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Current Pain and Headache Reports

Published in:

23-11-2022 | Migraine | Secondary Headache (M Robbins, Section Editor)

Headache After Vaccination: An Update on Recent Clinical Trials and Real-World Reporting

Authors: Kimberly N. Garces, Alexandra N. Cocores, Peter J. Goadsby, Teshamae S. Monteith

Published in: Current Pain and Headache Reports | Issue 12/2022

Abstract

Purpose of Review

The aim of this review is to characterize headache as a vaccine adverse event (VAE) in clinical trials.

Recent Findings

Of the recent phase III vaccine RCTs (non-COVID-19), 53 studies reported on headache (13 infectious agents). The median rate (interquartile range) of headache was 15.6% (IQR: 9.6–37.6%). Of these, 24.5% of the RCTs reported headache greater in the vaccine group compared to the placebo/control group. In the herpes zoster vaccination trials, headache was more common in all active groups: median rate 33.9% (IQR: 29.7–40.5%) as compared to placebo: median rate 17.7% (IQR: 15.4–23.8%). Influenza and HPV vaccination trials were the 2nd and 3rd most common to have headache as a VAE. Of the 6 widely distributed COVID-19 vaccinations, median rate of post-vaccination headache was 39% (IQR: 28–50%).

Summary

Headache is a common VAE in vaccine trials. Standardized grading methods, predictors of persistence, and treatment regimens are warranted.

Biswas N, Mustapha T, Khubchandani J, Price JH. The nature and extent of COVID-19 vaccination hesitancy in healthcare workers. J Community Health. 2021;46(6):1244–51. https://doi.org/10.1007/s10900-021-00984-3.CrossRef

Stovner LJ, Hagen K, Linde M, Steiner TJ. The global prevalence of headache: an update, with analysis of the influences of methodological factors on prevalence estimates. J Headache Pain. 2022;23(1):34. https://doi.org/10.1186/s10194-022-01402-2.CrossRef

Ward BJ, Makarkov A, Seguin A, Pillet S, Trepanier S, Dhaliwall J, et al. Efficacy, immunogenicity, and safety of a plant-derived, quadrivalent, virus-like particle influenza vaccine in adults (18–64 years) and older adults (>/=65 years): two multicentre, randomised phase 3 trials. Lancet. 2020;396(10261):1491–503. https://doi.org/10.1016/S0140-6736(20)32014-6.CrossRef

Chang LJ, Meng Y, Janosczyk H, Landolfi V, Talbot HK, Group QHDS. Safety and immunogenicity of high-dose quadrivalent influenza vaccine in adults >/=65years of age: a phase 3 randomized clinical trial. Vaccine. 2019;37(39):5825–34. https://doi.org/10.1016/j.vaccine.2019.08.016.CrossRef

Vesikari T, Nauta J, Lapini G, Montomoli E, van de Witte S. Immunogenicity and safety of quadrivalent versus trivalent inactivated subunit influenza vaccine in children and adolescents: a phase III randomized study. Int J Infect Dis. 2020;92:29–37. https://doi.org/10.1016/j.ijid.2019.12.010.CrossRef

Endo M, Tanishima M, Ibaragi K, Hayashida K, Fukuda T, Tanabe T, et al. Clinical phase II and III studies of an AS03-adjuvanted H5N1 influenza vaccine produced in an EB66((R)) cell culture platform. Influenza Other Respir Viruses. 2020;14(5):551–63. https://doi.org/10.1111/irv.12755.CrossRef

Chu K, Xu K, Tang R, Tian X, Hu J, Yang T, et al. Immunogenicity and safety of an inactivated quadrivalent influenza vaccine: a randomized, double-blind, controlled phase III study in healthy population aged >/=3 years. Vaccine. 2020;38(37):5940–6. https://doi.org/10.1016/j.vaccine.2020.06.071.CrossRef

Lan PT, Toan NT, Thang HA, Thang TC, Be LV, Thai DH, et al. A phase 2/3 double-blind, randomized, placebo-controlled study to evaluate the safety and immunogenicity of a seasonal trivalent inactivated split-virion influenza vaccine (IVACFLU-S) in healthy adults in Vietnam. Hum Vaccin Immunother. 2019;15(12):2933–9. https://doi.org/10.1080/21645515.2019.1613127.CrossRef

Loebermann M, Fritzsche C, Geerdes-Fenge H, Heijnen E, Kirby D, Reisinger EC. A phase III, open-label, single-arm, study to evaluate the safety and immunogenicity of a trivalent, surface antigen inactivated subunit influenza virus vaccine produced in mammalian cell culture (Optaflu(R)) in healthy adults. Infection. 2019;47(1):105–9. https://doi.org/10.1007/s15010-018-1233-2.CrossRef

10.

