In a trial that says a great deal about the lack of progress
in finding new drugs to treat Parkinson's disease, British
researchers have revisited selegiline � a drug that lost
favour as a Parkinson's treatment a decade ago after being
linked to increased mortality. The drug's deathblow came
in 1995, when a study by the Parkinson's Disease Research
Group of the United Kingdom (UK-PDRG) closed its selegiline
arm after finding 57% higher mortality in patients taking
selegiline and levodopa than in those taking levodopa
alone. Suspicions that the high mortality of the 1995
study was a fluke, as well as a dearth of other options,
prompted Keith Wheatley, PhD and colleagues to perform
a meta-analysis of several previous studies comprising
3,525 patients. Their research was published in the August
13 issue of the British Medical Journal.
Selegiline belongs to the family
of monoamine oxidase type B inhibitors (MAOBIs) and
trials of lazabemide and rasagiline � close cousins
of selegiline � were also included in the meta-analysis.
Some subjects were given the drug with levodopa, others
without. Results were measured versus placebo, levodopa
or both, with all other aspects of treatment the same
in both arms. All the patients in these trials had early
Parkinson's disease with no history of motor complications
and none had received antiparkinsonian drugs for more
than a year.
The researchers analyzed mortality,
clinical disability rating scales, need for levodopa,
motor complications, side effects and treatment withdrawals.
On the crucial issue of mortality, they found that the
famous 1995 UK-PDRG trial was the only one to register
significantly increased mortality among the subjects
taking MAOBIs. This study dragged the overall mortality
for MAOBIs upwards so that, overall, subjects taking
MAOBIs in this meta-analysis were 13% more likely to
die, though this finding lacked statistical significance.
Unified Parkinson's disease rating
scale scores at three months were 2.7 points better
in the MAOBI patients than in the controls. The bulk
of that improvement was in motor skills and the best
results were seen in reduced need for levodopa. Overall,
patients taking MAOBIs needed just 57% as much levodopa
as those on placebo.
The MAOBI treatment groups reported
36% more side effects, but there was little data on
the type of adverse events suffered. Overall, the researchers
concluded that MAOBIs are safe.
Selegiline would be an attractive
option, since the generic pill costs under 40� a dose.
The world, however, has moved on, and if MAOBIs are
to reclaim their place in the treatment of Parkinson's,
they will have to be tested against newer drugs such
as dopamine agonists. Such a trial is now underway at
the University of Birmingham in the UK and should decide
if MAOBIs are fated to make a comeback.
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