Primary Generalized Tonic-Clonic Seizures
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Fertility, Pregnancy, and Lactation
Cross References
References
Anti-convulsant Agents: Cannabidiol and Fenfluramine
Developmental History of Cannabidiol and Fenfluramine in Developmental and Epileptic Encephalopathies
Pharmacology Cannabidiol
Indications of Cannabidiol
Pharmacokinetics of Cannabidiol
Clinical Studies
Adverse Events Profile and Interactions of Cannabidiol
Pharmacology Fenfluramine
Indications of Fenfluramine
Pharmacokinetics of Fenfluramine
Clinical Studies
Adverse Events Profile and Interactions of Fenfluramine
Therapeutic Advances in Developmental and Epileptic Encephalopathies
Cross-References
References
Anti-convulsant Agents: Cenobamate
Chemistry: Developmental History
Pharmacology and Mechanism of Action
Indications (of Marketed Products)
Clinical Studies
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
Cross-References
References
Anti-convulsive Drug Use in Status Therapy: Adults
Introduction
First Line: Benzodiazepines (Table 1)
Lorazepam (LZP)
Diazepam (DZP)
Midazolam (MDZ)
Clonazepam (CLZ)
Second Line: Iv AEDs (Table 2)
Phenobarbital (PB)
Phenytoin and Fosphenytoin (PHT, PPHT)
Valproate (VPA)
Levetiracetam (LEV)
Lacosamide (LCM)
Brivaracetam (BRV)
Third Line: Coma Induction (Table 3)
Barbiturates (BBT): Pentobarbital (PTB), Thiopental (THP)
Midazolam (MDZ)
Propofol (PRO)
Other Treatments
Ketamine
Inhalational Anesthetics
Immunomodulatory Treatments
Allopregnanolone (Brexanolone)
Nonpharmacological Strategies
Orally Administered AEDs
Perampanel (PER)
Topiramate (TPM)
Pregabalin (PGB)
Conclusion
Cross-References
References
Anti-convulsive Drug Use in Status Treatment in Children
Introduction
First-Line Treatment in the Pre-Hospital Setting (Phase 5-10 min)
Early-Phase Treatment in the Hospital Setting (Phase 5-20 min)
Expanded Treatment in the Hospital Setting (Phase 20-40 min)
Treatment of Refractory Pediatric SE in the Hospital Intensive Care Setting (Phase >40 min)
Pharmacological Considerations in Specific Pediatric SE Subtypes
Cross-References
References
Rational Antiepileptic Treatment in Childhood
Introduction
Rational Antiepileptic Treatment
Particularities of Pediatric Pharmacokinetics and Dynamics
Level 1: Seizure Type-Specific AET in Children
Rational and Optimized Pharmacological Treatment of Childhood Epilepsies
Level 2: Syndrome-Specific Antiepileptic Treatment
Neonatal Seizures
West Syndrome
Dravet Syndrome (DS)
Doose Syndrome
Lennox-Gastaut Syndrome (LGS)
Nonpharmacological Therapies
Childhood Absence Epilepsy (CAE)
CSWS and LKS
Level 3: Gene-Specific Antiepileptic Treatment
References
Guidelines on Anti-convulsant Agents
Introduction
Epilepsies: Diagnosis and Management. NICE Clinical Guideline (National Institute for Health and Care Excellence (NICE) 2012) ...
ILAE Treatment Guidelines: Evidence-Based Analysis of Antiepileptic Drug Efficacy and Effectiveness as Initial Monotherapy for...
Updated ILAE Evidence Review of Antiepileptic Drug Efficacy and Effectiveness as Initial Monotherapy for Epileptic Seizures an...
Efficacy and Tolerability of the New Antiepileptic Drugs, I: Treatment of New-Onset Epilepsy (French et al. 2004a)
Practice Guideline Update Summary: Efficacy and Tolerability Of The New Antiepileptic Drugs I: Treatment of New-Onset Epilepsy...
Efficacy and Tolerability of the New Antiepileptic Drugs II: Treatment of Refractory Epilepsy (French et al. 2004b)
Practice Guideline Update Summary: Efficacy and Tolerability of the New Antiepileptic Drugs II: Treatment-Resistant Epilepsy (...
First Epileptic Seizure and Epilepsy in Adulthood (Erster epileptischer Anfall und Epilepsien im Erwachsenenalter) (Elger et a...
