News about Deprenyl
nijusan
Selegiline Does Not Increase Parkinson's Death Rate
ST. PAUL, MN -- December 27, 2000 -- Researchers have debated for years
whether the drug selegiline increases the risk of death for Parkinson's
patients even though others have suggested that the drug may slow the
progression of the disease. A new study shows that there is no increased
death rate for patients who use the drug in combination with levodopa, the
most common drug for Parkinson's.
The study is published in the December 26 issue of Neurology, the scientific
journal of the American Academy of Neurology.
"This is exciting news because this drug is the first that showed even the
possibility of slowing the course of this disease, not just treating its
symptoms," said neurologist William Langston, MD, of The Parkinson's
Institute in Sunnyvale, California, who co-authored an accompanying
editorial on the study. "But when a study came out several years ago
reporting that it raised the death rate, near-panic ensued. Even though
there were criticisms of that study and other studies failed to confirm the
original results, there was a chilling effect on the use of selegiline. This
study should dispel any remaining doubts."
The study examined people newly diagnosed and receiving drugs for
Parkinson's disease in the Tayside region of Scotland from 1989 to 1995.
Those 97 cases were compared to 902 people from the community who did not
have Parkinson's disease. The study looked at the death rates for people
taking levodopa alone, selegiline alone, or selegiline in addition to other
antiparkinsonian drugs, and compared the death rates in each of these groups
with people who did not have Parkinson's disease.
Overall, those with Parkinson's were twice as likely to die during the study
period than their healthy counterparts. But those patients who were taking
selegiline in combination with levodopa were no more likely to die during
the study than the people without Parkinson's. People taking levodopa alone
had the highest death rate among the three treatment groups, according to
study author Peter Donnan, PhD, of the University of Dundee in Dundee,
Scotland.
Selegiline has been used as a treatment for Parkinson's for nearly 25 years,
but excitement about the drug peaked in the mid-1980s when research
suggested that it may have neuroprotective effects, thereby slowing the
effects of the disease on the brain. But a later study raised doubts about
that theory.
"The debate has been whether selegiline actually affects the progression of
the disease or whether it just affects the symptoms," Dr. Langston said.
"While proving that selegiline -- or any anti-parkinsonian drug -- is
neuroprotective remains beyond our technical grasp, this study shows us that
at the very least treating patients with selegiline and levodopa is not a
bad thing, and in fact may be a very good thing."
RArmant
>Selegiline Does Not Increase Parkinson's Death Rate
>
>ST. PAUL, MN -- December 27, 2000 -- Researchers have debated for years
>whether the drug selegiline increases the risk of death for Parkinson's
>patients even though others have suggested that the drug may slow the
>progression of the disease. A new study shows that there is no increased
>death rate for patients who use the drug in combination with levodopa, the
>most common drug for Parkinson's.
The only studies I have heard of where selegiline might cause problems
is when it is taken with l-dopa. Has any study of selegiline taken whithout
other anti-parkinson's medication shown a negative effect?
What are good nutrient supplements to prevent brain damage from
excessive dopamine in the brain?
nijusan
taking levodopa alone, selegiline alone, or selegiline in addition to other
antiparkinsonian drugs, and compared the death rates in each of these groups
with people who did not have Parkinson's disease."
However, this press release I forwarded doesn't make any points re: these
two populations.
I gather that the study _does_ include data on folk taking only selegiline
(albeit folk with Parkinsons pathology) in comparison to death rates of
unmedicated normals.
My searches for this article (free) on-line have been unsuccessful so far:
I'll hafta' wait for a day-off to go up to the UVic medical library to get
this issure of _Neurology_ and get the data "unfiltered" by the popular
press.
RX'ing of deprenyl really slowed down after reports of early mortality....
perhaps Docs will resume more liberal use of it in PD now.
mik...@my-deja.com
"nijusan" <nij...@canada.com> wrote:
>
>
> Selegiline Does Not Increase Parkinson's Death Rate
>
> ST. PAUL, MN -- December 27, 2000 -- Researchers have debated for years
> whether the drug selegiline increases the risk of death for Parkinson's
> patients even though others have suggested that the drug may slow the
> progression of the disease. A new study shows that there is no increased
> death rate for patients who use the drug in combination with levodopa,
Here's the abstract, tho' it doesn't answer the monotherapy question:
Neurology 2000;55:1785-1789
Selegiline and mortality in subjects with Parkinson’s disease
A longitudinal community study
P.T. Donnan, PhD;, D.T. Steinke, MSc;, C. Stubbings, BSc;, P.G. Davey,
MD; and T.M. MacDonald, MD
From the Medicines Monitoring Unit (MEMO), Department of Clinical
Pharmacology, University of Dundee, Ninewells Hospital & Medical School,
Dundee, Scotland, UK.
OBJECTIVE: To estimate mortality by drug use in a cohort of patients with
PD relative to age- and sex-matched comparators.
METHODS: two longitudinal cohorts of patients with 7 and 11 years’
duration of PD were constructed with matched comparators in Tayside,
Scotland. Subjects were eligible for inclusion if they received a first
prescription for an anti-Parkinson’s drug from July 1989 to December
1995, with no PD drug prescription in the previous 6 months. Those who
had previously taken a neuroleptic drug or were younger than 40 years of
age were excluded.
RESULTS: Overall, subjects with PD in relation to comparators had higher
mortality with a rate ratio (RR) of 1.76 (95% CI 1.11, 2.81) in the 7-
year cohort. There was significantly greater mortality in patients with
PD who received levodopa monotherapy (RR = 2.45, 95% CI 1.42, 4.23)
relative to the comparators, adjusting for previous cardiovascular drug
use and diabetes. However, there was no significant difference in
mortality in those with PD receiving combination therapy of selegiline
with levodopa and other drugs in relation to the comparators (RR = 0.92,
95% CI 0.37, 2.31).
