Title:The Neuropharmacology of Cluster Headache and other Trigeminal Autonomic Cephalalgias
Volume: 13
Issue: 3
Author(s): Alfredo Costa, Fabio Antonaci, Matteo Cotta Ramusino and Giuseppe Nappi
Affiliation:
Keywords:
Headache, preventive treatments, symptomatic treatments, treatment guidelines, trigeminal autonomic cephalalgias.
Abstract: Trigeminal autonomic cephalalgias (TACs) are a group of primary headaches including
cluster headache (CH), paroxysmal hemicrania (PH) and short-lasting unilateral neuralgiform headache
with conjunctival injection and tearing (SUNCT). Another form, hemicrania continua (HC), is also
included this group due to its clinical and pathophysiological similarities. CH is the most common of
these syndromes, the others being infrequent in the general population. The pathophysiology of the
TACs has been partly elucidated by a number of recent neuroimaging studies, which implicate brain
regions associated with nociception (pain matrix). In addition, the hypothalamic activation observed in
the course of TAC attacks and the observed efficacy of hypothalamic neurostimulation in CH patients suggest that the
hypothalamus is another key structure. Hypothalamic activation may indeed be involved in attack initiation, but it may
also lead to a condition of central facilitation underlying the recurrence of pain episodes. The TACs share many
pathophysiological features, but are characterised by differences in attack duration and frequency, and to some extent
treatment response. Although alternative strategies for the TACs, especially CH, are now emerging (such as
neurostimulation techniques), this review focuses on the available pharmacological treatments complying with the most
recent guidelines. We discuss the clinical efficacy and tolerability of the currently used drugs. Due to the low frequency of
most TACs, few randomised controlled trials have been conducted. The therapies of choice in CH continue to be the
triptans and oxygen for acute treatment, and verapamil and lithium for prevention, but promising results have recently
been obtained with novel modes of administration of the triptans and other agents, and several other treatments are
currently under study. Indomethacin is extremely effective in PH and HC, while antiepileptic drugs (especially
lamotrigine) appear to be increasingly useful in SUNCT. We highlight the need for appropriate studies investigating
treatments for these rare, but lifelong and disabling conditions.
