ScienceDaily (Dec. 17, 2008) — A new study shows that antidepressant drugs which only affect serotonin, often used as first choice treatments, may not be best for depression in people with Parkinson's disease. The new research is published in the December 17, 2008, online issue of Neurology®, the medical journal of the American Academy of Neurology. Depression affects up to 50 percent of people with Parkinson's disease.
The study is the first to compare an older antidepressant that targets two receptors in the brain with a newer generation serotonin only-based drug and placebo. It is also the largest placebo-controlled study for Parkinson's disease depression.
In the study, scientists gave 52 people diagnosed with Parkinson's disease and depression either nortriptyline, a tricyclic antidepressant (TCA), paroxetine CR, a selective serotonin reuptake inhibitor (SSRI) or a placebo pill. Tricyclics affect both norepinephrine and serotonin, two different receptors in the brain. The people were tested for improvement of depression symptoms at two, four and eight weeks after starting treatment.
The study found that the people who took nortriptyline were nearly five times more likely to see improvement in depression symptoms when compared with the people who took paroxetine CR.
"I think that this study shows a number of important things. First, that people with Parkinson's disease can respond to antidepressants. This is important because depression in Parkinson's disease is underrecognized, underappreciated and undertreated. Commonly, the attitude is, of course you're depressed, you have a serious illness. This study shows that patients should have hope that they can be helped," said study author Matthew Menza, MD, a Professor of Psychiatry and Neurology with UMDNJ-Robert Wood Johnson Medical School in Piscataway, NJ. "Second, the study suggests that we may need to use medications that affect both serotonin and norepinephrine, not just serotonin, in the brain to be successful in treating depression related to Parkinson's disease."
Menza also says that in addition to the older antidepressant, nortriptyline, that was tested in the study, there are newer mediations that affect both serotonin and norepinephrinem, and these need to be tested.
Tricyclic antidepressants are one of the older classes of antidepressants and have been used since the 1950s. Tricyclics have an increased risk of overdose and death due to toxic effects on the heart and brain. "People on a tricyclic antidepressant should have their dosages monitored closely by their doctor," said Menza.
The study was supported by the National Institute for Neurological Disorders and Stroke (NINDS).
Adapted from materials provided by American Academy of Neurology.
Saturday, December 27, 2008
Tuesday, December 16, 2008
* Types of Cognitive Problems You Might Expect in PD Cases
Parkinson’s disease aka PD is often viewed as a chronic illness that affects motor coordination only. However, doctors are increasingly recognizing that other problems are also manifested as well such as cognitive impairment. Thought processes, memory, attention span and memory alterations are a part of PD. For the most part, most treatments for the disease focus on motor skill improvement; therefore, the cognitive problems sometimes are ignored or not treated.
Predominance of Cognitive Problems
If you are looking to understand cognition, it is a broad term that is used to categorize a number of mental abilities, namely the brain’s ability to process, store and utilize information. Attention span, memory, language, conceptual thinking, concrete problem solving and even visual perception are all involved areas of cognitive thinking. It is important to note that virtually all people with Parkinson’s disease will experience some type of interruption in cognitive function and can range from minor issues to more severe problems.
You may consider a cognitive impairment as a minor inconvenience while another may experience issues severe enough to impact quality of life. Dementia is classified as a cognitive impairment and this involves several interruptions in the cognitive area. Some Parkinson’s patients may have mild motor coordination problems but have dementia which calls for supervised living while others may not develop dementia until the latest stages of Parkinson’s.
Cognitive difficulties are often classified in different areas so that experts can better identify ways to help. It is important to note that your general intelligence and memories acquired before PD usually stay with you. If you develop a cognitive issue, memories and skills learned after PD cognitive symptoms are displayed could be lost and have to be relearned. Here are a few examples of cognitive dysfunction:
* Memory interruption ñ If you have already learned certain information, it is not uncommon to forget something or how to do it without memory cues. When you have PD, having visual cues helps to retain information as well as repetition, especially if you want to recall that information later.
* Executive dysfunction ñ This is a broad term that covers problem solving, project planning and other mental acrobatic tasks. Freezing mid-task is common so it is important for PD patients to focus on one thing at a time.
* Attention deficit ñ Not quite like ADD, in PD patients, there is a problem with attention. It is best to focus on one thing at a time as multi-tasking can cause problems. For instance, PD patients may find it hard to take a leisurely walk and talk with a companion at the same time. Even listening to music and walking can be an issue.
* Slowed cognitive function ñ Sometimes the ability to retrieve memories or process information that pertains to a problem can be an issue with PD patients. This condition called bradyphrenia can cut short your independence, especially in the workplace.
Memory devices and visual cues are the best things that can prompt your memory should cognitive function become an issue. In addition, some doctors are prescribing medications used on Alzheimer’s patients in the hopes it can slow down the progression of the disease or stop it all together, at least cognitive-wise.
Predominance of Cognitive Problems
If you are looking to understand cognition, it is a broad term that is used to categorize a number of mental abilities, namely the brain’s ability to process, store and utilize information. Attention span, memory, language, conceptual thinking, concrete problem solving and even visual perception are all involved areas of cognitive thinking. It is important to note that virtually all people with Parkinson’s disease will experience some type of interruption in cognitive function and can range from minor issues to more severe problems.
You may consider a cognitive impairment as a minor inconvenience while another may experience issues severe enough to impact quality of life. Dementia is classified as a cognitive impairment and this involves several interruptions in the cognitive area. Some Parkinson’s patients may have mild motor coordination problems but have dementia which calls for supervised living while others may not develop dementia until the latest stages of Parkinson’s.
Cognitive difficulties are often classified in different areas so that experts can better identify ways to help. It is important to note that your general intelligence and memories acquired before PD usually stay with you. If you develop a cognitive issue, memories and skills learned after PD cognitive symptoms are displayed could be lost and have to be relearned. Here are a few examples of cognitive dysfunction:
* Memory interruption ñ If you have already learned certain information, it is not uncommon to forget something or how to do it without memory cues. When you have PD, having visual cues helps to retain information as well as repetition, especially if you want to recall that information later.
* Executive dysfunction ñ This is a broad term that covers problem solving, project planning and other mental acrobatic tasks. Freezing mid-task is common so it is important for PD patients to focus on one thing at a time.
* Attention deficit ñ Not quite like ADD, in PD patients, there is a problem with attention. It is best to focus on one thing at a time as multi-tasking can cause problems. For instance, PD patients may find it hard to take a leisurely walk and talk with a companion at the same time. Even listening to music and walking can be an issue.
* Slowed cognitive function ñ Sometimes the ability to retrieve memories or process information that pertains to a problem can be an issue with PD patients. This condition called bradyphrenia can cut short your independence, especially in the workplace.
Memory devices and visual cues are the best things that can prompt your memory should cognitive function become an issue. In addition, some doctors are prescribing medications used on Alzheimer’s patients in the hopes it can slow down the progression of the disease or stop it all together, at least cognitive-wise.
Friday, December 12, 2008
Treatment Helps Parkinson's Patients Talk Clearly
Reported by: Mary King
Wednesday, Dec 10, 2008 @01:03pm EST
HAGERSTOWN - A new treatment in Washington County aims to break down the communication barrier for Parkinson's disease patients.
Carolyn Reed was diagnosed with Parkinson’s disease ten years ago, but it wasn’t until recently that her illness made talking a challenge.
"I could hear them but they couldn't hear me," she said.
Pathologists say it's is common obstacle for Parkinson’s patients. It's called - disarthrea. A patient's speech can become softer and harder to understand.
Speech language pathologist Kymberli Dixon says, "It's difficult for them to be able to gage the amount of loudness or effort that's required for them to be understood at a normal conversational level."
The hardest part for Carolyn Reed was that no one, not even her husband, could understand her, but when she came here to total rehab care all of that changed.
"You're talking about one month of treating a patient and seeing a life change in 4 weeks," Dixon said.
The results were achieved using the Lee Silverman Voice Treatment, a therapy that has been around for years but remains hard to find because therapists must be certified.
Carolyn was the guinea pig at Washington County Hospital. Therapists used a sound pressure level meter to gauge how loud Carolyn was talking and progressively brought her voice back.