References
Part XIII: Applied Neuropsychopharmacotherapy
Neuropsychopharmacotherapy: Emergency Psychiatry
Introduction
Definition of Psychiatric Emergencies
Syndromes and Disorders Relevant to Emergency Psychiatry
Diagnostics
Psychiatric Findings
General Principles in the Diagnosis of Psychiatric Emergencies
Procedure for Initial Contact
Verbal Crisis Intervention
General Information on the Pharmacotherapy of Psychiatric Emergencies
Therapy of Selected Psychiatric Emergencies
Disturbances of Consciousness and Confusion
Delirium
Pharmacotherapy of Delirium (Without Alcohol Withdrawal Delirium)
Pharmacotherapy of Alcohol Withdrawal Delirium
Stupor and Catatonia
Psychomotor Agitation
Management of Agitation and Aggression
Treatment of Psychomotor Agitation: Critical Consideration of Possible Interventions
Nonpharmacological Interventions
Fixation and Spatial Isolation
Pharmacological Treatment of Agitation
Oral Dosage Forms
Sublingual Dosage Forms
Intramuscular Dosage Forms
Intravenous Dosage Forms
Inhaled Dosage Forms
Management of Agitation in Special Subpopulations
Agitation in Geriatric Patients
Agitation in Pregnant Patients
Intoxications
Alcohol
Cocaine
Opiates
Amphetamines
Specific Measures for Withdrawal Symptoms from Individual Substances
Alcohol Withdrawal
Benzodiazepine Withdrawal
Anxiety Disorders
Suicidality
Diagnostics
Measures and Therapy
Nonpharmacological Measures
Pharmacological Measures
Pharmacologically Induced Psychiatric Emergencies
Neuroleptic Malignant Syndrome (NMS)
Central Serotonergic Syndrome
Central Anticholinergic Syndrome
References
Psychopharmacotherapy of Obsessive-Compulsive and Related Disorders
Introduction
Psychopharmacotherapy of Obsessive-Compulsive Disorder
Serotonin Reuptake Inhibitors in the Management of OCD
Antipsychotics in the Management of OCD
Glutamatergic Agents in the Management of OCD
Other Agents in the Management of OCD
Summary
Psychopharmacotherapy of Body Dysmorphic Disorder
Serotonin Reuptake Inhibitors (SRIs) in the Management of BDD
Antipsychotics in the Management of BDD
Other Agents in the Management of BDD
Summary
Psychopharmacotherapy of Hoarding Disorder
Serotonin Reuptake Inhibitors (SRIs) in the Management of HD
Antipsychotics in the Management of HD
Other Agents in the Management of HD
Summary
Psychopharmacotherapy of Trichotillomania (Hair-Pulling Disorder)
Serotonin Reuptake Inhibitors (SRIs) in the Management of TTM
Antipsychotics in the Management of TTM
Other Agents in the Management of TTM
Summary
Psychopharmacotherapy of Excoriation (Skin-Picking Disorder)
Selective Serotonin Reuptake Inhibitors (SSRIs) in the Management of SPD
Antipsychotics in the Management of SPD
Glutamatergic Agents in the Management of SPD
Summary
Psychopharmacotherapy of Other Body-Focused Repetitive Behavior
Psychopharmacotherapy of Substance/Medication-Induced Obsessive-Compulsive and Related Disorder
Psychopharmacotherapy of Obsessive-Compulsive and Related Disorder Due to Another Medical Condition
Conclusion
Cross-References
References
Treatment of Sleep Disorders in Specific Psychiatric Diseases
Major Depression
Introduction
Subjective Sleep
Polysomnographic Findings in Drug-Free Patients with Depression
Sleep EEG in High-Risk Probands for Affective Disorders
Contribution of the HPA System to Sleep-EEG Abnormalities in Depression
Effects of Antidepressants on Sleep
Effects of Antidepressants on Subjective Sleep
Effects of Antidepressants on Sleep EEG in Patients with Depression and Healthy Subjects
State and Vulnerability Markers Related to Antidepressive Pharmacotherapy
Cordance Derived from REM Sleep As a Predictor of Therapy Response
Therapy of Insomnia in Major Depression
Pharmacotherapy of Insomnia in Major Depression
