Chronic Migraine (CM)

Definition

• Headaches on 15 or more days per month (tension-type and/or migraine character)
• In a patient with a prior history of migraine
• With at least 8 of those days per month meeting migraine criteria
• For at least 3 consecutive months

Epidemiology

• Patients with episodic migraine transition to CM at approximately 2.5% per year.
• On average, people with CM have 22 headache days per month.
• An estimated 7.5% of patients with episodic migraine will meet CM criteria at least once within a 15-month period.
• CM typically begins in the second or third decade of life as episodic migraine, then progresses.
• The evolution from episodic to chronic migraine is gradual in the majority, but abrupt in ~30% of patients. - Bradley and Daroff's Neurology in Clinical Practice

Risk Factors for Developing CM

• High baseline attack frequency (the strongest predictor)
• Obesity
• Stressful life events
• Snoring (likely via sleep disruption)
• Cutaneous allodynia (increased skin sensitivity)
• Overuse of opioids or barbiturate combination products (a major modifiable risk factor)
• Coexistent sleep disorders and mood disorders (depression, anxiety) can worsen the underlying condition

Clinical Features

• On some days, headaches retain classic migraine features (throbbing pain, nausea, photophobia, phonophobia).
• On other days, symptoms are indistinguishable from tension-type headache.
• These patients do NOT have "mixed" or "combined tension-vascular headaches" - that is an outdated term.
• CM frequently coexists with Medication Overuse Headache (MOH), which must be identified and managed simultaneously.

Secondary Causes to Exclude ("Red Flags")

• Progressively worsening headaches over < 3 months
• New neurological symptoms or focal signs
• Papilledema
• Headaches provoked by Valsalva (cough, sneeze)
• Positional headaches (upright or supine relief/worsening)
• Systemic symptoms (fever, weight loss, myalgias)
• Thunderclap/sudden-onset headache
• Onset after age 50

Treatment

Preventive Treatments (Evidence-Based)

Other Preventives (Less Rigorous Evidence, Frequently Used)

• Gabapentin
• Divalproex sodium (valproate)
• Amitriptyline
• Beta-adrenergic blockers

Acute Treatment Caution

• Patients with CM must limit acute medication use to prevent development of Medication Overuse Headache (MOH), which can perpetuate the cycle of chronification.

Recent Evidence (2024-2026)

• A network meta-analysis (PMID 40011869) compared strategies for medication-overuse headache (a major CM complication).
• IHS evidence-based guidelines (PMID 41117312) now cover non-invasive neuromodulation devices (e.g., transcranial magnetic stimulation) as acute and preventive migraine treatments.
• A 2025 meta-analysis on migraine-related disability (PMID 41105531) confirms that higher headache frequency (as in CM) is directly associated with greater disability burden.

Treatment of Serious Chronic Migraine (2 Years Duration)

Step 1: First - Screen and Address Complicating Factors

• Medication Overuse Headache (MOH) - if the patient is using acute pain medications (especially opioids, triptans, NSAIDs) on >10-15 days/month, MOH is likely perpetuating the cycle and must be addressed by withdrawing the overused drug
• Comorbid depression or anxiety - treat these aggressively; they worsen migraine
• Sleep disorders - obstructive sleep apnea, poor sleep hygiene
• Obesity - a modifiable risk factor for CM progression
• Caffeine overuse

Step 2: Preventive (Prophylactic) Treatment

First-Line Preventives

Second-Line / Advanced Preventives (for Refractory CM)

• Atogepant and Rimegepant - oral daily use for prevention

Step 3: Acute (Abortive) Treatment

For Moderate-Severe Attacks (First-Line)

• Triptans (5-HT 1B/1D agonists) - rapid and effective; act at onset of headache (after aura if present)
  • Rizatriptan or Eletriptan - most efficacious in the class
  • Sumatriptan - widely used; available oral, nasal spray, and SC injection
  • Zolmitriptan - similar to sumatriptan; nasal spray useful when nausea is prominent
  • Frovatriptan / Naratriptan - slower onset but longer acting, fewer recurrences
  • Contraindicated in ischemic heart disease, cerebrovascular disease, uncontrolled hypertension
• NSAIDs - naproxen 500 mg combined with sumatriptan reduces recurrence rate; useful adjunct
• Dihydroergotamine (DHE) - very effective; nasal spray or IV/IM injection; avoid in vascular disease or pregnancy

For Patients Who Can't Take Triptans

• Lasmiditan (dittan - 5-HT 1F agonist) - no vasoconstrictive effect; safe in cardiovascular disease
• Rimegepant / Ubrogepant (oral CGRP antagonists) - acute use; low side-effect profile

