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 Small open study with Provigil in PD for EDS 
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Joined: Fri Aug 11, 2006 1:46 pm
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Location: SF Bay Area (Northern CA)
Post Small open study with Provigil in PD for EDS
The psychostimulant modafinil (Provigil) is used by several here to deal with fatigue and excessive daytime sleepiness (EDS). This medication has not been studied widely -- not even in Parkinson's Disease, where some studies show that 51% of those with PD have EDS. This post is about a preliminary report of a small open study from Sweden that was recently published in the journal "Neuropsychiatric Disease and Treatment."

The Swedish author of this article describes the importance of treating excessive daytime sleepiness in Parkinson's Disease as follows: "Sustaining wakefulness throughout all stages of the disease is crucial for participating in life and maintaining a social life. Thus, every measure taken to improve wakefulness in PD patients is of the utmost importance, especially in elderly patients as they often suffer from comorbidity and polypharmacy, both potential contributors to sleepiness. ... Professional caregivers as well as relatives need to be observant in assessing daytime sleepiness in PD patients as it can impair QoL [quality of life] for patients and probably their caregivers as well."

In the Swedish study, elderly PD patients (all of whom lived in care facilities) with severe excessive daytime sleepiness took modafinil (100mg twice a day) for a 3-week period. "The modafinil treatment started with 100 mg in the morning for one week, followed by another 100 mg at lunch for another 2 weeks. At the start, after 1 week, and 3 weeks the following tests were performed: ESS, severity of PD by Schwab & England (S & E), CGI-S (Clinical Global Impression ­ Severity scale), appetite score, body weight as well as side effects of treatment." Modafinil was found to be a "safe and modestly effective for the treatment of EDS." And no "drug interactions or adverse side effects [were] observed." Note that this study was not placebo-controlled or randomized.

EDS was identified using the Epworth Sleepiness Scale. "The ESS is an 8-item questionnaire in which the probability to fall asleep is assessed for 8 different situations using a Likert scale ranging from 0 (never fall asleep) to 3 (high risk to fall asleep) with a maximum score of 24. The cut-off score of 10 points was chosen [for the study]."

"Excluded [from this pilot study] were those patients with other treatable causes for EDS such as: sleep apnea, rapid eye movement sleep behavior disorder (RBD), severe comorbidity or receiving hypnotics. Also excluded were patients with symptomatic or unstable cardiovascular disease, severe cognitive impairment (mini-mental test [MMT] < 15) or receiving antipsychotic and antidepressant medications."

Here's a link to the full article (which is available online for free), the abstract, and a few excerpts about EDS:


http://dovepress.com/getfile.php?fileID=6022 --> PDF of the full article


Neuropsychiatric Disease and Treatment
Published Date: March 2010, Volume 2010:6

Daytime sleepiness in elderly Parkinson’s disease patients and treatment with the psychostimulant modafinil: A preliminary study

Author: Johan Lökk
Institution of Neurobiology, Caring Sciences, and Society, Karolinska Institute, Stockholm, Sweden

Background: Patients with Parkinson’s disease (PD) or Parkinsonian syndromes often report excessive daytime sleepiness (EDS). The aim of this study was to evaluate the effects of the psychostimulant modafinil on elderly, institutionalized, severely impaired PD patients with EDS.

Method: A three-week open study on ten institutionalized PD patients scoring >10 points on the Epworth Sleepiness Scale (ESS) with modafinil eventually on 100 mg twice a day. Patients were assessed at the start, week 1, and week 3 with ESS, Clinical Global Impression (CGI) scale severity of PD and appetite.

Results: Reduction of ESS score and PD severity over time were found as well as a significant increase in appetite and reduction in CGI score.

Conclusion: Modafinil 100 mg twice a day was safe and modestly effective for the treatment of EDS in elderly, institutionalized PD patients. Sustaining wakefulness throughout all stages of PD is crucial for participating in life, maintaining social life, and improving quality of life.


