Migraine Pain Management

Current Pharmacological and Non-pharmacological Options

1st Edition - October 24, 2024
Imprint: Academic Press
Editor: Stephen B. Shrewsbury
Language: English
Paperback ISBN:
9 7 8 - 0 - 4 4 3 - 2 4 7 0 5 - 7
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 2 4 7 0 4 - 0

Migraine Management: Current Pharmacological and Non-pharmacological Options is a comprehensive guide to established, recent, and ongoing pharmaceuticals and device developme… Read more

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Migraine Management: Current Pharmacological and Non-pharmacological Options is a comprehensive guide to established, recent, and ongoing pharmaceuticals and device development projects. The book provides detailed information on the historical developments of migraine pain management, druggable targets, drugs action mechanisms, drugs for acute treatment and preventive care of patients, administration routes, and alternative treatments. This is the ideal reference for academic researchers interested in anti-migraine pharmacology. It will also be a perfect reference for physicians and care professionals involved in the well-being of migraine patients.

Title of Book
Cover image
Title page
Table of Contents
Copyright
Contributors
Part I. Foundations and historical development of migraine pain management
Chapter 1. Introduction
1 Introduction
1.1 Global
1.2 United States
1.3 Europe
1.4 Japan
1.5 China and other (non European/American) countries
1.6 India
1.7 Africa
1.8 Latin America
2 Historical perspective
2.1 Early human history
2.2 Ancient Greece and Persia
2.3 Early second millennium
2.4 Late second millennium
3 Diagnosis
3.1 Migraine without aura
3.1.1 Diagnostic criteria
3.2 Migraine with aura
3.2.1 Diagnostic criteria
3.3 Chronic migraine
3.3.1 Diagnostic criteria
4 Genetics
5 Screening
6 Comorbidities
6.1 Psychiatric
6.2 Neurological
6.3 Gastrointestinal
6.4 Cardiovascular
6.5 Other medical issues
7 Migraine management—provision of care
8 Migraine advocacy
9 Pharmacotherapies
10 Non-pharmacological options
Chapter 2. Neuroanatomy and neurophysiology of migraine
1 Introduction
1.1 Mechanisms
1.1.1 Migraine initiation and premonitory symptoms
1.1.2 Aura phase
1.1.3 Headache phase
1.1.4 Peripheral sensitization
1.1.5 Intracellular signaling
1.1.6 Satellite glia and Schwann cells
1.1.7 Central sensitization
1.2 Further topics—a novel thought
1.2.1 Metabolic disturbances
1.2.2 Glymphatic system
1.2.3 Sex hormones
2 Conclusions
Chapter 3. Historical overview of migraine product development
1 Introduction
2 Academia
3 Industry
3.1 Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs)
3.2 Other nonspecific drug therapies useful for migraine management
3.3 Ergotamine (tartrate)
3.4 Dihydroergotamine (mesylate)
3.4.1 CMC issues
3.5 Sumatriptan
3.6 Other triptans
3.7 Botulinum toxin
3.8 Ditans
3.9 CGRP
3.10 AntiCGRP monoclonal antibodies
3.11 Gepants
4 Regulations
4.1 FDA
4.2 EMA
4.3 Japanese PMDA
4.4 ICH
4.5 Chinese NMPA
4.6 Indian CDSCO
4.7 Australian Therapeutic Goods Administration (TGA)
4.8 UK Medicines and Healthcare Regulatory Authority (MHRA)
4.9 Germany BfArM
4.10 Canada—Health Canada
4.11 Latin America
4.12 World Health Organization (WHO)
5 Nonpharmacological options
5.1 The role of smartphone apps (digital health)
5.2 Herbal medicines
5.3 Phototherapy
5.4 Neuromodulation
5.5 Acupuncture
5.6 Manual therapies
5.7 Nutraceuticals
5.8 Mindfulness
Chapter 4. Comorbidities in migraine
1 Introduction
2 Cerebral-cardiovascular comorbidity
2.1 White matter hyperintensities and infarct-like cerebral lesions
2.2 Patent foramen ovale (PFO)
2.3 Others
3 Psychiatric comorbidity
3.1 Obsessive compulsive disorder (OCD)
3.2 Major depressive disorder (MDD)
4 Metabolic disorders and migraine
4.1 Metabolic syndrome
4.2 Diabetes mellitus
4.3 Obesity
5 Other pain syndromes and migraine
5.1 Low back pain
6 Epilepsy and migraine
7 Sleep-related disorders and migraine
7.1 Sleep disordered breathing
7.2 Hypo-arousability
8 Gastrointestinal disorders and migraine
8.1 Periodontitis
8.2 Gastroesophageal reflux disease (GERD)
8.3 Helicobacter pylori disease
8.4 Gastrointestinal dysmotility
8.5 Inflammatory bowel disease (IBD)
9 Autoimmune disorders and migraine
9.1 Multiple sclerosis (MS)
9.2 Rheumatoid arthritis (RA)
9.3 Asthma
10 Discussion
11 Summary
Chapter 5. Not all migraine attacks are the same
1 Introduction
2 Interviewing a headache patient
2.1 Initial interview
2.2 Evaluating disability
3 Diagnosing different types of migraine
3.1 Migraine without aura
3.2 Migraine with aura
3.3 Menstrual migraine
4 Building a toolkit for different migraine attacks
4.1 Migraine without aura
4.2 Intolerance or contraindication to triptans
4.3 Triptan non-responders
4.4 Migraine with aura
4.5 Hemiplegic migraine
4.6 Nausea
4.7 Fast and slow onset
4.8 Late treatment/waking with migraine
4.9 Menstrual migraine
4.10 Pregnancy and lactation
4.11 Perimenopause
4.12 Mild to moderate headache
4.13 Intolerance or hypersensitivity to pharmacological options
4.14 Medication overuse headache
5 Discussion
6 Conclusion
Chapter 6. Challenges and controversies; pharmacokinetics, linguistics, semantics and statistics
