Monday, September 21, 2015

ritalin and Parkinson's

Ritalin (methylphenidate) is a dopamine reuptake inhibitor that also prevents a-syn misfolding.
Summary, seems more likely to help if STN is being used, not on l-dopa, and/or have a certain type of gene. Often increases sleeplessness, but has been used to reduce daytime sleepiness.  Appears to help quality of life, mood, apathy, and facial dystonia, but has primarily been used for improving gait and freezing.

The following are quotes from the indicated articles.

methylphenidate may be acting on the pathway directly involved in facial dystonias.
http://www.ncbi.nlm.nih.gov/pubmed/25951177

methylphenidate had a positive effect on anhedonia [ability to feel pleasure] and vigor in PD patients.
http://www.ncbi.nlm.nih.gov/pubmed/22824349

In patients undergoing subthalamic nucleus stimulation, .. methylphenidate improves gait and F[freezing] and may relieve apathy. However, the drug failed to improve cognition in this population.   ... 
http://www.ncbi.nlm.nih.gov/pubmed/24011636

The following had the most information in the full text of the article:
[This study specifically: ] Methylphenidate improved gait hypokinesia and freezing in patients with advanced Parkinson's disease receiving subthalamic nucleus stimulation....

[this study's comments on past studies:]
A dose of between 0.5 and 1 mg/kg/d was associated with an improvement in voluntary movements and less rigidity.
With STN: 
Dopaminergic apathy notably occurs in PD patients undergoing STN stimulation after the tapering of dopaminergic medications. The symptoms can be relieved by the administration of dopamine agonists. 
Chronic administration of high-dose MPD (for three months) was associated with a significant reduction in apathy (as measured on the Lille Apathy Rating Scale (LARS)) in a subgroup of seven advanced-stage PD patients undergoing STN stimulation.
However, the study was not specifically designed to assess apathy. Methylphenidate (5 mg, twice a day) also sharply reduced severe apathy in a non-stimulated patient at an earlier stage of PD.
In conclusion, there are still too few data to draw firm conclusions as to the value of MPD in apathy in PD - although a beneficial effect is plausible.
Gait:
 Four open-label studies have assessed the efficacy of MPD in gait hypokinesia. ... MPD (20 mg) in 21 non-demented, non-stimulated PD patients who were free of major postural or gait disorders and had stable dopaminergic regimens. The researchers observed significant improvements in all gait parameters. The second study (by Nutt et al) found that 0.2 or 0.4 mg/kg MPD had effects on gait or on the performance of a tapping task when administered two hours after the infusion of levodopa but when not administered alone.
The third open-label study (by Pollak et al) examined the effect of low-dose (10 mg) MPD on FoG in five patients with severe PD during the "off" state. Low-dose MPD was associated with improvements in all gait parameters and FoG. . Lastly, Devos et al decided to test the effect of high-dose (1 mg/kg) MPD on gait disorders because low doses of the drug (~0.25 mg/kg) may only occupy half the striatal DaTs in humans. Over a three-month period, MPD was administered to 17 advanced PD patients [this is not the study that was negative] undergoing STN stimulation. Acute administration of MPD (in both the presence and absence of levodopa) was associated with a lower number of steps and a lower test completion time (relative to the “off-drug, on-stim” condition). Methylphenidate and levodopa reduced the parameters to a similar extent and had additive effects in this population. Twelve of the 17 patients displayed FoG episodes in either the “off drugs, on-stim” or the “off-stim, on-levodopa” condition. There was a non-significant trend towards a lower number of FoG episodes in the “on-levodopa, on-MPD” condition. In contrast to previous studies, chronic administration of high-dose MPD (in both the presence and absence of dopaminergic medications) clearly had an effect on gait disorders in advanced PD.
Mood, Apathy:
MPD ’s effects were [previously] mostly attributed to its impact on mood (ie its euphoriant action), which was associated with increased restless and insomnia in some patients. This might explain (at least in part) why MPD has not been further developed in PD. In fact, MPD has always been considered as a treatment for attention disorders, with potentially valuable effects on cognition and behaviour but not (at least directly) motor symptoms. ....high-dose MPD (for three months) was associated with a significant reduction in apathy ( Lille Apathy Rating Scale (LARS)) in a subgroup of seven advanced-stage PD patients undergoing STN stimulation. However, the study was not specifically designed to assess apathy. Methylphenidate (5 mg, twice a day) also sharply reduced severe apathy in a non-stimulated patient at an earlier stage of PD
Cognitive performance:
The various studies of MPD and cognitive function have yielded conflicting results. The absence of a clear, beneficial effect of MPD on attention disorders in PD was recently confirmed in a double-blind, placebo-controlled, randomized study of 69 patients.
(full text)
http://www.ncbi.nlm.nih.gov/pubmed/22658702

[this study was really the only one out of several that was negative] MPD did not improve gait and tended to worsen measures of motor function, sleepiness, and quality of life  (17 patients completed the trial, up to 80 mg/day),   ( Full text) 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068005/

methylphenidate on severe gait disorders (e.g. the FoG) and non-motor symptoms in advanced PD. ... may have significant value in the treatment of PD. However, there is a lack of randomized controlled trials in this field.
http://www.ncbi.nlm.nih.gov/pubmed/23160937

had conflicting results in advanced PD subjects.
http://www.ncbi.nlm.nih.gov/pubmed/23917951

methylphenidate is effective in patients with Parkinson's disease with motor and gait disorders. [especially in people with genotype varients of "SLC6A3"]
http://www.ncbi.nlm.nih.gov/pubmed/25805645

Long-lasting isolated freezing of gait with good response to methylphenidate:
http://www.ncbi.nlm.nih.gov/pubmed/25907032

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