Non-Pharmacological Treatment of Insomnia in Patients with Depression
Pharmacotherapy of Hypersomnia in Depressed Patients
Bipolar Disorder
Introduction
Subjective Sleep
Polysomnographic Findings in Drug-Free Patients with Mania
Sleep-EEG Effects of Drugs Used to Treat Bipolar Disorder
Therapy of Bipolar Disorder
Pharmacotherapy
Non-Pharmacological Treatment
Schizophrenia
Introduction
Subjective Sleep
Polysomnographic Findings in Drug-Free Patients with Schizophrenia
Pathophysiology
Effects of Antipsychotics on Sleep EEG
Effects in Healthy Subjects
Sleep-EEG Effects After Antipsychotics in Patients with Schizophrenia
Therapy of Insomnia in Patients with Schizophrenia
Pharmacotherapy
Non-Pharmacological Treatment
Posttraumatic Stress Disorder
Introduction
Subjective Sleep
Insomnia
Posttraumatic Nightmares
Polysomnographic Findings
Comorbid Sleep Disorders
Therapy of Sleep Disturbances in PTSD
Pharmacotherapy of Insomnia
Pharmacotherapy of Nightmares
Non-Pharmacological Treatment of Insomnia and Nightmares
Generalized Anxiety Disorder
Introduction
Subjective Sleep
Polysomnographic Findings
Therapy of Insomnia in GAD
Pharmacotherapy
Non-Pharmacological Treatment
Cross-References
References
Pharmacotherapy of Sleep Disorders During Pregnancy and Nursing
Sleep Disturbances in Pregnancy and Nursing
Epidemiologic Data
Physiologic Alterations of Perinatal Sleep
Sleep Disorders as Risk Factor for Maternal and Offspring Health Problems
Options of Treatment: Principal Considerations
Perinatal Pharmacotherapy
Non-pharmacological Options of Treatment
Experiences with Specific Drugs for Sleep Disorders in Pregnancy and Nursing
Drugs for Insomnia
Sedating Phytotherapeutics
Benzodiazepines and Hypnotic Benzodiazepine Receptor Agonists
Sedating Antidepressants
Sedating Antipsychotics
Antihistamines
Melatonin and Melatonin Receptor Agonists
Orexin Receptor Antagonists
Drugs for Treatment of Restless Legs Syndrome
Restless Legs Syndrome
Dopamine Agonists and Levodopa
Pregabalin and Gabapentin
Drugs for Treatment of Narcolepsy and Hypersomnia
Narcolepsy
Stimulants
Sodium Oxybate
Conclusion
Cross-References
References
Therapy of Sleep Disorders in Parkinson´s Disease
Introduction
REM-Sleep Behavior Disorder
Diagnosis of RBD
Treatment of RBD
Insomnia
Diagnosis of Insomnia
Treatment of Insomnia
Due to Motor Complications
Due to Non-motor Symptoms
Restless Legs Syndrome and Periodic Limb Movement Disorder
Diagnosis of RLS and PLMD
Treatment of RLS and PLMD
Sleep Disordered Breathing in PD
Diagnosis of Sleep-Disordered Breathing
Treatment of Sleep-Disordered Breathing
Excessive Daytime Sleepiness
Diagnosis of Excessive Daytime Sleepiness
Treatment of EDS
Cross-References
References
Psychopharmacotherapy of Depressive Disorders
Introduction
Treatment of Major Depressive Disorder
Indication and Efficacy of Antidepressant Agents
First-Line Treatment
Symptom-Based Approach in the First-Line Treatment (Baune et al. 2019)
How to Proceed in Case of Nonresponse
Dose Escalation
Antidepressant Switch
Initial Maintenance Treatment (Continuation)
Extended Maintenance Treatment for Prevention of Recurrence
Subtypes of Depression
Difficult-to-Treat Depression (DTD)
Definition
Augmentation Strategies
Lithium
Second-Generation Antipsychotics (SGA)
Thyroid Hormones
Combination Treatment
Second-Line Antidepressant Agents
Monoamine Oxidase (MAO) Inhibitors (MAOI)
Tricyclic Antidepressants
Adjunctive Treatment
Complementary and Off-Label Adjunctive Treatment
Chronotherapeutic Interventions
NMDA Antagonists
Neuromodulation
Electroconvulsive Therapy (ECT)
Repetitive Transcranial Magnetic Stimulation (rTMS)
Vagus Nerve Stimulation (VNS)
Transcranial Direct Current Stimulation (tDCS)
Deep Brain Stimulation (DBS)
Cross-References
References
Lithium in Psychiatric Indications
