Differential efficacy of non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: A meta-analysis

Ilse F de Coo, Juana Ca Marin, Stephen D Silberstein, Deborah I Friedman, Charly Gaul, Candace K McClure, Alok Tyagi, Eric Liebler, Stewart J Tepper, Michel D Ferrari, Peter J Goadsby, Ilse F de Coo, Juana Ca Marin, Stephen D Silberstein, Deborah I Friedman, Charly Gaul, Candace K McClure, Alok Tyagi, Eric Liebler, Stewart J Tepper, Michel D Ferrari, Peter J Goadsby

Abstract

Background: Two randomized, double-blind, sham-controlled trials (ACT1, ACT2) evaluated non-invasive vagus nerve stimulation (nVNS) as acute treatment for cluster headache. We analyzed pooled ACT1/ACT2 data to increase statistical power and gain insight into the differential efficacy of nVNS in episodic and chronic cluster headache.

Methods: Data extracted from ACT1 and ACT2 were pooled using a fixed-effects model. Main outcome measures were the primary endpoints of each study. This was the proportion of participants whose first treated attack improved from moderate (2), severe (3), or very severe (4) pain intensity to mild (1) or nil (0) for ACT1 and the proportion of treated attacks whose pain intensity improved from 2-4 to 0 for ACT2.

Results: The pooled population included 225 participants (episodic: n = 112; chronic: n = 113) from ACT1 (n = 133) and ACT2 (n = 92) in the nVNS (n = 108) and sham (n = 117) groups. Interaction was shown between treatment group and cluster headache subtype (p < 0.05). nVNS was superior to sham in episodic but not chronic cluster headache (both endpoints p < 0.01). Only four patients discontinued the studies due to adverse events.

Conclusions: nVNS is a well-tolerated and effective acute treatment for episodic cluster headache.

Trial registration: The studies were registered at clinicaltrials.gov (ACT1: NCT01792817; ACT2: NCT01958125).

Keywords: Episodic cluster headache; acute treatment; chronic cluster headache; meta-analysis; neuromodulation; non-invasive vagus nerve stimulation.

Figures

Figure 1.
Figure 1.
Proportion of participants who responded at 15 minutes for the first treated attack. cCH: chronic cluster headache; CH: cluster headache; CI: confidence interval; eCH: episodic cluster headache; nVNS: non-invasive vagus nerve stimulation; OR: odds ratio. Note: p values are from logistic regression; pooled analyses included study as a covariate.
Figure 2.
Figure 2.
Proportion of all treated attacks that achieved pain-free status at 15 minutes. cCH: chronic cluster headache; CH: cluster headache; CI: confidence interval; eCH: episodic cluster headache; GEE: generalized estimating equation; nVNS: non-invasive vagus nerve stimulation. Note: p values are from F tests; pooled analyses included study as a fixed effect. Graphed data are GEE model adjusted percentages with 95% CIs. Data for number of subjects using treatment/total number of subjects with data (n/N) attacks are unadjusted numbers.
Figure 3.
Figure 3.
Pain-free (a) or responder (b) status at 15 minutes for ≥ 50% of attacks. cCH: chronic cluster headache; CH: cluster headache; CI: confidence interval; eCH: episodic cluster headache; nVNS: non-invasive vagus nerve stimulation; OR: odds ratio. Note: OR > 1 favors nVNS. p values are from logistic regression; pooled analyses included study as a covariate.