Sarkar S, Bokade C, Garg K, Kumar R, Sanmukhani J, Mittal R. Immunogenicity and safety of the first indigenously developed Indian tetravalent influenza vaccine (split virion) in healthy children (6 months to 17 years of age): a randomized, multicenter, phase III clinical trial. Hum Vaccin Immunother. 2021;17(3):681–9. https://doi.org/10.1080/21645515.2020.1794683.CrossRef

11.

Ward BJ, Seguin A, Couillard J, Trepanier S, Landry N. Phase III: randomized observer-blind trial to evaluate lot-to-lot consistency of a new plant-derived quadrivalent virus like particle influenza vaccine in adults 18–49 years of age. Vaccine. 2021;39(10):1528–33. https://doi.org/10.1016/j.vaccine.2021.01.004.CrossRef

12.

Song JY, Lee J, Woo HJ, Wie SH, Lee JS, Kim SW, et al. Immunogenicity and safety of an egg-based inactivated quadrivalent influenza vaccine (GC3110A) versus two inactivated trivalent influenza vaccines with alternate B strains: a phase randomized clinical trial in adults. Hum Vaccin Immunother. 2019;15(3):710–6. https://doi.org/10.1080/21645515.2018.1536589.CrossRef

13.

Beran J, Reynales H, Poder A, Yu CY, Pitisuttithum P, Yuan LL, et al. Prevention of influenza during mismatched seasons in older adults with an MF59-adjuvanted quadrivalent influenza vaccine: a randomised, controlled, multicentre, phase 3 efficacy study. Lancet Infect Dis. 2021;21(7):1027–37. https://doi.org/10.1016/S1473-3099(20)30694-0.CrossRef

14.

Yamazaki Y, Ikeda M, Imada T, Furuno K, Mizukami T, de Solom R, et al. A phase 3, multicenter, single-arm, open-label study to assess the safety, tolerability, and immunogenicity of a single dose of 13-valent pneumococcal conjugate vaccine in Japanese participants aged 6–64 years who are considered to be at increased risk of pneumococcal disease and who are naive to pneumococcal vaccines. Vaccine. 2021;39(43):6414–21. https://doi.org/10.1016/j.vaccine.2021.08.106.CrossRef

15.

Klein NP, Peyrani P, Yacisin K, Caldwell N, Xu X, Scully IL, et al. A phase 3, randomized, double-blind study to evaluate the immunogenicity and safety of 3 lots of 20-valent pneumococcal conjugate vaccine in pneumococcal vaccine-naive adults 18 through 49 years of age. Vaccine. 2021;39(38):5428–35. https://doi.org/10.1016/j.vaccine.2021.07.004.CrossRef

16.

Song JY, Chang CJ, Andrews C, Diez-Domingo J, Oh MD, Dagan R, et al. Safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, followed by sequential PPSV23 vaccination in healthy adults aged>/=50years: a randomized phase III trial (PNEU-PATH). Vaccine. 2021;39(43):6422–36. https://doi.org/10.1016/j.vaccine.2021.08.038.CrossRef

17.

Bastidas A, de la Serna J, El Idrissi M, Oostvogels L, Quittet P, Lopez-Jimenez J, et al. Effect of recombinant zoster vaccine on incidence of herpes zoster after autologous stem cell transplantation: a randomized clinical trial. JAMA. 2019;322(2):123–33. https://doi.org/10.1001/jama.2019.9053.CrossRef

18.

Dagnew AF, Ilhan O, Lee WS, Woszczyk D, Kwak JY, Bowcock S, et al. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in adults with haematological malignancies: a phase 3, randomised, clinical trial and post-hoc efficacy analysis. Lancet Infect Dis. 2019;19(9):988–1000. https://doi.org/10.1016/S1473-3099(19)30163-X.CrossRef

19.

Vink P, Delgado Mingorance I, Maximiano Alonso C, Rubio-Viqueira B, Jung KH, Rodriguez Moreno JF, et al. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in patients with solid tumors, vaccinated before or during chemotherapy: a randomized trial. Cancer. 2019;125(8):1301–12. https://doi.org/10.1002/cncr.31909.CrossRef

20.

