Nitroglycerin-induced cluster headache attacks characterised comprehensively

Results from the first single-blind, placebo-controlled study using intravenous nitroglycerin in cluster headache were presented at the MTIS 2020 Virtual Symposium [1]. Weight-adjusted intravenous nitroglycerin effectively and reliably induced cluster headache attacks, cranial autonomic symptoms, and non-headache symptoms in cluster headache patients.

Cluster headache is a primary headache disorder characterised by recurrent attacks of unilateral excruciating headache, ipsilateral cranial autonomic symptoms, and agitation. Attacks last 15-180 minutes and can recur up to 8 times a day.

Due to the episodic nature of cluster headache, nitroglycerin has been used as a method to induce cluster headache attacks for decades. However, the primary route of administration was sublingual, which has an unreliable bioavailability. Therefore, the current study used weight-adjusted intravenous nitroglycerin (0.5 μg/kg/min).

This single-blind, placebo-controlled study comprehensively investigated the stages of cluster headache attacks: non-headache symptoms, cranial autonomic symptoms, and pain onset. Participants were patients with episodic or chronic cluster headache and underwent 3 study visits in total: (i) during the first visit, 33 participants were unblinded and received intravenous nitroglycerin for 20 minutes; (ii) if an attack was triggered, they were asked to return for blinded visits either receiving nitroglycerin (n=25) or blinded placebo infusions (n=24), in random order; (iii) the clinical phenotype was recorded.

Nitroglycerin triggered cluster headache attacks in 79% of patients during the unblinded nitroglycerin visit and 76% during the blinded nitroglycerin visit. Nitroglycerin also induced non-headache symptoms and cranial autonomic symptoms with the attacks:

• non-headache symptoms: occurred in 91% participants during the unblinded nitroglycerin visit, and 84% during the blinded nitroglycerin visit; and
• cranial autonomic symptoms: occurred in 94% participants during the unblinded nitroglycerin visit, and 97% during the blinded nitroglycerin visit.

Time until the start of cluster headache attacks was shorter in the episodic cluster headache group compared with the chronic cluster headache group. During the nitroglycerin-induced cluster headache attacks, non-headache symptoms started early and were followed by cranial autonomic symptoms and pain. Finally, time until nitroglycerin-induced cluster headache attacks was shorter in the episodic group versus chronic cluster headache group. This observation highlights potential differences between subgroups of patients with cluster headache.

 

1. Wei DY. Placebo-controlled intravenous nitroglycerin phenotyping of acute attacks cluster headache. MTIS 2020 Virtual Symposium, abstract MTV20-DP-025.

Posted on 27 October 202019 November 2021