Psychiatric conditions and general practitioner attendance prior to HPV vaccination and the risk of referral to a specialized hospital setting because of suspected adverse events following HPV vaccination: a register-based, matched case–control study

Abstract

Aim

No association between human papilloma virus (HPV) vaccination and numerous diseases has been found. Still, a large number of Danish women are reporting suspected adverse events. Other factors may play a role, and the aim of this study is to examine the association between psychiatric conditions, general practitioner (GP) attendance and indicators of psychological symptoms prior to HPV vaccination and the risk of referral to an HPV center following vaccination.

Study design and setting

Register-based, matched case–control study. Cases were identified from five Danish, regional HPV centers, and health data for cases and controls were obtained from national registries.

Participants

Cases were defined as women referred to an HPV center between January 1, 2015 and December 31, 2015 (n=1,496). Each case was matched with five controls on age, region and time of first vaccine registration. The total study population consisted of 8,976 women.

Results

Overall, women above 18 years who had been referred to an HPV center were more likely to have used psychiatric medication (odds ratio [OR]: 1.88 [95% CI 1.48–2.40]) or to have been hospitalized because of a psychiatric disorder within 5 years prior to the first vaccine registration (OR: 2.13 [95% CI 1.59–2.86]). Specifically, referred women were more likely to have used antipsychotics, antidepressants, attention deficit hyperactivity disorder (ADHD) medication or anxiolytics, and to have been hospitalized for affective disorders or anxiety, but not to have been hospitalized for schizoid, ADHD or eating disorders. In addition, they were more likely to have had talk therapy or psychometric test performed prior to vaccination (OR: 1.72 [95% CI 0.1.35–2.18] and OR: 1.67 [95% CI 1.30–2.13], respectively). Referred women of all ages had higher use of GP before vaccination. Population attributable fraction analyses indicated that psychiatric medication, hospitalization due to a psychiatric disorder and use of talk therapy, or psychometric test “explained” 13%, 10%, 12% and 11% of the referrals, respectively. Results did not change substantially when adjusted for potential confounders.

Conclusion

Women referred to HPV centers because of suspected adverse events after vaccination more often had preexisting psychiatric conditions, psychological symptoms or frequent GP attendance prior to HPV vaccination.

Keywords:

• papillomavirus vaccines
• adverse drug events
• psychoactive drugs
• general practice

Acknowledgments

Collected data: Dr. Med. Erik Østergaard, Department of Woman-Child and Urology, Aalborg University Hospital, Dr. Med. Michael Nielsen, Department of Neurology, Aalborg University Hospital, Dr. Med. Svend Stenvang Pedersen, Department of Infectious Diseases, Odense University Hospital, Dr. Med. Niels Fisker, H.C. Andersen Children’s Hospital, Odense University Hospital, Dr. Med. Martin Faber Boxill, Department of Pediatrics, Regional Hospital of Viborg, Dr. Med. Dan Pradsgaard, Department of Pediatrics, Regional Hospital of Viborg, Dr. Med. Vibeke Neergaard Sørensen, Diagnostics Centre, Regional Hospital of Silkeborg, Dr. Med. Reinar Bue Falck Juvik, Diagnostics Centre, Sjælland University Hospital Roskilde, Dr. Med. Lise Heilmann Jensen, Department of Pediatrics, Sjælland University Hospital Roskilde and Dr. Med. Jesper Mehlsen, Frederiksberg Syncope Centre, Frederiksberg Hospital.

Ethics coordinator: Hanne Birgitte Hede Jørgensen, Center for Integrated Register-based Research at Aarhus University (CIRRAU). This work was supported by the Program for Clinical Research Infrastructure (PROCRIN) established by the Lundbeck Foundation and the Novo Nordisk Foundation and administered by the Danish Regions, as well by an unrestricted grant from the Lundbeck Foundation (grant number: R155–2012-11280). The funding sources had no role in the design and conduct of the study; the collection, analysis and interpretation of data; or the preparation, review or approval of the manuscript. The Danish Data Protection Agency (journal number 2015–57-0002) and the Danish Patient Safety Authority approved the study. According to Danish legislation, ethical approval of registry studies is not required. The abstract of this paper was presented at the Nordic Epi Congress in September 2017 as a poster presentation with final findings. The abstract was published in the “Abstract book,” in the congress app and online (https://mkon.nu/nordicepi).

Disclosure

The authors report no conflicts of interest in this work.