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Letters to the Editor
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Parkinson's disease
Selegiline has a valuable role
From Dr D. MacMahon, MB BS, FRCP, and
Dr J. R. Playfer, MD, FRCP
We read with interest the news item “Patients with Parkinson’s
disease should not be started on selegiline” (PJ, 3 August, p150).
The headline was reminiscent of the style of journalism that surrounded
selegiline in 1995 when Lees et al published their interim mortality data,
since when the debate over the safety of selegiline has continued in the
medical press.
Your news item referred to a review published in the French journal,
Prescrire, which attempted to review the data surrounding the use of selegiline
in the treatment of Parkinson’s disease. The article itself presented
some of the published data on selegiline, but failed to pick up some important
publications surrounding the issue of mortality — this was the driver
behind the above title, which we believe to be inaccurate on two grounds.
The authors highlight the only study that has ever shown a statistically
significant increase in mortality, the UKPDRG published in 1995.1 Unfortunately,
the authors fail to recognise that the results from this open trial have
never been supported by results of other numerous controlled studies that
have been published since. Notably, a meta-analysis of five long-term,
prospective, controlled studies showed no increase in mortality associated
with selegiline with or without concurrent use of levodopa. In a further
six studies not included in the meta-analysis, there was also no evidence
for increased mortality. The Medicines Control Agency sponsored an analysis
from the General Practice Database and this showed no increase in mortality
with selegiline.3 Indeed when the UKPDRG reported the results of their
10-year follow up last year they commented: “We concur that there
is no proven causal link between selegiline and increased mortality in
patients with PD.4
The authors of the Prescrire article also highlight that there are some
concerns that selegiline is metabolised to amphetamine and other amphetamine
metabolites and this may cause adverse symptoms (particularly insomnia)
or contribute to toxicity. This is an avoidable problem. A buccally absorbed
preparation (Zelapar) is available, which has been demonstrated to have
a more predictable pharmacokinetic and pharmacodynamic profile than generic
selegiline. Zelapar 1.25mg by buccal absorption has equal efficacy to
10mg generic selegiline and shows a highly significant reduction in amphetamine
metabolites by avoiding liver metabolism.5
Used appropriately, selegiline has a simple but sometimes valuable role
to play in the management of Parkinson’s disease, both in monotherapy
and as an adjunct to levodopa.6 There is consensus that treatment of this
disease must be individualised and it is now widely agreed that selegiline
should be avoided in the presence of postural hypotension, dementia or
psychosis, and in general frailer patients with concurrent diseases.7
However, despite these cautions, there is considerably more evidence in
favour of its safety than there is against it.
Doug MacMahon
Consultant Physician
Royal Cornwall Hospitals NHS Trust
J. R. Playfer
Consultant Geriatrician
Royal Liverpool and Broadgreen University Hospital
References
1. Lees AJ. Comparison of therapeutic effects and mortality data of levodopa
and levodopa combined with selegiline in patients with early, mild Parkinson’s
disease. United Kingdom Parkinson’s Disease Research Group. BMJ 1995;
311:1602–7.
2. Olanow CW, Myllyla VV, Sotaniemi KA, Larsen JP, Palhagen S, Przuntek
H et al. Effect of selegiline on mortality in patients with Parkinson’s
disease: a meta-analysis. Neurology 1998;51:825–30.
3. Evans SJW, Sivanathan T. Proceedings of the fifth annual meeting of
the European Society of Pharmacovigilance. Berlin: 1997; Abstract 44.
4. Lees AJ, Katzenschlager R, Head J, Ben-Shlomo Y. Ten-year follow-up
of three different initial treatments in de-novo PD: a randomised trial.
Neurology 2001;57; 1687–94.
5. MacMahon D. Current drug treatment of Parkinson’s disease. Prescriber
2002; 5 January: 21–32.
6. Primary Care Task Force. Parkinson’s aware in primary care. London:
Parkinson’s Disease Society; 1999.
7. Bhatia K, Brooks DJ, Burn DJ, Clarke CE, Grosset DG, MacMahon DG et
al. Updated guidelines for the management of Parkinson’s disease.
Hosp Med 2001;62: 456–70.
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