Historical Review
Mechanisms of Action
Lithium and Its Role in Treatment of Psychiatric Disorders
Bipolar Disorders
Lithium in Maintenance Treatment of BD
Lithium in the Treatment of Acute Mania
Lithium in Bipolar Depression
Lithium in Episodes with Mixed Features and Rapid Cycling
Lithium in Unipolar Depression
Treatment of Acute Major Depressive Episodes
Adjunctive Treatment: Augmentation with Lithium
Adverse Effects of Lithium
Lithium Treatment over the Life Span
Lithium in Pregnancy and Postpartum Women
Discontinuation of Lithium
Lithium and Its Anti-suicidal Properties
Concluding Remarks
Cross-References
References
Psychopharmacotherapy of Pain
Introduction
Pharmacological Approaches
Tricyclic Antidepressants (TCAs)
SSRIs
Fluoxetine
Paroxetine
Escitalopram
SNRIs
Venlafaxine
Duloxetine
Atypical Antidepressants
Trazodone
Mirtazapine
Bupropion
Milnacipran
Opioids
Benzodiazepines (BZDs)
Neuroleptics
Typical Neuroleptics
Atypical Neuroleptics
Quetiapine
Risperidone
Olanzapine
Aripiprazole
Antiepileptic Drugs
Valproic Acid (VPA)
Carbamazepine (CBZ)
Oxcarbazepine (OXC)
Lamotrigine (LTG)
Topiramate (TPM)
Levetiracetam (LEV)
Brivaracetam (BRV)
Gabapentin (GBP)
Pregabalin (PGB)
Cannabinoids
Nonpharmacological Approaches
Conclusion
References
Use of Antipsychotics in the Treatment of Eating Disorders
Introduction
Studies Testing Antipsychotics in Eating Disorders
Meta-Analyses of Antipsychotics in Eating Disorders
Neuronal and Molecular Pharmacodynamic Mechanisms
Clinical Recommendations
Limitations and Future Research Directions
Cross-References
References
Psychopharmacotherapy of PTSD
Introduction
Psychotherapy of PTSD
Exposure-Based Interventions
Cognitive-Based Interventions
Eye Movement Desensitization and Reprocessing
Pharmacotherapy of PTSD
Selective Serotonin Reuptake Inhibitors
Non-SSRIs
Conclusion
Cross-References
References
Pharmacotherapy of Personality Disorders
Introduction
Personality Disorders: Diagnosis
Personality Disorders: Epidemiology
Pharmacotherapy of Personality Disorders: General Aspects
General Treatment Plan
Pharmacotherapy of PD Disorders According to Their Subtypes
Cluster A, in Particular Schizotypal Personality Disorder
Cluster B, in Particular Borderline Personality Disorder
Antidepressants
Antipsychotics
Mood Stabilizers
Other Drug Classes
Cluster C, in Particular Anxious-Avoidant Personality Disorder
Conclusions
Cross-References
References
Psychopharmacotherapy of Sexual Disorders
Hypersexuality/Sexual Addiction
Introduction
Definition of the Nosographic Framework-Epidemiology
Psychopharmacological Treatment
Psychological Treatment
Pharmacological Treatment
Noninvasive Brain Stimulation Methods
Conclusion
Paraphilic Disorders (and/or Sex Offenders)
Introduction
Definitions and Clinical Characteristics
Paraphilic Disorders and Sexual Offending
Clinical/Paraclinical Assessment
Careful clinical assessment is a necessary prerequisite before treatment
Clinical and Sociodemographic Factors Need to Be Specified as Following (Table 1)
Psychometric Tests
Paraclinical Assessment
Psychopharmacological Treatment
Treatment Choice and Goals
Psychological Therapies
Pharmacological Treatments
Surgical Treatments
Hormonal Treatments
Treatment Guidelines for Paraphilic Disorders (Thibaut et al. 2020)
Treatment Choice
Prior Assessment
Treatment Duration
Conclusion
Cross-References
Supplement: Chemical Names and Pharmacokinetics of the Main Compound Cited in this Chapter
References
Neuropharmacology of Dementias
Epidemiology of Dementias
AD
Cholinesterase Inhibitors (ChEI)
Tacrine
Donepezil
Pharmacology
Clinical Studies
Rivastigmine
Pharmacology
Clinical Studies
Oral Versus Transdermal Rivastigmine
Galantamine
Pharmacology
Clinical Studies
Summary of ChEI
Memantine
Pharmacology
Clinical Studies