References

    1. May A. Cluster headache: Pathogenesis, diagnosis, and management. Lancet 2005; 366: 843–855.
    1. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 2013; 33: 629–808.
    1. Nesbitt AD, Goadsby PJ. Cluster headache. BMJ 2012; 344: e2407.
    1. Dodick D, Lipton RB, Martin V, et al. Consensus statement: Cardiovascular safety profile of triptans (5-HT agonists) in the acute treatment of migraine. Headache 2004; 44: 414–425.
    1. Ekbom K, Monstad I, Prusinski A, et al. Subcutaneous sumatriptan in the acute treatment of cluster headache: A dose comparison study. The Sumatriptan Cluster Headache Study Group. Acta Neurol Scand 1993; 88: 63–69.
    1. Cohen AS, Burns B, Goadsby PJ. High-flow oxygen for treatment of cluster headache: A randomized trial. JAMA 2009; 302: 2451–2457.
    1. Cittadini E, May A, Straube A, et al. Effectiveness of intranasal zolmitriptan in acute cluster headache: A randomized, placebo-controlled, double-blind crossover study. Arch Neurol 2006; 63: 1537–1542.
    1. Rapoport AM, Mathew NT, Silberstein SD, et al. Zolmitriptan nasal spray in the acute treatment of cluster headache: A double-blind study. Neurology 2007; 69: 821–826.
    1. van Vliet JA, Bahra A, Martin V, et al. Intranasal sumatriptan in cluster headache: Randomized placebo-controlled double-blind study. Neurology 2003; 60: 630–633.
    1. Goadsby PJ, de Coo IF, Silver N, et al. Non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: A randomized, double-blind, sham-controlled ACT2 study. Cephalalgia 2018; 38: 959–969.
    1. Silberstein SD, Mechtler LL, Kudrow DB, et al. Non-invasive vagus nerve stimulation for the acute treatment of cluster headache: Findings from the randomized, double-blind, sham-controlled ACT1 study. Headache 2016; 56: 1317–1332.
    1. Martinez J, Goadsby P, Dodick D, et al. Study CGAL: A placebo-controlled study of galcanezumab in patients with episodic cluster headache: Results from the 8-week double-blind treatment phase [MTIS2018-176]. Cephalalgia 2018; 38: S145–S146.
    1. Gaul C, Diener HC, Silver N, et al. Non-invasive vagus nerve stimulation for PREVention and Acute treatment of chronic cluster headache (PREVA): A randomised controlled study. Cephalalgia 2016; 36: 534–546.
    1. Möller M, Schroeder CF, May A. Vagus nerve stimulation modulates the cranial trigeminal autonomic reflex. Ann Neurol 2018; 84: 886–892.
    1. Schroeder CF, Möller M, May A. nVNS sham stimulation significantly affects the trigeminal-autonomic reflex: A single-blind, randomized, controlled study. Neurology. In press.
    1. Akerman S, Simon B, Romero-Reyes M. Vagus nerve stimulation suppresses acute noxious activation of trigeminocervical neurons in animal models of primary headache. Neurobiol Dis 2017; 102: 96–104.
    1. Bohotin C, Scholsem M, Bohotin V, et al. Vagus nerve stimulation attenuates heat- and formalin-induced pain in rats. Neurosci Lett 2003; 351: 79–82.
    1. Frangos E, Komisaruk BR. Access to vagal projections via cutaneous electrical stimulation of the neck: fMRI evidence in healthy humans. Brain Stimul 2017; 10: 19–27.
    1. Marmura MJ, Pello SJ, Young WB. Interictal pain in cluster headache. Cephalalgia 2010; 30: 1531–1534.
    1. Manzoni GC, Taga A, Russo M, et al. Age of onset of episodic and chronic cluster headache – a review of a large case series from a single headache centre. J Headache Pain 2016; 17: 44.
    1. Torelli P, Cologno D, Cademartiri C, et al. Primary and secondary chronic cluster headache: Two separate entities?. Cephalalgia 2000; 20: 826–829.
    1. Naegel S, Holle D, Obermann M. Structural imaging in cluster headache. Curr Pain Headache Rep 2014; 18: 415.
    1. Naegel S, Holle D, Desmarattes N, et al. Cortical plasticity in episodic and chronic cluster headache. Neuroimage Clin 2014; 6: 415–423.
    1. D'Andrea G, Leone M, Bussone G, et al. Abnormal tyrosine metabolism in chronic cluster headache. Cephalalgia 2017; 37: 148–153.
    1. de Tommaso M, Ambrosini A, Brighina F, et al. Altered processing of sensory stimuli in patients with migraine. Nat Rev Neurol 2014; 10: 144–155.
    1. Bahra A, Gawel MJ, Hardebo JE, et al. Oral zolmitriptan is effective in the acute treatment of cluster headache. Neurology 2000; 54: 1832–1839.
    1. Gaul C, Roguski J, Dresler T, et al. Efficacy and safety of a single occipital nerve blockade in episodic and chronic cluster headache: A prospective observational study. Cephalalgia 2017; 37: 873–880.
    1. Mitsikostas DD, Edvinsson L, Jensen RH, et al. Refractory chronic cluster headache: A consensus statement on clinical definition from the European Headache Federation. J Headache Pain 2014; 15: 79.
    1. Paemeleire K, Bahra A, Evers S, et al. Medication-overuse headache in patients with cluster headache. Neurology 2006; 67: 109–113.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir