#341: Headache Update: Making Migraines Less Painful with Dr. Kevin Weber

June 20, 2022 | By Chris Chiu

Video

SNNOOPing around the new CGRP medications, ditans, and devices to rescue your patients from migraines!

Dr. Kevin Weber @KwebMD (Ohio State University Wexner Medical School) takes the pain out of headache management!  Have the confidence to prescribe new CGRP-antagonists and ditans for migraine prevention and acute relief.  We also dive deep into when to order imaging and alternatives like infusions and devices. 

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Credits

• Producer, writer, and show notes: Isabel Valdez PA-C
• Infographic: Edison Jyang
• Cover Art: Chris Chiu MD
• Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP; Chris Chiu MD   
• Reviewer: Molly Heublein MD
• Showrunner: Matthew Watto MD, FACP
• Technical Production: PodPaste
• Guest: Dr. Kevin Weber

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Show Segments

• Intro, disclaimer, guest bio
• Guest one-liner, Picks of the Week
• Case from Kashlak Definitions
• Imaging for headaches
• Labs
• Headache types
• Acute Migraine Treatment
• Ditans
• Anti-cgrp medications
• Prophylactic Migraine Treatment
• CGRP antagonists
• Devices
• Take home points
• Outro

Headache Update Pearls

1. Skip imaging when a patient has a normal neurological exam and has symptoms consistent with a migraine headache.  If history/exam is suggestive of a secondary headache, order an MRI of the brain without contrast for most patients.
2. Secondary causes of headaches can be recalled with the mnemonic SNNOOP10.
3. Be familiar with a few triptans to use as first line treatments for abortive therapy such as rizatriptan, naratriptan, or sumatriptan.
4. Lasmiditan works much like triptan for abortive treatment without causing vasoconstriction (so might be a better choice for patients with vascular disease) but comes with an 8-hour driving restriction.
5. CGRP-receptor blockers are a new option for migraine treatment.  These can be abortive (like ubrogepant or rimegepant oral) or preventative (rimegepant every other day or Atogepant daily oral or injectable monoclonal CGRP medications like fremanezumab, erenumab, and galcanezumab or eptinezumab via infusion).

Headache Update:  Making Migraines Less Painful

Headache Work-up Basics

Imaging

Neuroimaging is unnecessary in patients with headaches that are consistent with migraine and who have a normal neurological exam.  Imaging can be considered for the following reasons: unusual, prolonged, or persistent headache; changes in frequency and/or severity of the migraine; or first or worst migraine, as recommended by the American Headache Society Updated Guidelines for Neuroimaging in Migraine.  Less common scenarios in which to consider imaging for migraines include but are not limited to: brainstem aura, confusional, hemiplegic, side-locked, or post-traumatic headaches. The preferred imaging modality is MRI of the brain without contrast.  However, an MRI of the brain with contrast can be considered in a patient with a history of cancer or in a positional headache where a spinal leak is being investigated.  CT scan imaging of the brain has limited uses and is preferred in the acute setting in headaches described as the “worst headache of my life” or abrupt thunderclap headache; ie in instances where subarachnoid hemorrhaging, ruptured aneurysm, or skull fracture need to be evaluated (Evans 2020).

SNNOOP-10 for Secondary Headaches

Headaches that meet criteria for a secondary cause can be recalled with the mnemonic SNNOOP10 (Do 2019).  

Labs 

Lab tests tend to be lower yield in Dr. Weber’s opinion, but one could order routine labs such as blood counts, metabolic panel, thyroid function tests, Vitamin B12 with methylmalonic acid (MMA), and Vitamin D.  Evidence exists linking Vitamin D deficiency with migraine headaches (Ghorbani et al 2019; Zhang et al 2021). 

Headache history and categorization

In Dr. Weber’s opinion, a simple approach of headache categorization in primary care as tension-type, migraine, or other headaches can be utilized.  The other primary headaches types to consider include cluster-type, trigeminal autonomic cephalgias, and occipital neuralgia.

Details of the history to review in patients with headache include neck pain and changes in stress or mood (Vgontzas et al 2021). Sleep pattern changes such as changing to night shifts can also be the culprits of headaches (Appel et al 2020).  Dr Weber reminds patients to stay hydrated and eat regular meals to avoid triggering or worsening a headache. 

Cervicogenic headache 

Cervicogenic headaches are secondary headaches that stem from the neck as noted by the International Criteria of Headache Disorders (ICHD-3) that by definition respond to cervical block treatments. These are independent of migraine-type headaches. Based on Dr. Weber’s opinion, migraine headaches, especially chronic migraine, often have cervicogenic components that may benefit from physical therapy (Fernandez de la Penas 2015).

