Analysis of factors associated with hiccups based on the Japanese Adverse Drug Event Report database

PLoS One. 2017 Feb 14;12(2):e0172057. doi: 10.1371/journal.pone.0172057. eCollection 2017.


Hiccups are occasionally experienced by most individuals. Although hiccups are not life-threatening, they may lead to a decline in quality of life. Previous studies showed that hiccups may occur as an adverse effect of certain medicines during chemotherapy. Furthermore, a male dominance in hiccups has been reported. However, due to the limited number of studies conducted on this phenomenon, debate still surrounds the few factors influencing hiccups. The present study aimed to investigate the influence of medicines and patient characteristics on hiccups using a large-sized adverse drug event report database and, specifically, the Japanese Adverse Drug Event Report (JADER) database. Cases of adverse effects associated with medications were extracted from JADER, and Fisher's exact test was performed to assess the presence or absence of hiccups for each medication. In a multivariate analysis, we conducted a multiple logistic regression analysis using medication and patient characteristic variables exhibiting significance. We also examined the role of dexamethasone in inducing hiccups during chemotherapy. Medicines associated with hiccups included dexamethasone, levofolinate, fluorouracil, oxaliplatin, carboplatin, and irinotecan. Patient characteristics associated with hiccups included a male gender and greater height. The combination of anti-cancer agent and dexamethasone use was noted in more than 95% of patients in the dexamethasone-use group. Hiccups also occurred in patients in the anti-cancer agent-use group who did not use dexamethasone. Most of the medications that induce hiccups are used in chemotherapy. The results of the present study suggest that it is possible to predict a high risk of hiccups using patient characteristics. We confirmed that dexamethasone was the drug that has the strongest influence on the induction of hiccups. However, the influence of anti-cancer agents on the induction of hiccups cannot be denied. We consider the results of the present study to be helpful for the prevention and treatment of hiccups.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects*
  • Databases, Factual*
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects*
  • Female
  • Hiccup / chemically induced*
  • Hiccup / epidemiology*
  • Hiccup / physiopathology
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged


  • Antineoplastic Agents
  • Dexamethasone

Grants and funding

This work was supported by KAKENHI from the Japan Society for the Promotion of Science (Grant Number 15K08111).