Carolyn's daughter, Alys Dahbura, said, "I don't have to ask her as often to speak up or repeat herself."
Two other patients have completed the program in Washington County. They're back to doing things they never thought they'd do again. For Carolyn, that includes reading to her granddaughter
Carolyn's also using her new found voice to spread the news about the treatment.
Wednesday, Dec 10, 2008 @01:03pm EST
HAGERSTOWN - A new treatment in Washington County aims to break down the communication barrier for Parkinson's disease patients.
Carolyn Reed was diagnosed with Parkinson’s disease ten years ago, but it wasn’t until recently that her illness made talking a challenge.
"I could hear them but they couldn't hear me," she said.
Pathologists say it's is common obstacle for Parkinson’s patients. It's called - disarthrea. A patient's speech can become softer and harder to understand.
Speech language pathologist Kymberli Dixon says, "It's difficult for them to be able to gage the amount of loudness or effort that's required for them to be understood at a normal conversational level."
The hardest part for Carolyn Reed was that no one, not even her husband, could understand her, but when she came here to total rehab care all of that changed.
"You're talking about one month of treating a patient and seeing a life change in 4 weeks," Dixon said.
The results were achieved using the Lee Silverman Voice Treatment, a therapy that has been around for years but remains hard to find because therapists must be certified.
Carolyn was the guinea pig at Washington County Hospital. Therapists used a sound pressure level meter to gauge how loud Carolyn was talking and progressively brought her voice back.
Carolyn's daughter, Alys Dahbura, said, "I don't have to ask her as often to speak up or repeat herself."
Two other patients have completed the program in Washington County. They're back to doing things they never thought they'd do again. For Carolyn, that includes reading to her granddaughter
Carolyn's also using her new found voice to spread the news about the treatment.
Sunday, December 7, 2008
Drug Treatment For Parkinson's Disease Can Help Confirm Suspected Diagnosis, Neurologist Says
ScienceDaily (Dec. 3, 2008) —
Levodopa has long been proven to provide the greatest relief of all available medications in the treatment of Parkinson's disease. It also is the most cost-effective drug for managing the full range of problems associated with this chronic neurological disorder, which affects an estimated one million Americans.
In the Dec. 4 issue of the New England Journal of Medicine, Henry Ford Hospital neurologist Peter A. LeWitt, M.D., writes that levodopa should be used not only for treating both early and advanced stages of Parkinson's disease, but also for confirming a suspected diagnosis of Parkinson's disease.
"Within a few minutes after taking an oral dose of levodopa, a patient can recover from previous impairments in speech, dexterity and gait," says LeWitt. "Though the start of levodopa can be postponed if the clinical manifestations of Parkinson's disease are mild and tolerable, it may be the only effective option to control discomfort and disability even for mildly affected patients."
Affecting 1 to 2 percent of the population over the age of 60, Parkinson's disease is a degenerative disorder of the central nervous system that causes tremors and impairs a person's motor skills, speech, balance and posture. Its cause is unknown, but many clues are guiding clinical trials.
A small region deep within the brain is the source for the symptoms of Parkinson's disease. When brain neurons in this part of the brain begin to die, these cells can no longer manufacture the molecule dopamine, a chemical critical for controlling movement. Levodopa replaces the deficient dopamine, reversing most features of Parkinson's disease.
Among patients with Parkinson's disease, the pace and extent of progression in neurologic deficits can greatly vary. The burden on quality of life spans a wide spectrum too, Dr. LeWitt says, from minimal discomfort and disability to marked impairment of capabilities such as independence, safety and communication.
While it is shown to improve motor impairments, levodopa often does not provide relief from the tremors and can cause involuntary movements and other side effects, requiring physicians to carefully re-assess the treatment regimen.
In the first few weeks of use, the dose of levodopa given to the patient may need to be adjusted to achieve maximum benefit. Over time, levodopa dosing often needs to be tailored to a patient's needs, sometimes in combination with other medications to optimize its effects.
"Although available controlled-release preparations are designed for more extended drug delivery, they generally do not achieve the same effects as immediate-release tablets taken closer together," writes Dr. LeWitt.