Background
"Patients with Parkinsonian syndromes and Parkinson’s disease (PD) often report excessive daytime sleepiness (EDS). This is a change in the state of consciousness with a difficulty to maintain wakefulness has no generally accepted definition. EDS can be identified using the Epworth Sleepiness Scale (ESS) with greater sensitivity and selectivity than other tests. EDS commonly occurs in PD patients with prevalence figures ranging from 15% (versus 1%­7% in controls) to 51%. There is an estimation of a 6% yearly increase of EDS in PD patients. EDS may cause reduced self esteem and self consciousness, impaired work performance and social interaction resulting in loss of independence and social isolation. Many patients do not have a clear awareness of their own sleepiness; even though EDS is often detrimental to a person’s quality of life (QoL). These are also the consequences with the acquainted fatigue syndrome, which contrasts to EDS through the lack of physical and mental energy. The EDS state can also be misdiagnosed with depression and memory impairment. Various psychiatric and medical health problems may also arise with EDS and even fatal accidents have occurred when drivers have fallen asleep at the wheel. The development of such a pathological sleepiness seems to affect especially males, cognitively impaired patients with advanced disease, having orthostatic hypotension or drug-induced psychosis."

"After exclusion and treatment of any organic causes of EDS, the first step of treatment should be lifestyle interventions to improve the sleep pattern; this being a prerequisite for day-time alertness. This includes no caffeine, no intake of fluids after 6 pm, regular bedtime, normal room temperature, darkness and quietness in the bedroom. If EDS persists adjustment using dopaminergic and psychotropic drugs should be the next step, bearing in mind the balance between motor deterioration and alertness. A third is the possibility of administering a psychostimulant drug in a low and slow manner, to help the patient tune up his alertness, thereby possibly increasing their quality of life."

"Psychostimulants have a long tradition in treating cancer-related fatigue, depression associated with malignancies and opioid-induced sedation. One rather new psychostimulant, modafinil, was approved in 1998 for the use in attention deficit hyperactive disorder (ADHD) and has been used to treat fatigue in multiple sclerosis and amyotrophic lateral sclerosis. Small studies with modafinil in PD patients have shown reduced EDS symptoms without worsening of Parkinsonian symptoms thereby allowing a further increase in dopaminergic therapy in patients previously unable to tolerate this because of EDS occurring as a side effect. In these studies modafinil was well tolerated at doses of 100­200 mg daily with few side-effects. However, other small studies with modafinil have failed to improve EDS on PD patients compared to placebo. Moreover, recently there is also data of a tentative neuroprotective effect of modafinil in a marmoset PD model."

Discussion
"The dynamics of EDS is not fully understood, although there seems to be a complex interaction between PD disease, dysfunction in the sleep-wake regulatory system and pharmacological side effects of dopaminergic drugs. The prevalence of EDS increases with age and they are common in PD. Treatment possibilities of EDS in PD depend upon the condition itself, as well as the individual patient, and include a variety of nonpharmacological processes such as bright light therapy and short naps at regular intervals during the day as well as scheduled activities. Sometimes wakefulness-promoting medications are necessary. Such medications, independent of their mode of action, are prescribed to alleviate EDS."

"An off-label use of modafinil, as in this study, must have a well-founded rationale for use and must be undertaken, in agreement and understanding, with the patient and/or relatives, together with consideration of the cost­benefit issues. Such off-label use is a necessary function of the art of medicine and brings with it increased responsibilities for the prescriber. Liability will rest with the prescriber if the patient suffers adverse side effects. In addition, when prescribing off-label medications, the prescriber must make a careful risk assessment of the risks and benefits for the individual patients, as well as informing the patient that the prescription is off-label. It is noteworthy that prescribing a drug in an off-label manner is not prohibited for doctors and sometimes such a prescription can even constitute the standard care in many cases. For a long time levodopa has been prescribed for restless legs syndrome and during the last years cholinesterase inhibitors are prescribed off-label to a remarkable proportion of patients with vascular dementia, Parkinson’s disease dementia and Lewy Body dementia."

[Robin's note: Exelon, a cholinesterase inhibitor, is FDA-approved for use in PDD. This would not be considered off-label use for this particular medication.]