Curran D, Kim JH, Matthews S, Dessart C, Levin MJ, Oostvogels L, et al. Recombinant zoster vaccine is efficacious and safe in frail individuals. J Am Geriatr Soc. 2021;69(3):744–52. https://doi.org/10.1111/jgs.16917.CrossRef

21.

Ocran-Appiah J, Boutry C, Herve C, Soni J, Schuind A, Group Z-S. Safety of the adjuvanted recombinant zoster vaccine in adults aged 50 years or older. A phase IIIB, non-randomized, multinational, open-label study in previous ZOE-50 and ZOE-70 placebo recipients. Vaccine. 2021;39(1):6–10. https://doi.org/10.1016/j.vaccine.2020.10.029.

22.

Schmader KE, Levin MJ, Chen M, Matthews S, Riley ME, Woo W, et al. Impact of reactogenicity after two doses of recombinant zoster vaccine upon physical functioning and quality of life: an open phase III trial in older adults. J Gerontol A Biol Sci Med Sci. 2021;76(3):485–90. https://doi.org/10.1093/gerona/glaa127.CrossRef

23.

Schmader KE, Levin MJ, Grupping K, Matthews S, Butuk D, Chen M, et al. The impact of reactogenicity after the first dose of recombinant zoster vaccine on the physical functioning and quality of life of older adults: an open-label, phase III trial. J Gerontol A Biol Sci Med Sci. 2019;74(8):1217–24. https://doi.org/10.1093/gerona/gly218.CrossRef

24.

Lopez-Fauqued M, Campora L, Delannois F, El Idrissi M, Oostvogels L, De Looze FJ, et al. Safety profile of the adjuvanted recombinant zoster vaccine: pooled analysis of two large randomised phase 3 trials. Vaccine. 2019;37(18):2482–93. https://doi.org/10.1016/j.vaccine.2019.03.043.CrossRef

25.

Mikamo H, Yamagishi Y, Murata S, Yokokawa R, Han SR, Wakana A, et al. Efficacy, safety, and immunogenicity of a quadrivalent HPV vaccine in Japanese men: a randomized, phase 3, placebo-controlled study. Vaccine. 2019;37(12):1651–8. https://doi.org/10.1016/j.vaccine.2019.01.069.CrossRef

26.

Joura EA, Ulied A, Vandermeulen C, Rua Figueroa M, Seppa I, Hernandez Aguado JJ, et al. Immunogenicity and safety of a nine-valent human papillomavirus vaccine in women 27–45years of age compared to women 16–26 years of age: an open-label phase 3 study. Vaccine. 2021;39(20):2800–9. https://doi.org/10.1016/j.vaccine.2021.01.074.CrossRef

27.

Chen W, Zhao Y, Xie X, Liu J, Li J, Zhao C, et al. Safety of a quadrivalent human papillomavirus vaccine in a Phase 3, randomized, double-blind, placebo-controlled clinical trial among Chinese women during 90months of follow-up. Vaccine. 2019;37(6):889–97. https://doi.org/10.1016/j.vaccine.2018.12.030.CrossRef

28.

Thiem VD, Quang ND, Tuan NH, Cheon K, Gallagher N, Luxembourg A, et al. Immunogenicity and safety of a nine-valent human papillomavirus vaccine in Vietnamese males and females (9 to 26 years of age): an open-label, phase 3 trial. Hum Vaccin Immunother. 2021;17(7):1980–5. https://doi.org/10.1080/21645515.2020.1865739.CrossRef

29.

Su YY, Lin BZ, Zhao H, Li J, Lin ZJ, Qiao YL, et al. Lot-to-lot consistency study of an Escherichia coli-produced bivalent human papillomavirus vaccine in adult women: a randomized trial. Hum Vaccin Immunother. 2020;16(7):1636–44. https://doi.org/10.1080/21645515.2019.1691413.CrossRef

30.

Dhingra MS, Peterson J, Hedrick J, Pan J, Neveu D, Jordanov E. Immunogenicity, safety and inter-lot consistency of a meningococcal conjugate vaccine (MenACYW-TT) in adolescents and adults: a phase III randomized study. Vaccine. 2020;38(33):5194–201. https://doi.org/10.1016/j.vaccine.2020.06.013.CrossRef

31.

Esteves-Jaramillo A, Koehler T, Jeanfreau R, Neveu D, Jordanov E, Singh DM. Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in >/=56-year-olds: a phase III randomized study. Vaccine. 2020;38(28):4405–11. https://doi.org/10.1016/j.vaccine.2020.04.067.CrossRef

32.

