New Approaches to Treating Migraines

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A recent paper, by M. S. Robbins (of Weill Cornell Medical College) and published in the May 2021 issue of JAMA: The Journal of the American Medical Association, reviews the diagnosis and management of common types of primary headaches. The review is based on information obtained from 94 articles (over a third being randomized clinical trials) published between 2010 and 2021.

This post includes a summary of the paper’s section on migraine headaches. A subsequent post will cover tension headaches and cluster headaches.

What Are Primary Headaches?

Headaches usually occur when pain-sensitive structures in the head and neck (e.g., muscles, arteries, veins, sinuses, meninges) experience pressure, irritation, inflammation, and the like.

Headaches come in many forms, differing from each other in terms of frequency, location, intensity of pain, etc. Another differentiating factor is the cause of the headache: Secondary headaches are caused by (or related to) other health issues—e.g., brain tumor, cerebral aneurysm, stroke, concussion, neck injury, gastrointestinal disorder, the flu, ear or sinus infection, dehydration. Primary headache disorders, by contrast, are not a symptom of another health issue.

Primary headaches comprise:

• Tension-type headaches
• Migraines
• Other primary headache disorders (e.g., new daily persistent headache)
• Trigeminal autonomic cephalalgias (TACs)

TACs, which include cluster headaches, are rare. Most prevalent are tension-type headaches, though migraines are the most disabling of the common primary headaches.

What Are Migraine Headaches?

Migraine is a common neurological condition (prevalence of approximately 12 percent) affecting millions of Americans each year. Migraine headache pain can be moderate or severe, is usually (not always) one-sided, and typically described as throbbing or pulsating.

Migraine headaches often run in families, are more prevalent in women, and most common in people in their late 30s (migraine prevalence and severity decrease with age).

The causes of migraine are probably a combination of genetic and environmental factors. Migraine pathophysiology might involve multiple brain structures (e.g., brainstem, hypothalamus, trigeminal nerve) and processes (e.g., cortical spreading depression, the release of inflammatory calcitonin gene-related peptide) during different phases of a migraine attack.

Depending on the patient, migraines can be triggered by many factors, like hormonal changes in women (e.g., menstruation), emotional stress, alcohol, medications, hunger, dehydration, foods (e.g., chocolate, aged cheeses, and other tyramine-rich foods), light, noise, smells, insomnia, and major environmental and weather changes. Since migraine triggers are not the same for everyone, it would be useful to keep a diary of one’s migraine attacks to help identify potential migraine triggers.

Migraine has four phases—though not all migraine patients experience all phases—as described below.

1. Prodrome: Premonitory symptoms (e.g., mood changes, yawning, food cravings) occur hours or even a day or two before the migraine attack.
2. Aura: Symptoms (e.g., flashing lights and zigzag lines, pins and needles, numbness) develop gradually, last an hour at most, and occur before/during the attack.
3. Pain phase: Characterized by pulsing pain, nausea, vomiting, light sensitivity, sound sensitivity, and/or odor sensitivity. Attacks last from four hours to three days.
4. Postdrome: Fatigue, exhaustion, and confusion are commonly reported for a day or so after the attack, though some patients report feeling euphoric and refreshed instead.

For most migraine patients, migraine attacks are episodic, while for 2.5 percent, migraines become chronic (i.e. attacks on 15 or more days per month for at least three months). However, over two years, about a quarter of chronic migraine cases revert back to episodic migraine.

Some factors associated with the change from episodic migraine to chronic migraine are drinking too much caffeine, persistent and frequent nausea, depression, anxiety, obesity, pain disorders, snoring and obstructive sleep apnea, medication overuse (e.g., opioids, triptans, barbiturates, non-steroidal anti-inflammatory drugs or NSAIDs), and allodynia. Allodynia refers to the experience of pain from something not usually associated with pain (e.g., a light touch).

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How Can You Treat Migraine Headaches and Prevent Migraine Attacks?

During attacks, laying down in a dark, quiet room helps reduce the intense pain and nausea. Indeed, migraine pain and nausea are often worsened by activity and exposure to light, sound, and smells.

But many people find they need medical help because their symptoms are severe or their migraine attacks occur frequently. Initially, these patients typically try over-the-counter analgesics and painkillers like Advil and Motrin (both containing ibuprofen) or Excedrin (containing aspirin, paracetamol, and caffeine). But what other medical treatments for migraine are available (see Table 1)?

Source: Arash Emamzadeh (adapted from Robbins 2021)

Generally speaking, the most effective pharmacological treatments for migraine headaches (acute migraine attacks) are “Acetaminophen, 1000 mg; NSAIDs, such as naproxen sodium [Aleve], 550 mg; and combination products that include caffeine.” Effective secondary treatments for migraine headaches comprise “triptans, such as rizatriptan [Maxalt], 10 mg, or eletriptan [Relpax], 40 mg.” If two or more “triptan medications are ineffective, contraindicated, or not tolerated, gepants, such as rimegepant [Nurtec ODT] or ubrogepant [Ubrelvy], or lasmiditan [Reyvow] may be prescribed.”

Other treatments for migraine headaches include neuromodulation therapies:

• Single-pulse transcranial magnetic stimulation (sTMS)
• Non-invasive vagus nerve stimulation (nVNS)
• External trigeminal nerve stimulation (eTNS)
• Remote electrical neuromodulation (REN)

Commonly used interventions for preventing migraine headaches comprise antihypertensives (drugs that treat high blood pressure) like propranolol (Inderal) and candesartan (Atacand); antidepressants, such as the tricyclic antidepressant amitriptyline (Elavil), or the serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressant venlafaxine (Effexor); and anticonvulsants/antiepileptics like topiramate (Topamax).

“A typical therapy,” Robbins explains, “consists of candesartan, 16 mg, daily or topiramate, 50 mg, twice daily.” For non-responders, monoclonal antibodies (e.g., eptinezumab, brand name Vyepti), botulinum toxin (Botox), and neuromodulation devices mentioned above should be considered.

Some research suggests certain vitamins, minerals, and supplements like coenzyme Q10, vitamin B2 (riboflavin), melatonin, magnesium, and butterbur could be beneficial too.

Other interventions for preventing migraine headaches include mindfulness meditation practices, cognitive behavioral therapy, and thermal biofeedback.

Last, patients may want to seriously consider psychological stress management techniques and relaxation practices (e.g., deep breathing, progressive muscle relaxation), regular physical exercise, healthy eating, weight control, sufficient sleep, and other healthy lifestyle factors.

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