Since we've all had so much fun with the controversial DBS thread that I posted, I thought I would do it again with the interesting finding from this long term study comparing L-dopa with agonists and MAO-B inhibitors as initial therapy for PD. Before we go to far, let me say that I don't take L-dopa or agonists and am not trying to be a proponent of any of the drugs. I also know that the trial was open label and that the volunteers were on the older side (60 or older). So, no need to point that out. I just think this is an interesting, and potentially important, finding.

Despite what many of us may think, there has been growing evidence to suggest that early, low dose LD is the best early approach to PD. Without getting into a debate about whether LD causes dyskinesias, there has been more and more evidence that starting earlier does not increase the rate or timing of developing them.

Some of the findings:

* People taking levodopa consistently reported a very small, but statistically significant better quality of life and milder motor symptoms than people taking other treatments, both soon after beginning therapy and in the long term, up to seven years.

*People initiating treatment with MAO-B inhibitors reported slightly more improvement in mobility than those who started with dopamine agonists.

The study found that levodopa works slightly better than MAO-B inhibitors or dopamine agonists as an initial therapy for people with PD. Participants treated with levodopa reported milder motor symptoms and slightly better quality of life than people taking other treatments. However, it should be noted that the differences were so mild that regardless of which therapy a person took first, the effects were very similar long-term. No medically significant short- or long-term benefit was found for initiating therapy with levodopa or one of the alternatives to dopamine.

When the overall benefits and risks are considered, the study authors nevertheless suggest that levodopa may be the best initial and long-term therapy for people with PD.

What are the take-home messages from this study? First, the fear that people have surrounding levodopa continues to be unfounded. People who took levodopa as an initial therapy in this study developed dyskinesias at nearly the same rate as those who started with the other PD medications. Second, for the seven-year duration of this study, levodopa did not appear to lose its effectiveness nor did it appear to speed disease progression.


http://www.pdf.org/en/science_news/r.../pr_1402434593

http://www.thelancet.com/journals/la...683-8/fulltext


As I have been debating for a while now what my next drug will be when needed, I would love to see some comments and thoughts, but please, lets keep this one on a conversational level and withhold any personal attacks.

According to the link below, the median follow up was only 3 years. Not enough time for a clear distinction to arise IMHO.

http://www.medpagetoday.com/Neurolog...sDisease/46260

thanks for that tupelo3, very interesting.

the 60year age is significant but i think anyone older than 55 at least won't have to worry so much about starting l-dopa and doctors will also stop worrying and let patients get off agonists sooner if they don't like them.

for advanced pd'ers like me and even the newly diagnosed, the bigger issue is what do you take when the sinemet honeymoon is over cuz there is no one a day l-dopa pill or a patch like there is for agonists. rytary is going to be too expensive imho for most of us - the new sinemet CR from impax. there needs to be a "cure". and neuroprotection!


if somene were to tell me 12 years ago we'd still debating l-dopa vs agonists i wouldn't have believed them, of course i thought there would be a cure by now or we'd at least be able to slow progression and we'd be debating which neuroprotective agent to take!

will have to go back and read the studies done to get agonists approved.

Good point Lab. They kept the enrollment open so long that the 7 year follow-up ended up with a 3 year average. They did indicate, though, that the trend held up across all terms. It would be interesting to see the data and just look at 5 years or longer. The sample size seems more than large enough.

I was more concerned about the average age being over 70, which is on the older side for analyzing initial drugs. Can you extrapolate that to those DXed in their 40s and 50s. Still, I think the evidence is growing in support of starting LD sooner rather than later.

No doubt about it, ST, we need something neuroprotective. I truly believe that in the next 12 years we will see significant advances in interventional drugs. Not sure about a cure, but feel very strongly we will have progression slowing drugs.

As I read it the authors are acknowledging this is a limited study which needs to be redone. With all due respect I think these authors admit the study is not definitive and are not drawing a conclusion.

The authors state they are awaiting a validating study. i.e. this one is not definitive. They admirably understand and list the limitations of their study and acknowledge that open studies (not blind) are not accurate as they are awaiting a study that meets that requirement. They also acknowledge that many people changed treatment types during the study which invalidates data for those participants. This data was not removed invalidating the results to an unknown degree.