1 Introduction
2 Controversies
2.1 Emerging practices and products
2.1.1 Adrenomedullin and amylin
2.1.2 Blockade of ATP-sensitive potassium channels
2.1.3 GLP-1 receptor agonists (semaglutide, exenatide, lixisenatide, liraglutide, dulaglutide)
2.1.4 Homeopathy
2.1.5 Hypnosis and hypnotherapy
2.1.6 Ketamine (intravenous)
2.1.7 Melatonin
2.1.8 Psilocybin and other classic psychedelics
2.1.9 Vasoactive intestinal polypeptide
3 Comorbidities
3.1 Angiomas (arterio-venous malformations and Sturge-Weber syndrome)
3.2 Autoimmune disease (including multiple sclerosis)
3.3 Behçet's disease
3.4 Chronic fatigue syndrome
3.5 Fibromyalgia
3.6 HaNDL syndrome
3.7 Hypothyroidism
3.8 Idiopathic intracranial hypertension (IIH)
3.9 Intracranial tumors
3.10 MELAS
3.11 Meniere's disease
3.12 Motion sickness
3.13 POTS (postural (orthostatic) tachycardia syndrome)
3.14 Restless leg syndrome
3.15 Sleep apnea
3.16 Summary of emerging comorbidities
4 Challenges
4.1 Clinical research
4.2 Biostatistics
4.2.1 Prespecification
4.2.2 Independent confirmation of results
4.2.3 Complexity issues
4.2.4 Missing data
4.2.5 Blinding and endpoints
4.2.6 Other issues
4.2.7 The ‘scandal’ of poor medical research
4.2.8 What treatment effects should we measure and for whom?
4.2.9 Heterogeneity of treatment effects (HTE)
4.2.10 HTE: N of 1 versus aggregate statistical analysis
4.2.11 HTE and migraine risk susceptibility phenotypes: Examples of individual (N of 1) versus aggregate analysis
4.2.12 Cause and effect: What types of evidence should we consider?
4.3 The causal revolution
4.3.1 Cause and effect: Beliefs and biases on the origin of migraine attacks (i.e., triggers and risk factors)
4.3.2 The trigger theory: Where did it come from, where did we go wrong and what's next?
4.4 Biomarkers and too much Bacon: The failure of reductionism in biomarker research
4.4.1 No biomarker
4.4.2 Medical reductionism
4.4.3 Less Bacon, more holism: Dynamic network biomarkers?
4.5 The placebo response
4.6 Pharmacokinetics (PK)
5 Summary
Part II. Druggable targets
Chapter 7. Calcitonin gene-related peptide (CGRP) and its role in migraine
1 Introduction
2 CGRP—the neuropeptide
2.1 CGRP -discovery and structure
2.2 Regulation of expression and neuropeptide release and metabolism
3 Expression of CGRP in the nervous system
3.1 The peripheral nervous system (PNS)
3.1.1 Sensory ganglia
3.2 The central nervous system
3.2.1 Brainstem
3.2.2 Forebrain
3.2.3 Cerebellum
4 CGRP receptor
4.1 Discovery and overview
4.2 Structure, activation, intracellular signaling, and recycling
4.3 Family of receptors
5 Migraine and CGRP
5.1 The role of the trigeminovascular system in migraine
5.2 Clinical evidence of the role of CGRP in migraine
5.3 CGRP and its effect in migraine
5.4 Peripheral role of CGRP—peripheral sensitization
5.5 Central sensitization and other central CGRP involvement
5.6 Cortical spreading depression
5.7 Photophobia
6 Targeted therapeutics
6.1 History of drug therapies
6.1.1 The gepants
6.1.2 CGRP monoclonal antibodies
7 Future direction and conclusion
Chapter 8. PACAP
1 Introduction
1.1 Pituitary adenylate cyclase-activating polypeptide: Discovery, receptors, and distribution
2 Mechanisms in migraine
2.1 Clinical studies
2.2 Preclinical studies
3 A novel target for the treatment of migraine
4 Summary
Chapter 9. Src family kinases (SFKs) in migraine
1 Introduction
1.1 Overview of Src family kinases characteristics
2 SFKs in migraine
2.1 Overview of migraine pathogenesis and existing therapy
2.2 SFKs in preclinical migraine models
2.2.1 SFKs in cortical spreading depolarization
