Clinician-reviewed CDS · Browser-local · Source-linkedRead more…
This tool is educational and informational. It does not replace clinical judgment. Verify preventive treatment selection, contraindication screening, and evidence grading against the cited source before acting.
Not prospectively validated. No clinical tool replaces bedside assessment.
This runs entirely in your browser; we store nothing. Even so, enter only clinical data (age, vitals, exam findings) -- not names, MRNs, or other identifiers.
Tarvinder Singh, MD -- Vascular Neurologist. March 2026.
Migraine Prevention -- Clinic
Narrows preventive options by migraine burden, acute medication overuse, current regimen status, and safety constraints. Shows what fits now, what has been tried, and what to adjust next.
Evidence level key (AHS grading)
Level A -- Established as effective. Two or more Class I studies.
Level B -- Probably effective. One Class I or two or more Class II studies.
Level C -- Possibly effective. One Class II or two or more Class III studies.
Level U -- Insufficient evidence to determine efficacy.
Headache days / month
≥ 15 qualifies as chronic; ≥ 20 is high burden
Migraine days / month
≥ 10 is high burden
Duration at this burden
≥ 3 months for chronic classification
Impairment days / month
≥ 4 is high burden
At a glance
Start with headache days, migraine days, and months at this burden. Those are the inputs that actually change the preventive sequence.
Common default fits before tailoring: Amitriptyline | Candesartan | Propranolol.
Evidence
Amitriptyline
Level BBest choice for patients with comorbid insomnia or tension-type headache overlap. Migraine doses (10–75 mg) are far below antidepressant doses (150–300 mg).
Candesartan
Level BBest tolerated of the BP-lowering preventives — fewer side effects than beta-blockers (no fatigue, no exercise intolerance, no depression). Head-to-head with propranolol showed similar efficacy. First choice for hypertensive patients who are athletes or have mood concerns.
Propranolol
Level AFirst choice for patients with comorbid hypertension or performance anxiety. Avoid in athletes — exercise intolerance is a deal-breaker. Long-acting formulation improves adherence.
Topiramate
Level AStart low, go slow. Cognitive side effects are dose-dependent — many patients tolerate 50 mg but not 100 mg. The weight loss effect makes this a strategic first choice for obese patients with migraine.
Amitriptyline
Tricyclic antidepressant
Start 10–25 mg at bedtime, titrate to 25–75 mg nightly
Best choice for patients with comorbid insomnia or tension-type headache overlap. Migraine doses (10–75 mg) are far below antidepressant doses (150–300 mg).
More bedside detail
Cautions: Sedation — dose at bedtime; may be beneficial for comorbid insomnia Weight gain — common at higher doses Dry mouth, constipation, urinary retention (anticholinergic effects) ECG screening recommended if dose >75 mg or cardiac history (QTc prolongation)
How to use it: Take 1–2 hours before bedtime to avoid morning grogginess. Start at 10 mg in elderly or sensitive patients.
Couch 2011: Placebo-controlled trial of amitriptyline in episodic migraine and chronic daily headache.(PMID 21070231 pending verification)
Candesartan
ARB (angiotensin II receptor blocker)
Start 8 mg daily, titrate to 16 mg daily
Best tolerated of the BP-lowering preventives — fewer side effects than beta-blockers (no fatigue, no exercise intolerance, no depression). Head-to-head with propranolol showed similar efficacy. First choice for hypertensive patients who are athletes or have mood concerns.
More bedside detail
Cautions: Monitor blood pressure — hypotension at higher doses Check renal function and potassium periodically Avoid in bilateral renal artery stenosis
How to use it: Once daily, any time of day. Allow 8–12 weeks at target dose before assessing efficacy.
Tronvik 2003: First RCT of candesartan 16 mg vs placebo. Significant reduction in headache days.(PMID 12503978 pending verification)
Stovner 2014: Triple-blind crossover of candesartan vs propranolol vs placebo. Similar efficacy, better tolerability.(PMID 24335848 pending verification)
Propranolol
Beta-blocker (non-selective)
Start 40 mg daily (divided BID or LA daily), titrate to 80–240 mg daily
First choice for patients with comorbid hypertension or performance anxiety. Avoid in athletes — exercise intolerance is a deal-breaker. Long-acting formulation improves adherence.
