It seems we have no treatment disease-modifying for PD.
That's been supposed for rasagiline, but no scientific evidence so far
There is no such study , actually I am not aware if it ever has been tested with that aim in PD
It is used mainly in the treatment of l-dopa dyskinesias
There is an interesting study reported by Inzelberg et al in Mov Disord 2006: 593 PD patients from Italy and Israel were studied (44% treated with amantadine = AM; 56% no amantadine = NoAM). Dementia was reached by 20% of the sample. PD duration until dementia was significantly longer for those treated with AM (9.1 yrs), compared to NoAM pts (5.9 yrs; p=0.006). MMSE scores were significantly higher in the AM group, compared to the NoAM group (p=0.01). AM use may delay onset of dementia in PD.
Thank you so much Linda A Hershey this is very interesting. Despite the 2003 Cochrane review concluded evidence was inadequate to support the use of amantadine for Parkinson's disease [DOI:10.1002/14651858.CD003468] I think similarity of mechanism of action with memantine could be the starting point for new studies. Amantadine is a NMDA receptor antagonist as well as an anticholinergic, specifically a nicotinic alpha-7 antagonist just like Memantine.
To my knowledge, the best and lacking any side-effects treatment is Melatonin, at high doses, such as 800 mg/day before going to bed. We have 10 patients treated in such a way and Parkinson's symptoms disappeared in 5 of them while in the other 5 (more advanced disease) the improvements were very good: speech, walking without fatigue, tremor, etc...
Thanks for your contribution Jesùs Devesa. Can you tell me if the administration of high doses of melatonin was associated with levodopa or any other drugs usually used for PD treatment?
Yes, it was associated with the prescriptions made by the neurologists before treating these patients. There was not any contraindication and no adverse effects appeared. In fact, Melatonin is produced in practically all the cells in the organism, in any animal or vegetal species, even in unicellulars. You can use it without problems, excepting for a slight somnolence in the morning that lasts 2-3 days.
Dear Jessus , is your experience with melatonin published anywhere? what you say is really amazing !
No, because these doses of Melatonin are "off label". Therefore we can't publish more than case by case or we would be sanctioned because of a "non authorized clinical trial". So, to publish only one case and then another one and another one.... is not too pleasant. But Melatonin works very well, for many neurodegenerative or mitochondrial diseases; even more, it is very useful too in cancer, both alone or combined with chemotherapy.
but do you really mean 800mg at night ?? is that correct??
this is a huge dose!
This is a good question
Amantadine attracted a lot of interest, it is cheap and useful for some movement disorders including dopa-related dyskinesias, drug-related Parkinsonism and chorea. The mechanism of action is unknown, amantadine has several mechanism including antiglutamatergic and anticholinergic properties
there are several retrospective papers suggesting that amantadine might be neuroprotective for PD (see Rajput et al)
Yes, 800 mg at night. No problems with it. In one case we prescribed 1 gr/day, just before going to bed at night. It is useful too in Lateral Amyotrophic Sclerosis, decreasing the rate of progression of the disease. We treat with melatonin any patient in our Medical Center; doses ranged from 20 mg (children) to 800 mg. We use it independently of the kind of disease (TBI, stroke, cerebral palsy, neurodegenerative diseases, etc) because melatonin plays a very important role as a neuroprotective hormone. It lacks any adverse effects, at least we didn't see any in more than 8000 patients already treated. I take 200 mg/day, no problems. See: Reiter RJ et al., Int J Mol Sci 2017
Although board certified in neurology, I have and will practiced neuro-ophthalmology. There are a lot of ocular motility disorders associated with or even the heralding signs of Parkinsonism. Will be happy to participate
any drug with anticholinergic action such as amantadine may induce dementia and its pathology , and PD patients are in risk , this drug must not be used in old people , even in younger people they induce memory problems!
Amantadine has some efficacy as an antidyskentic in patients experiencing complications of levodopa therapy, demonstrated in my own research and others'. I have worked with a number of proponents of amantadine and I've never had anyone suggest that it might modify the disease course. Or course, management of dyskinesia could, for example, prevent falls, thus preventing complications that could impact survival.
There are several retrospective documents suggesting that amantadine may be neuroprotective for PD (e.g. Rajput) as suggested by Pedro J Garcia-Ruiz and that's one of the reasons for my interest in this topic. However, as rightly says Peter Schmidt no scientific evidence seems to prove that Amantadine can modify the disease course so far
A neuroprotective effect does not mean a disease modiffying effect. The physiopathology of parkinson is even more complex than we already know about. Further research is likely to demosntrate no modiffying diseas effect based in principles of disease. Otherwise, changes in the natural development of the disease would be difficult to meassure, since the problem is particularely different between human individuals. An experimental design would be a good begining.
I fully agree with you Victor, but my interest is focused above all on the possibility that amantadine can modify the outcome of PD by acting on cognitive disorders and short -medium term memory deficit as well.
Thank you for your help.
Melatonin, at high doses (800 mg/day), works very well in Parkinson, and lacks any adverse effects.
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