2.2.2 SFKs in migraine-associated neuroinflammation
2.2.3 SFKs in mediating changes in cerebral blood flow
2.2.4 SFKs in migraine-related hypersensitivity
2.3 SFKs, a convergent hub in mediating migraine pain transmission
2.3.1 SFKs in migraine is partially TRPA1-dependent
2.3.2 SFKs couple to P2X7 receptor-Panx1 complex
2.3.3 SFKs couple to NMDA receptor/Panx1 complex
2.4 SFKs inhibition potential for clinical migraine therapy
2.5 Challenges and future perspective
2.6 Conclusion
Abbreviations
Chapter 10. Delta opioid receptor system
1 Introduction
2 The opioid system
3 δOR distribution
4 δOR modulation of migraine
4.1 δOR Modulation of migraine with aura
4.2 Migraine regulation by peripheral and central δOR
4.3 Dynamic regulation of δOR
5 Clinical trials with δOR agonists
6 Conclusion
Chapter 11. Piezo channels in peripheral trigeminal nociception
1 Introduction
2 Structure of piezo channels
3 Analyzing functional attributes and distinct contributions of Piezo1 and Piezo2 in nociception
4 Mechanisms of mechanotransduction of the piezo channels in migraine pathology
5 Important agonists of piezo channel
5.1 Yoda1
5.2 Jedi1/2
6 Therapeutic interventions in attenuating migraine pain: Modulation of piezo channels
7 Innovative anti-migraine therapies targeting heterogeneous ion channels via prevention of endocannabinoid hydrolysis
8 Nociceptive signaling involving interaction of endocannabinoids with TRP1 receptors
9 Modulation of endogenous cannabinoids (EndoCBs) in nociception
10 Summary
List of abbreviations
Chapter 12. TRP channel antagonists
1 Introduction
1.1 TRP channels in the peripheral and central nervous system
1.2 Molecular identification of TRP channels
1.3 Selected TRP channels as targets for the treatment of human migraine
2 TRP channels in migraine and the trigeminovascular system
2.1 TRPA1 as a receptor for environmental migraine triggers
2.2 TRP channels and processing of negative emotions and pain in the amygdala
2.3 TRP channels and photophobia
2.4 TRP channels and cortical spreading depression
2.5 TRP channels and white matter lesions in migraine
2.6 GWAS and PheWAS studies in migraine
2.7 TRP channel expression
2.7.1 TRPM8
2.7.2 TRPV1
2.7.3 TRPA1
2.7.4 TRPC4
2.7.5 TRPC5
2.7.6 TRPM3
2.7.7 TRP channel drug discovery
3 TRPM8 antagonists
4 TRPV1 antagonists
5 TRPA1 antagonists
6 TRPC4/5 antagonists
7 TRPM3 antagonists
8 Conclusions
Part IIIa. Drugs—acute management
Chapter 13. Simple analgesics and combination oral products
1 Introduction
2 Acetaminophen/paracetamol
3 Aspirin
4 Ibuprofen
5 Naproxen
6 Diclofenac
7 Ketorolac
8 Indomethacin
9 Celecoxib
10 Acetaminophen/aspirin/caffeine
11 Butalbital/Fioricet
12 Summary
Chapter 14. Medical cannabis and cannabinoids
1 Introduction to the endocannabinoid system (ECS): A crucial regulator of homeostasis
1.1 Role of the ECS in pain management
2 Phytocannabinoids and endocannabinoids
2.1 Definition of phytocannabinoids and differences from endocannabinoids
2.2 Phytocannabinoid historical medicinal use
2.3 Overview of major phytocannabinoids and their properties
2.4 Phytocannabinoid interaction with the ECS
2.5 Phytocannabinoids' modulation of pain perception
3 The ECS and migraine pathogenesis
3.1 The role of astrocytes and neuroinflammation in migraine pain modulation
3.2 The role of anandamide in migraine pain modulation
3.3 ECS involvement in migraine pathogenesis
3.4 The potential of cannabinoids in managing migraines
3.5 Role of cannabidiol (CBD) in astrocyte modulation
4 Therapeutic use of medical cannabis in migraines: Current evidence
4.1 Effectiveness of medical cannabis in reducing migraine symptoms