Journal reference:
1. LeWitt PA. Levodopa for the treatment of Parkinson's disease. N Engl J Med, 2008; 359: 2468-2476
Adapted from materials provided by Henry Ford Health System, via EurekAlert!, a service of AAAS.
Henry Ford Health System (2008, December 3). Drug Treatment For Parkinson's Disease Can Help Confirm Suspected Diagnosis, Neurologist Says. ScienceDaily. Retrieved December 7, 2008, from http://www.sciencedaily.com /releases/2008/12/081203184405.htm
Levodopa has long been proven to provide the greatest relief of all available medications in the treatment of Parkinson's disease. It also is the most cost-effective drug for managing the full range of problems associated with this chronic neurological disorder, which affects an estimated one million Americans.
In the Dec. 4 issue of the New England Journal of Medicine, Henry Ford Hospital neurologist Peter A. LeWitt, M.D., writes that levodopa should be used not only for treating both early and advanced stages of Parkinson's disease, but also for confirming a suspected diagnosis of Parkinson's disease.
"Within a few minutes after taking an oral dose of levodopa, a patient can recover from previous impairments in speech, dexterity and gait," says LeWitt. "Though the start of levodopa can be postponed if the clinical manifestations of Parkinson's disease are mild and tolerable, it may be the only effective option to control discomfort and disability even for mildly affected patients."
Affecting 1 to 2 percent of the population over the age of 60, Parkinson's disease is a degenerative disorder of the central nervous system that causes tremors and impairs a person's motor skills, speech, balance and posture. Its cause is unknown, but many clues are guiding clinical trials.
A small region deep within the brain is the source for the symptoms of Parkinson's disease. When brain neurons in this part of the brain begin to die, these cells can no longer manufacture the molecule dopamine, a chemical critical for controlling movement. Levodopa replaces the deficient dopamine, reversing most features of Parkinson's disease.
Among patients with Parkinson's disease, the pace and extent of progression in neurologic deficits can greatly vary. The burden on quality of life spans a wide spectrum too, Dr. LeWitt says, from minimal discomfort and disability to marked impairment of capabilities such as independence, safety and communication.
While it is shown to improve motor impairments, levodopa often does not provide relief from the tremors and can cause involuntary movements and other side effects, requiring physicians to carefully re-assess the treatment regimen.
In the first few weeks of use, the dose of levodopa given to the patient may need to be adjusted to achieve maximum benefit. Over time, levodopa dosing often needs to be tailored to a patient's needs, sometimes in combination with other medications to optimize its effects.
"Although available controlled-release preparations are designed for more extended drug delivery, they generally do not achieve the same effects as immediate-release tablets taken closer together," writes Dr. LeWitt.
Journal reference:
1. LeWitt PA. Levodopa for the treatment of Parkinson's disease. N Engl J Med, 2008; 359: 2468-2476
Adapted from materials provided by Henry Ford Health System, via EurekAlert!, a service of AAAS.
Henry Ford Health System (2008, December 3). Drug Treatment For Parkinson's Disease Can Help Confirm Suspected Diagnosis, Neurologist Says. ScienceDaily. Retrieved December 7, 2008, from http://www.sciencedaily.com /releases/2008/12/081203184405.htm
Tuesday, December 2, 2008
Management of Dyskinesias in Parkinson Disease
Professor Yasser Metwally
November 19, 2008 — Dyskinesias, along with motor fluctuations, are the main motor complications of levodopa therapy. A retrospective analysis of studies investigating incidence of dyskinesias with levodopa treatment estimated that slightly more than one third of patients who had PD had dyskinesias after 4 to 6 years [1]. Early-onset PD and higher doses of levodopa are the biggest risk factors for the development of dyskinesias [2,3]. Dyskinesias may affect any part of the body and can be choreic or dystonic. They may manifest when plasma levodopa levels are at their peak (peak-dose dyskinesias), as plasma levodopa levels are rising and falling (diphasic dyskinesias), or when plasma levodopa levels are low (off-state dystonia). Dyskinesias typically are mild but may interfere with quality of life when painful or severe, as seen in advanced PD [4].
