Memantine for Prophylactic Treatment of Migraine Without Aura: A Randomized Double‐Blind Placebo‐Controlled Study

Noruzzadeh, Rezvan; Modabbernia, Amirhossein; Aghamollaii, Vajiheh; Ghaffarpour, Majid; Harirchian, Mohammad Hossein; Salahi, Sarvenaz; Nikbakht, Nikta; Noruzi, Nahid; Tafakhori, Abbas

doi:10.1111/head.12732

Cited by 62 publications

(77 citation statements)

References 21 publications

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“…In some protocols, a headache diary provided a qualitative method to evaluate pain level, classified as (i) mild; (ii) moderate; or (iii) severe pain . Other studies used pain intensity scales to rate pain level using 0‐10 scales . We believe that analysis by mean ± SD (performed in the studies) should not be the most sensitive and appropriate way to evaluate the pain level measured by qualitative methods.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Noninvasive Brain Stimulation on Pain Control in Migraine Patients: A Systematic Review and Meta‐Analysis

et al. 2016

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Low or very low quality of evidence suggests that our primary outcome evaluation failed to find support for the superiority of NIBS over sham treatment. Although, subgroup analysis reveals that tDCS have moderate to high effects and could be a promising nonpharmacological alternative to pain control, mainly for painkiller intake reduction. However, there is a need for larger controlled trials with methodological rigor, which could increase the power of result inference.

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Section: Discussionmentioning

confidence: 99%

Efficacy of Noninvasive Brain Stimulation on Pain Control in Migraine Patients: A Systematic Review and Meta‐Analysis

et al. 2016

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“…Memantine inhibits cortical spreading depolarization in animal models [50]. Two observational studies [128,129] and one randomized, double-blind, placebo-controlled study [130] have reported efficacy of memantine as a migraine preventive therapy. It is not approved for migraine prevention.…”

Section: Memantinementioning

confidence: 99%

Glutamate and Its Receptors as Therapeutic Targets for Migraine

2018

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There is substantial evidence indicating a role for glutamate in migraine. Levels of glutamate are higher in the brain and possibly also in the peripheral circulation in migraine patients, particularly during attacks. Altered blood levels of kynurenines, endogenous modulators of glutamate receptors, have been reported in migraine patients. Population genetic studies implicate genes that are involved with glutamate signaling in migraine, and gene mutations responsible for familial hemiplegic migraine and other familial migraine syndromes may influence glutamate signaling. Animal studies indicate that glutamate plays a key role in pain transmission, central sensitization, and cortical spreading depression. Multiple therapies that target glutamate receptors including magnesium, topiramate, memantine, and ketamine have been reported to have efficacy in the treatment of migraine, although with the exception of topiramate, the evidence for the efficacy of these therapies is not strong. Also, because all of these therapies have other mechanisms of action, it is not possible to conclude that the efficacy of these drugs is entirely due to their effects on glutamate receptors. Further studies are needed to more clearly delineate the possible roles of glutamate and its specific receptor subtypes in migraine and to identify new ways of targeting glutamate for migraine therapy.

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“…The potential efficacy of memantine for the treatment of migraine has been tested clinically including in open‐label pilot studies, a case series, and most recently a randomized placebo‐controlled trial, which taken together suggest effectiveness (Bigal, Rapoport, Sheftell, Tepper, & Tepper, ; Cammarata & Krusz, ; Charles, Flippen, Romero Reyes, & Brennan, ; Kew & Kemp, ; Noruzzadeh et al., ; Spengos, Theleritis, & Paparrigopoulos, ). Memantine is generally well tolerated because of its relatively fast channel off‐rate and partial untrapping (Parsons et al., ).…”

Section: Introductionmentioning

confidence: 99%

N‐Methyl‐d‐aspartate receptor open‐channel blockers memantine and magnesium modulate nociceptive trigeminovascular neurotransmission in rats

Hoffmann

Storer

Park

et al. 2019

Eur J of Neuroscience

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Experimental and clinical studies suggest that the low‐affinity N‐methyl‐d‐aspartate (NMDA) receptor open‐channel blockers Mg2+ and memantine are effective in reducing trigeminal nociceptive activation. The aim of this study was to investigate the apparent effectiveness of these channel blockers using a model of trigeminal activation in vivo. Rats were anaesthetized before electrically stimulating the dura mater adjacent the middle meningeal artery. Neurons responding to stimulation were recorded extracellularly using electrophysiological methods. l‐Glutamate or NMDA, and Mg2+, memantine, or sodium controls were applied locally using microiontophoresis. Microiontophoretic application of Mg2+ or memantine into the trigeminocervical complex inhibited mechanically and electrically stimulated craniovascular afferents, and l‐glutamate or NMDA‐evoked neuronal activity at the second‐order trigeminal synapse of craniovascular afferents. By contrast, intravenous administration of MgSO4 (100 mg/kg) or memantine (10 mg/kg) did not significantly affect electrically stimulated afferent‐evoked activity within the trigeminocervical complex. The Mg2+ and memantine concentrations achieved after systemic administration may not effectively inhibit activation of the trigeminocervical complex, perhaps providing an explanation for the relatively poor efficacy of these NMDA receptor open‐channel blockers for headache treatment in clinical studies. Nevertheless, the present results suggest blocking of NMDA‐receptor open channels inhibits nociceptive activation of the trigeminocervical complex. Further exploration of such channel blockers as a therapeutic strategy for primary head pain is warranted.

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Memantine for Prophylactic Treatment of Migraine Without Aura: A Randomized Double‐Blind Placebo‐Controlled Study

Cited by 62 publications

References 21 publications

Efficacy of Noninvasive Brain Stimulation on Pain Control in Migraine Patients: A Systematic Review and Meta‐Analysis

Efficacy of Noninvasive Brain Stimulation on Pain Control in Migraine Patients: A Systematic Review and Meta‐Analysis

Glutamate and Its Receptors as Therapeutic Targets for Migraine

N‐Methyl‐d‐aspartate receptor open‐channel blockers memantine and magnesium modulate nociceptive trigeminovascular neurotransmission in rats

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