Chronic migraine: an update on physiology, imaging, and the mechanism of action of two available pharmacologic therapies. Non-pharmacological approaches for migraine. Butterbur is a shrub with a long history of use for medicinal purposes. The authors conclude that candesartan is comparable to other migraine prophylaxis medications, particularly beta blockers that showed in a meta-analysis a 33 percent improvement in headache index . Agosti R, Duke RK, Chrubasik JE, Chrubasik S. Effectiveness of Petasites hybridus preparations in the prophylaxis of migraine: a systematic review. Gales, B. J., Bailey, E. K., Reed, A. N. & Gales, M. A. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for the prevention of migraines. PMC Xiao C, Zhou C, Atlas G, Delphin E, Ye JH. sharing sensitive information, make sure youre on a federal 25(2), 411416 (2018). Candesartan; Challenging migraine patients; Migraine; Prevention; Treatment response. Less evidence is available for other antidepressants, although at least other tricyclics and the selective serotonin-norepinephrine reuptake inhibitor venlafaxine [56] are probably also effective for migraine prophylaxis. PubMed Central Prophylactic Treatment of Migraine With an Angiotensin II ReceptorBlocker: A Randomized Controlled Trial | Headache | JAMA | JAMA Network Context. Monograph. Angiotensin II AT(1) blockade normalizes cerebrovascular autoregulation and reduces cerebral ischemia in spontaneously hypertensive rats. It plays an important role in a multitude of biological processes, some of which might be linked to migraine pathogenesis [143]. So the authors concluded that onabotulinumtoxin A was effective in the treatment of patients with CDH, who do not receive other prophylactic medication [75]. Bookshelf However, clearly not all antiepileptics are similarly efficacious in migraine as in epilepsy. Neurology 78(17), 13371345 (2012). The number of headache days per month, compared to baseline, was reduced by 4.3days (SD: 8.4) at weeks 812 (p<0.001), and by 4.7days (SD: 8.7) at weeks 2024 of treatment (p<0.001). We reviewed the use of candesartan in every migraine patient through both electronic and physical records and the electronic prescription, analysing the prior prescription of candesartan individually. Kaube H, Goadsby PJ. Guidelines of the International Headache Society for controlled trials of preventive treatment of chronic migraine in adults. A comparative study of candesartan versus propranolol for migraine prophylaxis: A randomised, triple-blind, placebo-controlled, double cross-over study. Moreover, propranolol reduces the neuronal firing rate of noradrenergic neurons of the locus coeruleus [25]. Since 5-HT plays a pivotal role in the pathophysiology of migraine, the BABs-induced effects on this neurotransmitter could account for their prophylactic action on migraine. Candesartan yields clinical benefits in difficult-to-treat migraine patients, irrespective of previous failed preventives. The study was done in the Headache Unit of Hospital Clnico Universitario de Valladolid, Valladolid, Spain. https://doi.org/10.1038/s41598-021-83508-2, DOI: https://doi.org/10.1038/s41598-021-83508-2. Hence this receptor blockade may explain (part) of the efficacy of fluoxetine. Prophylactic migraine therapy: mechanisms and evidence. The 5-HT2C mechanism is shared with the old antiheadache drug methysergide and a receptor gene polymorphisms of 5-HT2C has been shown to modulate migraine susceptibility (in a Turkish population) [59]. 15(4), 684191 (1993). X-axis, duration in months; Y-axis, the proportion of patients (n=114). Alpha2-adrenoceptor blockade has been shown to block the antinociceptive effect of amitriptyline [57] and hence at least part of amitriptylines efficacy is thought to be mediated by 2-agonism, but multiple other channel and receptor effects of amitriptyline are known. Limmroth V, Michel MC. This effect of BABs on auditory evoked cortical potential could be due to a modulatory action on serotonergic transmission [34]. Montastruc P, Dang-Tran L, Carvajal A, Rostin M, Montastruc JL. Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. JAMA 289(1), 6569 (2003). The prevention of migraine: a critical review with special emphasis on beta-adrenoceptor blockers. ISSN 2045-2322 (online). Suppl. Silberstein SD, Goldberg J. Menstrually related migraine: breaking the cycle in your clinical practice. Cephalalgia 1992;12(1):217. In the subsequent years, several exploratory studies with BoNT-A using heterogeneous doses and injection paradigms were carried out in migraine and tension-type headache and chronic daily headache with inconclusive and mostly negative results [62, 63, 7174]. Final approval of completed manuscriptAll authors. Strenghtening the reporting of observational studies in epidemiology, International classification of headache disorders. Cephalalgia 38(1), 1211 (2018). Flow-diagram of screened, included, and excluded patients. Cephalalgia 29(9), 921927 (2009). One can generally expect a 50% reduction in attack frequency in every second patient with these compounds, if they are taken regularly. Diener HC, Scholz E, Dichgans J, Gerber WD, Jack A, Bille A, et al. Aurora SK, Gawel M, Brandes JL, Pokta S, Vandenburgh AM, Group BNAEMS Botulinum toxin type a prophylactic treatment of episodic migraine: a randomized, double-blind, placebo-controlled exploratory study. Curr. [. and D.G.