Migraine: physiology, new medications, and integrated approaches to management (Dacre, 1/14/2026)

A recording of this presentation is available HERE.

Many thanks to Dr. Mike Dacre for a presentation this week on Migraines. 

My notes:

Migraine syndrome is super common (~10% of all people), 1 billion people globally, 2nd cause of disability worldwide, 50% underdiagnosed and undertreated. 2:1 female to male ratio

• Migraine headaches 4-72 hours
• Note Pediatric usually max 2-4 hours (often not unilateral)
• Classic pattern of prodrome>> aura>> headache>> postdrome

What causes migraine? Has long been thought of as a blood vessel problem (spasm vs dilation)>> pain often pulsatile, worse with movement/position changes, vasoconstrictors (caffeine, ergo alkaloids) then migraines get better, vasodilators (Viagra) make migraines worse. 

BUT this understanding is now known to not be true. In actuality, the blood vessel changes are SECONDARY. Now belief is that migraine is primarily a disease of neuronal activity: large ion shifts (potassium, glutamate, ATP across cell membranes)>> two receptors particularly notable now, include CGRP receptor and PACAP

• CGRP is potent vasodilator, but is a side effect of activation of this cascade>> mast cell degranulation, inflammation and sensitization
• get irritation and inflammation around the blood vessels, causing painful vasodilation

Migraines tend to start in the brainstem (where trigeminal nerve originates), direction impacts the type of migraine a person experiences. Where it moves, impacts the symptoms/manifestations

I love this simple diagram of how genetic set point+ cumulative burden push people toward migraine thresholds and lead to migraine syndromes:

Migraine headaches can move from being episodic to being chronic/intractable. Once you get migraines frequently enough, you can get medication overuse headaches, which then push you to central sensitization, which makes you more likely to get migraines. Similar to chronic pain syndrome progression>> it is not uncommon for people with headache syndromes to not seek care, overtake meds, and then have their disease progress to central sensitization and "chronification".

Abortive Treatments

Medications 

• NSAIDs are very effective (shouldn't be taken more than QOD due to risk of medication overuse headache)
• acetaminophen and caffeine can potentiate/help (care with overuse)
• Excedrin is "worse" for medication overuse (no more than 5 times/month)
• Corticosteroids + PPI
• short course of prednisone has good evidence (NNT 9)
• Triptans (actually inhibit CGRP release)
• should be used in episodic migraine, more effective when done before pain starts (aura phase), not useful after 1 hour after onset of pain
• NNT 4-5
• Sumatriptan and Rizatriptan are most commonly used (familiarity)> no head to head trials
• Care with vasoconstriction effect (e.g. contraindicated in CAD, uncontrolled Htn)

• Opioids don't work well, high risk for misuse/dependence
• Caffeine is very effective in some people for aborting migraine, but people with > 2 cups coffee/day have more frequent and worse migraines
• Ditans: not available in US (schedule 5) but do see them in Middle East and Latin America

Nerve Blocks

Greater occipital nerve block>> safe and effective even in people who don't have predominant occipital pain, helps to abort migraine. 

• can be done with or without ultrasound
• Can do block + anti-emetic + steroid
• lidocaine+ bupivacaine
• very safe (low vascular, infection risk)

Preventive Treatments

Medications

• Beta blockers all work (propranolol, metoprolol)
• TCA: Amitriptyline
• SNRIs
• ARBs
• Anti-seizure meds (e.g. valproate, topiramate)>> best responders are people who failed other classes
• Anti-CGRPs: American Headache Society released guidelines in 2024 that these meds are first line for anyone with migraine >15 days/month ($600-700/month)
• safe and effective
• can be prescribed by PCPs
• can get covered by PHP (prior auth)
• one comparison study vs. topiramate, better tolerated
  
  
• Gepants
• remigapant, ubrogopant (can be used for ppx and abortive)
• Supplements
• Magnesium 400mg/day (moderate evidence)
• Riboflavin 400mg/day (good evidence)
• Coq10 (not great evidence) 100 TID
• Botox NNT 9 (50% reduction in HA days)
• Acupuncture NNT 11 (weekly acupuncture, 50% reduction in HA days)
• OMT/PT/massage are all also very effective, studies to support their use in reducing HA days

Summary:

Ehlers-Danlos Syndrome, Dysautonomia, and MCAS: Diagnosis and Management in Primary Care (Ohringer, 9/3/25)

 A recording of this presentation is available HERE.