Mixed headache

In Dr. Weber’s expert opinion, headaches may exist in a continuum where patients may have a mixed headache picture of tension-headache and migraine headache.  His approach is to tease out the severe migrainous headache days that are debilitating and associated with nausea, vomiting, photophobia, phonophobia from the rest of the headache days, and treat accordingly. 

Migraine Treatment

Status Migrainosus Treatment and Migraine Cocktail Basics 

In Dr. Weber’s expert opinion, status migrainosus treatment could be addressed with off label use of a steroid taper, chlorzoxazone or a migraine cocktail. Dr. Weber recommends prednisone 60mg taper or a shorter dexamethasone taper.  He also utilizes muscles relaxers such as chlorzoxazone on a schedule for approximately five days.  In Dr. Weber’s experience in his institution, a migraine cocktail could also be employed; these usually includes an NSAID such as ketorolac, an antiemetic, diphenhydramine, magnesium, a muscle relaxer such as methocarbamol, valproic acid and a steroid such as dexamethasone (Vecsei 2018).  Infusion with this cocktail could be considered after a patient fails oral treatments or otherwise has treatment contraindications.

Triptans

Triptans are excellent abortive therapies for many patients with migraine, but due to their potential for vasoconstriction and serotonin syndrome may not be the best choice for all patients.  Dr. Weber’s expert practice is to avoid using triptans in patients with coronary artery disease, peripheral vascular disease, or history of ischemic stroke. Serotonin syndrome has been studied extensively and the risk is more theoretical than actual (Orlova et al 2018).  

Primary care providers should be familiar with a few triptans, preferably generic formulations such as rizatriptan and naratriptan.   Rizatriptan has a faster onset of action compared to other triptans and has fewer side effects than sumatriptan (Lines 2001).  Naratriptan is longer acting but has a slower onset (Tfelt-Hansen 2000, Hansen 2021).  Of the triptans, sumatriptan is the oldest and tends to have the most side effects but does come in multiple forms (oral, intranasal, injectable).

Chest pain can be a not uncommon side effect of triptans, but reassuringly it is rarely cardiac.  It can help to warn patients of this potential side effect in advance (Nappi 2003).  Triptans can be taken with other rescue medications including NSAIDs or combination analgesics containing acetaminophen, aspirin, and caffeine (Marmura 2015). 

Dr. Weber suggests avoiding the use of less favorable treatment options such as the combination butalbital, acetaminophen and caffeine due to its addictive potential (Marmura 2015).

Ditans

“Ditans” are centrally acting serotonin agonists. Lasmiditan is the only drug available in this class as of this recording. This drug is similar in action as triptan but in contrast does not cause vasoconstriction, so may be a good choice for a patient unable to take triptans due to vascular disease.  Patients may experience dizziness and sedation since this drug is more centrally-acting.  Patients are advised not to drive for 8-hours after taking lasmiditan (DeJulio 2021, Beauchene and Levien 2021). 

Oral CGRP-Receptor Antagonists aka: the Gepants

Calcitonin gene related peptide (CGRP) is a protein that has been linked to migraines and induces vasodilation. When CGRP is blocked, it does not contribute to vasoconstriction but can help prevent or abort migraines.  Because of this property, CGRP-receptor antagonists are attractive options for migraine treatment in patients with cardiovascular risk factors (Messina and Goadsby, 2019; Hutchinson 2021). 

These newer agents are subject to variable insurance coverage and in some cases may be covered when triptans are contraindicated or after the patient has failed to improve with two triptans. 

As of this recording, the two available gepants for abortive therapy are ubrogepant and rimegepant.  These medications are metabolized by the CYP-system and as such, subject to drug-drug interactions.  These drugs have a good side effect profile and do not tend to cause rebound or medication overuse headaches. These can be taken with other abortive medications including triptan and NSAIDs. Ubrogepant is dosed once and can be repeated after two or more hours (Zhang et al 2021). Rimegepant is taken only once a day as a rescue agent (Croop et al 2019). 

Preventive therapies

CGRP-Receptor Antagonists

Some oral CGRP-receptor antagonists are FDA approved for migraine prevention.  Atogepant is the once daily oral gepant that can be taken for prophylaxis (Ailani et al 2021).  Rimegepant is taken orally once every other day for prophylaxis (Croop et al 2021).  

CGRP Monoclonal Antibodies

Currently, there are four CGRP monoclonal antibodies available for the use of migraine headache prevention (Yuan 2019). Fremanezumab, erenumab, galcanezumab and eptinezumab are very well tolerated with few side effects such as injection-site reaction and are not associated with immunosuppression.  As of early 2022, the safety of using two gepants together for rescue and prevention is still being studied (Berman et al 2020; Mullin et al 2020).

