Skip to main content
SpringerLink
Log in

Hiccups in Parkinson’s disease: an analysis of cases reported in the European pharmacovigilance database and a review of the literature

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Background

Some reports have suggested an association between dopamine agonists and hiccups, involuntary contractions that merit full clinical attention because they can be very debilitating. Many drugs frequently used to treat hiccups are formally contraindicated in Parkinson’s disease due to their liability to worsen motor symptoms, making the treatment of hiccups problematic in this disease. The objective of the present study was to analyze all spontaneous reports of hiccups from the European Pharmacovigilance Database in patients with Parkinson’s disease and/or on dopaminergic drugs. Finally, we sought to identify evidence-based recommendations on the management of hiccups in Parkinson’s disease.

Methods

We searched for all reports of hiccups in the European Pharmacovigilance Database (EudraVigilance) and calculated proportional reporting ratios for dopamine agonists and hiccups. We reviewed the literature on Parkinson’s disease, dopamine agonists, and hiccups, searching for specific treatment recommendations for hiccups in this disease.

Results

Both rotigotine and pramipexole fulfilled the criteria to generate a safety signal. We found 32 and 13 cases of hiccups associated with dopamine agonists in EudraVigilance and the literature, respectively. There were no specific recommendations for the management of hiccups in Parkinson’s disease in the clinical guidelines consulted.

Conclusions

We have found evidence that rotigotine and pramipexole are associated with the appearance of hiccups and that this adverse reaction occurs predominantly in males. Given the scarce information available, specific recommendations are needed in clinical guidelines for the adequate management of hiccups in Parkinson’s disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Miwa H, Kondo T (2010) Hiccups in Parkinson’s disease: an overlooked non motor symptom? Parkinsonism Relat Disord 16:249–251

    Article  PubMed  Google Scholar 

  2. Bagheri H, Cismondo S, Montastruc JL (1999) Hoquet d'origine médicamenteuse: enquête à partir de la Banque Nationale de Pharmacovigilance. Therapie 54:35–39

    CAS  PubMed  Google Scholar 

  3. Sharma P, Morgan JC, Sethi KD (2006) Hiccups associated with dopamine agonists in Parkinson disease. Neurology 66:774

    Article  PubMed  Google Scholar 

  4. Kim MJ, Chung EJ (2011) Hiccups associated with dopaminergic treatments in Parkinson's disease. Alzheimer’s and Parkinson’s diseases: advances, concepts and new challenges neurodegenerative 8: 1. [Poster]

  5. Collins DR, Wanklyn P (2002) Hiccoughs, an unusual dyskinetic side-effect of L-dopa. Age Ageing 31:405–406

    Article  PubMed  Google Scholar 

  6. Gerschlager W, Bloem BR (2009) Hiccups associated with levodopa in Parkinson’s disease. Mov Disord 24:621

    Article  PubMed  Google Scholar 

  7. Lester J, Raina GB, Uribe-Roca C (2007) Hiccup secondary to dopamine agonists in Parkinson’s disease. Mov Disord 22:1667–1668

    Article  PubMed  Google Scholar 

  8. Moja MC (2010) Hiccups associated with non-ergoline dopamine agonists in Parkinson’s disease. Mov Disord 25:1292

    Article  Google Scholar 

  9. Yardimci N, Benli S, Zileli T (2008) A diagnostic challenge of Parkinson’s disease: intractable hiccups. Parkinsonism Relat Disord 14:446–447

    Article  PubMed  Google Scholar 

  10. Giugni J, Seijo D, Micheli F (2010) Are hiccups non-motor symptoms? Parkinsonism Relat Disord 10:690

    Article  Google Scholar 

  11. Steger M, Schneemann M, Fox M (2015) Systemic review: the pathogenesis and pharmacological treatment of hiccups. Aliment Pharmacol Ther 42:1037–1050

    Article  CAS  PubMed  Google Scholar 

  12. Lertxundi U, Peral J, Mora O et al (2008) Antidopaminergic therapy for managing comorbidities in patients with Parkinson’s disease. Am J Health Syst Pharm 65:414–419

    Article  PubMed  Google Scholar 

  13. Capellá D, Laporte JR (1993) La notificación espontánea de reacciones adversas a medicamentos. In: Laporte JR, Tognoni G (eds) Principios de epidemiología del medicamento, 2nd edn. p 147–170