"Daytime sleepiness may cause social handicap and impair QoL and has long been neglected among PD issues. Sustaining wakefulness throughout all stages of the disease is crucial for participating in life and maintaining a social life. Thus, every measure taken to improve wakefulness in PD patients is of the utmost importance, especially in elderly patients as they often suffer from comorbidity and polypharmacy, both potential contributors to sleepiness. Therefore, in this study, we exclusively recruited elderly PD patients. Professional caregivers as well as relatives need to be observant in assessing daytime sleepiness in PD patients as it can impair QoL for patients and probably their caregivers as well."


Tue Apr 06, 2010 3:49 pm
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Joined: Sun Mar 14, 2010 1:11 am
Posts: 20
Post Re: Small open study with Provigil in PD for EDS
robin wrote:
The psychostimulant modafinil (Provigil) is used by several here to deal with fatigue and excessive daytime sleepiness (EDS). This medication has not been studied widely -- not even in Parkinson's Disease, where some studies show that 51% of those with PD have EDS. This post is about a preliminary report of a small open study from Sweden that was recently published in the journal "Neuropsychiatric Disease and Treatment."

The Swedish author of this article describes the importance of treating excessive daytime sleepiness in Parkinson's Disease as follows: "Sustaining wakefulness throughout all stages of the disease is crucial for participating in life and maintaining a social life. Thus, every measure taken to improve wakefulness in PD patients is of the utmost importance, especially in elderly patients as they often suffer from comorbidity and polypharmacy, both potential contributors to sleepiness. ... Professional caregivers as well as relatives need to be observant in assessing daytime sleepiness in PD patients as it can impair QoL [quality of life] for patients and probably their caregivers as well."

In the Swedish study, elderly PD patients (all of whom lived in care facilities) with severe excessive daytime sleepiness took modafinil (100mg twice a day) for a 3-week period. "The modafinil treatment started with 100 mg in the morning for one week, followed by another 100 mg at lunch for another 2 weeks. At the start, after 1 week, and 3 weeks the following tests were performed: ESS, severity of PD by Schwab & England (S & E), CGI-S (Clinical Global Impression ­ Severity scale), appetite score, body weight as well as side effects of treatment." Modafinil was found to be a "safe and modestly effective for the treatment of EDS." And no "drug interactions or adverse side effects [were] observed." Note that this study was not placebo-controlled or randomized.

EDS was identified using the Epworth Sleepiness Scale. "The ESS is an 8-item questionnaire in which the probability to fall asleep is assessed for 8 different situations using a Likert scale ranging from 0 (never fall asleep) to 3 (high risk to fall asleep) with a maximum score of 24. The cut-off score of 10 points was chosen [for the study]."

"Excluded [from this pilot study] were those patients with other treatable causes for EDS such as: sleep apnea, rapid eye movement sleep behavior disorder (RBD), severe comorbidity or receiving hypnotics. Also excluded were patients with symptomatic or unstable cardiovascular disease, severe cognitive impairment (mini-mental test [MMT] < 15) or receiving antipsychotic and antidepressant medications."

Here's a link to the full article (which is available online for free), the abstract, and a few excerpts about EDS:


http://dovepress.com/getfile.php?fileID=6022 --> PDF of the full article


Neuropsychiatric Disease and Treatment
Published Date: March 2010, Volume 2010:6

Daytime sleepiness in elderly Parkinson’s disease patients and treatment with the psychostimulant modafinil: A preliminary study

Author: Johan Lökk
Institution of Neurobiology, Caring Sciences, and Society, Karolinska Institute, Stockholm, Sweden

Background: Patients with Parkinson’s disease (PD) or Parkinsonian syndromes often report excessive daytime sleepiness (EDS). The aim of this study was to evaluate the effects of the psychostimulant modafinil on elderly, institutionalized, severely impaired PD patients with EDS.

Method: A three-week open study on ten institutionalized PD patients scoring >10 points on the Epworth Sleepiness Scale (ESS) with modafinil eventually on 100 mg twice a day. Patients were assessed at the start, week 1, and week 3 with ESS, Clinical Global Impression (CGI) scale severity of PD and appetite.