This week's Grand Rounds, by Dr. Alison Ohringer, was so phenomenal that I have literally been thinking about it nonstop since she finished. The topic-- Ehlers-Danlos Syndrome, Dysautonomia, and MCAS-- doesn't exactly sound titillating, but after years in primary care taking care of patients with chronic symptoms that I don't always know what to do with -- I had a serious physician "AHA moment". 

Dr. Ohringer started with a silly meme that has now become an earworm for me: "If you cannot connect the issues, think connective tissues." 

I have long thought of rheumatology and/or autoimmunity as a linking factor for non-specific symptoms in patients, particularly in women with fatigue, dizziness, and other systemic malfunctions. I also have long dreamed of studying how our enteric nervous system interacts with the central nervous system (leading to diarrhea, constipation, and anxiety), but I cannot say I had specifically tied in connective tissues to the issues-- until yesterday. 

If you are a primary care provider, I definitely recommend watching this one! If you just want my notes, here goes. . .

Hypermobility= the ability of a joint to move beyond the normal range (can be isolated and/or benign (e.g. gymnasts) or generalized and/or symptomatic, impacting multiple joints and leading to pain, fatigue and can be associated with other symptoms)

Spectrum of severity of hypermobility:

Ehlers-Danlos Syndrome (EDS):  a group of conditions characterized by one or more of several common features: skin hyperextensibility, joint hypermobility, and tissue fragility, with subtypes distinguished by family history, clinical criteria, and oftentimes genetic testing. 

Hypermobile Ehlers-Danlos Syndrome (hEDS), previously referred to as EDS type III, the most common subtype, is diagnosed by hx and clinical criteria. There is no genetic test. Many experience symptoms of Mast Cell Activation Syndrome (MCAS), Postural Orthostatic Tachycardia Syndrome (POTS) and related dysautonomia, small fiber neuropathy, and migraine 

Hypermobility Spectrum Disorder (HSD) is diagnosed by history and clinical criteria, on a spectrum ranging from asymptomatic to chronic pain. Some may have some of the hEDS comorbidities, though they may be less severe 

Prevalence:

• EDS 1/20-40,000 (vascular EDS 1/100K)
• hEDS 1/3000-5000
• HSD: ~1/500

Remember that there are connective tissues in skin, tendons/ligaments, cartilage, joint capsules, blood vessels, bones, and organs including the GI tract. Also recall that mast cells reside in connective tissues

This schematic below depicts Dr. Ohringer's explanation for the relationships between the issues. Note that MCAD=Mast cell activation disorders.

In this schematic, "Triggers" (including inhaled allergens, skin exposures, foods ingested) set off a sympathetic nervous system (fight/flight) mode that then triggers histamine>> leading to an activation of H1 receptors (allergic reactions, rash, hives), H2 receptors (GI, stomach, acid reflux, diarrhea), H3 receptors (mood and neurotransmitters: anxiety, OCD) and H4 receptors (small fiber pain and itch).

Symptoms of mast cell activation include a variety of organ systems, including not only allergy, but also cardiologic (hypotension, tachycardia), GI (diarrhea, cramping), and constitutional (fatigue and even memory/concentration problems).

