The National Institutes of Health conducted a double-blind trial of Aricept (donepezil) in 1998-89 to investigate the value of using the medication to treat the mental and movement symptoms associated with Progressive Supranuclear Palsy (PSP). The trial was under the sponsorship of its manufacturer. Aricept is commonly used to treat Alzheimer's disease and it was thought to perhaps offer some help in treating those with PSP.
In Alzheimer's disease the symptoms are connected with problems involving acetylcholine a neurotransmitter. Aricept blocks the action of anticholinesterase whose function is to block the action of acetylcholine. This results in increasing the availability of the acetylcholine that is present. Dopamine is normally in adequate supply with Alzheimer's and the designed benefit of Aricept is to achieve more of a balance between dopamine and acetylcholine.
With Parkinson's disease the problem is a shortage of dopamine - there is a normal amount of acetylcholine. Thus, Aricept is not recommended to treat Parkinson's disease. It's use may even contribute to the worsening of the disease.
With PSP there is a shortage of acetylcholine, dopamine and a third neurotransmitter called GABA. It might be possible to increase the action of all three neurotransmitters but it would require several different medications and discovering what might and what might not work would take intensive research. You would need to increase the availability of all three neurotransmitters.
In the Aricept trial for PSP twenty-one patients received placebo or donepezil (10mg.) for six weeks seperated by a one-month washout period in between . Donepezil led to mild improvement on only one of several neuropsychological tests, the Double Memory Test. There was also a mild improvement in two measures of overall ease in performing everyday activities: the Activities of Daily Living section of the Uniform Parkinsonian Rating Scale and the Mobility Score of the Parkinson's Disability Questionnaire.
But there were also serious side-effects reported that were found to be caused by or made worse by the use of the medication. Generally these problems disappeared when the medication was discontinued. There is no way to know whether there was any long-term damage done.
The trials noted that the small improvement in a few of the patients and the real possibility that the medication might worsen the patient's overall condition did not warrant recommending the use of Aricept to treat patients with Progressive Supranuclear Palsy.
Neurology 2001 Aug 14;57(3):467-73
There is no effective treatment for progressive supranuclear palsy (PSP). Because results of immunochemical and pharmacologic studies suggest that the cholinergic system may play a role in the cognitive and motor features of PSP, the authors investigated the effects of donepezil (10 mg/day), an acetylcholinesterase inhibitor, in 21 patients with PSP (mean age +/- SD; 65.7 +/- 4.7 years) by a randomized, double-blind, placebo-controlled crossover trial.
Donepezil and placebo were administered for 6 weeks each with a 1-month washout period. Patients were evaluated before and at the end of each treatment phase. Outcome measures evaluated neuropsychiatric, global cognitive, frontal, memory, motor, and activities of daily living (ADL) status.
Two patients withdrew during the washout phase because of unrelated medical problems. Donepezil-induced systemic side effects were transient and generally mild. Because of worsening of motor function, three patients received 5 mg/day of donepezil. All patients achieved blood and CSF therapeutic levels of donepezil. While the patients were taking donepezil, their Double Memory Test scores improved, whereas their ADL/mobility scores significantly worsened.
The findings suggest that acetylcholinesterase inhibitors such as donepezil have at best selective, modest effects on cognition in patients with PSP. In light of its deleterious effects on ADL/mobility, donepezil is not recommended for this patient population.
The following message appeared on Internet and covers one family's experience with Aricept when used to treat PSP. This applies to the experience of one patient. Your experience, if you decide to try Aricept may differ.
Date: 7/26/00 12:38:39 AM Eastern Daylight Time
From: jboerger@dcwi.com (J. Boerger)
In the last issue of PSP Advocate, there was an article by Dr. Litvan about a study she had done on the effects of this medication on PWPSP, and went on to state that it will actually make them worse. I know that for a fact as Mayo's put her on that and withinin a month she was unable to move her feet and she was in a nursing home for a month. Dr. was out of town and she was having severe leg cramps(one of many side effects). I refused it for her and it took six weeks before she could walk again(with help). She is doing reasonably well and I feel that her condition has stabilized. I am giving her a number of supplements suggested by Jean Carper, in her book "The Miracle Brain". I would suggest that all read it and if th PWPSP hasn't progressed too far, possibly they could help. I fell that what I have given her has helped. Also she had her second full body massage this afternoon and there was a world of difference afterwards. I think we will go to every 2 weks for a while the first was a month ago.
Jim tlcg Marguerite 67/2+