Results: Reduction of ESS score and PD severity over time were found as well as a significant increase in appetite and reduction in CGI score.

Conclusion: Modafinil 100 mg twice a day was safe and modestly effective for the treatment of EDS in elderly, institutionalized PD patients. Sustaining wakefulness throughout all stages of PD is crucial for participating in life, maintaining social life, and improving quality of life.


Background
"Patients with Parkinsonian syndromes and Parkinson’s disease (PD) often report excessive daytime sleepiness (EDS). This is a change in the state of consciousness with a difficulty to maintain wakefulness has no generally accepted definition. EDS can be identified using the Epworth Sleepiness Scale (ESS) with greater sensitivity and selectivity than other tests. EDS commonly occurs in PD patients with prevalence figures ranging from 15% (versus 1%­7% in controls) to 51%. There is an estimation of a 6% yearly increase of EDS in PD patients. EDS may cause reduced self esteem and self consciousness, impaired work performance and social interaction resulting in loss of independence and social isolation. Many patients do not have a clear awareness of their own sleepiness; even though EDS is often detrimental to a person’s quality of life (QoL). These are also the consequences with the acquainted fatigue syndrome, which contrasts to EDS through the lack of physical and mental energy. The EDS state can also be misdiagnosed with depression and memory impairment. Various psychiatric and medical health problems may also arise with EDS and even fatal accidents have occurred when drivers have fallen asleep at the wheel. The development of such a pathological sleepiness seems to affect especially males, cognitively impaired patients with advanced disease, having orthostatic hypotension or drug-induced psychosis."

"After exclusion and treatment of any organic causes of EDS, the first step of treatment should be lifestyle interventions to improve the sleep pattern; this being a prerequisite for day-time alertness. This includes no caffeine, no intake of fluids after 6 pm, regular bedtime, normal room temperature, darkness and quietness in the bedroom. If EDS persists adjustment using dopaminergic and psychotropic drugs should be the next step, bearing in mind the balance between motor deterioration and alertness. A third is the possibility of administering a psychostimulant drug in a low and slow manner, to help the patient tune up his alertness, thereby possibly increasing their quality of life."

"Psychostimulants have a long tradition in treating cancer-related fatigue, depression associated with malignancies and opioid-induced sedation. One rather new psychostimulant, modafinil, was approved in 1998 for the use in attention deficit hyperactive disorder (ADHD) and has been used to treat fatigue in multiple sclerosis and amyotrophic lateral sclerosis. Small studies with modafinil in PD patients have shown reduced EDS symptoms without worsening of Parkinsonian symptoms thereby allowing a further increase in dopaminergic therapy in patients previously unable to tolerate this because of EDS occurring as a side effect. In these studies modafinil was well tolerated at doses of 100­200 mg daily with few side-effects. However, other small studies with modafinil have failed to improve EDS on PD patients compared to placebo. Moreover, recently there is also data of a tentative neuroprotective effect of modafinil in a marmoset PD model."

Discussion
"The dynamics of EDS is not fully understood, although there seems to be a complex interaction between PD disease, dysfunction in the sleep-wake regulatory system and pharmacological side effects of dopaminergic drugs. The prevalence of EDS increases with age and they are common in PD. Treatment possibilities of EDS in PD depend upon the condition itself, as well as the individual patient, and include a variety of nonpharmacological processes such as bright light therapy and short naps at regular intervals during the day as well as scheduled activities. Sometimes wakefulness-promoting medications are necessary. Such medications, independent of their mode of action, are prescribed to alleviate EDS."

"An off-label use of modafinil, as in this study, must have a well-founded rationale for use and must be undertaken, in agreement and understanding, with the patient and/or relatives, together with consideration of the cost­benefit issues. Such off-label use is a necessary function of the art of medicine and brings with it increased responsibilities for the prescriber. Liability will rest with the prescriber if the patient suffers adverse side effects. In addition, when prescribing off-label medications, the prescriber must make a careful risk assessment of the risks and benefits for the individual patients, as well as informing the patient that the prescription is off-label. It is noteworthy that prescribing a drug in an off-label manner is not prohibited for doctors and sometimes such a prescription can even constitute the standard care in many cases. For a long time levodopa has been prescribed for restless legs syndrome and during the last years cholinesterase inhibitors are prescribed off-label to a remarkable proportion of patients with vascular dementia, Parkinson’s disease dementia and Lewy Body dementia."