4.2 Patient experiences and perspectives on medical cannabis for migraines
4.3 Efficacy and safety of medical cannabis in migraine treatment
5 Medical cannabis dosing and safety considerations
5.1 Medical cannabis safety: COMPASS study
5.2 Dosing and administration of medical cannabis
5.2.1 Medical cannabis dosing guidelines
5.3 Quick overview of consensus based recommendations
5.4 Latest clinical practice guidelines
5.4.1 Clinical trials on dosing regimens
5.4.2 Real-world evidence and observational studies
6 Clinical approach to medical cannabis prescribing in migraine
7 Legal and regulatory framework for cannabinoid authorizations
7.1 Uruguay
7.2 Canada
7.3 United States (USA)
7.4 United Kingdom (UK)
7.5 Australia
8 Future directions
9 Summary
Chapter 15. Ergots
1 Introduction
2 DHE
2.1 Pharmacokinetic profile of DHE and ergotamine
2.2 Pharmacodynamic profile of DHE
2.3 Pharmacologic comparison with ergotamine
2.4 Safety and tolerability comparison between DHE and ergotamine
2.5 Efficacy, safety and tolerability of DHE by route of administration
2.5.1 Inhaled DHE
2.5.2 IM and SC DHE in adults
2.5.3 IV DHE in adults
2.5.4 IV DHE in pediatrics
2.5.5 DHE in outpatient infusion centers
2.5.6 DHE in pregnancy
2.5.7 Other uses of DHE
3 Other ergots and their indications
3.1 Ergotamine
4 Methysergide
5 Methylergonovine
6 Ergonovine
7 Lysergic acid diethylamide
8 Bromocriptine
8.1 Parkinson disease
8.2 Endocrine indications
8.2.1 Type 2 diabetes mellitus
9 Conclusion
Chapter 16. Triptans
1 Introduction
2 Sumatriptan
2.1 Subcutaneous sumatriptan
2.2 Oral sumatriptan formulations
2.2.1 Sumatriptan-naproxen
2.3 Nasal spray sumatriptan formulations
2.3.1 Sumatriptan nasal powder
2.3.2 Intranasal sumatriptan coformulated with DDM (Tosymra)
2.4 Sumatriptan transdermal electrophoresis patch (Zecuity)
2.5 Rectal sumatriptan
2.6 Sumatriptan: Safety in pregnancy
2.7 Sumatriptan safety
2.8 Serotonin syndrome
2.9 Sumatriptan conclusions
3 Zolmitriptan
3.1 Dosing and formulations
3.2 Pharmacokinetics
3.2.1 Tablets
3.2.2 Oral formulation
3.2.3 Orally disintegrating table
3.2.4 Nasal formulation
3.3 Migraine acute therapy clinical trial data
3.3.1 Pain freedom at 2h
3.3.2 Headache relief at 2h
3.3.3 Comparison with other active comparators
3.3.4 Sustained pain relief at 24h
3.4 Adverse events
3.5 Other indications
3.5.1 Menstrual migraine prevention
3.5.2 Cluster headache acute therapy
3.6 Zolmitriptan conclusions
4 Naratriptan
4.1 Naratriptan conclusions
5 Rizatriptan
5.1 Rizatriptan pharmacokinetics
5.2 Rizatriptan efficacy
5.3 Rizatriptan safety
5.4 Rizatriptan conclusions
6 Almotriptan
6.1 Almotriptan pharmacokinetics
6.2 Almotriptan dosing
6.3 Almotriptan safety
6.4 Almotriptan efficacy
6.5 Almotriptan summary
7 Eletriptan
7.1 Eletriptan pharmacokinetics
7.2 Eletriptan safety and efficacy
7.3 Eletriptan conclusions
8 Frovatriptan
8.1 Frovatriptan safety
8.2 Frovatriptan efficacy
8.3 Frovatriptan - other indications
8.4 Frovatriptan summary
9 Triptan comparison data
Chapter 17. Beta blocker (timolol) eye drops
1 Introduction
2 Migraine pathophysiology
3 Migraine management
3.1 Beta-blockers in migraine
3.2 Oral timolol as prophylactic migraine treatment
3.3 Ophthalmic timolol and migraines
3.3.1 Ophthalmic timolol pharmacokinetics
3.3.2 Ophthalmic timolol for migraine treatment
3.3.3 Ophthalmic timolol side effects
3.3.4 Study limitations
4 Conclusions
Chapter 18. Lasmiditan (and the ditan class)
1 Introduction: Migraine
2 Serotonin
3 5-HT1F receptor as a pharmacological target in migraine
4 Lasmiditan
4.1 Phase 1 clinical trials
4.2 Phase II clinical trials