CONCLUSIONS: Subjects with PD had twice the rate of mortality relative to
age- and sex-matched comparators. However, those subjects who received
selegiline at any time in combination with co-careldopa or co-beneldopa
showed no significant difference in mortality compared with the
comparators. Monotherapy with levodopa was associated with the highest
mortality.
-Michael
>
Sent via Deja.com
http://www.deja.com/
nijusan
the PopPress article was "off", eh? _Maybe_ the entire study includes it
and the abstact doesn't?
Winter QQ
more complicated than that.
thanks.
Winter
mik...@my-deja.com
In article <92o8ui$obd$1...@nnrp1.deja.com>,
[Nijusan replied]: 'Jeez,,, there's nothing about monotherapy in this
abstract at all! Hmmm, the PopPress article was "off", eh? _Maybe_ the
entire study includes it and the abstact doesn't?'
Yes and no. It turns out this was a pretty damned small cohort (a total
of 103 souls, of which 6 were thrown out). There were 64 deprenyl + (some
L-dopa drug) patients, vs. just 12 monotherapy subjects. The RR for
combination therapy was 0.92, but p=0.858, ie. the same as the controls
...
.... as far as they can tell ...
... from a tiny group.
Of course, the D monotherapy group numbers are thus even harder to make
sense of. The RR was 1.96, but p = 0.516. Again, no difference ... as far
as they can tell ... but the numbers sure LOOK nasty.
And yet, you look at the survival graph, and it's even weirder: all four
deaths in the D mono group dropped dead ~125 days into it; thereafter,
the survival line parallel to the X axis.
At ~1750 days ff, survival for all D groups is roughly the same as for
controls. The levodopa group, OTOH, drops like flies thru'out.
Does any of this mean anything at all? Who knows? Except that L-dopa,
alone, is a bad idea.
Pretty overblown study. I'm surprised that some evident authorities seem
to take it seriously ... perhaps they hadn't seen the paper?
OTOH, it does reference some other papers which look to me like D
monotherapy is, at worst (AND at best) harmless, mortality-wise (for
Parkinson's patients!):
Neurology 1998 Sep;51(3):825-30
Effect of selegiline on mortality in patients with Parkinson's disease: a
meta-analysis.
Olanow CW, Myllyla VV, Sotaniemi KA, Larsen JP, Palhagen S, Przuntek H,
Heinonen EH, Kilkku O, Lammintausta R, Maki-Ikola O, Rinne UK
METHODS: We performed a meta-analysis on five long-term, prospective,
randomized trials of selegiline in patients with untreated PD. Included
in the analysis were four randomized, double-blind, placebo-controlled
studies and one randomized, double-blind, placebo-controlled study of 2
years' duration followed by long-term, open follow-up.
RESULTS: The mean duration of follow-up was 4.1 +/- 1.8 years. There were
14 deaths in 297 selegiline-treated patients (4.7%) and 17 deaths in 292
non-selegiline-treated patients (5.8%).
The hazard ratio for mortality was 1.02 (95% CI 0.44 to 2.37; p = 0.96).
An analysis restricted to patients receiving only levodopa with or
without selegiline noted 11 deaths in 257 levodopa/selegiline-treated
patients (4.3%) and 11 deaths in 254 patients treated with levodopa alone
(4.3%). The hazard ratio was 1.06 (95% CI 0.44 to 2.55; p = 0.90). Death
rate per 1,000 patient years was 11.4 in the selegilinegroup and 14.2 in
the nonselegiline group. Kaplan-Meier survival curvesreflecting pooled
survival data showed no significant difference in duration of survival.
The hazard ratio was 0.84 (95% CI 0.41 to 1.70; p = 0.63) for selegiline-
versus non-selegiline-treated patients and 1.05 (95% CI 0.46 to
2.43; p = 0.91) for selegiline/levodopa- versus levodopa-treated
patients.
CONCLUSION: These results contrast with those of the PDRG-UK study and
demonstrate no increase in mortality associated with selegiline treatment
whether or not patients also received levodopa.
PMID: 9748034, UI: 98418830
[Presumably, this analysis included the following 2]:
Ann Neurol 1998 Mar;43(3):318-25
Mortality in DATATOP: a multicenter trial in early Parkinson's disease.
Parkinson Study Group.
... We examined mortality among the 800 patients with early Parkinson's
disease who were not requiring levodopa and who were randomly assigned in
the DATATOP trial to receive deprenyl, tocopherol, combined treatments,
or placebo. ... After an average of 8.2 years of observation, the overall
death rate of our subjects was 17.1% (137 of 800) or 2.1% per year. The
mortality rate was unaffected by deprenyl, tocopherol, or combined
treatment assignments and was about that expected for an age- and gender-
matched US population without Parkinson's disease.
Neither deprenyl, tocopherol, nor their combined treatments affected the
duration of life in our early Parkinson's disease patients.
The deprenyl-related delay in disability that we reported previously was
not associated with a deprenyl-related reduction in mortality.
PMID: 9506548, UI: 98165373
Acta Neurol Scand 1997 Apr;95(4):211-8
Selegiline as the primary treatment of Parkinson's disease--a long-term
double-blind study.
Myllyla VV, Sotaniemi KA, Hakulinen P, Maki-Ikola O, Heinonen EH
... A randomized, prospective, double-blind study on 44 patients with PD
needing levodopa therapy after the initial double-blind treatment with
placebo or selegiline was carried out. The patients were followed-up for
5 years under combination therapy. RESULTS: ... There was no
difference in mortality between the two groups. ...
PMID: 9150811, UI: 97295169
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