  14. Evans SJW, Waller PC, Davis S (2001) Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports. Pharmacoepidemiol Drug Saf 10:483–486

    Article  CAS  PubMed  Google Scholar 

  15. Summary of product characteristics. Available from http://www.ema.europa.eu. Accessed 15 May 2016

  16. US Package Insert. Available form: https://www.accessdata.fda.gov/scripts/cder/drugsatfda/. Accessed 15 May 2016

  17. Wilcox SK, Garry A, Johnson M (2009) Novel use of amantadine: to treat hiccups. J Pain Symptom Manag 38:460–465

    Article  CAS  Google Scholar 

  18. Lembo AJ, Aronson MD, Park L. Overview of hiccups. UpToDate. Available from www.uptodate.com. Last updated May 2, 2016. Accessed 9 May 2016

  19. NICE clinical guideline 35. Parkinson’s disease. Diagnosis and management in primary and secondary care. Available from www.guidance.nice.org.uk/CG35. Accessed 20 May 2016

  20. Moretto EN, Wee B, Wiffen PJ, Murchison AG (2013) Interventions for treating persistent and intractable hiccups in adults. Cochrane Database Syst Rev. Available from www.tripdatabase.com. Accessed 11 May 2016

  21. Lee G, Kim RB, Go SI et al (2016) Gender differences in hiccup patients: analysis of published case reports and case-control studies. J Pain Symptom Manag 51:278–283

    Article  Google Scholar 

  22. Kalia LV, Lang AE (2015) Parkinson's disease. Lancet 29:386:896–386:912

    Google Scholar 

  23. Lertxundi U, Isla A, Solinís MA, Domingo-Echaburu S, García M, Aguirre C, García-Moncó JC (2015) Adverse reactions to antipsychotics in Parkinson disease: an analysis of the Spanish pharmacovigilance database. Clin Neuropharmacol 38:69–84

    CAS  PubMed  Google Scholar 

  24. Lertxundi U, Isla A, Solinís MA, Domingo-Echaburu S, Hernandez R, Peral-Aguirregoitia J, Medrano J, García-Moncó JC Medication errors in Parkinson's disease inpatients in the Basque Country. Parkinsonism Relat Disorde. doi:10.1016/j.parkreldis.2016.12.028

Download references

Author information

Authors and Affiliations

  1. Pharmacy Service, Araba Mental Health Network, C/Alava 43, 01006, Vitoria-Gasteiz, Alava, Spain

    U. Lertxundi

  2. Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Lascaray Research Center, University of the Basque Country UPV/EHU, Paseo de la Universidad, 7, 01006, Vitoria-Gasteiz, Spain

    A.C Marquínez, M.Á Solinís, B. Calvo, A. Del Pozo-Rodríguez & A. Isla

  3. Pharmacy Service, Alto Deba Integrated Health Organization, Avda. Nafarroa 16, 20500, Arrasate Gipuzkoa, Spain

    S. Domingo-Echaburu

  4. Basque Pharmacovigilance Unit, Hospital de Galdakao-Usansolo, Galdakao, Spain

    M. García & C. Aguirre

Authors
  1. U. Lertxundi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A.C Marquínez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Domingo-Echaburu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M.Á Solinís
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B. Calvo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Del Pozo-Rodríguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. García
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C. Aguirre
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A. Isla
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Unax Lertxundi, Ana Marquinez, Saioa Domingo-Echaburu, Maria Angeles Solinis, Ana del Pozo, Begoña Calvo, Montserrat García, and Carmelo Aguirre participated in the conception, manuscript preparation, writing the first draft, and the review and critique of the manuscript. Montserrat Garcia and Carmelo Aguirre searched for hiccup cases in Eudravigilance database.

Corresponding author

Correspondence to U. Lertxundi.

Ethics declarations

Financial disclosures

Financial disclosure related to research covered in this article: The Departamento de Salud. Gobierno Vasco provided a grant of 20.300€ to the investigators.

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Figure S1

(DOCX 32 kb)

Table S1

(DOCX 14 kb)

Table S2

(DOCX 15 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lertxundi, U., Marquínez, A., Domingo-Echaburu, S. et al. Hiccups in Parkinson’s disease: an analysis of cases reported in the European pharmacovigilance database and a review of the literature. Eur J Clin Pharmacol 73, 1159–1164 (2017). https://doi.org/10.1007/s00228-017-2275-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00228-017-2275-6

Keywords

Search

Navigation