4.3 Phase III clinical trials
4.4 Other trials
4.4.1 GLADIATOR (long term open label)
4.4.2 CENTURION (consistency of effect)
5 Lasmiditan: Mechanism of action and limitations
5.1 Driving performance
5.2 Lasmiditan and CGRP
6 Conclusion
Chapter 19. Gepants
1 Introduction
2 Trigeminovascular system
3 CGRP signaling
4 Gepants, CGRP receptor antagonists
5 Gepants for acute treatment of migraine attacks
5.1 Ubrogepant
5.2 Rimegepant
5.3 Zavegepant
6 Gepants for prophylaxis in migraine
6.1 Rimegepant
6.2 Atogepant
7 Conclusion
Part IIIb. Drugs—prevention
Chapter 20. Antidepressants, Antihypertensives & others
1 Introduction
2 Candesartan
3 Flunarizine
4 Serotonin-norepinephrine reuptake inhibitors (SNRIs)
5 Tricyclic antidepressants (TCAs)
6 Beta blockers
6.1 Propranolol
6.2 Metoprolol
6.3 Timolol
7 Conclusion
Chapter 21. Anti-seizure medications for the management of migraine
1 Introduction - Overview of the antiseizure medications for migraine prevention
2 Topiramate (Topamax) TPM
2.1 Adverse effects and managements
2.2 Combination therapy
3 Valproic acid/divalproex sodium (Depakote)-VPA
4 Gabapentin and Pregabalin (Lyrica)
4.1 Mechanism of action
5 Levetiracetam (Keppra)
5.1 Mechanism of action
5.2 Common adverse effects
6 Zonisamide (Zonagran)
6.1 Mechanisms of action
6.2 Adverse effects
7 Lacosamide (Vimpat)
7.1 Mechanism of action
7.2 Adverse effects
8 Lamotrigine (Lamictal)
8.1 Adverse effects
9 Carbamazepine (Tegretol) and oxcarbazepine (Trileptal)
9.1 Mechanism of action
9.2 Adverse effects
10 Acetazolamide (Diamox)
10.1 Mechanism of action
10.2 Adverse effects
11 Perampanel (Fycompa)
11.1 Mechanism of action
11.2 Adverse effects
12 Carisbamate
13 Vigabatrin (Sabril)
13.1 Mechanism of action
13.2 Adverse effects
14 Tiagabine (Gabitril)
14.1 Mechanism of action
15 Phenobarbital
15.1 Mechanism of action
16 Phenytoin (Dilantin)
16.1 Mechanism of action
17 Summary
Chapter 22. OnabotulinumtoxinA
1 Introduction
3 Mechanism of action
4 Clinical trials
4.1 Early studies
4.1.1 Tension type headache
4.1.2 Migraine
4.1.3 Phase 3 - PREEMPT program
4.1.4 PREEMPT analyses and clinical assessment of OnabotulinumtoxinA
4.1.5 Medication overuse
4.1.6 Migraine-specific quality of life
4.1.7 HIT-6
4.1.8 COMPEL
4.1.9 The FORWARD study
4.1.10 Predicting response to onabotA
5 Issues in clinical practice
5.1 Wearing off
5.2 Dose selection
5.3 Immunogenicity
5.4 Special populations
5.4.1 Pregnancy and lactation
5.4.2 Adolescent migraine
6 PREEMPT injection methodology
6.1 Possible improvements of injection locations
6.2 Different injection techniques
6.3 Cranial suture injections
6.4 Discontinuation of treatment
7 Practice management
8 Summary
Chapter 23. Gepants (for prevention)
1 Introduction
2 Pharmacology
3 Atogepant
3.1 Pharmacokinetics and pharmacodynamics
3.2 Indications and dosing
3.3 Drug interactions
3.4 Clinical trials
4 Rimegepant
4.1 Pharmacokinetics and pharmacodynamics
4.2 Indications and dosing
4.3 Drug interactions
4.4 Clinical trials
5 Applications to clinical practice
Chapter 24. (CGRP) Monocloncal antibodies
1 Introduction
2 Mechanism of action and pharmacological features
2.1 Pharmacological overview
2.1.1 Erenumab
2.1.2 Galcanezumab
2.1.3 Fremanezumab
2.1.4 Eptinezumab
3 Registrational RCTs
3.1 Episodic migraine prevention
3.1.1 Erenumab
3.1.2 Fremanezumab
3.1.3 Galcanezumab
3.1.4 Eptinezumab
3.2 Chronic migraine prevention
3.2.1 Erenumab
3.2.2 Fremanezumab
3.2.3 Galcanezumab
3.2.4 Eptinezumab
3.3 Patients with previous experience of ineffective therapies
3.3.1 Erenumab
3.3.2 Fremanezumab
3.3.3 Galcanezumab
3.3.4 Eptinezumab