One way of treating dyskinesias is to modify the antiparkinsonian regimen. Peak-dose dyskinesias are related directly to the amount of levodopa given per dose, so decreasing individual doses generally reduces dyskinesias. The amount of clinical benefit to motor symptoms in PD may decline, however, and patients may experience increasing “off” periods. Thus, a decrease in individual doses of levodopa often has to be combined with more frequent administration, a practice termed dose fractionation. There are significant limitations to this approach, however, which are detailed in the article by Dewey elsewhere in this issue. Discontinuing catechol-O-methyltransferase (COMT) inhibitors or monoamine oxidase (MAO)-B inhibitors also may be helpful in reducing peak-dose dyskinesias.
Sustained-release formulations in theory could reduce dyskinesias, as they are released slowly throughout the day. In practice, however, they tend to prolong the duration of dyskinesias and increase the severity of dyskinesias in the late afternoon or early evening [5]. Patients who have dyskinesias and are on sustained-release levodopa formulations may benefit from switching to immediate-release levodopa.
Diphasic dyskinesias can be difficult to treat. The same strategies can be tried, but there are no data to support one strategy over the other. Other options include overlapping the doses of levodopa to prevent trough plasma levodopa levels until late in the evening or administering very small doses of levodopa frequently (such as 50 mg of levodopa given hourly while awake) [6].
Strategies for treating off-state dystonias are similar to strategies to reduce motor fluctuations in PD and may include changing the levodopa dosing schedule or adding dopamine agonists, COMT inhibitors, or MAO-B inhibitors.
Recent evidence-based reviews recommend amantadine for treating dyskinesias in PD [7,8]. Amantadine is believed to have an antidyskinetic effect through its action at the N-methyl-D-aspartate receptor. Amantadine can reduce dyskinesias between 24% and 60% [9,10,11,12,13]. In one study, the effect of amantadine was maintained for up to a year. Some patients, however, are reported to have had rebound dyskinesias when amantadine was discontinued [12]. Side effects include confusion, peripheral edema, and livedo reticularis.
A double-blind, placebo-controlled trial of clozapine demonstrates an increase in “on” time without dyskinesias with a corresponding decrease in “on” time with dyskinesias [14]. The potential for agranulocytosis and the frequent blood monitoring required make it an unattractive agent, however. Buspirone is reported effective in one small crossover trial of 10 patients [15], but only seven patients completed the trial, and there are no other large randomized studies. Clinical trials of other drugs reported to be helpful for treating dyskinesias were uncontrolled or failed to show efficacy in large double-blind trials [6,16].
Although pallidotomy commonly was used as a surgical intervention for dyskinesias with good results [8], most surgical centers have turned to deep brain stimulation (DBS) to treat patients who have motor fluctuations and dyskinesias. There are two main targets for DBS in patients who have PD: the globus pallidus interna (GPi) and the subthalamic nucleus (STN). Although DBS of the GPi reduces dyskinesias in open-label reports and blinded evaluations of patients on and off stimulation [17,18], a recent practice parameter determined that there was insufficient evidence to determine the efficacy of GPi DBS for dyskinesias [7]. Part of this lack of evidence is because most centers prefer to place electrodes in the STN DBS. In a meta-analysis of outcomes, STN DBS reduced dyskinesias in patients who had PD by an average of 69.1% [19]. This occurs along with a reduction in levodopa dosage, which is mainly responsible for the improvement in dyskinesias. Based on existing studies, STN DBS is considered possibly effective for reducing motor fluctuations, dyskinesias, and antiparkinsonian medications in PD [7]. Adverse effects from DBS surgery may include surgical complications, such as hemorrhage, stroke, infection of the device, seizures, delirium, and stimulation-related effects, such as dystonia, confusion, paresthesias, dysarthria, and diplopia, depending on the stimulation site.
References
1. Ahlskog JE, Muenter MD. Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov Disord. 2001;16:448-458.
2. Schrag A, Schott JM. Epidemiological, clinical, and genetic characteristics of early-onset parkinsonism. Lancet Neurol. 2006;5:355-363.
3. Grandas F, Galiano ML, