PHARMACOEPIDEMIOLOGY AND PRESCRIPTION
Hiccups in Parkinson’s disease: an analysis of cases reported
in the European pharmacovigilance database and a review
of the literature
A. Del Pozo-Rodríguez
Received: 31 January 2017 /Accepted: 26 May 2017 / Published online: 9 June 2017
Springer-Verlag Berlin Heidelberg 2017
Background Some reports have suggested an association be-
tween dopamine agonists and hiccups, involuntary contrac-
tions 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 pres-
ent 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 recommenda-
tions on the management of hiccups in Parkinson’sdisease.
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 specif-
ic 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 recommenda-
tions 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 recommenda-
tions are needed in clinical guidelines for the adequate man-
agement of hiccups in Parkinson’sdisease.
Keywords Adverse drug reaction
Hiccups are sudden, involuntary, spasmodic contractions of
the diaphragm and external intercostal muscles that result in
inspiration, which abruptly end with the closure of the glottis.
Although little is known about the pathophysiological mech-
anisms underlying hiccups, it has been found that the causes
are heterogeneous, both peripheral and central factors contrib-
uting to their induction .
Some reports have suggested an association between dopa-
mine agonists and hiccups, although the information is scarce
[2–8]. Interestingly, a study carried out in Japan including 90
patients with Parkinson’s disease (PD) showed that hiccups
were more prevalent in individuals with the disease than in
healthy volunteers (20% in PD versus 3%). The authors sug-
gested that not only pharmacological (extrinsic) but also
Electronic supplementary material The online version of this article
(doi:10.1007/s00228-017-2275-6) contains supplementary material,
which is available to authorized users.
* U. Lertxundi
Pharmacy Service, Araba Mental Health Network, C/Alava 43,
01006 Vitoria-Gasteiz, Alava, Spain
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
Pharmacy Service, Alto Deba Integrated Health Organization, Avda.
Nafarroa 16, 20500 Arrasate Gipuzkoa, Spain
Basque Pharmacovigilance Unit, Hospital de Galdakao-Usansolo,
Eur J Clin Pharmacol (2017) 73:1159–1164