-A. Interestingly, BABs also regulate the firing rate of periaqueductal gray matter (PAG) neurons via a GABA-mediated action [26]. Ser. 3 It enrolled 60 patients, 18 to 65 years of age, who experienced migraines with or without auras 2 to 6 times per month. 44(2), 360366 (2010). Mauskop A, Altura BT, Cracco RQ, Altura BM. The secondary endpoints were the reduction in headache days per month by weeks 2024 from baseline and the 50% and 75% responder rates at weeks 812 and weeks 2024 (from baseline). Real world effectiveness and tolerability of candesartan in the treatment of migraine: a retrospective cohort study, https://doi.org/10.1038/s41598-021-83508-2. Whitcup SM, Turkel CC, DeGryse RE, Brin MF. Li F, Qiu E, Dong Z, Liu R, Wu S, Yu S. Protection of flunarizine on cerebral mitochondria injury induced by cortical spreading depression under hypoxic conditions. Erectile dysfunction (ED) is often a symptom . CAS J. Headache Pain 15, 2 (2014). Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine model. This potential is increased in amplitude, lacks habituation and is normalized by BABs in association with a clinical improvement in migraine [35]. the contents by NLM or the National Institutes of Health. Eighty-four patients (70%) had chronic migraine and 53 (42.7%) had medication-overuse headache. The headache outpatient clinic receives patients both directly from primary care and secondary care. Candesartan cilexetil (Atacand) is a medication prescribed to treat high blood pressure. Groenewegen WA, Heptinstall S. A comparison of the effects of an extract of feverfew and parthenolide, a component of feverfew, on human platelet activity in-vitro. Several antiepileptic drugs (AEDs) acting at different pre- and post-synaptic sites have been studied and proven effective for migraine prevention with the best clinical trial evidence in terms of migraine preventive action being available for topiramate and valproate [7]. Brain energy metabolism has been found to be abnormal in migraine headache [128]. Clinical Research Ethics Committee CEIm rea de Salud Valladolid Este approved the study. J. Med. The mean (SD) number of preventive treatments used prior to candesartan was 3.75 (2.3). All these neurotransmitters and neuropeptides are key signaling molecules in chronic migraine and it is therefore likely that, altogether, these mechanisms are important in the current notion of migraine prevention because they are capable of disrupting the cascade of events that leads to peripheral and central sensitization, mainly via the block of release of inflammatory neuropeptides from stimulated trigeminal sensory neurons [7678, 86]. Materazzi S, Benemei S, Fusi C, Gualdani R, De Siena G, Vastani N, et al. It has also been shown to inhibit glutamate-mediated excitatory neurotransmission and facilitate GABA-A-mediated inhibition. Riboflavin catalyzes the activity of flavoenzymes in the mitochondrial respiratory chain and improves the clinical and biochemical abnormalities in patients with inborn errors of mitochondrial metabolism [129, 130]. A neural circuit for circadian regulation of arousal. Propranolol inhibits nitric oxide production by blocking inducible nitric oxide synthase (NOS). As a library, NLM provides access to scientific literature. Candesartan is in a class of medications called angiotensin II receptor antagonists. CNS-related (side-)effects of beta-blockers with special reference to mechanisms of action. Schmerz 2017. Diagnosis and management of migraine in ten steps, Optimal treatment strategy of fremanezumab in migraine prevention: a systematic review with network meta-analysis of randomized clinical trials, Low adherence to the guideline for the acute treatment of migraine, Migraine abortive treatment in children and adolescents in Israel, Paediatric migraine: evidence-based management and future directions, Medication adherence in patients with cluster headache and migraine: an online survey, Triptan efficacy does not predict onabotulinumtoxinA efficacy but improves with onabotulinumtoxinA response in chronic migraine patients, https://doi.org/10.1007/s00415-020-09989-9, http://creativecommons.org/licenses/by/4.0/, Migraine: from pathophysiology to treatment. Therefore, it could be hypothesized that BABs have a significant effect on the excitability of the visual system (and probably more generally the cortex) in migraine patients. Ann. Hypotensive activity of TCV-116, a newly developed angiontensin II receptor antagonist, in spontaneously hypertensive rats. Mittra S, Datta A, Singh SK, Singh A. The international classification of headache disorders: 2nd edition. In a double-blind randomized study, it was shown that propranolol and metoprolol decreased VEP amplitude in migraine patients. 112(8), 642646 (2002). Flunarizine is a nonselective calcium antagonist, which has also been shown to block voltage-gated sodium channels [51, 52]. Wolthausen J, Sternberg S, Gerloff C, May A. official website and that any information you provide is encrypted We also observed that patients with daily headache had 61% less odds of responding compared with those without daily headache, similarly to other retrospective studies where patients with daily headache had 84% lower odds7. The exact mechanism by which BoNT-A reduces migraine days in chronic migraineurs is not yet fully understood, although an increasing body of evidence suggests the dominant hypothesis that the toxin exerts its antinociceptive action via peripheral mechanisms [76]. Drinovac V, Bach-Rojecky L, Lackovic Z. Italian Guidelines for primary headaches: 2012 revised version. In the same preclinical study, valproate also downregulated the expression of CGRP in brain tissue. We used data from the study by Trovnik et al.4 in which, after 12weeks of treatment, the reduction of headache days per month in patients treated with candesartan was 4.9days higher than the placebo group (standard deviation 10.6). RAS may play a role also in migraine pathogenesis. Internet Explorer). We explored the 50% responder rate in patients with prior use of 02 migraine prophylactics, where the percentage of patients with a 50% response was 41.7% at weeks 812; however, we did not find statistically significant results showing that the response in those patients was higher. It is currently unclear which of the noted mechanisms is key for topiramates effect in migraine prevention. This is a tertiary academic hospital with a reference population of 280,000 patients. PubMed National Library of Medicine Table 1 shows the distribution of patients according to the number of headache days per month they had before starting treatment. This is a decision you and your doctor will make. Jain NK, Kulkarni SK. Lanteri-Minet, M., Valade, D., Geraud, G., Lucas, C. & Donnet, A. Soc. For these reasons, we aimed to evaluate the effectiveness and tolerability of candesartan in real-world practice and to explore possible predictors of a clinically relevant response. Inclusion in an NLM database does not imply endorsement of, or agreement with, For example, several migraine preventives such as propranolol, topiramate, valproate, amitriptyline [11], and flunarizine [12], but also CGRP antagonists [13] have been shown to suppress CSD. Treatment with telmisartan, a long-acting angiotensin II receptor blocker, prevents migraine attacks in Japanese non-responders to lomerizine. As a matter of fact, the effect of this class of drugs has been reported to be blocked by antagonizing opioid receptors [97]. In our study, the 50% responder rate was 32.5% after 3months, compared to 31.6%4 and 43%5 of pivotal trials. nasal . Tassorelli, C. et al. In line with other real-world studies or even clinical trials assessing the effectiveness of headache therapies, we used as control the month prior to the use of candesartan. CM is defined as a headache on 15 days per month for 3 months, of which 8 days meets the criteria for migraine with or without aura or responds to migraine-specific treatment [ 5 ]. Diener HC, Dodick DW, Aurora SK, Turkel CC, DeGryse RE, Lipton RB, et al. In clinical trials comparing the efficacy of candesartan as an antihypertensive versus other angiotensin-converting enzyme inhibitors (ACEIs) or placebo, the adverse events rate of candesartan was 11%27 and 16.1%28. Would you like email updates of new search results? Analysis and interpretation of dataC.S.-R., A.P.-G. and D.G.-A. Niazi AK, Andelova M, Sprenger T. Is the migrainous brain normal outside of acute attacks? BoNT-A adheres to the nerve cells and enters inside through the endocytosis mechanism and inhibits fusion of intracellular vesicles with the nerve membrane [80] by cleaving SNAP-25 [81]. Indeed, blockade of 1 receptors could inhibit noradrenaline (NA) release and tyrosine hydroxylase activity, the rate-limiting step in NA synthesis [24]. Pain Headache Rep. 23(11), 85 (2019). Although these compounds were initially developed for other indications and differ in their mechanisms of action, some general themes can be identified from the mechanisms at play. Ther. Another RCT contradicted these findings and found oral magnesium to be no different than placebo on interim analysis in a sample of refractory migraine patients and therefore halted recruitment prior to achieving the planned sample size [141]. Odds ratios (OR) with confidence intervals (CI) 95% were calculated. B., Viguera Romero, J. MOH criteria were fulfilled by 53/120 (42.7%) patients. This action could be explained by the regulation of degradation of the inhibitory protein of NF-kB and of expression of inducible NOS by parthenolide, the active constituent of feverfew [101]. The drug is now widely used for this purpose in many countries, although no confirmatory study has been published. FOIA This could influence the results by increasing the positive predictive value of the migraine diagnosis after 201321. Koella WP. Furthermore, flunarizine acts as a D2 dopamine antagonist and has in this regard been shown to possess (at high doses) comparable antipsychotic efficacy as haloperidol [53]. Neurotherapeutics). Antinociceptive and anti-inflammatory effects of Tanacetum parthenium L. extract in mice and rats. Traffic of botulinum toxins A and E in excitatory and inhibitory neurons. The median dose of candesartan was 8 mg and the median treatment period was 6 months. Scientific Reports (Sci Rep) Etminan, M., Levine, M. A. H., Tomlinson, G. & Rochon, P. A. Efficacy of angiotensin II receptor antagonists in preventing headache: a systematic overview and meta-analysis. We did a sub-analysis of the number of prior prophylactics, analysing patients with 02 compared with those with three or more prior prophylactics. Stovner LJ, Linde M, Gravdahl GB, Tronvik E, Aamodt AH, Sand T, Hagen K. Cephalalgia. There are more than three placebo-controlled trials each supporting the superiority of the tricyclic antidepressant amitriptyline and of the selective serotonin reuptake inhibitor (SSRI) fluoxetine over placebo for migraine prevention [55]. Accessibility Dolly JO, Aoki KR. Sci. Journal of hypertension supplement : official journal of the International Society of Hypertension. Noradrenaline reuptake is inhibited only at higher doses. Aoki KR. Silberstein S, Mathew N, Saper J, Jenkins S. Botulinum toxin type A as a migraine preventive treatment. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. We audited the clinical records of 253 patients who attended the King's College Hospital, London, from February 2015 to December 2017, looking specifically at their response to candesartan. Riboflavin is a vitamin that plays an important role in cellular energy production through its two active coenzyme forms that are involved in oxidation-reduction reactions during a variety of cellular processes [127]. Hanbauer I, Kopin IJ, Guidotti A, Costa E. Induction of tyrosine hydroxylase elicited by beta adrenergic receptor agonists in normal and decentralized sympathetic ganglia: role of cyclic 3,5 - adenosine monophosphate. There are seven serotypes of botulinum toxin [68], the serotype A has been used in human therapy since 1980 when Scott proposed BoNT-A injection into extraocular muscles as an alternative to strabismus surgery [69]. Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF, et al. Table 1 shows the number of prior prophylactic treatments. PMID: 32542525 DOI: 10.1007/s00415-020-09989-9 Abstract Randomized studies have reported a positive effect of candesartan, an angiotensin II receptor antagonist, in migraine prevention. Aston-Jones G, Chen S, Zhu Y, Oshinsky ML. The structure and mode of action of different botulinum toxins. Moreover, the safety of long-term use of feverfew needs to be established [106]. Retrospective cohort study including all patients with migraine who received candesartan between April 2008-February 2019. Silberstein SD, Stark SR, Lucas SM, Christie SN, Degryse RE, Turkel CC, et al. Supplementary table 5 shows the sensitivity analysis of response predictors, with similar results. Pfaffenrath V, Wessely P, Meyer C, Isler HR, Evers S, Grotemeyer KH, et al. Sommer C. Is serotonin hyperalgesic or analgesic? An odds ratio value below 1 indicates a negative association; here, patients with daily headache had 61% lower odds of responding to candesartan, and each prior prophylactic decreased the probability of response by 21%. Johnson ES, Kadam NP, Hylands DM, Hylands PJ. J. Hypertens. To date, two randomized, controlled studies support the use of candesartan for migraine prophylaxis but with limited external validity. Cortical spreading depression (CSD) could also represent a target for BABs in migraine. We refer the interested reader to the article by Puledda and Shields in this issue (Puledda and Shields. Migraine prevalence, disease burden, and the need for preventive therapy. At the time of candesartan initiation, the mean age of patients was 45.9years (SD: 11.5). 5 Previously known variously as 'migra. Benjamini, Y. Botulinum toxin type A for the prophylactic treatment of chronic daily headache: a randomized, double-blind, placebo-controlled trial. [. Puledda F, Goadsby PJ. 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