More bedside detail
Cautions: Fatigue and exercise intolerance are common Do not stop abruptly — taper over 1–2 weeks (rebound tachycardia) May mask hypoglycemia symptoms in diabetic patients
How to use it: Can use long-acting (LA) formulation for once-daily dosing. Target resting heart rate 55–60 bpm as dose guide.
Cochrane Review (Linde): 26 placebo-controlled trials, high-quality evidence for efficacy.(PMID 15106196 pending verification)
Topiramate
Anticonvulsant (carbonic anhydrase inhibitor)
Start 25 mg daily, titrate to 50–100 mg daily over 4–8 weeks
Start low, go slow. Cognitive side effects are dose-dependent — many patients tolerate 50 mg but not 100 mg. The weight loss effect makes this a strategic first choice for obese patients with migraine.
More bedside detail
Cautions: Cognitive side effects (word-finding difficulty, "brain fog") — most common reason for discontinuation Weight loss — may be beneficial in obese patients, detrimental in underweight Paresthesias (tingling) are common and dose-related Taper slowly to avoid rebound seizures in epilepsy patients
How to use it: Evening dosing may reduce daytime cognitive effects. Allow 8–12 weeks at target dose before assessing efficacy.
Brandes 2004 (MIGR-002): RCT, 50/100/200 mg vs placebo. 49% responder rate at 100 mg vs 23% placebo.(PMID 14982912 pending verification)
Silberstein 2004 (MIGR-001): Large RCT confirming dose-response efficacy.(PMID 15096395 pending verification)
Valproate / Divalproex
Anticonvulsant
Start 250 mg BID, titrate to 500–1000 mg daily (divided BID or ER daily)
Level A evidence but practical use declining due to teratogenicity, weight gain, and availability of CGRP therapies. Most useful for patients with comorbid epilepsy or bipolar disorder.
More bedside detail
Cautions: Weight gain — common and significant Tremor, hair loss, GI upset Monitor LFTs and CBC at baseline and periodically Drug interactions with lamotrigine, warfarin, aspirin
How to use it: Extended-release (ER) formulation reduces GI side effects. Therapeutic range for migraine is often lower than for epilepsy.
Mathew 1995: RCT, 500-1500 mg vs placebo. ~50% responder rate at higher doses.(PMID 7872882 pending verification)
Klapper 1997: Dose-controlled study confirming 500-1000 mg efficacy.(PMID 9137847 pending verification)
Venlafaxine XR
SNRI antidepressant
Start 37.5 mg daily, titrate to 75–150 mg daily
Good choice for patients with comorbid depression or anxiety. Better tolerated than amitriptyline for daytime function (less sedation, less weight gain).
More bedside detail
Cautions: Nausea during initial titration — take with food Blood pressure monitoring needed at doses ≥150 mg (noradrenergic effect) Discontinuation syndrome — never stop abruptly, taper over 2–4 weeks
How to use it: Use extended-release (XR) formulation. Take in the morning. Allow 6–8 weeks at target dose before assessing efficacy.
Atogepant (Qulipta)
CGRP receptor antagonist (oral gepant)
Atogepant 30 mg or 60 mg once daily
First oral CGRP-targeted preventive. Appeals to patients who prefer pills over injections. FDA-approved for both episodic and chronic migraine prevention.
More bedside detail
Cautions: Constipation and nausea (less common than erenumab) Dose adjustment needed with strong CYP3A4 inhibitors (30 mg dose) Hepatotoxicity signal in clinical trials — monitor LFTs if concern
How to use it: Once daily with or without food. Reduce to 30 mg daily with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin).
ADVANCE (Ailani 2021): Phase 3 RCT, episodic migraine. 10/30/60 mg all superior to placebo.(PMID 34407343 pending verification)
PROGRESS (Pozo-Rosich 2023): Phase 3 RCT, chronic migraine. 30 mg BID and 60 mg QD both effective.(PMID 37516125 pending verification)
Eptinezumab (Vyepti)
CGRP ligand monoclonal antibody
Eptinezumab 100 mg IV quarterly (300 mg if needed)
The only IV CGRP mAb — advantage is guaranteed compliance (administered in office). Fastest onset of any CGRP mAb (day 1 efficacy in trials). Consider for adherence-challenged patients.
More bedside detail
Cautions: Requires IV infusion in office/infusion center (~30 min) Use cautiously in clinically important vascular disease or severe constipation Hypersensitivity reactions (rare but monitor during infusion) Nasopharyngitis reported
How to use it: IV infusion over ~30 minutes every 3 months. No loading dose needed. Observe for 1 hour after first infusion.
PROMISE-1 (Ashina 2020): Phase 3 RCT, episodic migraine. Day-1 onset of efficacy.(PMID 32075406 pending verification)
PROMISE-2 (Lipton 2020): Phase 3 RCT, chronic migraine. 100/300 mg both effective.(PMID 32209650 pending verification)
Erenumab (Aimovig)
CGRP receptor monoclonal antibody
Erenumab 70 mg or 140 mg SC monthly
Only CGRP mAb targeting the CGRP receptor (not the ligand). Constipation is more common than with other CGRP mAbs. Self-administered monthly autoinjector.
More bedside detail
Cautions: Constipation — most common side effect (unique to erenumab among CGRP mAbs, likely due to receptor blockade) Hypertension reported in post-marketing data — monitor BP Injection site reactions
How to use it: SC injection into abdomen, thigh, or upper arm. Room temperature for 30 min before injection. Allow 12 weeks before assessing efficacy.
STRIVE (Goadsby 2017): Phase 3 RCT, 955 patients. 70/140 mg reduced monthly migraine days by 3.2/3.7 vs 1.8 placebo.(PMID 29171821 pending verification)
Fremanezumab (Ajovy)
CGRP ligand monoclonal antibody
225 mg SC monthly OR 675 mg SC quarterly
The quarterly dosing option (675 mg every 3 months) is unique among CGRP mAbs — ideal for patients who prefer fewer injections.
More bedside detail
Cautions: Injection site reactions Use cautiously in clinically important vascular disease or severe constipation Limited long-term safety data beyond 3 years
How to use it: Quarterly dosing: three 225 mg injections at separate sites on the same day. Store refrigerated.
HALO CM (Silberstein 2017): Phase 3 RCT in chronic migraine, NEJM. Monthly/quarterly both effective.(PMID 29171818 pending verification)
Galcanezumab (Emgality)
CGRP ligand monoclonal antibody
Loading: 240 mg SC (two 120 mg injections), then 120 mg SC monthly
Loading dose provides faster onset than other CGRP mAbs. Also FDA-approved for episodic cluster headache (the only preventive with this indication).
More bedside detail
Cautions: Injection site reactions (redness, pain, swelling) Use cautiously in clinically important vascular disease or severe constipation Limited long-term safety data beyond 3 years
How to use it: SC injection. Loading dose: two 120 mg injections at separate sites on day 1. Then 120 mg monthly.
EVOLVE-1 (Stauffer 2018): Phase 3 RCT. Monthly migraine days reduced 4.7 (120 mg) vs 2.8 placebo.(PMID 29813147 pending verification)
EVOLVE-2 (Skljarevski 2018): Phase 3 RCT confirming EVOLVE-1 results.(PMID 29848108 pending verification)
OnabotulinumtoxinA (Botox)
Neurotoxin (chemodenervation)
155 units across 31 injection sites (PREEMPT protocol), every 12 weeks
PREEMPT protocol is specific — must inject all 31 sites. Many insurers require failure of 2–3 oral preventives first. Allow 2–3 treatment cycles (6–9 months) before declaring failure.
More bedside detail
Cautions: FDA-approved ONLY for chronic migraine (≥15 headache days/month) Not effective for episodic migraine (<15 days/month) Neck pain and injection site soreness common Ptosis (drooping eyelid) possible — technique-dependent
How to use it: PREEMPT protocol: 5 units per site across 7 muscle groups bilaterally. Office procedure taking 15–20 minutes. Repeat every 12 weeks.
PREEMPT pooled (Dodick 2010): Two phase 3 RCTs, 1384 chronic migraine patients. Significant reduction in headache days.(PMID 20487038 pending verification)
CoQ10 (Coenzyme Q10)
Mitochondrial supplement
CoQ10 100 mg TID (300 mg daily total)
Targets mitochondrial dysfunction in migraine pathophysiology. Limited but positive RCT data. Very safe — reasonable to add to any regimen. Often combined with magnesium and riboflavin ("migraine supplement triad").
More bedside detail
Cautions: May reduce effectiveness of warfarin — monitor INR GI upset at higher doses
How to use it: Take with fatty food for better absorption. Ubiquinol form may have better bioavailability than ubiquinone. Allow 3 months for assessment.
Sandor 2005: RCT, 300 mg vs placebo. 47.6% responder rate vs 14.4% placebo (NNT 3).(PMID 15728298 pending verification)
Magnesium (Oral)
Mineral supplement
Magnesium 400–600 mg daily (oxide or citrate)
Low-risk, inexpensive, widely available. Particularly effective in migraine with aura and menstrual migraine. Can be combined with any prescription preventive. Many migraine patients are magnesium-deficient.
More bedside detail
Cautions: Diarrhea is dose-limiting — citrate better tolerated than oxide Reduce dose in renal impairment
How to use it: Magnesium glycinate or citrate preferred for absorption. Oxide is cheapest but worst GI tolerance. Take with food. Split dose if GI intolerance.
Peikert 1996: RCT, 600 mg trimagnesium dicitrate. 41.6% reduction in attack frequency vs 15.8% placebo.(PMID 8792038 pending verification)
Riboflavin (Vitamin B2)
Vitamin supplement
Riboflavin 400 mg daily
Excellent safety profile — essentially no side effects. Takes 3 months to see full benefit. Good starting point for patients reluctant to take prescription medications or as add-on therapy.
More bedside detail
Cautions: Bright yellow urine — warn patients (harmless)
How to use it: Can be taken as single 400 mg dose or divided. Available over the counter. Safe to combine with any other preventive.
Schoenen 1998: RCT, 400 mg vs placebo. 59% responder rate vs 15% placebo (NNT 2.3).(PMID 9484373 pending verification)
Biofeedback
Behavioral therapy
8-12 sessions; practice exercises daily between sessions
AAN Level A evidence. Thermal biofeedback (hand-warming) and EMG biofeedback (muscle tension reduction) both effective. Particularly useful for patients who want to avoid medications, pregnant patients, and children/adolescents.
More bedside detail
Cautions: Requires initial in-person sessions for training with equipment Home practice compliance is essential for benefit
How to use it: Begin with therapist-guided sessions using biofeedback equipment. Practice relaxation exercises 15-20 minutes daily at home. Can transition to app-based tools for maintenance.
Cognitive Behavioral Therapy (CBT) for Migraine
Behavioral therapy
6-8 structured sessions over 8-12 weeks; maintenance sessions as needed
AAN Level A evidence — as effective as many preventive medications. Ideal for patients who prefer non-pharmacologic approaches, have significant stress triggers, or have comorbid anxiety/depression. Telehealth CBT has shown equivalent efficacy.
More bedside detail
Cautions: Requires patient commitment to homework and practice between sessions Cost and access to trained headache-specific CBT therapists may be limiting
How to use it: Seek a therapist trained in headache-specific CBT. Telehealth options expand access. Key components: cognitive restructuring, relaxation training, behavioral activation, trigger management.
Mindfulness-Based Stress Reduction (MBSR)
Mind-body therapy
8-week structured program, 2.5 hours/week plus daily home practice
MBSR teaches non-judgmental awareness of pain and stress. Not about eliminating headache — about changing the response to it. Most effective as adjunct to pharmacologic therapy. Growing telehealth availability.
More bedside detail
Cautions: Not a substitute for pharmacologic therapy in severe/frequent migraine
How to use it: Structured 8-week program. Daily home practice of 20-45 minutes. Available in-person and online. Jon Kabat-Zinn protocol is the standard.
Wells 2021: RCT of MBSR vs headache education in episodic migraine. MBSR showed greater improvement in disability scores.(PMID 33315046 pending verification)
Cefaly (External Trigeminal Nerve Stimulation)
Neuromodulation device
20 minutes daily (preventive mode); can also use acute mode during attack
FDA-cleared for both acute and preventive migraine. No systemic side effects — excellent option for patients who cannot tolerate medications, are pregnant, or prefer non-pharmacologic approaches. Available over-the-counter.
More bedside detail
Cautions: Not effective for all patients — trial period recommended Device cost not always covered by insurance
How to use it: Apply electrode pad to forehead over supraorbital nerves. 20-minute daily session for prevention. Separate 60-minute acute mode for active attacks.