3.4 Open-label extension studies
3.4.1 Erenumab
3.4.2 Fremanezumab
3.4.3 Galcanezumab
3.4.4 Eptinezumab
3.5 Other outcomes of efficacy
3.5.1 Medication overuse
4 Prognostic factors
4.1 Obesity
4.2 Autonomic symptoms
4.3 Triptan response
4.4 Medication overuse
4.5 Anxiety and depression
4.6 Biomarkers
5 Tolerability and side effects
5.1 Local reactions
5.2 Gastrointestinal effects
5.3 Anti-vasodilatory properties
5.4 Weight changes
6 Specific migraine populations
6.1 Aura
6.2 Elderly
6.3 Pregnancy
6.4 Discontinuation and resumption
7 Strategies in non-responders
7.1 Add-on
7.2 Switching therapies
8 Conclusions
Part IV. Administration routes
Chapter 25. Oral drug delivery in migraine: Advantages and disadvantages
1 Introduction
2 Advantages and disadvantages of oral dosing
3 Physiologic factors in oral drug absorption
3.1 pH of luminal fluids
3.2 Gastric emptying and small intestinal transit time
3.3 Regional variation in the intestinal membrane
3.4 Volume of GI fluids
3.5 Bile salts and pancreatic enzymes
3.6 Microbiome
3.7 Age, sex, race
3.8 Weight
3.9 Food
3.10 GI effects of migraine
4 The need for alternatives
4.1 Oral liquid formulations
4.2 The SMEDDS technology
5 Celecoxib oral solution
5.1 Pharmacokinetics
5.2 Efficacy
5.3 Safety and tolerability
6 Summary and conclusions
Chapter 26. Nasal and orally inhaled therapies for acute treatment of migraine
1 Introduction
2 Devices
3 Nasal anatomy and respiratory physiology
4 Inhaled therapies for acute migraine
4.1 Nonsteroidal anti-inflammatory drugs
4.1.1 SPRIX (ketorolac tromethamine)
4.1.2 ROX-828 (ketorolac with lidocaine)
4.2 Ergots
4.2.1 Dihydroergotamine
4.3 Triptans
4.3.1 Sumatriptan formulations
4.4 Calcitonin gene-related peptide (CGRP) receptor blocker
4.4.1 ZAVZPRET (Zavegepant)
4.5 Opiates
4.5.1 STADOL nasal spray (butorphanol)
4.6 Antipsychotics
4.6.1 Loxapine
4.6.2 Prochlorperazine
5 Comparison of nasal formulations of drugs approved for treatment of acute migraines
6 Summary
7 Conclusion
Chapter 27. Subcutaneous/IM/transcutaneous (“injectables”)
1 Introduction
2 Dihydroergotamine
2.1 Inpatient use
2.2 Preliminary studies and pharmacokinetics
2.3 Outpatient use and comparison of DHE with sumatriptan
3 Subcutaneous sumatriptan
3.1 Program overview
3.2 Pharmacokinetics
3.3 Placebo-controlled efficacy studies
3.4 Adverse event considerations
3.5 Efficacy compared to other routes of administration
3.6 Novel delivery systems/dosage for sumatriptan
3.7 Dosage reduction
4 Zolmitriptan microneedle patch system
4.1 Rationale and system design
4.2 Pharmacokinetics
4.3 Placebo-controlled trial
4.4 Comparison with contemporary trials of similar design
4.5 Long term safety of microneedle systems
5 Discussion/conclusions of injectable migraine products
Chapter 28. Acute intravenous infusions for migraine
1 Introduction
2 General approach to outpatient infusion
3 Intravenous neuroleptics
3.1 Extrapyramidal symptoms
3.2 Diphenhydramine
3.3 Intravenous promethazine
3.4 Intravenous metoclopramide
3.5 Intravenous prochlorperazine
3.6 Intravenous droperidol
3.7 Intravenous chlorpromazine
3.8 Intravenous haloperidol
4 Intravenous dihydroergotamine
5 Intravenous ketorolac
6 Intravenous corticosteroids
7 Intravenous valproate sodium
8 Intravenous magnesium
9 Hospitalization for migraine infusion therapy
10 Criteria for inpatient hospitalization for migraine
10.1 Concern for secondary headache
10.2 Refractory migraine
10.3 Contraindication to outpatient treatment
10.4 Inpatient monitoring
11 Intravenous lidocaine
12 Intravenous ketamine
13 Summary
Part V. Alternative management (non-pharmacological options)
