A randomized controlled trial of intranasal ketamine in migraine with prolonged aura

Afridi, Shazia; Giffin, Nicola; Kaube, Holger; Goadsby, PJ

doi:10.1212/wnl.0b013e3182824e66

Cited by 129 publications

(116 citation statements)

References 38 publications

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“…These findings suggest that excitatory amino acid receptors (and NMDA in particular) play an important role in pain processing and the sensitization process which is also present in migraineurs (Vikelis and Mitsikostas, 2007). Ketamine, an NMDA antagonist, is so far the only promising treatment option for patients with severe or long-lasting migraine aura (Afridi et al, 2013). Another novel substance, tezampanel, which acts on the AMPA and kainate subtypes of ionotropic glutamate receptors (Alt et al, 2006), has also shown promising results in acute migraine therapy (Sang et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

A comparative assessment of two kynurenic acid analogs in the formalin model of trigeminal activation: a behavioral, immunohistochemical and pharmacokinetic study

et al. 2016

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Abstract:Kynurenic acid (KYNA) has well-established protective properties against glutamatergic neurotransmission, which plays an essential role in the activation and sensitization process during headache disorders. The goal of this study was to Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporationcompare the effects of two KYNA analogs, N-(2-N,N-dimethylaminoethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride (KA-1) and N-(2-N-pyrrolidinylethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride (KA-2), in the orofacial formalin test of trigeminal pain. Following pretreatment with KA-1 or KA-2, rats were injected with subcutaneous formalin solution in the right whisker pad. Thereafter, the rubbing activity and c-Fos immunoreactivity changes in the spinal trigeminal nucleus pars caudalis (TNC) were investigated. To obtain pharmacokinetic data, KA-1, KA-2 and KYNA concentrations were measured following KA-1 or KA-2 injection. Behavioral tests demonstrated that KA-2 induced a larger amelioration of formalin-evoked alterations as compared with KA-1 and the assessment of c-Fos immunoreactivity in the TNC yielded similar results. Although KA-1 treatment resulted in approximately four times larger area under the curve values in the serum relative to KA-2, the latter resulted in a higher KYNA elevation than in the case of KA-1. With regard to TNC, the concentration of KA-1 was under the limit of detection, while that of KA-2 was quite small and there was no major difference in the approximately 10-fold KYNA elevations. These findings indicate that the differences between the beneficial effects of KA-1 and KA-2 may be explained by the markedly higher peripheral KYNA levels following KA-2 pretreatment. Targeting the peripheral component of trigeminal pain processing would provide an option for drug design which might prove beneficial in headache conditions. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems CorporationReviewer #2: The Authors have tried to address the comments of the referees and partially improved the manuscript. Some issues still need improvement.The sentence 'glutamatergic neurotransmission, which plays an essential role in the activation and sensitization process during headache disorders' is incorrect. This statement may be true for some primary headaches (migraine and chronic migraine), but not for 'headaches' in general.The sentence was modified accordingly.The way the data are presented is still quite confusing:Description of the time boundaries for Phase I and II is missing in the Methods section. The Methods section was supplemented with the requested information.A Figure ( Table 1 reports the levels of significance for data presented in Figure 2: the table should be inglobated in said figure otherwise the reader is forced to go back and forth.The requested modification was done in Figure 2 and Table 1 was removed. Table 2 should be associated to a figure that illustrates mean+sd of time spent in rubbing during the 2 phases of formalin in the di...

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Section: Discussionmentioning

confidence: 99%

A comparative assessment of two kynurenic acid analogs in the formalin model of trigeminal activation: a behavioral, immunohistochemical and pharmacokinetic study

et al. 2016

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“…32 Intranasal ketamine also reduces the severity of pain in migraine. 33 Wink et al 34 reported a 29-year-old woman with autism who was treated with intranasal ketamine (20-60 mg) on 12 dosing occasions across 6 weeks. She showed improvements in mood, social interactions, flexibility, tolerance of changes in routine, motivation, and concentration.…”

Section: Intranasal Ketaminementioning

confidence: 99%

Intranasal Drug Delivery in Neuropsychiatry: Focus on Intranasal Ketamine for Refractory Depression

Andrade¹

2015

J. Clin. Psychiatry

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“…Unfortunately, effective treatments for aura signs and symptoms (in particular for those patients with substantial disability due to aura duration and severity) are not yet well established. Up to now, intranasal ketamine has shown to be effective in reducing severity (but not duration) of long-lasting aura [10]. Moreover, small studies or isolated case reports supported the role of a series of drugs in aborting migraine aura [11] [12] in modulating migraine with aura in particular, but none of these treatments is currently used in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

A Combination of Tanacetum parthenium, Griffonia simplicifolia and Magnesium (Aurastop) as Symptomatic Acute Treatment for Migraine Aura: A Retrospective Cohort Study

Zavarise¹,

Volta²

2017

OALib

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Background: effective treatments for migraine aura and related symptoms are not yet well established. In the last years, several herbal and/or nutraceutical preparations have been proposed as potential treatment. We report the results of a retrospective analysis on the synergistic effect of three nutraceutical components (Tanacetum parthenium, Griffonia simpliciofila and Magnesium, Aurastop®) as symptomatic treatment of migraine aura and related symptoms. Method: Forty-nine subjects with headache with aura were recruited from the headache Center of the Istituto Clinico Citta' di Brescia to enter the studied that consist to treat the first 3 aura attacks as usual and the next 3 taking a tablet of Aurastop at the beginning of the aura phenomena. They had to describe aura and headache characteristics of previous three attacks (t1) and the modification of these parameters with the assumption of Aurastop® for the following three attacks (t2). Results: A significant reduction (>50%) in aura duration (t1 = 33.6 ± 10.1 minutes vs. t2 = 9.4 ± 6.2 minutes, p < 0.01 FWER corrected) as well as in overall disability (median [interquartile range]) (t1 = 5[4 -5] vs. t2 = 1[1 -2], p < 0.01 FWER corrected) was evident. Furthermore, modification of aura type as well as a series of parameters more related to headache (number of headache attacks, duration, intensity, utilization of analgesics and response to symptomatic treatment) was influenced by Aurastop® utilization (p < 0.01 FWER corrected). No significant adverse effects were recorded after the assumption of Aurastop®. Conclusions: the combined and synergistic effect of Tanacetum parthenium, Griffonia simpliciofila and Magnesium (Aurastop®) highlights the idea that symptomatic treatment potentially modulating cortical spreading depression could deserve attention to miti-

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A randomized controlled trial of intranasal ketamine in migraine with prolonged aura

Abstract: This study provides class III evidence that intranasal ketamine is effective in reducing aura severity in patients with migraine with prolonged aura.

Cited by 129 publications

References 38 publications

A comparative assessment of two kynurenic acid analogs in the formalin model of trigeminal activation: a behavioral, immunohistochemical and pharmacokinetic study

A comparative assessment of two kynurenic acid analogs in the formalin model of trigeminal activation: a behavioral, immunohistochemical and pharmacokinetic study

Intranasal Drug Delivery in Neuropsychiatry: Focus on Intranasal Ketamine for Refractory Depression

A Combination of Tanacetum parthenium, Griffonia simplicifolia and Magnesium (Aurastop) as Symptomatic Acute Treatment for Migraine Aura: A Retrospective Cohort Study

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