Schoenen 2013: Sham-controlled RCT. eTNS reduced migraine days and acute medication use vs sham.(PMID 23390177 pending verification)
gammaCore (Non-Invasive Vagus Nerve Stimulation)
Neuromodulation device
Two 2-minute stimulations, 3 times daily for prevention
FDA-cleared for migraine and cluster headache (acute and preventive). Applied to the neck over the vagus nerve. Strongest evidence in cluster headache. Safe to combine with any pharmacologic therapy.
More bedside detail
Cautions: Avoid direct application over carotid sinus (vasovagal risk) Device cost and prescription requirement
How to use it: Handheld device applied to the neck. Two 2-minute stimulations per session, 3 sessions daily for prevention. Can also use acutely at headache onset.
Silberstein 2016: nVNS for acute treatment of migraine and cluster headache. Significant benefit in cluster headache; modest signal in migraine.(PMID 27412146 pending verification)
SpringTMS (Single-Pulse Transcranial Magnetic Stimulation)
Neuromodulation device
Four pulses twice daily for prevention; two pulses at aura/headache onset for acute
FDA-cleared for acute and preventive migraine. Best evidence in migraine with aura — the magnetic pulse may abort cortical spreading depression. Larger device limits portability compared to Cefaly/gammaCore.
More bedside detail
Cautions: Relative contraindication: epilepsy, metallic cranial implants Device is large — less portable than Cefaly or gammaCore
How to use it: Apply to the back of the head. Prevention: 4 pulses morning and evening. Acute: 2 pulses at aura onset, can repeat every 15 minutes up to 3 times.
Lipton 2010: Sham-controlled RCT of sTMS for acute migraine with aura. Significant pain-free response at 2h.(PMID 20206581 pending verification)
Aerobic Exercise Program
Exercise intervention
30-40 minutes moderate-intensity aerobic exercise, 3-5 times per week
A landmark RCT (Varkey 2011) showed aerobic exercise was equivalent to topiramate for migraine prevention. Walking, cycling, and swimming are well-tolerated. Start gradually — 15 min, 3x/week — and increase over 4-6 weeks.
More bedside detail
Cautions: Exercise can trigger migraine in some patients initially — advise gradual warm-up and cool-down Avoid exercising in extreme heat or without adequate hydration
How to use it: Start at 15 minutes 3x/week. Increase by 5 minutes per week. Target: 30-40 min at moderate intensity (can hold a conversation). Always warm up for 5-10 minutes.
Varkey 2011: RCT comparing exercise, relaxation, and topiramate. Exercise was non-inferior to topiramate for migraine prevention.(PMID 21890526 pending verification)
Dietary Trigger Management
Lifestyle intervention
Individualized trigger identification via food diary; eliminate confirmed triggers
Common triggers include alcohol (especially red wine), aged cheeses, processed meats (nitrates), MSG, and artificial sweeteners. Triggers are highly individual — a food diary for 4-6 weeks is more useful than a generic avoidance list.
More bedside detail
Cautions: Overly restrictive diets can lead to nutritional deficiency and disordered eating Not all commonly cited triggers (chocolate, cheese) are universal — individualize based on diary
How to use it: Keep a daily headache and food diary for 4-6 weeks. Eliminate suspected triggers one at a time for 4 weeks each. Reintroduce to confirm.
Martin 2016: Comprehensive trigger avoidance with food diary showed modest benefit in episodic migraine.(PMID 27699780 pending verification)
Hydration Protocol
Lifestyle intervention
2-3 liters of water daily, spread throughout the day
Dehydration is an underappreciated migraine trigger. Low-cost, zero-risk intervention. Particularly important in warm climates, with exercise, and in patients taking topiramate (which increases kidney stone risk).
More bedside detail
Cautions: Adjust for heart failure or renal conditions with fluid restriction
How to use it: Target 2-3L daily. Carry a water bottle. Front-load intake in the morning. Reduce caffeine and alcohol which are dehydrating.
Spigt 2012: RCT of increased water intake (1.5L/day additional). Modest reduction in headache hours and intensity.(PMID 22113647 pending verification)
Sleep Hygiene Optimization
Lifestyle intervention
Consistent sleep/wake schedule, 7-8 hours nightly, dark/cool bedroom
Sleep disruption is one of the most common migraine triggers. Consistent sleep/wake times — even on weekends — may reduce attack frequency by 25-30%. Foundation of any preventive regimen.