The mean followup is only three years with a max of 7 years and therefore not long enough to be appropriate for LD vs. agonist comparison. Problems with LD dk don't typically show up until after 7 years. The median age was 71 which makes it inappropriate for EOPD and long term study.

They state "We look forward to validated surveys of prescribing practices to learn whether the results of PD MED will be practice-changing or simply practice-validating," Lang and Marras wrote. This statement translates that a validated study is needed to draw accurate conclusions on whether this changes or validates our conclusions.

the followup was a median=3, not mean. so half the followups were greater than 3 years. brings home the fact that they had to go that long to recruit enough patients.
this was a complex study, it would be nice to read the paper before making any firm judgements.
it would be impossible to try to blind 3 very different drugs that have to be taken daily for up to 7 years. it would take about 1 day to figure out you were on azilect or selegilene because of their mild affects. agonists have to initially dose escalated weekly to eventually 3x/day, azilect is daily, sinemet can be more than 3x/day so everyone would have to be on the same dose with many people getting phoney doses. they can't reformulate the tablet or capsule to hide it's identity so what i've seen done is when blinding is desired, the pill is hidden in a large capsule with inert filler so the tablet(s) don't rattle around. finally, managing the preparation of these capsules, getting them to the patients, making sure patients wouldn't mix up different doses if they changed doseages while still having old meds around would be a nightmare. plus your doctor would have to know what you were taking since he/she had to adjust your meds as needed and was responsible for your well being. finally, there is no drug company involved nor a new drug, hard to believe patients/doctors/anyone would try to fake results or have a huge placebo affect getting excited about a new drug.

if found it interesting about 20% of the patients on agonists stopped while only 2% on sinemet stopped.

it will be interesting to see what more neurologists say.

I think maybe there is too much focus on the study design and flaws. Most of us are knowledgeable in reading research and understand these issues. Frankly, I don’t see them as being as bad in this study as many others that I've reviewed. We all know the problems of open label studies. However, those problems tend to be much less when everyone is receiving a drug or procedure, as in this study, as opposed to studies with a control placebo group. The placebo effect is likely to have occurred across all three groups here since they were all given a drug that would supposedly help them. I'm also not greatly concerned about the 3 year median time since the authors indicated the trends held throughout the full term (although it would certainly be nice to review the raw data of this trial).

In any case, I think everyone agrees that this wasn’t a perfect study. What I find more interesting, and the reason that I posted it in the first place, is that the results give some support to a growing trend in PD treatment to earlier use of LD. The "old" way of thinking is to delay LD for as long as possible. I am doing that right now, as are many others I know, including some on this board. What I would like to know and see is the definitive evidence leading to the conclusion that the "old" way is best. It's easy for us to refute the linked research due to study design. However, is there evidence to support the alternative? Without it, why would we conclude that the "old" method is best and need better research to prove the new "alternative" is better. Yes, I understand there is a relationship between LD and LID. I'm not refuting that. However, there is growing anectodal evidence among many MDS that delaying LD doesn’t necessarily delay LID. It just may shorten the honeymoon period, and in the interim, those who delay may not be getting the best treatment available. They may receive minor symptom relief from the MAO-B inhibitor, or more help along with many more side-effects from agonists. As part of my volunteer work in the PD community, I've spoken with many MDS about this issue. There is no definitive answer, for sure. However, I can tell you that many of the doctors are moving to using low-dose LD before agonists. Last year, Soccertese actually linked an interesting research round table discussing this issue and that’s what started me on my questioning of the doctors.

For many of us at who will be approaching this decision in the future, this research study and the anectodal reports are quite important. Do we go with the "old" method, delay LD and risk the effects of agonists. Or, do we start LD and risk early LID. Would love to see other's thoughts on this issue as opposed to design analysis of the research reports.

"Last year, Soccertese actually linked an interesting research round table discussing this issue and that’s what started me on my questioning of the doctors."

I couldn't find that link. Could someone please kindly repost it here?

this might be the site but webcasts don't seem to load for me.
http://www.theparkinsonsgroup.com/index.asp