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Dopamine agonist withdrawal syndrome
Managing dopamine agonist withdrawal
syndrome in Parkinson’s disease
Andrea J Lindahl MA, MD, FRCP, Douglas G MacMahon FRCP
Dopamine agonist withdrawal syndrome (DAWS) has recently been named in the
Archives of Neurology. It describes a cluster of symptoms occurring in Parkinson’s disease
patients with impulse control disorders on tapering down or withdrawal of their
dopamine agonist. Drs Lindahl and MacMahon discuss the risk factors for the
development of DAWS and some approaches to its management.
D
opamine agonists have become
widely used in the management
of Parkinson’s disease (PD) with
considerable benefits for many
patients. However, as their use has
extended, hitherto unrecognised
problems have emerged – most
recently impulse control disorders
(ICDs)1,2 and, as a consequence of
the need to down-titrate or withdraw the agonist, the recently
named dopamine agonist withdrawal syndrome (DAWS).3
Anecdotal experiences of the
adverse effects of sudden withdrawal of dopaminergic therapies
have been recognised for many
years – especially the physical manifestations of the neuroleptic malignant syndrome – and yet one still
hears horrific stories of wellintentioned, yet potentially disastrous, effects of agonist withdrawal.
The case report described by
Cunnington et al. in this issue (see
p. 24) is included to stimulate discussion, particularly among nonspecialists in movement disorders
who may not be familiar with these
syndromes. A recent posting on the
National Parkinson Foundation
website shows this still to be a very
real and live issue,4 and Parkinson’s
UK has recently established a
Steering Group to address the issue.
The prominence of ICDs has led to
increased recognition of the prevalence of DAWS, and an urgent need
for it to be managed better.
4
While dopaminergic medication, particularly dopamine agonists, may induce ICDs in a
minority of patients, the majority
are somehow protected from this
adverse effect. Antonini’s group
reported a prevalence of ICDs of
28 per cent in an Italian cohort
(and 20 per cent in controls). 5
Curiously, they also found in
another study that 17.5 per cent of
drug-naïve PD patients screened
positive for at least one ICD,
although none had a disorder
based on DSM-IV criteria, and so
were presumed to have less severe
illness.6 These frequencies were
similar to healthy controls.
Nevertheless, male patients with
early-onset PD appear to be more
susceptible to ICDs, and other predisposing factors – including personality traits, prior dependency on
drugs or alcohol and any family history of alcohol or drug abuse – are
contentious, but should suggest
caution. The possible identification
of genetic predisposition requires
a genome-wide search, with interesting analogies to dopaminergic
receptor genotypes predisposing to
gambling tendencies. Functional
imaging may also provide an
important tool to study this phenomenon in vivo.7
Management approaches
In terms of management, most
authors favour a gradual (rather
Progress in Neurology and Psychiatry
than sudden) withdrawal of
dopamine agonist, as tolerated,
with additional therapies to
address the dopaminergic deficit.
Other approaches have included
the off-licence use of apomorphine 8 and several case reports
have been published suggesting a
possible role for subthalamic stimulation9,10 (although this has also
been reported as a cause of ICDs11
and DAWS12); enteral carbidopa/
levodopa infusions; 13 carbama zepine;14 amantadine15 (although
this drug has also been incriminated in the genesis of the
syndrome); zonisamide;16 or clozapine.17 We have anecdotal experience (unpublished) of the use of
rotigotine patches, although these
too have also been rarely cited as
yet another cause of ICDs.18
The case of DAWS described in
this issue demonstrates the need
for careful monitoring of patients,
and the importance of patient and
carer/mentor education. It is
important to warn (and carefully
annotate for medicolegal reasons)
patients and their close family
before starting these drugs, and at
regular intervals thereafter, of the
importance of seeking help should
ICDs become apparent, and also
advocate caution during any drug
titration or surgery.
Potentially, the QUIP questionnaire (or a shorter simplified version thereof) may be helpful in
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Dopamine agonist withdrawal syndrome
clinical practice.19 Non-specialists
need to be aware of the consequences of ill-advised dosage
adjustment, and especially to exercise caution in the management of
nil by mouth situations when transdermal or enteral medication
should be carefully considered.