[Robin's note: Exelon, a cholinesterase inhibitor, is FDA-approved for use in PDD. This would not be considered off-label use for this particular medication.]

"Daytime sleepiness may cause social handicap and impair QoL and has long been neglected among PD issues. Sustaining wakefulness throughout all stages of the disease is crucial for participating in life and maintaining a social life. Thus, every measure taken to improve wakefulness in PD patients is of the utmost importance, especially in elderly patients as they often suffer from comorbidity and polypharmacy, both potential contributors to sleepiness. Therefore, in this study, we exclusively recruited elderly PD patients. Professional caregivers as well as relatives need to be observant in assessing daytime sleepiness in PD patients as it can impair QoL for patients and probably their caregivers as well."


Hello Robin,
This is a very informative article, thank you for sharing. I just wanted to share with you and others as well that if a person who has LBD and has no stiffness or ridgidity and only EDS may benefit from the Provigil, however IF they do experience the contractures that LBD can cause..be aware that this medication can also cause severe muscle contrations and sometimes seizures in some individuals, it depends on the person and the symptoms as I think that we (as caregivers or observers) are all finding that any kind of meds and what works for different people is usually found through trial and error. God bless!


Wed Apr 07, 2010 1:32 am
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Joined: Fri Aug 11, 2006 1:46 pm
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Location: SF Bay Area (Northern CA)
Post 
Certainly these advanced PD patients had rigidity, as this is a hallmark symptom of PD.

I couldn't find "muscle contractures" in the side effect list for Provigil. (rxlist.com)

Robin


PS. You might consider not quoting the preceding post in your reply, especially when the quoted text is so long.


Wed Apr 07, 2010 9:32 am
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Joined: Sun Mar 14, 2010 1:11 am
Posts: 20
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robin wrote:
Certainly these advanced PD patients had rigidity, as this is a hallmark symptom of PD.

I couldn't find "muscle contractures" in the side effect list for Provigil. (rxlist.com)

Robin


PS. You might consider not quoting the preceding post in your reply, especially when the quoted text is so long.


:oops: Sorry about that. There are alot of side affects that are not listed on drug labels and Im finding (as a caregiver) through trial and error that you have to be your own advocate and then spread awareness about other side affects that others may have not experienced while using this type of drug. I know of a few people that have experienced this side affect as well.


Wed Apr 07, 2010 11:20 am
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Joined: Fri Aug 11, 2006 1:46 pm
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Location: SF Bay Area (Northern CA)
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I don't read drug labels any more, mostly because the print is too small! I rely on the PDR or websites such as rxlist.com or drugs.com, as they are quite comprehensive.

If you have noticed an adverse reaction to Provigil in your loved one, I encourage you to alert the FDA about this. On fda.gov, you'll see an area called "Report a Problem."


Wed Apr 07, 2010 12:32 pm
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Joined: Fri Aug 11, 2006 1:46 pm
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Location: SF Bay Area (Northern CA)
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I received an email this morning from a patient:

"How did these researchers find any elderly person with PD who wasn't on an antidepressant, didn't have REM sleep disorder, or some severe comorbidity (such as as heart disease)??"


Wed Apr 07, 2010 1:44 pm
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Joined: Sun Mar 14, 2010 1:11 am
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robin wrote:
I don't read drug labels any more, mostly because the print is too small! I rely on the PDR or websites such as rxlist.com or drugs.com, as they are quite comprehensive.

If you have noticed an adverse reaction to Provigil in your loved one, I encourage you to alert the FDA about this. On fda.gov, you'll see an area called "Report a Problem."


I did report the problem and I spoke with her Neurologist as well and he said that sometimes this can happen, but they dont know why it happens.


Wed Apr 07, 2010 3:01 pm
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