Migraine Types & Medications

Class:

Selective serotonin receptor agonist (5-HT₁B/₁D agonist)

Mechanism of Action:

• Vasoconstriction: Activates 5-HT₁B receptors on cranial blood vessels → constricts dilated vessels
• Presynaptic inhibition: Activates 5-HT₁D receptors on trigeminal nerve terminals → blocks release of CGRP and substance P
• Blocks pain transmission: Inhibits trigeminal nucleus in brainstem

Sarah's Experience:

Works well for acute attacks but was using too frequently (medication overuse headache risk with >10 days/month use).

Forms Available:

Oral, nasal spray, subcutaneous injection (fastest onset ~10 min)

Contraindications:

• Ischemic heart disease, uncontrolled hypertension
• Hemiplegic or basilar migraine
• Within 24 hours of ergotamines or other triptans

Class:

Non-selective beta-adrenergic antagonist (β₁ and β₂ blocker)

Mechanism of Action:

• Blocks β-receptors: Prevents norepinephrine/epinephrine (catecholamines) from binding
• Reduces neuronal excitability: Decreases sympathetic nervous system activation
• Stabilizes blood vessels: Prevents excessive dilation
• Modulates serotonin: May affect 5-HT receptor sensitivity

Sarah's Experience:

Reduced migraine frequency from 4/week to 2/week, but caused exercise intolerance (blocks β₂ receptors in lungs and skeletal muscle → bronchoconstriction, reduced cardiac output).

Why Sarah Stopped:

As a graphic designer who enjoys running, the exercise intolerance was unacceptable. Side effect worse than benefit.

Other Uses:

Hypertension, angina, performance anxiety, essential tremor

Class:

Anticonvulsant with multiple mechanisms of action

Mechanism of Action (Multi-Modal):

• Blocks voltage-gated Na⁺ channels: Prevents excessive neuronal firing (reduces action potential frequency)
• Enhances GABA-A receptors: Opens Cl⁻ channels → hyperpolarization → more IPSPs → inhibitory effect
• Blocks AMPA/kainate glutamate receptors: Reduces excitatory transmission (fewer EPSPs)
• Inhibits carbonic anhydrase: May contribute to migraine prevention

Sarah's Experience:

Reduced migraines from 2/week to 1/week, BUT significant cognitive side effects ("brain fog," word-finding difficulty) earned it the nickname "Dopamax."

Why Sarah Stopped:

Cognitive impairment unacceptable for someone whose career requires creativity and clear thinking.

Common Side Effects:

Paresthesias (tingling), weight loss, kidney stones, cognitive slowing

Class:

Anticonvulsant, structurally related to GABA but doesn't bind GABA receptors

Mechanism of Action:

• Blocks presynaptic voltage-gated Ca²⁺ channels: Binds to α₂δ subunit of Ca²⁺ channels on presynaptic terminals
• Reduces Ca²⁺ influx: Less calcium enters presynaptic terminal when action potential arrives
• Fewer vesicles fuse: Reduced Ca²⁺ means less neurotransmitter release (glutamate, substance P, CGRP)
• Net effect: Decreases excitatory neurotransmission, reduces neuronal hyperexcitability

Sarah's Experience:

Reduced migraines to 1-2/month with tolerable side effects. Much better cognitive profile than topiramate.

Advantages:

• Generally well-tolerated
• Minimal cognitive side effects
• Also treats neuropathic pain
• Can be used with other preventives

Common Side Effects:

Dizziness, somnolence, peripheral edema (usually mild)

Class:

Monoclonal antibodies targeting CGRP pathway

Mechanism of Action:

Two approaches:

• Anti-CGRP antibodies (fremanezumab, galcanezumab): Bind to CGRP neuropeptide itself → prevents CGRP from binding to its receptor
• Anti-CGRP receptor antibodies (erenumab): Bind to CGRP receptor → blocks CGRP from activating receptor

Result: Blocks neurogenic inflammation, reduces vasodilation, decreases pain transmission in trigeminovascular system

Sarah's Experience:

Combined with gabapentin, reduced migraines to 1 every 2 months. Game-changer for quality of life.

Administration:

Monthly or quarterly subcutaneous injection. Must be given by injection because antibodies are proteins (would be digested if taken orally).

Advantages:

• Highly specific mechanism
• Minimal side effects
• No cognitive impairment
• No drug interactions

Disadvantages:

Expensive (~$600-700/month), requires injection, insurance may require failure of other preventives first

Class:

Nonsteroidal Anti-Inflammatory Drugs

Mechanism of Action:

• Inhibits COX enzymes: Blocks cyclooxygenase (COX-1 and COX-2)
• Reduces prostaglandin synthesis: Prostaglandins cause inflammation, vasodilation, and sensitize nociceptors to pain
• Decreases neurogenic inflammation: Reduces inflammatory cascade in trigeminovascular system
• Anti-inflammatory + analgesic: Reduces both inflammation and pain perception

Use in Migraine:

• Acute treatment: Mild to moderate migraines, especially early in attack
• Preventive use: Menstrual migraine (naproxen 2-3 days before expected migraine)
• Combination therapy: Often combined with triptans or antiemetics

Common Examples:

• Ibuprofen (Advil, Motrin): 400-800 mg
• Naproxen (Aleve): 500-550 mg
• Aspirin: 900-1000 mg

Cautions:

Medication-overuse headache if used >15 days/month. GI side effects, cardiovascular risk with chronic use.

Class:

Botulinum toxin type A

Mechanism of Action:

• Blocks acetylcholine release: Cleaves SNAP-25 protein needed for vesicle fusion at neuromuscular junction
• In migraine prevention: Also blocks release of pain neurotransmitters (CGRP, substance P, glutamate) from peripheral nerve terminals
• Prevents peripheral sensitization: Blocks pain signals before they reach central nervous system
• Reduces muscle tension: Relaxes pericranial muscles (secondary benefit)

FDA Approved For:

Chronic migraine only (≥15 headache days/month with ≥8 migraine days/month)

Administration:

• 31 injections across 7 head/neck muscle areas
• Every 12 weeks (quarterly)
• Effect begins ~10-14 days, peaks ~1 month
• May take 2-3 treatment cycles for full benefit

Evidence:

Reduces migraine days by 8-9 days/month in chronic migraine patients. Not effective for episodic migraine.

Side Effects:

Neck pain, muscle weakness, injection site reactions. Rare: dysphagia, ptosis