Migraine Management

Drug Treatments

Migraine medications are aimed at stopping symptoms and preventing future attacks.
They fall into two broad categories:

1. Pain-relieving medications

Also known as acute or abortive treatment, these types of drugs are taken during migraine attacks and are designed to stop symptoms:

  • Nonsteroidal anti-inflammatory drug (NSAID)

    • NSAID Like aspirin, Ibuprofen, Naproxen. The painkilling action of NSAIDs reduces the direct effect of inflammation on pain-nerve stimulation and sensitivity.
    • The most commonly reported adverse reactions are indigestion and other gut complaints, headaches, dizziness, drowsiness.
  • Paracetamol

    • Paracetamol (acetaminophen) is generally not considered an NSAID because it has only minor anti-inflammatory activity. It treats pain mainly by blocking COX-2 and inhibiting endocannabinoid reuptake almost exclusively within the brain, but not much in the rest of the body.
    • The most commonly reported adverse reactions have included nausea, vomiting and constipation.
  • Triptans

    • Triptans are powerful drugs, a family of tryptamine-based drugs (sumatriptan, naratriptan, zolmitriptan, eletriptan and almotriptan). This drug class was first introduced in the 1990s. Triptans have largely replaced ergotamines, an older class of medications used to relieve migraine and cluster headaches. They act as vasoconstrictors by mimicking the action of serotonin.
    • Their main contraindication is the coronary arterial disease (C.A.D.), hypertension, heart disease, diabetes and stroke. The most commonly reported adverse effects are dizziness, drowsiness, fatigue, dry mouth, feeling hot or, conversely, cold sweats. They can also cause a feeling of tightness in the throat or chest, muscle pain, especially in the neck, or an increase in blood pressure. All of these signs are sometimes collected under the name of “triptan syndrome”
  • Ergot Alkaloids

    • Derivatives of ergot are vasoconstrictors. Ergotamine is the most frequently used but there is also dihydroergotamine or DHE mainly used in the treatment of migraine and introduced in the 1970s. The 5-hydroxytryptamine (5-HT) receptor family mediates the effects of several drugs highly effective in migraine primarily by activating 5-HT(1B), 5-HT(1D), and 5-HT(1F) receptors. Ergotamine, dihydroergotamine, and methysergide, as well as the “triptan” sumatriptan, are all agonists for these receptors.
    • Side effects of ergotamine include nausea and vomiting. At higher doses, it can cause raised arterial blood pressure, vasoconstriction (including coronary vasospasm) and bradycardia or tachycardia. Severe vasoconstriction may cause symptoms of intermittent claudication.
  • Opiates

    • Opioids are substances that act on opioid receptors to produce morphine-like effects. [2]Medically they are primarily used for pain relief, including anesthesia.[3]  Opioids bind to specific opioid receptors in the nervous system and other tissues. There are three principal classes of opioid receptors, μ, κ, δ (mu, kappa, and delta). There are “weak” opioid pain relievers and minor opioids such as codeine, dihydrocodeine and tramadol; and strong opioids: morphine and its derivatives.
    • The main side effects include constipation, drowsiness, nausea, vomiting, dizziness, decreased alertness, urine retention and apnea. The most dangerous side effect is their addictive nature (USA opioid epidemic).

2. Preventive treatment and medications

The acute treatment aims to stop the migraine attack and relieves the acute pain that a patient suffers during the onset of a migraine attack. When it comes to the prevention treatment, the aim there is different.

The aim with prevention is to actually reduce the frequency of the attacks, reduce the severity and the duration of the attacks. These types of drugs are taken regularly, often daily, to reduce the severity or frequency of migraines.

  • Beta-Blockers

    • The use of beta blockers for the treatment of migraine began in the late ’60s, when by accident migraine sufferers being treated for cardiovascular disease found that their migraine attacks lessened. Further research in the ’70s led to propranolol being the first of this class of medications to be approved by the FDA for migraine prevention. Subsequently the FDA also approved the use of timolol. Several other beta blockers have been shown in research trials to also be effective for migraine prevention.
    • These include metoprolol, nadolol and atenolol. Beta blockers appear to act by helping to stabilize the blood vessels and limiting the tendency for the blood vessels to over-dilate. Other mechanisms may include reducing the excitability of the nervous system, effects on the serotonin and reducing anxiety.
    • Contraindications for their use are respiratory diseases such as asthma or chronic bronchitis. Side effects include low blood pressure and slow heart rate. They need at least 4-6 weeks of therapy to show their efficacy.
  • Calcitonin Gene-Related Peptide (CGRP)