Combination of ChEI and Memantine in AD
Meta-Analysis of ChEI and Memantine Treatment of AD Patients
Ginkgo Biloba
Pharmacology
Clinical Studies
PD and DLB
Memantine in PDD and DLB
VaD and Vascular Cognitive Impairment (VaCI)
Rivastigmine and VaD and VaCI
Donepezil in VaD and VaCI
Galantamine and VaCI, VaD, and Combined VaD and AD
Memantine and VaD
Summary of Pharmacological Treatment of VaD and VCI
Neuropsychiatric Symptoms in Dementias
Frontotemporal Dementia (FTD)
New Perspectives
Cross-References
References
Pharmacotherapy of Psychosis in Parkinson´s Disease
Pathophysiology
Structural Magnetic Resonance Imaging
PET and SPECT Imaging
Functional MRI
Lewy Pathology
Neurotransmitter Systems
Dopaminergic System
Serotonergic System
Cholinergic System
Glutamatergic System
GABA System
Pharmacological Management of PD Psychosis
Atypical Anti-psychotics
Clozapine
Quetiapine
Pimavanserin
Other Atypical Anti-psychotics
Acetyl-Cholinesterase Inhibitors
Rivastigmine
Donepezil
Tacrine
Galantamine
Anti-depressants
Future Perspectives: Emerging Therapies
Conclusion
Cross-References
References
Psychopharmacotherapy in Patients with Tics and Other Motor Disorders
Tics
Typical Antipsychotics
Haloperidol
Pimozide
Fluphenazine
Atypical Antipsychotics
Risperidone
Aripiprazole
Olanzapine
Quetiapine
Ziprasidone
Benzamide
Tiapride
Sulpiride
α-Adrenergic Agonists
Guanfacine
Clonidine
Alternatives
Tetrabenazine
Tetrahydrocannabinol
Atomoxetine
Baclofen
Clonazepam
Topiramate
Huntington Disease
Clinical Features and Treatments
Motor Symptoms
Psychiatric Symptoms
Cognitive Impairment
Psychopharmacotherapy
Tetrabenazine
Typical Antipsychotics
Phenothiazines
Haloperidol
Benzamides
Atypical Antipsychotics
Aripiprazole
Risperidone
Clozapine
Olanzapine
Quetiapine
Ziprasidone
Benzodiazepines
Pridopidine
Summary
References
Pharmacotherapy of Alcohol Use Disorders
Introduction
Drugs Available
Selection of Outcome Criteria
Drugs Available
Medications Approved for Treatment of AUD
Opioid Antagonists
Nalmefene
Acamprosate
Other Medications
Baclofen
Gabapentin
Topiramate
Future Perspectives
Ketamine
Varenicline
Ondansetron
Others
Pharmacogenetics
References
Psychopharmacotherapy in Forensic Psychiatry
Introduction
Schizophrenia and Other Psychotic Disorders
Paraphilic Disorders
Personality Disorders
Mental Disabilities
Substance-Related Disorders
Cross-References
References
Part XIV: Implementation of Neuropsychopharmacotherapy
Effects of Psychopharmacological Medicines upon Driving Ability
Epidemiology
Categorization of Psychotropic Medicines
Benzodiazepines and ``Newer Hypnotic Drugs´´
Z-Drugs
Melatonin
OTC Sleep Aids: Antihistamines
Treatment of Patients
Antidepressants
Tricyclic Antidepressants
Non-tricyclic Antidepressants
Treatment of Patients
Antipsychotics
Treatment of Patients
Psychostimulants
Treatment of Patients
Conclusions
Cross-References
References
Psychopharmacological Agents During Pregnancy and Nursing
Pharmacotherapy in Pregnancy and Breastfeeding
Antipsychotics
Antipsychotics During Pregnancy
Antipsychotics During Nursing
Antidepressants
Antidepressants During Pregnancy
Antidepressants During Nursing
Mood Stabilizers
Mood Stabilizers in Pregnancy
Lithium
Valproate
Carbamazepine
Lamotrigine
Mood Stabilizers During Nursing
Anxiolytics and Hypnotics
Anxiolytics and Hypnotics in Pregnancy
Benzodiazepines
Pregabalin
Buspirone
Hypnotics
Anxiolytics During Nursing
Other Psychotropic Drugs
Other Psychotropics in Pregnancy
Cognitive Drugs
Anticholinergic Drugs
Disulfiram
Acamprosate
Methadone
Buprenorphine
Naltrexone
Modafinil
Stimulants (Methylphenidate, Amphetamine/Dextroamphetamine, Lisdexamfetamine)
Atomoxetine
Other Psychotropics During Nursing
Cross-References
References
Neuropsychopharmacotherapy in Children and Adolescents
