Aktuelles zum Cluster-Kopfschmerz: Unterschied zwischen den Versionen

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 == Neues seit 2021 ==
 {{Anker|Neues seit 2021 (Stand 23.09.2026)}}
-''Zusammengestellt am 23.09.2026. Jede Angabe wurde an der Quelle geprüft; die Fundstellen stehen in den [[#Einzelnachweise|Einzelnachweisen]] am Ende der Seite. Die Studien sind mit allen Zahlen und in Alltagssprache auf der Seite [[Studien zum Cluster-Kopfschmerz]] erklärt.''
+''Die Fundstellen stehen in den [[#Einzelnachweise|Einzelnachweisen]] am Ende der Seite. Die Studien sind mit allen Zahlen und in Alltagssprache auf der Seite [[Studien zum Cluster-Kopfschmerz]] erklärt.''
 === Leitlinien und Klassifikation ===
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 * '''2021, Kortison zur Überbrückung:''' Wer zusätzlich zu Verapamil Prednison bekam, hatte in der ersten Woche im Mittel 7,1 Attacken, mit Placebo waren es 9,5.<ref name="OBERMANN2021">{{cite journal |author=Obermann M, Nägel S, Ose C u. a. |title=Safety and efficacy of prednisone versus placebo in short-term prevention of episodic cluster headache: a multicentre, double-blind, randomised controlled trial |journal=Lancet Neurol |volume=20 |issue=1 |pages=29–37 |year=2021 |pmid=33245858 |doi=10.1016/S1474-4422(20)30363-X}} Zehn deutsche Kopfschmerzzentren; 100 mg Prednison für 5 Tage, dann Abbau um 20 mg alle 3 Tage, zusätzlich Verapamil; 109 Patienten ausgewertet; erste Woche 7,1 gegen 9,5 Attacken. Die Differenz in der ersten Woche betrug 2,4 Attacken (p = 0,002; 95-%-Vertrauensbereich −4,8 bis −0,03). Im Wortlaut (am 23.09.2026 über Europe PMC geprüft): „done in ten specialised headache centres in Germany“; „116 patients were randomly assigned (57 patients to prednisone and 59 patients to placebo); 109 patients were included in the mITT analysis“; „Participants in the prednisone group had a mean of 7·1 (SD 6·5) attacks within the first week compared with 9·5 (6·0) attacks in the placebo group (difference -2·4 attacks, 95% CI -4·8 to -0·03; p=0·002).“; „The study was stopped early due to slow recruitment and expired funding.“</ref> → [[Studien zum Cluster-Kopfschmerz#Zur Überbrückung, bis die Vorbeugung wirkt|Studien zur Überbrückung]]
 * '''2025, Kortison-Spritze am Hinterkopf:''' Zu Beginn der Phase gegeben, sparte sie über drei Monate nicht nachweisbar Verapamil (Hauptziel verfehlt).<ref name="BRANDT2025">{{cite journal |author=Brandt RB, Mulleners WM, Couturier E u. a. |title=Greater occipital nerve injection with methylprednisolone as transitional therapy in episodic cluster headache: results from an RCT |journal=Cephalalgia |volume=45 |issue=9 |pages=03331024251370324 |year=2025 |pmid=40990636 |doi=10.1177/03331024251370324}} Im Wortlaut: „the mean daily dose of verapamil during the total 12-week study period did not differ (232 ± 188 mg vs. 244 ± 143 mg“; „the median number of attacks at week 1 (7 (interquartile range = 2-11.75) vs. 10“; „This study failed to establish its primary endpoint.“; „There were no serious AEs.“ Am 23.09.2026 über Europe PMC geprüft. Weiter: „80 mg of methylprednisolone (n = 36) or placebo (n = 34)“.</ref>
-* '''2025 und 2026, Antikörper gegen CGRP:''' Eptinezumab und Erenumab verfehlten in je einer Studie ihr Hauptziel.<ref name="ALLEVIATE">{{cite journal |author=Jensen RH, Tassorelli C, Tepper SJ u. a. |title=Efficacy and safety of eptinezumab in episodic cluster headache: a randomized clinical trial |journal=JAMA Neurol |volume=82 |issue=7 |pages=706–714 |year=2025 |pmid=40388178 |doi=10.1001/jamaneurol.2025.1317}} Im Wortlaut: „There was no statistically significant difference between eptinezumab and placebo in the change from baseline in the number of weekly attacks over weeks 1 to 2 (least-squares mean [SE], -4.0 [0.93] vs -4.6 [0.89]; between-group difference, 0.7; 95% CI, -1.3 to 2.6; P = .50).“; „More eptinezumab-treated participants achieved 50% or greater response vs placebo over week 2 (50.9% … vs 37.3%“; Woche 4 „66.7% … vs 50.5%“. Am 23.09.2026 über Europe PMC geprüft. Weiter: „The study took place at 64 sites across Europe, the US, and Japan.“; „(eptinezumab, n = 118; placebo, n = 113)“.</ref><ref name="CHERUB01">{{cite journal |author=Mecklenburg J, Gaul C, Fitzek M u. a. |title=Erenumab for chronic cluster headache: a randomized clinical trial |journal=JAMA Netw Open |volume=8 |issue=6 |pages=e2516318 |year=2025 |pmid=40526384 |doi=10.1001/jamanetworkopen.2025.16318}} Im Wortlaut: „The primary end point was not met over weeks 5 and 6 of the double-blind phase because the mean (SD) reduction of weekly CH attacks was -7.3 (8.6) per week for erenumab and -5.9 (10.5) per week for placebo“; „erenumab (13 [31.7%]) and placebo (18 [45.0%])“; „Recruitment was stopped prematurely“. Am 23.09.2026 über Europe PMC geprüft. Weiter: „Loading dose of erenumab (280 mg subcutaneously) or matching placebo“, „followed by another dose of erenumab (140 mg subcutaneously) or placebo 4 weeks later“; „erenumab (n = 41) or placebo (n = 40)“; „More participants reported adverse events with erenumab than placebo (27 [65.9%] vs 17 [42.5%])“; „Calcitonin gene-related peptide (CGRP) is involved in the pathophysiology of cluster headache (CH).“ Die unerwünschten Ereignisse waren „mostly of mild or moderate intensity“.</ref> Alle vier kontrollierten Antikörper-Studien zusammen ergaben weniger als eine Attacke pro Woche Unterschied zum Placebo, und selbst der ist nicht gesichert.<ref name="YUAN2026">{{cite journal |author=Yuan L, Zhang YX, Kulachai P u. a. |title=Efficacy and safety of calcitonin gene-related peptide monoclonal antibodies for cluster headache: a systematic review and frequentist-Bayesian meta-analysis |journal=J Neurol |volume=273 |issue=7 |pages=371 |year=2026 |pmid=42249970 |doi=10.1007/s00415-026-13887-x}} Im Wortlaut: „Four trials (655 participants) were included. The pooled MD was - 0.81 attacks per week (95%CI - 2.24 to 0.62; P = 0.265“; „a discrepancy driven by high placebo rates (27-53%)“; „Bayesian analysis showed an 81.1% posterior probability of any benefit, but only 17.9% probability that the true reduction reached 2 or more attacks per week“; „Modest benefit cannot be excluded, but clinically meaningful efficacy remains uncertain.“ Am 23.09.2026 über Europe PMC geprüft. Weiter: „have transformed migraine prevention“.</ref> → [[Studien zum Cluster-Kopfschmerz#Antikörper und Tabletten gegen CGRP|Studien zu CGRP]]
+* '''2025 und 2026, Antikörper gegen CGRP:''' Eptinezumab und Erenumab verfehlten in je einer Studie ihr Hauptziel.<ref name="ALLEVIATE">{{cite journal |author=Jensen RH, Tassorelli C, Tepper SJ u. a. |title=Efficacy and safety of eptinezumab in episodic cluster headache: a randomized clinical trial |journal=JAMA Neurol |volume=82 |issue=7 |pages=706–714 |year=2025 |pmid=40388178 |doi=10.1001/jamaneurol.2025.1317}} Im Wortlaut: „There was no statistically significant difference between eptinezumab and placebo in the change from baseline in the number of weekly attacks over weeks 1 to 2 (least-squares mean [SE], -4.0 [0.93] vs -4.6 [0.89]; between-group difference, 0.7; 95% CI, -1.3 to 2.6; P = .50).“; „More eptinezumab-treated participants achieved 50% or greater response vs placebo over week 2 (50.9% … vs 37.3%“; Woche 4 „66.7% … vs 50.5%“. Am 23.09.2026 über Europe PMC geprüft. Weiter: „The study took place at 64 sites across Europe, the US, and Japan.“; „(eptinezumab, n = 118; placebo, n = 113)“.</ref><ref name="CHERUB01">{{cite journal |author=Mecklenburg J, Gaul C, Fitzek M u. a. |title=Erenumab for chronic cluster headache: a randomized clinical trial |journal=JAMA Netw Open |volume=8 |issue=6 |pages=e2516318 |year=2025 |pmid=40526384 |doi=10.1001/jamanetworkopen.2025.16318}} Im Wortlaut: „The primary end point was not met over weeks 5 and 6 of the double-blind phase because the mean (SD) reduction of weekly CH attacks was -7.3 (8.6) per week for erenumab and -5.9 (10.5) per week for placebo“; „erenumab (13 [31.7%]) and placebo (18 [45.0%])“; „Recruitment was stopped prematurely“. Am 23.09.2026 über Europe PMC geprüft. Weiter: „Loading dose of erenumab (280 mg subcutaneously) or matching placebo“, „followed by another dose of erenumab (140 mg subcutaneously) or placebo 4 weeks later“; „erenumab (n = 41) or placebo (n = 40)“; „More participants reported adverse events with erenumab than placebo (27 [65.9%] vs 17 [42.5%])“; „Calcitonin gene-related peptide (CGRP) is involved in the pathophysiology of cluster headache (CH).“ Die unerwünschten Ereignisse waren „mostly of mild or moderate intensity“.</ref> Eine Auswertung von vier kontrollierten Antikörper-Studien ergab zusammen weniger als eine Attacke pro Woche Unterschied zum Placebo, und selbst der ist nicht gesichert.<ref name="YUAN2026">{{cite journal |author=Yuan L, Zhang YX, Kulachai P u. a. |title=Efficacy and safety of calcitonin gene-related peptide monoclonal antibodies for cluster headache: a systematic review and frequentist-Bayesian meta-analysis |journal=J Neurol |volume=273 |issue=7 |pages=371 |year=2026 |pmid=42249970 |doi=10.1007/s00415-026-13887-x}} Im Wortlaut: „Four trials (655 participants) were included. The pooled MD was - 0.81 attacks per week (95%CI - 2.24 to 0.62; P = 0.265“; „a discrepancy driven by high placebo rates (27-53%)“; „Bayesian analysis showed an 81.1% posterior probability of any benefit, but only 17.9% probability that the true reduction reached 2 or more attacks per week“; „Modest benefit cannot be excluded, but clinically meaningful efficacy remains uncertain.“ Am 23.09.2026 über Europe PMC geprüft. Weiter: „have transformed migraine prevention“.</ref> Beim episodischen Cluster-Kopfschmerz war Galcanezumab in einer Studie wirksamer als Placebo. Die europäische Leitlinie von 2023 empfiehlt es deshalb schwach, für sonst nicht behandelbare Fälle; die europäische Arzneimittelbehörde hat es für den Cluster-Kopfschmerz nicht zugelassen.<ref name="EANGALCA">May A, Evers S, Goadsby PJ u. a.: European Academy of Neurology guidelines on the treatment of cluster headache. Eur J Neurol 2023;30(10):2955–2979, doi:[https://doi.org/10.1111/ene.15956 10.1111/ene.15956]. Am 23.09.2026 im Volltext gelesen. S. 2965: „Weak recommendation for galcanezumab in episodic cluster headache based on a low level of evidence.“; S. 2969: „In a randomized placebo-controlled double-blind trial in episodic cluster headache, galcanezumab 300 mg sc was more efficacious than placebo in reducing weekly attack frequency at the primary endpoint of 3 weeks“; „Galcanezumab is now licensed for the treatment of episodic cluster headache by the US Food and Drug Administration, whereas the European Medicines Agency has not approved this indication.“; S. 2971: „Galcanezumab 300 mg sc every month is recommended in otherwise intractable patients based on one RCT despite missing labeling by the European authorities.“</ref> → [[Studien zum Cluster-Kopfschmerz#Antikörper und Tabletten gegen CGRP|Studien zu CGRP]]
 * '''2021 und 2026, Stimulation am Hinterkopf:''' 2021 half eine schwache Stimulation so gut wie eine starke.<ref name="ICON2021">{{cite journal |author=Wilbrink LA, de Coo IF, Doesborg PGG u. a. |title=Safety and efficacy of occipital nerve stimulation for attack prevention in medically intractable chronic cluster headache (ICON): a randomised, double-blind, multicentre, phase 3, electrical dose-controlled trial |journal=Lancet Neurol |volume=20 |issue=7 |pages=515–525 |year=2021 |pmid=34146510 |doi=10.1016/S1474-4422(21)00101-0}} Im Wortlaut: „We enrolled 150 patients and randomly assigned 131 (87%) to treatment; 65 (50%) patients to 100% ONS and 66 (50%) to 30% ONS.“; „a median change of -5·21 (-11·18 to -0·19; p<0·0001) attacks per week“; „The difference in median weekly mean attack frequency between groups at the end of the masked phase in weeks 21-24 was -2·42 (95% CI -5·17 to 3·33).“ Am 23.09.2026 über Europe PMC geprüft. Weiter: Ausgangswert „median 15·75“; „decreased from baseline to 7·38“; „median change from baseline -4·08“ (100 %) und „-6·50“ (30 %); „17 with 100% ONS and eight with 30% ONS were labelled as serious, given they required brief hospital admission for minor hardware-related issues“.</ref> 2026 wurde die Stimulation mit echtem Placebo verglichen und war nicht besser als Placebo.<ref name="ONS2026">{{cite journal |author=Fogh-Andersen IS, Sørensen JCH, Petersen AS, Jensen RH, Meier K |title=Safety and efficacy of occipital nerve stimulation as treatment of chronic cluster headache: an investigator-initiated, double-blind, randomized, placebo-controlled study |journal=J Headache Pain |volume=27 |issue=1 |pages=77 |year=2026 |pmid=41803706 |doi=10.1186/s10194-026-02312-3}} Im Wortlaut: „Thirty-eight participants underwent occipital nerve stimulator implantation and were randomly assigned to burst occipital nerve stimulation (n = 19) or placebo (n = 19). After the randomized trial phase, the proportion of ≥30% responders was 18.81% … in the burst occipital nerve stimulation group and 50.02% … in the placebo group.“; „eight were treatment-related serious adverse events“; „Occipital nerve stimulation reduced attack frequency but was not superior to placebo.“ Am 23.09.2026 über Europe PMC geprüft. Weiter: „paresthesia-free burst occipital nerve stimulation“; „12-week randomized, double-blind burst occipital nerve stimulation treatment period“.</ref> → [[Studien zum Cluster-Kopfschmerz#Nervenstimulation und Operationen zur Vorbeugung|Studien zu Nervenstimulation]]
 * '''2022 und 2024, Psilocybin:''' In der verblindeten Studie mit Placebo zeigte sich kein gesicherter Unterschied; in einer kleinen, ebenfalls verblindeten Wiederholung ohne Placebogruppe halbierten sich die Attacken etwa.<ref name="SCHINDLER2022">{{cite journal |author=Schindler EAD, Sewell RA, Gottschalk CH u. a. |title=Exploratory investigation of a patient-informed low-dose psilocybin pulse regimen in the suppression of cluster headache: results from a randomized, double-blind, placebo-controlled trial |journal=Headache |volume=62 |issue=10 |pages=1383–1394 |year=2022 |pmid=36416492 |doi=10.1111/head.14420}} Psilocybin 0,143 mg/kg oder Placebo, drei Gaben im Abstand von etwa 5 Tagen. Im Wortlaut: „A total of 16 participants were randomized to receive experimental drug and 14 were included in the final analysis.“; „the change in cluster attack frequency was 0.03 … attacks/week with placebo … and -3.2 … attacks/week with psilocybin … p = 0.251“; „Psilocybin was well-tolerated without any unexpected or serious adverse events.“; „Efficacy outcomes were negative, owing in part to the small number of participants.“ Am 23.09.2026 über Europe PMC geprüft.</ref><ref name="SCHINDLER2024">{{cite journal |author=Schindler EAD, Sewell RA, Gottschalk CH u. a. |title=Psilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial |journal=J Neurol Sci |volume=460 |pages=122993 |year=2024 |pmid=38581739 |doi=10.1016/j.jns.2024.122993}} Wiederholung mindestens 6 Monate nach der ersten Runde; alle erhielten Psilocybin. Im Wortlaut: „Ten participants completed the extension phase and all ten were included in the final analysis.“; „cluster attack frequency was significantly reduced from baseline (18.4 … to 9.8 … attacks/week; p = 0.013“; „A reduction of approximately 50% was seen regardless of individual response to psilocybin in the first round.“ Am 23.09.2026 über Europe PMC geprüft. Zum Aufbau: „We carried out a blinded extension phase to consider the safety and efficacy of repeating the pulse regimen.“</ref> → [[Studien zum Cluster-Kopfschmerz#Psilocybin|Studien zu Psilocybin]]