Chapter 29. The role of digital platforms and smartphone apps
1 Introduction
2 History
2.1 Digital diaries (2009–2012)
2.2 Advanced tracking and analytical insights (2012–2022)
2.3 Telehealth integration and biofeedback (2015–present)
2.4 Personalized treatment and preventative care (2018–present)
3 Current digital technology
4 Collecting patient data: The digital (r)evolution
4.1 Digital diaries: Early applications and observations on use
4.2 Challenges of digital data entry
5 Analytics: “Big” versus “little” data
5.1 Availability of larger, highly diverse data: Big data
5.2 Enabling individualized data: “Little data” and precision medicine
6 Clinical trials versus real world studies
6.1 A new analytical opportunity through continuous data capture in the real world
7 Toward improved migraine management
7.1 Factors associated with migraine attack occurrence
7.2 Menstruation as a reference trigger?
7.3 Broad-spectrum trigger studies
7.4 Is stress really a migraine trigger?
7.5 Is alcohol really a migraine trigger?
7.6 Migraine attack prediction
7.7 Tracking therapeutic effectiveness
7.8 Tracking medication use: Avoiding overuse
7.9 Monitoring migraine progression
7.10 Emergence of digital biomarkers
7.11 Diagnostic biomarkers
7.12 Monitoring biomarkers
7.13 Prognostic biomarkers
7.14 Therapeutic responder biomarkers
8 Emergence of digital interventions (DTx)
9 Summary
9.1 What's next?
Chapter 30. Herbal medicines
1 Introduction
2 Topical Capsicum annuum and capsaicin
3 Zingiber officinale (ginger) and other pungent herbs
4 Other topical pungent herbal remedies
5 Nonpungent topical herbs
6 Coriander and herbal formulations
7 Cannabis sativa (cannabis)
8 Feverfew: Famous or flop?
9 Butterbur
10 Ginkgo biloba
11 Menstrual migraines
12 Conclusion
Chapter 31. Phototherapy
1 Introduction
1.1 Emergence of phototherapy
1.2 Types of phototherapies
2 Retinal-brain circuitry
2.1 Photosensitive cells in the retina
2.2 Neural pathways: Retina to brain
3 Management of migraine
3.1 Photoneuromodulation
3.1.1 Migraine relief: Photoneuromodulation's emerging role
3.1.2 Visual pathway in migraine
3.1.3 Managing migraine via the visual pathway
3.2 Pain management
3.2.1 Therapy
3.2.2 Photoneuromodulation circuitry
3.3 Photoneuromodulation, a comprehensive approach
3.3.1 Migraine comorbidities
3.3.2 Sleep and circadian rhythms
3.3.3 Depression and anxiety
3.3.4 Cognition
4 Future technologies
4.1 The importance of models
4.2 A need for characterization and optimization
4.3 Devices in development
5 Summary
Chapter 32. Neuromodulation
1 Introduction
2 Invasive neuromodulation
2.1 Suboccipital stimulation with implanted stimulator
2.1.1 Mechanism and application
2.1.2 Supporting studies
2.1.3 Clinical considerations
2.2 Sphenopalatine ganglion stimulation
2.2.1 Mechanism and application
2.3 Spinal cord stimulation
2.3.1 Mechanism and application
2.3.2 Supporting studies
2.3.3 Clinical considerations
2.4 Deep brain stimulation
2.4.1 Mechanism and application
3 Noninvasive
3.1 Noninvasive vagal nerve stimulation
3.1.1 Mechanism and application
3.1.2 Supporting studies
3.1.3 Clinical considerations
3.2 Transcutaneous supraorbital nerve stimulation (external trigeminal nerve stimulation)
3.2.1 Mechanism and application
3.2.2 Supporting studies
3.2.3 Clinical considerations
3.3 Combined occipital and trigeminal nerve stimulation
3.3.1 Mechanism and application
3.3.2 Supporting studies
3.3.3 Clinical considerations
3.4 Remote electrical neuromodulation (REN)
3.4.1 Mechanism and application
3.4.2 Supporting studies
3.4.3 Clinical considerations
3.5 Auricular transcutaneous vagus nerve stimulator (NEMOS/VITOs)
3.5.1 Mechanism and application
3.5.2 Supporting studies
3.5.3 Clinical considerations
3.6 Single pulse transcranial magnetic stimulation
3.6.1 Mechanism and application
3.6.2 Supporting studies
3.6.3 Clinical considerations
3.7 Repetitive transcranial magnetic stimulation
3.7.1 Mechanism and application
3.7.2 Supporting studies
3.7.3 Clinical considerations
3.8 Transcranial direct current stimulation
3.8.1 Mechanism and application
3.8.2 Supporting studies
3.8.3 Clinical considerations
4 Conclusion