Introduction
Stimulants and Non-stimulants for ADHD
Evidence for ADHD Medications
Management of ADHD Medication
Antidepressants for Anxiety, Affective, and Obsessive-Compulsive Disorders
Anxiety Disorders
Affective Disorders, Including Pediatric Major Depression
Obsessive-Compulsive Disorders
Selection and Dosing of Antidepressants
Therapy with Antipsychotics
Management Strategies with Antipsychotics
Cross-References
References
Infantile Spasms: Pharmacotherapy Challenges
Introduction
Spasms and Their Variants
EEG in the Infantile Spasm and West Syndromes
Neurodevelopmental Outcome
Etiopathogenesis
Classification
Structural-Metabolic Causes
Infectious-Immune Causes
Genetic Causes
Current Treatments
ACTH (Adrenocorticotropic Hormone, Corticotropin)
Corticosteroids
Vigabatrin (GVG, Gamma-Vinyl-GABA)
Combinatory Treatments
Second-Line and Emerging Treatments
Conclusions: What We Have and What We Need
Summary of Treatments
Mechanisms
Short-Term Requirements for Treatment of IS
Further Research and Its Complexity
Cross-References
References
Psychopharmacotherapy in Aged Patients
Developmental History
Pharmacology
Pharmacokinetics
Mechanism of Action
Indications (of Marketed Products)
Evidence-Based Data
Side Effects/Adverse Reactions and Toxicology
Combination Therapy: Interactions
References
Pharmacotherapy of Alzheimer´s Disease (AD) and Behavioral and Psychological Symptoms of Dementia (BPSD) in Frail Older Patien...
Pharmacotherapy in Frail Older Patients with AD/BPSD
Acetylcholinesterase Inhibitors
Antidepressants
Antipsychotics
Anti-convulsants
Conclusions
References
Management of Sexual Dysfunction in Neurodegenerative Diseases
Introduction
Parkinsonisms
Neurological Basis, Prevalence, and Gender Differences in Sexual Dysfunction
Dopaminergic Drug Effect on Sexuality
Sexual Assessment
Treatment of SD
Dementia
Inappropriate Sexual Behaviors in Dementias
Sexual and Marital Problems in Couples with Dementia
Diagnosis and Treatment of Sexual Problems and Inappropriate Sexual Behaviors in Dementia
Sexual Dysfunction in Amyotrophic Lateral Sclerosis
Conclusions
Cross-References
References
Clinical Problems of Drugs Used to Treat Movement Disorders
Introduction
Parkinson´s Disease (PD)
Levodopa
Levodopa/Carbidopa Intestinal Gel Infusion (LCIG)
Dopamine Agonists
Catechol-O-Methyltransferase Inhibitors (COMT Inhibitors)
Monoamine Oxidase Type B Inhibitors (MAO-B Inhibitors)
Dopamine Reuptake Inhibitors
Dopamine Receptor Agonists
Others
Anticholinergics
Glutamate Receptor Antagonists
Dystonia
Botulinum Toxin (BT)
Anticholinergics
GABAergics
Antidopaminergics
Anti-convulsants
Essential Tremor
Beta-Adrenergic Blockers (Beta-Blockers)
Anti-convulsants
Botulinum Toxin (BT)
Spasticity
Botulinum Toxin (BT)
Baclofen
Alpha-2 Agonists
Tolperisone
Dantrolene
Dyskinesias
Cross-References
References
Post-stroke Depression: Genetics, Mechanisms, and Treatment
Post-stroke Depression: Genetics, Mechanisms, and Treatment
Genetic Risk Factors of Post-stroke Depression
Biomarkers of Post-stroke Depression
Animal Models of Stroke
Treatment
Conclusion
Cross-References
References
Combination Therapies and Switching of Agents in Depression and Bipolar Disorders
Introduction
Major Depressive Disorder
Combination Therapies
Antidepressant Combinations
Combination of Antipsychotics and Antidepressants
Psychotic Depression
Switching of Antidepressants
Changing to SSRI or SNRI
Putative Mechanism of Action in Antidepressant Medication
Bipolar Disorder
Mania
Combination Therapies
Switching of Agents
Possible Mechanisms of Action
Bipolar Depression
Combination Therapies
Switching of Agents
Possible Mechanisms of Action
Conclusions
Cross-References
References
Pharmacotherapy of Alcohol Dependence: Treatment Readiness and Compliance Barriers