MCAS (mast cell activation syndrome) = MCAD + abnormal labs

Dysautonomia and POTS:

Dysautonomia: all disorders of the autonomic nervous system resulting from imbalanced sympathetic/parasympathetic activation - can be a clinical diagnosis, can be diagnosed with certain tests 

POTS: a form of dysautonomia meeting 2 specific diagnostic criteria: - History of orthostatic intolerance with or without systemic symptoms - Correlation of symptoms with a sustained increase in upright HR by at least 30 bpm (40 bpm if pt <20yo) within 10 minutes of standing or head-up tilt, without orthostatic hypotension

Common symptoms in patients with MCAD and POTS/dysautonomia 

General: fatigue, night sweats, anaphylaxis, weight changes 

HEENT: itchy/watery eyes, nasal congestion, itchy throat 

Cardiac: light headedness, pre-syncope, palpitations, tachycardia, labile BP 

Pulm: shortness of breath, wheeze, cough 

GI: refractory acid reflux, intermittent abdominal pain, nausea, vomiting, diarrhea 

GU: bladder irritability and frequent voiding, uterine cramps, heavy menstrual bleeding 

Derm: hives, itch, flushing, rash MSK: long bone pain 

Neuro: LH/dizziness, brain fog, neuropathy

Diagnosis and Evaluation:

1. Assess for hypermobility using the Beighton Score (score  results dependent on puberty and age)
2. Assess for EDS "red flags" (screening for vascular EDS and risk for ruptures, see image below)
3. Eval for hEDS then possibly for HSD once the red flags for the high-risk, genetic EDS subtypes have been ruled out 
4. Eval for comorbid dysautonomia and/or MCAD
5. Rule out mimics (e.g. iron-deficiency, vit D deficiency, allergy, GERD, etc)
   
   
   
   
   
   
   

Management

This was my favorite part of the presentation-- for a cohort of patients that almost feel untreatable, Dr. Ohlinger gave us SO many ways to consider treating these patients. The general idea is outlined again on her schematic in green (details below). Trigger avoidance, mast cell stabilizers, Autonomic Nervous System regulation, and H1/H2 blockers.

Trigger Avoidance: 

Low-Histamine Diet 

AVOID • Aged cheeses/Cured meats • Fermented foods (sauerkraut, kimchi, yogurt) • Alcohol (especially red wine) • Vinegar-containing foods (pickles, soy sauce) • Certain fish (tuna, mackerel, sardines) • Leftover meats and fish • High histamine fruits: strawberries, citrus fruits, bananas, pineapples, papayas, plums, etc. • High histamine vegetables: spinach, eggplant, avocado, tomatoes, pumpkin, etc. 

INCLUDE: Foods that are generally safe include: • Fresh meat and freshly caught fish • Fresh fruits (excluding those listed above) • Fresh vegetables (excluding those listed above) • Dairy substitutes (rice milk, coconut milk) 

GOOD Eating Habits • Eat fresh, home-cooked meals. • Freeze leftovers immediately to prevent histamine formation. • Limit processed and packaged foods

Mast Cell Stabilizers:

Autonomic Nervous System Regulation

• Systemic symptoms: Glycemic control [1st line],  Duloxetine or venlafaxine [1st line] 
• Compression: Compression socks (ideally to thigh) [1st line] Abdominal binder IF no pelvic floor dysfunction [2nd line] 
• Electrolyte repletion: Daily oral rehydration solution [1st line] • Normalyte powder, or LMNT powder, or DIY with ¾ tsp table salt, 2 tsp powdered sugar, ¼ tsp cream of tartar, squeeze of lemon for taste, all in 750 mL water 1-2x/day
• Autonomic nervous system retraining: Vagal tone exercises [1st line]  see image below
• Symptomatic orthostatic tachycardia from POTS: Cardio-selective beta blocker (or propranolol if no asthma/resp sx) [1st line] Ivabradine (Corlanor) 5mg bid [2nd line] Fludrocortisone [3rd line] Midodrine [4th line] 

H1/H2 Blockade

H1: allegra, loratadine, etc

H2: high dose famotidine 

Pro Tips:

1) IF you cannot get a patient in with a genetic counselor, primary care CAN order an Invitae Genetic Panel

2) Low hanging fruit for everyone: 

    

• Iron repletion for goal ferritin >50 (or >100 if baseline inflammation)

• Ferrous sulfate or iron bisglycinate M/W/F (Pure Encapsulations OptiFerin-C) if GI sx from other iron • Vitamin D repletion for goal vitamin D >30 

• Magnesium glycinate before bed is good for everyone who doesn't have diarrhea

I particularly appreciated how Dr. Ohlinger finished off her talk: with primary care strategies for managing what is a patient population that has often been dismissed, stigmatized, mislabeled, and struggled with a undeniably fragmented system. . .