Chapter 33. Acupuncture (for episodic and chronic migraine)
1 Introduction of acupuncture
2 Understanding of migraine in traditional Chinese medicine
2.1 Excessive liver fire
2.2 Qi stagnation and blood stasis
2.3 Liver depression and qi stagnation
2.4 Liver and kidney yin deficiency
3 Evidence for acupuncture for the prevention of migraine
3.1 Evidence for acupuncture for the prevention of migraine compared with conventional medications
3.1.1 Effects of acupuncture on the prevention of migraine
3.1.2 Effects of acupuncture on mental health of migraine
3.2 Evidence for acupuncture for the prevention of migraine compared with non-treatment/sham acupuncture
3.2.1 Effects of acupuncture on the prevention of migraine
3.2.2 Effects of acupuncture on mental health of migraine
3.2.3 Effects of acupuncture on the prevention of menstrual migraine
4 Evidence for acupuncture for the treatment of migraine episode
4.1 Evidence for acupuncture for the treatment of migraine in attack stage compared with conventional medications
4.2 Evidence for acupuncture for the treatment of migraine in attack stage compared with non-treatment/sham acupuncture
5 Clinical practice guidance
5.1 Basic principles for acupuncture treatment of migraine
5.1.1 Intervention by stages
5.1.2 Focus on prevention treatment
5.1.3 Treating mental and physical simultaneously
5.2 Implementation
5.2.1 Attention to laws and regulations
5.2.2 Attentions of implementation institutions
5.2.3 Attention of practitioners
5.2.4 Patient-related precautions
5.3 Clinical practice guidance to acupuncture treatment for the prevention of migraine
5.3.1 Basic guidance
5.3.2 Clinical practice guidance to acupuncture prophylactic treatment of migraine with the comorbidity of depression/anxiety
5.3.3 Clinical practice guidance to acupuncture prophylactic treatment of migraine with analgesic dependence
5.3.4 Clinical practice guidance to acupuncture prophylactic treatment of menstrual migraine and menstrual-related migraine
5.4 Clinical practice guidance to acupuncture treatment of migraine in attack stage
5.4.1 Basic guidance
5.4.2 Clinical practice guidance to acupuncture treatment of menstrual migraine patients and menstrual-related migraine patients in attack stage
6 Summary
Chapter 34. Manual therapies
1 Introduction
2 Visible upper cervical pathology in cervicogenic headache and migraine
3 The emergence of the trigeminocervical complex
4 Anesthetic blocks: The “benchmark” of cervical relevancy?
4.1 Upper cervical spine
4.1.1 C2-3 zygapophyseal joint
4.1.2 C2-3 intervertebral disc
4.2 Greater occipital nerve
4.3 Occipital nerve stimulation
5 Replicating characteristic head pain
6 Manual cervical reproduction and resolution
7 Patterns and characteristics of one-sided head pain
8 Summary
Chapter 35. Nutraceuticals and diets
1 Introduction
2 Metabolic enhancers
2.1 Riboflavin and its combinations
2.1.1 Riboflavin
2.1.2 Riboflavin combinations
2.2 Combination of B vitamins
2.3 Vitamin D3
2.4 Coenzyme Q10 (ubiquinone)
2.5 Alpha-lipoic acid
2.6 Magnesium
2.7 l-Carnitine
2.8 Combinations
3 Substrate-based treatments
3.1 Diets
3.2 Omega-3
4 Conclusions
Chapter 36. Mindfulness
1 Mindfulness
1.1 What is mindfulness?
1.2 Origins of mindfulness
1.3 Mindfulness interventions
2 Mindfulness and Pain
2.1 Components of pain
2.1.1 Sensation
2.1.2 Cognition
2.1.3 Affect
2.2 How does mindfulness address pain?
3 Existing mindfulness literature
3.1 Short-term mindfulness meditation
3.1.1 Clinical symptoms
3.1.2 Brain structure and function
3.2 Long-term mindfulness meditation for migraine
3.2.1 Clinical symptoms
3.2.2 Brain structure and function
3.2.3 Patient perspectives
4 Unraveling the mechanisms of meditation
4.1 Current research
4.2 Future research
5 Integrating mindfulness into migraine management
5.1 Which patients might benefit from mindfulness?
5.2 How can patients get involved in mindfulness?
Part VI. Summary and conclusion
Chapter 37. Final perspectives
1 Introduction
2 Part 1
3 Part 2
4 Part 3a
5 Part 3b
6 Part 4
7 Part 5
8 Summary
Index

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Stephen B. Shrewsbury

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