Perhaps one could suggest that
this is a suitable topic to be aired at
journal clubs, grand rounds and
other postgraduate events in order
to increase awareness among
colleagues and improve patient
care from both hospitals’ and
patients’ perspectives. There is a
wealth of up to date information
and resources on ICDs for healthcare professionals and patients on
the Parkinson’s UK website
www.parkinsons.org.uk or by calling its helpline on 0808 800 0303.
Declaration of interests
Dr MacMahon is a Trustee of
Parkinson’s UK.
Dr Lindahl is a Consultant
Neurologist and Dr MacMahon is a
Consultant Physician at University
Hospitals, Coventry and
Warwickshire NHS Trust, Coventry
References
1. Driver-Dunkley E, Samanta J, Stacy M.
Pathological gambling associated with
dopamine agonist therapy in Parkinson’s disease. Neurology 2003;61:422-3.
2. Weintraub D, Koester J, Potenza MN, et al.
Impulse control disorders in Parkinson’s disease. Arch Neurol 2010;67(5):589-95.
3. Rabinak CA, Nirenberg MJ. Dopamine agonist withdrawal syndrome in Parkinson’s disease. Arch Neurol 2010;67(1):58-63.
4. http://forum.parkinson.org/index.php?/
topic/10922-going-through-daws-when-getting-off-mirapex-due-to-icd/ accessed 23.5.11.
5. Isaias IU, Siri C, Cilia R, et al. The relationship
between impulsivity and impulse control disorders in Parkinson’s disease. Movement Disord
2008;23(3):411-5.
6. Antonini A, Siri C, Santangelo G, et al .
Impulsivity and compulsivity in drug-naïve
patients with Parkinson's disease. Movement
Disord 2011;26(3):464-8. doi: 10.1002/
mds.23501. Epub Feb 10, 2011.
7. Cilia R, van Eimeren T. Impulse control disorders in Parkinson’s disease: seeking a
roadmap toward a better understanding. Brain
Struct Funct 2011; May 4. [Epub ahead of print]
8. Schlesinger I, Erikh I, Zaaroor M. Dopamine
agonist withdrawal syndrome: the apomorphine solution. Arch Neurol 2010;
67(9):1155, author reply 1156.
9. Bandini F, Primavera A, Pizzorno M, Cocito
L. Using STN DBS and medication reduction as
a strategy to treat pathological gambling in
Parkinson’s disease. Parkinsonism Relat Disord
2007;13:369-71.
z Comment
10. Halbig TD, Tse W, Frisina PG, et al .
Subthalamic deep brain stimulation and
impulse control in Parkinson’s disease. Eur J
Neurol 2009;16:493-7.
11. Demetriades P, Rickards H, Cavanna AE.
Impulse control disorders following deep brain
stimulation of the subthalamic nucleus in
Parkinson’s disease: clinical aspects. Parkinsons
Dis 2011;2011:658415.
12. Nirenberg MJ. Dopamine agonist withdrawal
syndrome and non-motor symptoms after
Parkinson’s disease surgery. Brain 2010;133(11):
e155, author reply 156. Epub 2010, Jul 21.
13. Gerschlager W, Bloem BR. Managing pathological gambling in Parkinson’s disease with
enteral levodopa/carbidopa infusions.
Movement Disord 2009;24:1858-60.
14. Bach JP, Oertel WH, Dodel R, Jessen F.
Treatment of hypersexuality in Parkinson’s disease with carbamazepine – a case report.
Movement Disord 2009;24:1241-42.
15. Thomas A, Bonanni L, Gambi F, et al. Pathological gambling in Parkinson disease is reduced
by amantadine. Ann Neurol 2010;68:400-4.
16. Bermejo PE, Ruiz-Huete C, Anciones B. Zonisamide in managing impulse control disorders in
Parkinson’s disease. J Neurol 2010;257:1682-5.
17. Rotondo A, Bosco D, Plastino M, et al .
Clozapine for medication-related pathological
gambling in Parkinson disease. Movement
Disord 2010;25:1994-5.
18. Wingo TS, Evatt M, Scott B, et al. Impulse
control disorders arising in 3 patients treated
with rotigotine. Clin Neuropharmacol 2009;
32(2):59-62.
19. Weintraub D, Hoops S, Shea JA, et al .
Validation of the questionnaire for impulsivecompulsive disorders in Parkinson's disease.
Movement Disord 2009;24(10):1461-7. [QUIP
questionnaire]
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