Group MMRS. A second dose of a measles-mumps-rubella vaccine administered to healthy four-to-six-year-old children: a phase III, observer-blind, randomized, safety and immunogenicity study comparing GSK MMR and MMR II with and without DTaP-IPV and varicella vaccines co-administration. Hum Vaccin Immunother. 2019;15(4):786–99. https://doi.org/10.1080/21645515.2018.1554971.CrossRef

33.

Baccarini CI, Simon MW, Brandon D, Christensen S, Jordanov E, Dhingra MS. Safety and immunogenicity of a quadrivalent meningococcal conjugate vaccine in healthy meningococcal-naive children 2–9 years of age: a phase III, randomized study. Pediatr Infect Dis J. 2020;39(10):955–60. https://doi.org/10.1097/INF.0000000000002832.CrossRef

34.

Nolan T, Santolaya ME, de Looze F, Marshall H, Richmond P, Henein S, et al. Antibody persistence and booster response in adolescents and young adults 4 and 7.5 years after immunization with 4CMenB vaccine. Vaccine. 2019;37(9):1209–18. https://doi.org/10.1016/j.vaccine.2018.12.059.CrossRef

35.

Vesikari T, Peyrani P, Webber C, Van Der Wielen M, Cheuvart B, De Schrevel N, et al. Ten-year antibody persistence and booster response to MenACWY-TT vaccine after primary vaccination at 1–10 years of age. Hum Vaccin Immunother. 2020;16(6):1280–91. https://doi.org/10.1080/21645515.2020.1746110.CrossRef

36.

Anez G, Hedrick J, Simon MW, Christensen S, Jeanfreau R, Yau E, et al. Immunogenicity and safety of a booster dose of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in adolescents and adults: a phase III randomized study. Hum Vaccin Immunother. 2020;16(6):1292–8. https://doi.org/10.1080/21645515.2020.1733867.CrossRef

37.

Vesikari T, Ostergaard L, Beeslaar J, Absalon J, Eiden JJ, Jansen KU, et al. Persistence and 4-year boosting of the bactericidal response elicited by two- and three-dose schedules of MenB-FHbp: a phase 3 extension study in adolescents. Vaccine. 2019;37(12):1710–9. https://doi.org/10.1016/j.vaccine.2018.11.073.CrossRef

38.

Tipton M, Daly W, Senders S, Block SL, Lattanzi M, Mzolo T, et al. MenACWY-CRM conjugate vaccine booster dose given 4–6years after priming: results from a phase IIIb, multicenter, open label study in adolescents and adults. Vaccine. 2019;37(42):6171–9. https://doi.org/10.1016/j.vaccine.2019.08.065.CrossRef

39.

Nolan T, Booy R, Marshall HS, Richmond P, Nissen M, Ziegler JB, et al. Immunogenicity and safety of a quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine 6 years after MenC priming as toddlers. Pediatr Infect Dis J. 2019;38(6):643–50. https://doi.org/10.1097/INF.0000000000002334.CrossRef

40.

Jiang F, Zhang R, Guan Q, Mu Q, He P, Ye X, et al. Immunogenicity and safety of a live attenuated varicella vaccine in children 1–12 years of age: a randomized, blinded, controlled, non-inferiority phase 3 clinical trial. Contemp Clin Trials. 2021;107:106489. https://doi.org/10.1016/j.cct.2021.106489.CrossRef

41.

Asatryan A, Meyer N, Scherbakov M, Romanenko V, Osipova I, Galustyan A, et al. Immunogenicity, safety, and reactogenicity of combined reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine administered as a booster vaccine dose in healthy Russian participants: a phase III, open-label study. Hum Vaccin Immunother. 2021;17(3):723–30. https://doi.org/10.1080/21645515.2020.1796423.CrossRef

42.

Vesikari T, Langley JM, Segall N, Ward BJ, Cooper C, Poliquin G, et al. Immunogenicity and safety of a tri-antigenic versus a mono-antigenic hepatitis B vaccine in adults (PROTECT): a randomised, double-blind, phase 3 trial. Lancet Infect Dis. 2021;21(9):1271–81. https://doi.org/10.1016/S1473-3099(20)30780-5.CrossRef

43.

Chaparro M, Gordillo J, Domenech E, Esteve M, Barreiro-de Acosta M, Villoria A, et al. Fendrix vs Engerix-B for primo-vaccination against hepatitis B infection in patients with inflammatory bowel disease: a randomized clinical trial. Am J Gastroenterol. 2020;115(11):1802–11. https://doi.org/10.14309/ajg.0000000000000926.CrossRef

44.

Lee J, Choi JH, Wie SH, Park SH, Choi SM, Lee MS, et al. A phase III study to evaluate the immunogenicity and safety of GC1107 (adult tetanus diphtheria vaccine) in healthy adults. J Korean Med Sci. 2019;34(4):e31. https://doi.org/10.3346/jkms.2019.34.e31.CrossRef

45.

Arredondo JL, Villagomez Martinez SM, Concepcion Morales M, Meyer S, Toh ML, Zocchetti C, et al. Immunogenicity and safety of a tetravalent dengue vaccine and a bivalent HPV vaccine given concomitantly or sequentially in girls aged 9 to 14 years in Mexico. Vaccine. 2021;39(25):3388–96. https://doi.org/10.1016/j.vaccine.2021.04.064.CrossRef

46.

Shen H, Wang Z, Yang B, Cai K, Jiang C, Xie R, et al. Immunogenicity and safety of purified vero cell-cultured rabies vaccine under Zagreb 2–1-1 or 5-dose Essen regimen in the healthy Chinese subjects: a randomized, double-blind, positive controlled phase 3 clinical trial. Hum Vaccin Immunother. 2021;17(2):351–7. https://doi.org/10.1080/21645515.2020.1778408.CrossRef

47.

Matson MA, Schenker E, Stein M, Zamfirova V, Nguyen HB, Bergman GE. Safety and efficacy results of simulated post-exposure prophylaxis with human immune globulin (HRIG; KEDRAB) co-administered with active vaccine in healthy subjects: a comparative phase 2/3 trial. Hum Vaccin Immunother. 2020;16(2):452–9. https://doi.org/10.1080/21645515.2019.1656967.CrossRef

48.

de Bruyn G, Gordon DL, Steiner T, Tambyah P, Cosgrove C, Martens M, et al. Safety, immunogenicity, and efficacy of a Clostridioides difficile toxoid vaccine candidate: a phase 3 multicentre, observer-blind, randomised, controlled trial. Lancet Infect Dis. 2021;21(2):252–62. https://doi.org/10.1016/S1473-3099(20)30331-5.CrossRef

49.

McCarty JM, Lock MD, Bennett S, Hunt KM, Simon JK, Gurwith M. Age-related immunogenicity and reactogenicity of live oral cholera vaccine CVD 103-HgR in a randomized, controlled clinical trial. Vaccine. 2019;37(11):1389–97. https://doi.org/10.1016/j.vaccine.2019.01.077.CrossRef

50.

Gray GE, Bekker LG, Laher F, Malahleha M, Allen M, Moodie Z, et al. Vaccine efficacy of ALVAC-HIV and bivalent subtype C gp120-MF59 in adults. N Engl J Med. 2021;384(12):1089–100. https://doi.org/10.1056/NEJMoa2031499.CrossRef

51.

Brogan PA, Hofer M, Kuemmerle-Deschner JB, Kone-Paut I, Roesler J, Kallinich T, et al. Rapid and sustained long-term efficacy and safety of canakinumab in patients with cryopyrin-associated periodic syndrome ages five years and younger. Arthritis Rheumatol. 2019;71(11):1955–63. https://doi.org/10.1002/art.41004.CrossRef

52.

Riveau G, Schacht AM, Dompnier JP, Deplanque D, Seck M, Waucquier N, et al. Safety and efficacy of the rSh28GST urinary schistosomiasis vaccine: a phase 3 randomized, controlled trial in Senegalese children. PLoS Negl Trop Dis. 2018;12(12):e0006968. https://doi.org/10.1371/journal.pntd.0006968.CrossRef

53.

Markman J, Resnick M, Greenberg S, Katz N, Yang R, Scavone J, et al. Efficacy of pregabalin in post-traumatic peripheral neuropathic pain: a randomized, double-blind, placebo-controlled phase 3 trial. J Neurol. 2018;265(12):2815–24. https://doi.org/10.1007/s00415-018-9063-9.CrossRef

54.

Song JY, Jeong HW, Yun JW, Lee J, Woo HJ, Bae JY, et al. Immunogenicity and safety of a modified three-dose priming and booster schedule for the Hantaan virus vaccine (Hantavax): a multi-center phase III clinical trial in healthy adults. Vaccine. 2020;38(50):8016–23. https://doi.org/10.1016/j.vaccine.2020.10.035.CrossRef

55.

Halperin SA, Das R, Onorato MT, Liu K, Martin J, Grant-Klein RJ, et al. Immunogenicity, lot consistency, and extended safety of rVSVDeltaG-ZEBOV-GP vaccine: a phase 3 randomized, double-blind, placebo-controlled study in healthy adults. J Infect Dis. 2019;220(7):1127–35. https://doi.org/10.1093/infdis/jiz241.CrossRef

56.

Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383(27):2603–15. https://doi.org/10.1056/NEJMoa2034577.CrossRef

57.

Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403–16. https://doi.org/10.1056/NEJMoa2035389.CrossRef

58.

Moderna TX I. Vaccines and related biological products advisory committee meeting, December 17, 2020: FDA Briefing Document 2020. Available from: https://www.fda.gov/media/144434/download.

59.

Sadoff J, Gray G, Vandebosch A, Cardenas V, Shukarev G, Grinsztejn B, et al. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. N Engl J Med. 2021;384(23):2187–201. https://doi.org/10.1056/NEJMoa2101544.CrossRef

60.

Ramasamy MN, Minassian AM, Ewer KJ, Flaxman AL, Folegatti PM, Owens DR, et al. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. Lancet. 2021;396(10267):1979–93. https://doi.org/10.1016/S0140-6736(20)32466-1.CrossRef

61.

Heath PT, Galiza EP, Baxter DN, Boffito M, Browne D, Burns F, et al. Safety and efficacy of NVX-CoV2373 Covid-19 vaccine. N Engl J Med. 2021. https://doi.org/10.1056/NEJMoa2107659.CrossRef

62.

Keech C, Albert G, Cho I, Robertson A, Reed P, Neal S, et al. Phase 1–2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. N Engl J Med. 2020;383(24):2320–32. https://doi.org/10.1056/NEJMoa2026920.CrossRef

63.

Pfizer-BioNTech COVID-19 vaccine BNT162, P-. Vaccines and related biological products advisory committee briefing document. 2020. Available from: https://www.fda.gov/media/144434/download.

64.

Pfizer-BioNTech COVID-19 Vaccine Reactions & Adverse Events. https://www.cdc.gov/vaccines/covid-19/info-by-product/pfizer/reactogenicity.html (2021). Accessed 28 Nov 2021.

65.

Frenck RW Jr, Klein NP, Kitchin N, Gurtman A, Absalon J, Lockhart S, et al. Safety, immunogenicity, and efficacy of the BNT162b2 Covid-19 vaccine in adolescents. N Engl J Med. 2021;385(3):239–50. https://doi.org/10.1056/NEJMoa2107456.CrossRef

66.

Lee YH, Song GG. Nocebo responses in randomized controlled trials of COVID-19 vaccines. Int J Clin Pharmacol Ther. 2021. https://doi.org/10.5414/CP204028.CrossRef

67.

Tanriover MD, Doganay HL, Akova M, Guner HR, Azap A, Akhan S, et al. Efficacy and safety of an inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. Lancet. 2021;398(10296):213–22. https://doi.org/10.1016/S0140-6736(21)01429-X.CrossRef

68.

Castaldo M, Waliszewska-Prosół M, Koutsokera M, Robotti M, Straburzyński M, Apostolakopoulou L, et al. Headache onset after vaccination against SARS-CoV-2: a systematic literature review and meta-analysis. J Headache Pain. 2022;23(1):41. https://doi.org/10.1186/s10194-022-01400-4.CrossRef

69.

Klugar M, Riad A, Mekhemar M, Conrad J, Buchbender M, Howaldt HP, et al. Side effects of mRNA-based and viral vector-based COVID-19 vaccines among German healthcare workers. Biology. 2021;10(8):752.

70.

Riad A, Pokorna A, Attia S, Klugarova J, Koscik M, Klugar M. Prevalence of COVID-19 vaccine side effects among healthcare workers in the Czech Republic. J Clin Med. 2021;10(7).

71.

Mattiuzzi C, Lippi G. Headache after COVID-19 vaccination: updated report from the Italian Medicines Agency database. Neurol Sci. 2021;42(9):3531–2. https://doi.org/10.1007/s10072-021-05354-4.CrossRef

72.

Herve C, Laupeze B, Del Giudice G, Didierlaurent AM, Tavares Da Silva F. The how’s and what’s of vaccine reactogenicity. NPJ Vaccines. 2019;4:39. https://doi.org/10.1038/s41541-019-0132-6.

73.

Goadsby PJ, Holland PR. An update: pathophysiology of migraine. Neurol Clin. 2019;37(4):651–71. https://doi.org/10.1016/j.ncl.2019.07.008.CrossRef

74.

Ferrari MD, Goadsby PJ, Burstein R, Kurth T, Ayata C, Charles A, et al. Migraine Nat Rev Dis Primers. 2022;8(1):2. https://doi.org/10.1038/s41572-021-00328-4.CrossRef

75.

Robbins MS, Grosberg BM, Napchan U, Crystal SC, Lipton RB. Clinical and prognostic subforms of new daily-persistent headache. Neurology. 2010;74(17):1358–64. https://doi.org/10.1212/WNL.0b013e3181dad5de.CrossRef

76.

Ekizoglu E, Gezegen H, Yalinay Dikmen P, Orhan EK, Ertas M, Baykan B. The characteristics of COVID-19 vaccine-related headache: clues gathered from the healthcare personnel in the pandemic. Cephalalgia. 2021:3331024211042390. https://doi.org/10.1177/03331024211042390.

77.

Gobel CH, Heinze A, Karstedt S, Morscheck M, Tashiro L, Cirkel A, et al. Clinical characteristics of headache after vaccination against COVID-19 (coronavirus SARS-CoV-2) with the BNT162b2 mRNA vaccine: a multicentre observational cohort study. Brain Commun. 2021;3(3):fcab169. https://doi.org/10.1093/braincomms/fcab169.

78.

Gobel CH, Heinze A, Karstedt S, Morscheck M, Tashiro L, Cirkel A, et al. Headache attributed to vaccination against COVID-19 (coronavirus SARS-CoV-2) with the ChAdOx1 nCoV-19 (AZD1222) vaccine: a multicenter observational cohort study. Pain Ther. 2021;10(2):1309–30. https://doi.org/10.1007/s40122-021-00296-3.CrossRef

79.

Consoli S, Dono F, Evangelista G, D’Apolito M, Travaglini D, Onofrj M, et al. Status migrainosus: a potential adverse reaction to Comirnaty (BNT162b2, BioNtech/Pfizer) COVID-19 vaccine-a case report. Neurol Sci. 2021. https://doi.org/10.1007/s10072-021-05741-x.CrossRef

80.

Silvestro M, Tessitore A, Orologio I, Sozio P, Napolitano G, Siciliano M, et al. Headache worsening after COVID-19 vaccination: an online questionnaire-based study on 841 patients with migraine. J Clin Med. 2021;10(24).

81.

Rattanawong W, Akaratanawat W, Tepmongkol S, Chutinet A, Tantivatana J, Suwanwela NC. Acute prolonged motor aura resembling ischemic stroke after COVID - 19 vaccination (CoronaVac): the first case report. J Headache Pain. 2021;22(1):93. https://doi.org/10.1186/s10194-021-01311-w.CrossRef

82.

Salai G, Bilic E, Primorac D, Lakusic DM, Bilic H, Lazibat I, et al. Benign fasciculation syndrome and migraine aura without headache: possible rare side effects of the BNT162b2 mRNA vaccine? A case report and a potential hypothesis. Vaccines (Basel). 2022;10(1).

83.

Suwanwela NC, Kijpaisalratana N, Tepmongkol S, Rattanawong W, Vorasayan P, Charnnarong C, et al. Prolonged migraine aura resembling ischemic stroke following CoronaVac vaccination: an extended case series. J Headache Pain. 2022;23(1):13. https://doi.org/10.1186/s10194-022-01385-0.CrossRef

84.

Sekiguchi K, Watanabe N, Miyazaki N, Ishizuchi K, Iba C, Tagashira Y, et al. Incidence of headache after COVID-19 vaccination in patients with history of headache: a cross-sectional study. Cephalalgia. 2021:3331024211038654. https://doi.org/10.1177/03331024211038654.

85.

Sharifian-Dorche M, Bahmanyar M, Sharifian-Dorche A, Mohammadi P, Nomovi M, Mowla A. Vaccine-induced immune thrombotic thrombocytopenia and cerebral venous sinus thrombosis post COVID-19 vaccination; a systematic review. J Neurol Sci. 2021;428:117607. https://doi.org/10.1016/j.jns.2021.117607.CrossRef

86.