Erenumab

• Oldest of the four monoclonal antibodies (Dodick et al 2018) 
• Mechanism of action: antibody that inhibits CGRP receptor 
• Has been associated with constipation (Kanaan et al 2020) and elevated blood pressure (Saely et al, 2021)
• Subcutaneous injection given with auto-injector once a month

Galcanezumab:  

• Mechanism of action: CGRP antibody (Detke et al 2019)
• Monthly subcutaneous injection given with auto-injector or prefilled syringe

Fremanezumab:

• Mechanism of action: CGRP antibody (Ferrari et al 2019)
• One monthly injection or three injections given together quarterly
• Subcutaneous injection given with auto-injector or prefilled syringe

Eptinezumab: 

• CGRP antibody.
• Newest of the treatments as of May 2022. 
• Given by IV every three months 

These new CGRP medications are expensive, and many insurance companies will have restrictions on their coverage for these medications, Dr. Weber notes that patients may be required to have tried and failed, or be ineligible for step therapy with two or three classic prophylactic agents, such as:

• Antihypertensive: beta-blockers-metoprolol, nadolol, atenolol; ARB-candesartan (Dorosch 2019); CCB-verapamil (Markley 1991)
• Anti-seizures agents: topiramate, valproic acid
• Tricyclic antidepressants: amitriptyline, nortriptyline
• SNRI: venlafaxine (Ozyalcin 2005)

Kashlak attendings remind us that many patients can do well with these older, inexpensive prophylactic medications so don’t feel the need to immediately jump to newer anti-CGRP medications from the start.  Consider secondary indications that a patient may have for certain medications, like hypertension or depression/anxiety, when selecting prophylactics.  

Supplements

Magnesium oxide or magnesium citrate are the best studied migraine prophylaxis in patients with menstrual migraine (Facchinetti et al 1991) or migraine with aura (Marmura 2015). Magnesium is a very safe option that can be taken daily, but it can worsen or cause diarrhea (von Luckner and Riederer 2018).  Additionally, evidence supports the use of coenzyme Q-10 and riboflavin in migraine prevention (Sazali 2021). Butterbur is a root with documented evidence for prevention but it has come under scrutiny due to a contamination from pyrrolizidine alkaloids (Din 2021). 

Neuromodulators 

The first device to come out on the market called Cephaly is a supraorbital nerve stimulator sticker that is applied on the forehead and can be used for both treatment (Kuruvilla et al 2022) or prevention (Ordas et al 2020). This has been out the longest and is currently available over-the-counter without a prescription.  This device does not have side effects and is safe to use in almost all patients. This poses an out-of-pocket cost to the patient since it is poorly covered by insurance. There is another, similar  devices in the pipeline that is a combination supraorbital and occipital nerve stimulator.

The remaining devices available require prescriptions. There is a vagal nerve stimulator available that has been approved for cluster and migraine headache, though the data is limited on the treatment of acute migraine or use with prevention (Blech et al 2020, Najib et al 2022). Transcranial magnetic stimulators have been used in the treatment of depression but have also been approved for the prevention and treatment of acute migraine (Misra and Bhoi 2012; Lipton et al 2010). Nerivio, a remote electrical neuromodulator, delivers pulses onto the arm and is controlled with a smartphone. 

Take-home points

• Typical migraines do not have to be imaged if the neurological exam is normal. 
• Consider imaging with an MRI if a patient reports concerning changes to the headaches such as systemic symptoms or if the patient is of advanced age or has a history of cancer or immunosuppression.  
• Get the patient started on older, oral treatments for prevention or rescue medications such as triptans to put the patient on the path for newer remedies if needed.

Links

1. Pick of the Week: Jack White Fear of the Dead
2. Imposter syndrome/phenomenon
3. The International Classification of Headache Disorders
4. SNNOOP-10
5. Curbsiders #4: Are You Afraid of Patients with Migraines?
6. Curbsiders #122: Headaches Advanced Class: Migraines, medication overuse and more!

Goal

Listeners will approach the treatment of acute and chronic migraines using classic and novel medications and discern criteria for imaging secondary headaches.  

Learning objectives

After listening to this episode listeners will…

1. General approach to classifying headaches
2. Recognize red flags in any headache
3. Develop an approach to diagnosing and differentiating types of headaches
4. Navigate newer treatment options such as CGRP antagonists to select the most appropriate treatment course 
5. Create a primer for acute and chronic headaches treatment
6. Recognize opportunities for headache prevention
7. Engage the patient is selecting the best treatment among novel medications

Disclosures

Dr. Weber reports he received grants and fellowship support from Abbvie, Amgen, Lundbeck, and Lilly. The Curbsiders report no relevant financial disclosures. 

Citation

Valdez I, Weber K, Chu C, Williams PN, Watto MF. “#341: Headache Update: Making Headaches Less Painful”. The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list June 20, 2022.