Revisiting the Role of Ergots in the Treatment of Migraine and Headache

Eric P. Baron, DO; Stewart J. Tepper, MD


Headache. 2010;50(8):1353–1361 

In This Article

Abstract and Introduction


The harmful side effects of the ergots described by early civilizations have been overcome with efficacious treatment for headaches including migraine, cluster, and chronic daily headache. Use of ergots contributed to initial theories of migraine pathogenesis and provided the substrate for development of the triptans. Triptans are very efficacious for many migraineurs, and since their widespread use, use of ergots has significantly declined. Unfortunately, there remain many migraineurs who benefit little from triptans, yet respond very well to ergots. Discoveries in migraine pathophysiology have given us better understanding of the complex processes involved, although there remain many unknown factors in migraine treatment. Additional, unrecognized therapeutic targets may exist throughout the neuronal connections of the brainstem, cortex, and cerebral vasculature. Ergots interact with a broader spectrum of receptors than triptans. This lack of receptor specificity explains potential ergot side effects, but may also account for efficacy. The role of ergots in headache should be revisited, especially in view of newer ergot formulations with improved tolerability and side effect profiles, such as orally inhaled dihydroergotamine. Redefining where in the headache treatment spectrum ergots belong and deciding when they may be the optimal choice of treatment is necessary.


Ergots are derived from the fungus Claviceps purpurea, which has a variety of harmful effects when ingested, including hallucinations, miscarriage, and vasoconstriction. These potential harmful effects were overcome by a combination of purification and scientific study, with ergot derivatives now providing a number of important treatments for migraine, cluster, and other disorders.

Use and study of ergots contributed to formulating theories of migraine pathophysiology, as well as providing the substrate for development of the triptans. Since the advent of the triptan era, use of ergots has significantly declined. Dihydroergotamine (DHE) continues to be utilized frequently by headache specialists for needs that triptans do not fit and, worldwide, methysergide, ergonovine (ergometrine), methylergonovine (methylergometrine), and other ergots are also used.

Initially, migraine was thought to be a vascular headache caused by vasodilation, and ergots felt to work by vasoconstriction. Migraine pathophysiology is currently felt to be neurogenic, with secondary vascular changes. Previously unrecognized therapeutic neuronal receptor targets exist throughout the neuronal connections between brainstem, cortex, and meninges.

Ergots interact with a multitude of receptors pivotal to the genesis and maintenance of migraine headache. While triptans are primarily serotonin 1B and 1D subreceptor-specific agonists (and some are also agonists at 1F), ergots have a broader spectrum of receptor actions. This wider spectrum of receptor interaction likely accounts for ergot efficacy observed when triptans and other medications fail, such as in status migrainosus and other refractory headaches. Therefore, the potential role for ergots in migraine treatment should not be forgotten, especially in view of newer ergot formulations with improved tolerability and side effect profiles such as orally inhaled (INH) DHE, in phase III trials at the time of this writing.

Ergots were introduced prior to modern criteria of efficacy and outcomes data, and often the literature on their use is archaic. However, based on the enormous experience, headache specialists have with DHE, and with ergotamine (E) and methysergide before it, revisited ergot use in headache treatment, and comparing and contrasting that use with triptans, is warranted.


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