Pawlowski C, Rincon-Hekking J, Awasthi S, Pandey V, Lenehan P, Venkatakrishnan AJ, et al. Cerebral venous sinus thrombosis is not significantly linked to COVID-19 vaccines or non-COVID vaccines in a large multi-state health system. J Stroke Cerebrovasc Dis. 2021;30(10):105923. https://doi.org/10.1016/j.jstrokecerebrovasdis.2021.105923.CrossRef

87.

Sanchez van Kammen M, Aguiar de Sousa D, Poli S, Cordonnier C, Heldner MR, van de Munckhof A, et al. Characteristics and outcomes of patients with cerebral venous sinus thrombosis in SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia. JAMA Neurol. 2021;78(11):1314–23. https://doi.org/10.1001/jamaneurol.2021.3619.

88.

Palaiodimou L, Stefanou MI, Katsanos AH, Aguiar de Sousa D, Coutinho JM, Lagiou P, et al. Cerebral venous sinus thrombosis and thrombotic events after vector-based COVID-19 vaccines: a systematic review and meta-analysis. Neurology. 2021;97(21):e2136-e47. https://doi.org/10.1212/WNL.0000000000012896.

89.

Garcia-Azorin D, Do TP, Gantenbein AR, Hansen JM, Souza MNP, Obermann M, et al. Delayed headache after COVID-19 vaccination: a red flag for vaccine induced cerebral venous thrombosis. J Headache Pain. 2021;22(1):108. https://doi.org/10.1186/s10194-021-01324-5.CrossRef

90.

Okais C, Gay C, Seon F, Buchaille L, Chary E, Soubeyrand B. Disease-specific adverse events following nonlive vaccines: a paradoxical placebo effect or a nocebo phenomenon? Vaccine. 2011;29(37):6321–6. https://doi.org/10.1016/j.vaccine.2011.05.045.CrossRef

91.

Amanzio M, Cipriani GE, Bartoli M. How do nocebo effects in placebo groups of randomized controlled trials provide a possible explicative framework for the COVID-19 pandemic? Expert Rev Clin Pharmacol. 2021;14(4):439–44. https://doi.org/10.1080/17512433.2021.1900728.CrossRef

92.

Smith LE, Sim J, Amlot R, Cutts M, Dasch H, Sevdalis N, et al. Side-effect expectations from COVID-19 vaccination: findings from a nationally representative cross-sectional survey (CoVAccS - wave 2). J Psychosom Res. 2021;152:110679. https://doi.org/10.1016/j.jpsychores.2021.110679.CrossRef

93.

Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58(3):e44-100. https://doi.org/10.1093/cid/cit684.CrossRef

94.

Hong SM, Park YW, Choi EJ. Steroid injections in pain management: influence on coronavirus disease 2019 vaccines. Korean J Pain. 2022;35(1):14–21. https://doi.org/10.3344/kjp.2022.35.1.14.CrossRef

95.

Spine Intervention Society. Preliminary recommendations on corticosteroid injections and COVID-19 vaccinations friday, January 22, 2021. Available from: https://www.spineintervention.org/news/548668/Preliminary-Recommendations-on-Corticosteroid-Injections-and-COVID-19-Vaccinations.htm.

96.

Chow RM, Rajput K, Howie BA, Varhabhatla N. The COVID-19 vaccine and interventional procedures: exploring the relationship between steroid administration and subsequent vaccine efficacy. Pain Pract. 2021;21(8):966–73. https://doi.org/10.1111/papr.13062.CrossRef

97.

Gelfand AA, Poland G. Migraine treatment and COVID-19 vaccines: no cause for concern. Headache. 2021;61(3):409–11. https://doi.org/10.1111/head.14086.CrossRef

Title: Headache After Vaccination: An Update on Recent Clinical Trials and Real-World Reporting
Authors: Kimberly N. Garces
Alexandra N. Cocores
Peter J. Goadsby
Teshamae S. Monteith
Publication date: 23-11-2022
Publisher: Springer US
Keywords: Migraine
COVID-19 Vaccination
Vaccination
COVID-19
Headache
Published in: Current Pain and Headache Reports / Issue 12/2022
Print ISSN: 1531-3433
Electronic ISSN: 1534-3081
DOI: https://doi.org/10.1007/s11916-022-01094-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Headache After Vaccination: An Update on Recent Clinical Trials and Real-World Reporting

Abstract

Purpose of Review

Recent Findings

Summary

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

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