More bedside detail
Cautions: Patients with sleep apnea need formal sleep evaluation — sleep hygiene alone is insufficient
How to use it: Implement as first step alongside any pharmacologic preventive. Key rules: same bedtime/wake time daily, no screens 1h before bed, dark and cool room, limit caffeine after noon.
Rains 2006: Behavioral sleep modification reduces migraine frequency in patients with comorbid insomnia.(PMID 17040332 pending verification)
Yoga
Mind-body exercise
3-5 sessions per week, 30-60 minutes each; emphasis on gentle flow and breathing
Gentle yoga emphasizing breathing (pranayama) and relaxation shows the best results for migraine. Avoid vigorous or heated styles. Integrates well with other behavioral interventions (CBT, mindfulness).
More bedside detail
Cautions: Avoid hot yoga — heat and dehydration can trigger migraine Certain inversions may worsen headache in some patients
How to use it: Start with beginner-level or gentle yoga classes. Focus on diaphragmatic breathing. Avoid hot yoga and extreme inversions. Can be done at home with guided video.
Acupuncture
Traditional/complementary therapy
12-16 sessions over 8-12 weeks; maintenance sessions monthly or as needed
Cochrane review shows acupuncture is slightly better than sham and comparable to prophylactic drugs for some patients. The true specific effect is unclear — benefit may come from relaxation, therapeutic relationship, and expectation. Reasonable option for patients who have tried standard therapies or prefer complementary approaches.
More bedside detail
Cautions: Sham-controlled evidence is weak — benefit may come partly from relaxation and placebo components Quality of evidence is moderate at best Ensure practitioner uses sterile, single-use needles
How to use it: Seek a licensed acupuncturist. Initial course of 12-16 sessions over 2-3 months. Reassess after 8 sessions. If no benefit by 12 sessions, unlikely to respond.
Linde 2016 Cochrane Review: Acupuncture shows modest benefit over sham for migraine prevention. Comparable to drug prophylaxis in some trials.(PMID 27351677 pending verification)
Butterbur (Petasites hybridus)
Herbal supplement
Butterbur 75 mg BID (PA-free preparation ONLY)
Was previously the only herbal therapy with AAN Level A evidence (2012). Retracted in 2015 due to hepatotoxicity concerns — even PA-free preparations may carry risk. NOT currently recommended by AAN. If a patient insists, monitor LFTs and use only verified PA-free sources.
More bedside detail
Cautions: SAFETY WARNING: Raw or unprocessed butterbur contains hepatotoxic pyrrolizidine alkaloids (PAs). Only PA-free preparations should be used. The branded PA-free product (Petadolex) was withdrawn from several markets due to reports of liver damage even with "PA-free" labeling AAN retracted its recommendation in 2015 — no longer endorsed by major guidelines Not recommended in pregnancy or breastfeeding
How to use it: NOT RECOMMENDED. If used despite warnings: PA-free preparation only, 75 mg BID, monitor LFTs at baseline, 1 month, and 3 months. Discontinue if transaminases elevate.
Previously rated Level A by AAN 2012. Recommendation retracted in 2015 due to hepatotoxicity concerns with non-PA-free preparations.
Feverfew (Tanacetum parthenium)
Herbal supplement
Feverfew 100-300 mg daily (standardized to 0.2-0.4% parthenolide)
Insufficient evidence to recommend. Some patients report benefit, but RCTs are small and inconsistent. If a patient wishes to try it, use a standardized extract (0.2% parthenolide minimum) and set a 3-month trial with clear outcome tracking.
More bedside detail
Cautions: Not regulated as a drug — product quality and standardization vary widely Avoid in pregnancy (possible uterotonic effects) Rebound headache possible on abrupt discontinuation
How to use it: Use standardized extract with minimum 0.2% parthenolide content. Take with food. Allow 3 months for assessment. Taper if discontinuing.
Pittler 2004 Cochrane Review: Mixed results across small RCTs. Insufficient evidence to establish efficacy.(PMID 14973986 pending verification)
Opioids for Prevention
Opioid analgesic
N/A — not recommended
No evidence for preventive efficacy. Accelerates chronification and medication overuse headache. Associated with worse outcomes in every longitudinal study.