Introduction
Pharmacological Treatment of Alcohol Use Disorders
Adoption of Pharmacological Treatment of Alcohol Use Disorders
Barriers to Pharmacological Treatment for AUDs
Strategies to Improve Availability and Adherence of Pharmacological Treatment
Conclusion and Future Directions
Cross-References
References
Pharmacotherapy for Cocaine Use Disorders
Introduction
Epidemiology
Clinical Phenomenology
General Treatment Approach
Withdrawal
Reduction of Use and Relapse Prevention
Dopamine Agonist Treatment as a Substitution Therapy
Conclusion and Future Directions
Cross-References
References
Therapy of Withdrawal Syndromes, Addiction Disorders, and Substitution Therapies
Introduction
Pre-withdrawal Treatment
Typology According to Lesch
Reduction of the Amount of Drinking
Drugs for Withdrawal Treatment
Complications of Withdrawal
Delirium Tremens and Meta-Alcoholic Psychoses
Alcohol-Induced Wernicke-Korsakoff Syndrome (Type I, III, or IV Patients)
Relapse Prevention and Treatment of Dependence
Comparison of Acamprosate and Naltrexone (and Nalmefene)
Substitution Treatment for Alcohol
Summary
Cross-References
References
Pharmacotherapy of ADHD in Adults
Introduction
Stimulants
Methylphenidate
Amphetamines
Efficacy of Stimulants
Implementation of Stimulant Treatment
Adverse Effects and Contraindications of Stimulant Treatment
Non-stimulants
Atomoxetine
Efficacy of ATX
Implementation of ATX Treatment
Adverse Effects and Contraindications of ATX Treatment
Other Substances
Food Supplements, Homeopathic Substances, and Herbal Substances
Outlook
Cross-References
References
Antipsychotic Drug Prescription and Behavioral Problems in Individuals with Intellectual Disability
Introduction; Clinical Practice
Epidemiology of Antipsychotic Drug Use in Individuals with ID
Prevalence and Indications for Use
Adverse Events; Prevalence, Diagnostics, and Monitoring
Adverse Events and Behavioral Problems
Effectiveness of Antipsychotics for Behavioral Problems
Studies
Discontinuation Studies
Monitoring of Effect of Antipsychotics on Psychiatric and Behavioral Symptoms
Behavioral Problems in People with Intellectual Disability
Prevalence and Associated Factors
Diagnostics and Treatment
Choice of Medication
Conclusions and Recommendations
Cross-References
References
Forced Migration and Mental Health Care
Introduction
Forced Migration
Risk Factors and Stressors
Barriers and Challenges in the Mental Health-Care System
Aims and Implications for the Mental Health-Care System
Cross-References
References
Ketamine in Psychiatric Disorders
Chemistry and Developmental History
Pharmacology
Pharmacokinetics
Administration, Bioavailability, and Distribution
Metabolism
Mechanisms of Action
Central Effects of Ketamine on Microscale Level: Effects on Neurotransmission and Intracellular Pathways
Central Effects of Ketamine on Macroscale Level: Effects on Regional Activation Patterns, Neurometabolite Levels, and Connecti...
Indications and Potential Future Indication of Ketamine
Ketamine in Major Depressive Disorder
Intranasal (S)-ketamine in Treatment-Resistant Major Depressive Disorder
Off-Label Administration of Ketamine in Major Depressive Disorder
Predictors of Treatment Response
Ketamine in Major Depressive Episodes of Bipolar Disorder
Ketamine in Suicidality
Potential Indications of Ketamine in Anxiety Disorders
Posttraumatic Stress Disorder
Generalized Anxiety Disorder and Social Anxiety Disorder
Obsessive Compulsive Disorder
Side Effects/Adverse Reactions and Toxicology
Side Effects of Intravenous Racemic Ketamine
Side Effects of Intranasal (S)-ketamine
Comparison of Side Effect Profiles of (S)-, (R)-, and Racemic Ketamine
Side Effects in Long-Term Usage of Ketamine
Combination Therapy: Interactions
Cross-References
References
Index