For Mild-Moderate Attacks

• Aspirin, Ibuprofen, Naproxen, Acetaminophen - first step for milder attacks

For Severe/Refractory Acute Attacks (Emergency)

• IV Valproate
• IV Metoclopramide (also helps nausea)
• IV Ketorolac
• Prochlorperazine
• SC Sumatriptan (fastest-acting triptan)

Step 4: Non-Pharmacological Strategies (Run Alongside Medications)

• Cognitive Behavioral Therapy (CBT) - reduces migraine frequency and disability; 8-10 sessions
• Biofeedback - one of the most evidence-based non-drug approaches
• Relaxation training
• Regular aerobic exercise - reduces frequency
• Sleep hygiene - consistent sleep/wake schedule
• Migraine trigger diary - identify and avoid personal triggers (certain foods, stress, dehydration, skipped meals, bright lights)
• Smoking cessation
• Acupuncture - used as adjunct in some patients

Step 5: Non-Invasive Neuromodulation (If Available)

• Transcranial magnetic stimulation (TMS)
• Non-invasive vagus nerve stimulation (nVNS)
• Transcutaneous supraorbital stimulation (Cefaly device)

Summary: Suggested Management Plan for This Patient

1. Rule out MOH - withdraw any overused acute medication
2. Start a first-line preventive (propranolol or topiramate) while titrating
3. If inadequate response after 3 months → add or switch to onabotulinumtoxinA (every 12 weeks, 2-3 cycles)
4. If still refractory → CGRP monoclonal antibody (erenumab, fremanezumab, or galcanezumab)
5. Use triptans for acute attacks, with strict frequency limits
6. Address comorbidities (depression, sleep, weight)
7. Integrate CBT + biofeedback throughout

Rizanet 10 - Drug Profile

What Is It?

Indication

• Acute treatment of migraine attacks (with or without aura) in adults
• It is not a preventive medication - it aborts an attack already in progress
• Not effective for other types of headache (tension, cluster)

Mechanism of Action

1. Stimulating 5-HT1B receptors on cranial blood vessels → causes vasoconstriction of dilated intracranial vessels
2. Stimulating 5-HT1D receptors on trigeminal nerve terminals → inhibits release of pro-inflammatory neuropeptides (including CGRP and substance P)
3. Together these actions stop the migraine cascade - reducing perivascular inflammation and blocking pain signal transmission

Dosing

Formulations

• Conventional film-coated tablets (swallow whole)
• Orally disintegrating tablets (MLT/wafer form) - dissolves on tongue, useful when nausea prevents swallowing

Pharmacokinetics

Common Side Effects

• Tingling / paresthesias (most common)
• Dizziness
• Somnolence / drowsiness
• Chest tightness / pressure (sensation, not necessarily cardiac)
• Neck/throat tightness
• Nausea
• Dry mouth
• Asthenia / fatigue
• Warm sensation / flushing

Serious Side Effects (Rare but Important)

• Coronary vasospasm / chest pain - can mimic cardiac ischemia; risk higher in patients with cardiac disease
• Stroke / TIA - rare
• Serotonin syndrome - especially if combined with SSRIs/SNRIs (symptoms: agitation, hyperthermia, tremor, rigidity)
• Severe peripheral ischemia
• Medication Overuse Headache - if used >10 days/month

Contraindications

• Ischemic heart disease (angina, previous MI)
• Coronary artery vasospasm (Prinzmetal angina)
• Cerebrovascular disease (stroke, TIA history)
• Peripheral vascular disease
• Uncontrolled hypertension
• Hemiplegic or basilar migraine
• Recent use of ergotamine or another triptan (within 24 hours)
• MAO inhibitor use (within 2 weeks) - rizatriptan is metabolized by MAO-A; combined use causes dangerous drug levels
• Severe renal or hepatic impairment - use with caution

Important Drug Interactions

Clinical Note for Your Migraine Patient: If your patient is on propranolol for CM prevention (as discussed earlier), they should use the 5 mg dose of rizatriptan, not the 10 mg dose, due to this pharmacokinetic interaction. - MedCentral Drug Monograph

How to Counsel Your Patient

1. Take as soon as migraine symptoms begin (headache phase - after aura completes if aura is present)
2. Can repeat once after 2 hours if headache returns - do not take more than 2 doses in 24 hours
3. Do not use for more than 10 days per month - risk of rebound/medication overuse headache
4. If using for chronic migraine, this is your acute rescue medication - you still need your preventive medication taken daily
5. Avoid if you have heart problems or are taking MAO inhibitors

Managing an Active Migraine Attack - Headache Phase

Key principle: Combining agents with different mechanisms is more effective than a single drug alone. - Bradley and Daroff's Neurology in Clinical Practice

Step 1: Give Rizanet 10 (Rizatriptan 10 mg) NOW

• Give Rizatriptan 10 mg orally immediately
• Takes effect in 1-2.5 hours
• Acts on 5-HT1B/1D receptors to:
  • Constrict dilated cranial vessels
  • Inhibit trigeminal neuropeptide (CGRP) release
  • Block pain signal transmission at the trigeminal nucleus
• If headache returns after initial relief → repeat dose after 2 hours (max 2 doses in 24 hours)

Important: If patient is on propranolol (for chronic migraine prevention), use 5 mg instead - propranolol increases rizatriptan levels by ~70%.