Validate lived experiences: “Your symptoms are real and recognized.” - Lean in to the "I don't know" with a commitment to find solutions together. - Use structured frameworks (Beighton, consensus criteria) when possible to guide workup. - Document functional impact clearly to support referrals and accommodations

Integrative Medicine for the Skeptic (Meckler, 1/24/2024)

 A recording of this presentation is available HERE. 

***

Many thanks to Dr. Gabriela Meckler, senior resident for her excellent presentation titled Integrative Medicine for the Skeptic. She covered the evidence behind some important herbs and supplements for common primary care conditions.

Dr. Meckler wanted us to feel comfortable knowing the data for some specific integrative remedies for common medical problems:

• Ginger for nausea and vomiting of pregnancy 
• 500-1500 mg BID to TID
• A metanalysis of 10 RCTs found that ginger at these doses is as effective as pyridoxine and metoclopramide, and dimenhydrinate
• Most common side effect: heartburn
• There is also some evidence for ginger in migraine, dysmenorrhea, metabolic syndrome, respiratory diseases, and milk volume in the early post partum period
• Take home: consider recommending ginger either alone or as an adjunct to the traditional rx'd in pregnancy. Stop ginger when nausea starts (to prevent heartburn)
• Daily Magnesium for migraine headache prophylaxis 
• 400-600mg/daily
• Safe in pregnancy
• Most common side effect: diarrhea
• PO magnesium alleviates frequency and intensity of migraine (statistically significant)
• IV magnesium has the best evidence for treatment of acute migraine, but oral has good evidence as ppx
• IV magnesium helped migraine within 15-45 minutes after initial infusion, and lasted up to 24 hours
• Additional supplements that may be useful in migraine: 
• Riboflavin 400mg/day reduces headache from 4 days/month to 2 days/month (must be taken for 3-6 months), 
• Butterbur (but careful, must come from trusted source to remove pyrrolizidine alkaloids)
• Ginger 400mg + ibuprofen, can also be used for dysmenorrhea (2 days prior to onset of menses)
• Side note on Licorice safety in pregnancy (licorice is often found in combination in ginger tea products)
• Licorice contains glycyrrhizin, which can act as a mineralocorticoid
• Side effects: hypertension, hypernatremia, hypokalemia, renin suppression
• Glycyrrhizin is often present in low doses in these teas, about 31mg/cup of tea. 

• A longitudinal cohort study in Finland found licorice consumption in pregnancy to be associated with  lower intelligence and memory scores, higher HPA-axis activity, and higher incidence of ADHD in offspring. This high dose of glycyrrhizin was >= 500mg/week, So a pregnant person would have to drink upwards of two cups of tea containing licorice every day to get an adverse event

• Turmeric for osteoarthritis pain
• 100-2000mg daily for knee OA
• In a study of turmeric vs. paracetamol 500 BID vs. 650 TID x 6 weeks for OA, both arms showed decrease in pain and stiffness, increase in function =equivalent to tylenol!
• 1000mg should be paired with 6 mg piperine -- black pepper extract -- (just a tiny amount) for improved absorption 
• Warming up turmeric increases absorption and likely efficacy
• Most common side effect: GI upset, diarrhea

Recommended Resources for practitioners and patients 

• Institute for Functional Medicine (ifm.org)
• Nurtritionfacts.org (Dr. Michael Greger)
• IHerb.com
• Consumerlabs.org (requires subscription)