    • A number of small molecule CGRP receptor blockers have been developed that show clinical efficacy in acute migraine. The first CGRP receptor blocker was called olcegepant. It was given intravenously and provided proof of concept that targeting CGRP was an effective migraine strategy.
    • Although the drug showed clinical effectiveness in phase II trials, there were difficulties in producing an orally available formulation and so drug development was discontinued.
    • The first orally available molecule of this class – the ‘gepants’- was called telcagepant but liver toxicity issues resulted in discontinuation. New oral gepants, including ubrogepant and rimegepant, are undergoing clinical trials. These have not shown liver toxicity to date.
    • It is hoped that the CGRP receptor blockers may provide an alternative to triptan therapy for acute migraine which has been associated with limited response, adverse effects, and the frequent need for repeat dosing or alternative analgesia.
    • Another approach in migraine therapy uses monoclonal antibodies to block CGRP activity. These humanized monoclonal antibodies to CGRP are administered subcutaneously or intravenously and have shown efficacy in preventing migraine attacks. The buzz surrounding this new migraine management class has to do with the fact that anti-CGRP peptide and anti-CGRP receptor antibodies have been developed specifically for migraine pathophysiology.
    • All four monoclonal antibodies have achieved similar results in Phase 3 trials to date for efficacy, tolerability, and safety. Upon injection, the monoclonal antibodies are distributed in many tissues, with the highest concentrations occurring in the lung, kidneys, heart and spleen; very little crosses into the brain. In trials, many patients saw their migraine days decrease by 2 to 5 per month. For up to one-third of patients, headaches improved by 75% or more. A smaller minority (20% in an intravenous trial; and about the same percentage in a galcanezumab subcutaneous trial) experienced almost 100% improvement.
    • As to side effects, they have been minimal in the short-term. Outside of local injection reactions, the monoclonal antibodies have been surprisingly well-tolerated and no cardiovascular or liver concerns have been raised. In the long-term, however, the medical community is concerned about cardiovascular risk. CGRP plays a role in cardiovascular homeostasis during ischemic events. It has vasodilatory effects and is important in the regulation of blood pressure. CGRP is also involved in wound healing; blocking it could, in theory, interfere. While the pending monoclonal antibodies do not cross the blood brain barrier, the pituitary gland lies outside of this barrier; CGRP and its receptors are found in the anterior pituitary. CGRP is also present in the gastrointestinal (GI) tract and plays a role in GI motility. It is possible that blocking CGRP could contribute to inflammatory bowel disease. As long-term effects are unknown, clinicians may take caution in prescribing.
  • Botox Injection

    • Botox is a brand of botulinum neurotoxin (BoNT), a protein substance originally derived from the Clostridium botulinum bacteria. Botox was introduced for the treatment of chronic migraine in 2000, after some people who received injections for cosmetic treatment of the facial lines reported an improvement in headaches.
    • Botox is a form of botulinum toxin, a neurotoxin produced by the bacteria that causes botulism. When the Botox botulinum toxin is purified and used in tiny doses in specific areas, it temporarily reduces muscle contractions for approximately 3 months.
    • Botox is only FDA-approved for chronic migraines, which means a headache on 15 or more days a month.  “The more frequent the headaches, the better the patient does with Botox,” says Dr. Andrew Blumenfeld, Director, The Headache Center of Southern California. Botox is not recommended for patients who experience fewer than 15 headache days a month.
    • Botulinum toxin is injected into the muscles of the head and neck and causes paralysis by blocking neuromuscular transmission (specifically acetylcholine relaxation). It relaxes the different muscles – the temporal muscle, the muscles of the neck, between the eyebrows – and can soothe the pain associated with the contractions of these facial muscles.
    • However, the botulinum toxin contained in Botox can spread to other body areas beyond where it was injected. This has caused serious life-threatening side effects in some people receiving botulinum toxin injections, even for cosmetic purposes.
    • Common Side Effects: muscle weakness near where the medicine was injected; trouble swallowing for several months after treatment; muscle stiffness, neck pain, pain in your arms or legs; blurred vision, puffy eyelids, dry eyes, drooping eyebrows, dry mouth, headache, tiredness, increased sweating in areas other than the underarms or bruising, bleeding, pain, redness, or swelling where the injection was given.
  • Co-analgesics

    Besides conventional analgesic treatments, there are other drugs which promote the action of analgesics or which act on the cause of pain, they are called co-analgesics:

    • antidepressants, the analgesic effect of which occurs before the antidepressant effect
    • neuroleptics, which also have an anxiolytic effect
    • benzodiazepines, which also have anxiolytic, muscle relaxant, amnesic, sedative and hypnotic effects
    • antiepileptics, which have an interest in pain of neurological origin
    • corticosteroids, the analgesic effect of which passes through an anti-inflammatory action

Non-Drug Treatments

1. Migraine surgery

The surgical operation aims to decompress the sensitive nerves of the head by spreading the ligaments, muscles or vessels that compress them. It is indicated when the disease is not controlled by conservative measures, which include medicines and behavioral therapy.

2. Neuromodulation

The International Neuromodulation Society defines therapeutic neuromodulation as “the alteration of nerve activity through targeted delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body.” In appropriate patients, this growing class of therapies, in common use since the 1980s, can help restore function or relieve symptoms that have a neurological basis.


3. Thermal Microcautery

Thermal microcautery (TMC) is a form of peripheral nerve field stimulation (PNFS). It is a new method of neuromodulation. There is activation of the A(touch), Aδ and c (fast and slow pain) nerve fibers possibly working by the mechanism of the Gate theory of pain (2). There is facilitation of the descending noxious inhibitory pathway, which is well known to be activated by noxious stimuli.