Step 2: Add an NSAID Alongside the Triptan

Step 3: Add an Antiemetic if Nausea is Present

• Relieves nausea/vomiting
• Restores gastric motility → improves triptan absorption
• Has independent antimigraine activity via dopamine D2 blockade

Watch for extrapyramidal side effects (akathisia, dystonia) with metoclopramide/prochlorperazine. Treat with diphenhydramine 25-50 mg if they occur.

If She Is in the Clinic / Has IV Access - Enhanced Protocol

If Triptan Fails or is Contraindicated

Non-Drug Measures (Right Now)

• Dark, quiet room - reduce light and sound stimulation
• Cold pack / ice on forehead or neck
• Rest - avoid physical activity (worsens pain)
• Hydration - small sips of water if not vomiting

Summary: What to Give Her Right Now

1. Rizatriptan 10 mg (Rizanet 10) orally  ← TAKE IMMEDIATELY
2. Naproxen 550 mg orally                 ← WITH the triptan
3. Metoclopramide 10 mg orally            ← IF nausea present
4. Dark, quiet room + cold pack           ← Immediately
5. Reassess in 2 hours
   → If no relief: repeat triptan OR switch to SC sumatriptan/DHE

Special Considerations: 21-Year-Old Female with Chronic Migraine

1. Rizanet 10 (Rizatriptan) - Still Appropriate RIGHT NOW

2. Stroke Risk - The Most Important Issue in Young Women

Estimated incidence of ischemic stroke in young women aged 25-34 with migraine with aura using oral contraceptives: 28 per 100,000 women - Bradley and Daroff's Neurology in Clinical Practice

Action Points:

• Ask: Does she have migraine WITH aura? If yes, this dramatically raises stroke risk
• Ask: Is she on combined oral contraceptives (COC)? If yes - serious risk combination
• Strongly advise: No smoking - if she smokes, smoking cessation is urgent
• Screen for hypertension and hyperlipidemia

3. Oral Contraceptive Guidance (IHS Task Force Recommendations)

• Migraine with aura + COC = HIGH stroke risk - COC is relatively contraindicated; consider progestogen-only pill or non-hormonal contraception instead
• Migraine without aura + COC - can use low-dose estrogen (<50 µg ethinyl estradiol) with caution; monitor closely
• Stop smoking before starting COC
• If on COC and she develops new aura, increased headache frequency, or unusual/prolonged aura - STOP COC immediately and reassess

Progestogen-only methods (mini-pill, Mirena IUD, Depo-Provera injection) do not significantly increase ischemic stroke risk and are preferred in migraineurs. - Bradley and Daroff's Neurology in Clinical Practice

4. Preventive Drug Choice - Teratogenicity is a Key Concern

Preferred Preventives for This Patient:

1. Propranolol (40-120 mg/day) - first choice; safe profile
2. Amitriptyline (10-50 mg at night) - if propranolol not tolerated
3. CGRP mAbs (erenumab etc.) - if refractory, with guaranteed contraception
4. OnabotulinumtoxinA - if refractory, discuss risks

5. Menstrual Migraine - Very Common at This Age

• Frovatriptan, Naratriptan, or Zolmitriptan - taken 2 days before expected menstrual onset and continued for 5-6 days (perimenstrual prophylaxis)
• NSAIDs (naproxen) - started 2 days before menstruation
• Magnesium supplementation - young women with migraine have low systemic magnesium; useful and safe

6. If She Becomes Pregnant

• Stop most preventive medications
• Acute attacks: Paracetamol (acetaminophen) first line; avoid NSAIDs especially in 3rd trimester
• Severe attacks in pregnancy: IV prochlorperazine + IV magnesium sulfate 1g are safer options
• Triptans in pregnancy: Limited data; generally avoided, but not proven harmful in early pregnancy
• Good news: ~70% of women experience significant improvement or remission of migraine during pregnancy (especially 2nd and 3rd trimester)

