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New Headache Treatments

Headache (Cephalea, Migraine) in its different forms is a highly disabling health problem which, in addition to severely altering quality of life, has important socio-health and socio-occupational consequences. More than 50% of people suffer from headache episodes. Migraine affects 14% of the world's population.

Headaches are often classified into primary and secondary headaches. The most common primary headaches are Migraine, Tension Headache, Cluster Headache and Trigeminal-Autonomic Headaches. The group of secondary headaches includes a wide range of medical conditions to which the headache is attributed (head and/or neck trauma, cranial and/or neck vascular disorder, non-vascular intracranial disorder, administration or suppression of drugs or toxic substances, infections, disorders of homeostasis, disorders of the skull, neck, eyes, ears, nose, sinuses, teeth, mouth or other facial or neck structures, and various psychiatric disorders). A third group includes painful cranial neuropathies, other facial pain and other forms of headache.

Classical treatments for acute migraine are made with triptans, non-steroidal anti-inflammatory drugs (NSAIDs) ( Aspirin, Ibuprofen, Naproxen, Diclofenac), Paracetamol and antiemetics (Domperidone, Metoclopramide), when necessary. Other commonly used drugs are antidepressants, antiepileptics, hypotensive agents and botulinum toxin A. The triptans (Almotriptan, Eletriptan, Flovatriptan, Naratriptan, Rizatriptan, Sumatriptan, Zolmitriptan) are a family of tryptamine-based drugs that act as serotonergic 5-HT1B and 5-HT1D receptor agonists at the level of blood vessels and nerve terminals. The first triptan was Sumatriptan, introduced in 1991 for the treatment of acute migraine and cluster headache. Triptans represent a form of symptomatic pharmacological intervention, not very effective in tension headaches, lacking a preventive profile.

Approximately 40-50% of headache patients are not candidates for NSAIDs, triptans and other commonly used molecules.

The important thing in this pathology of the central nervous system is to treat the cause rather than the symptom, as should be done with any other pathology. Although the causes of migraine and primary headaches are not clear, there is a genetic-familial component in more than 40% of cases, followed by vascular, hormonal, emotional and various organic problems.

As far as conventional treatment is concerned, approximately 40-50% of headache patients are not candidates for NSAIDs, triptans and other commonly used molecules due to potential side effects, and it is therefore recommended that a pharmacogenetic profile be performed prior to the initiation of chronic treatment with these pharmacological agents.

In recent years, major genetic studies have been carried out to identify the population at risk in order to set up preventive programmes, with the drawback of a lack of suitable new-generation drugs. New treatments for migraine, also under pharmacogenetic scrutiny, include anti-CGRP monoclonal antibodies (Galcanezumab), small molecules that bind to CGRP (Calcitonin gene-related peptide) and its receptors in brain structures, and the new generation of Gepants (Rimegepant). CGRP is a brain neuropeptide. Since 2018, the Food and Drug Administration (FDA) has approved six antagonists that block CGRP or its receptors in migraine. These new drugs are no more effective than conventional drugs (25% total pain remission, 50% pain attenuation), but they have fewer side effects and work in some patients who fail triptans, NSAIDs and other medications. CGRP is a potent vasodilator and there are concerns that CGRP antagonists may cause stroke or cardiovascular problems. Another attractive neuropeptide for headache is PACAP (Pituitary Adenylate-Cyclase-Activating Peptide), currently under study.

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