Summary: Key Adjustments for Her Being 21 Years Old

Clinical Assessment: 21F, 48 kg, Hb 16 g/dL with Chronic Migraine

🚨 The Haemoglobin of 16 g/dL is ABNORMAL in a Young Woman

Why Hb 16 Matters - Elevated Haemoglobin Causes

Common / Likely Causes at This Age:

Serious Causes to Exclude:

Critical Link: High Hb → Hyperviscosity → Headaches

High haemoglobin leads to blood hyperviscosity syndrome: headache, vertigo, dizziness, visual disturbances, vascular ischemia, and venous thrombosis. - Yamada's Textbook of Gastroenterology; Rosen's Emergency Medicine

• Hyperviscosity headaches do NOT respond to triptans - you need to treat the cause
• High Hb increases her stroke risk even further (on top of migraine-related stroke risk already elevated in young women)

How Hb 16 + Migraine Together Raise Stroke Risk Dramatically

1. Young woman with migraine → already 3.5x stroke risk
2. Elevated Hb / polycythaemia → increased blood viscosity → thrombotic risk
3. If she also has migraine WITH aura → 6.2x stroke risk
4. If on combined oral contraceptives → 13.9x stroke risk

Immediate Investigations Needed

Drug Considerations Given 48 kg Weight

Revised Management Plan for This Patient

Immediate (Today):

1. Rizatriptan 5 mg (not 10 mg, given 48 kg) for the current headache attack
2. Naproxen 250-500 mg (lower dose for 48 kg)
3. Metoclopramide 10 mg if nausea present
4. IV fluids / oral hydration - if dehydrated, this alone may lower Hb and help headache

Urgent Workup (This Week):

• FBC, haematocrit, JAK2 mutation, serum EPO, SpO2, renal function, MRI brain
• Do NOT prescribe long-term triptans or ergotamines until polycythaemia/cause is investigated - increased thrombotic risk

Preventive Treatment - Put on Hold Until Hb is Explained:

• If Hb cause is benign (dehydration/altitude) → proceed with propranolol
• If polycythaemia vera confirmed → haematology referral + aspirin may be part of PV treatment; headache management changes significantly
• Avoid COC absolutely until cause clarified

Summary Flag for This Patient

Bottom line: Hb of 16 in a 21-year-old woman is a red flag. Investigate before fully committing to a chronic migraine treatment plan.

The Breakup - A Critical Piece of Her History

Connecting the Timeline

The Science: How Emotional Loss Drives Chronic Migraine

1. Stress is a Direct Migraine Trigger

2. The Migraine-Depression-Anxiety Triangle

About 60% of people with migraine have a lifetime history of either anxiety or mood disorder. Anxiety precedes migraine, which then leads to depression. - Kaplan & Sadock's Comprehensive Textbook of Psychiatry

• Acute grief reaction / adjustment disorder - from the breakup
• Depression - loss of a person she equated with God-like devotion
• Anxiety - uncertainty about the future, self-worth, loneliness
• All of these feed directly into migraine chronification

3. About 65% of Migraine Disability is Psychiatric Comorbidity

"About 65% of migraine-associated disabilities can be attributed to comorbid physical and mental disorders." - Kaplan & Sadock's Psychiatry

What "Love Like God" Tells You Clinically

Psychiatric Screening - Do This Now

PHQ-2 (Depression screen - 2 questions):

1. "Over the past 2 weeks, have you felt down, depressed, or hopeless?"
2. "Have you had little interest or pleasure in doing things?"

GAD-2 (Anxiety screen):

1. "Have you felt nervous, anxious, or on edge?"
2. "Have you been unable to stop or control worrying?"

Crucially - Suicide/Self-harm Screening:

• A 21-year-old with intense attachment ("love like God") who has experienced a major loss is at risk for self-harm or suicidal ideation
• Ask directly and compassionately: "Sometimes when people go through a painful loss like this, they have thoughts of hurting themselves or not wanting to be here. Have you had any thoughts like that?"
• This must not be skipped

Revised Diagnosis: What She Likely Has

How This Changes Her Treatment Plan

"If patients with anxiety and/or depression suffer from migraine, it is critical to treat the ENTIRE SYNDROME rather than limiting the treatment goal to headache cessation." - Kaplan & Sadock's Psychiatry

Drug Changes - Choose a Preventive That Treats BOTH Migraine AND Depression/Anxiety:

Non-Drug Treatment - ESSENTIAL for Her:

How to Talk to Her - Approach as a Clinician

"What you're feeling - this pain in your heart and your head - they are connected. The love you had was real, the loss is real, and your body is responding to it. We are going to help both - the headaches AND how you are feeling inside."

Summary - The Complete Picture Now

The most important prescription you can write today is not just Rizanet 10 - it is compassion, a proper psychiatric screen, and a referral to psychological support alongside her migraine medications.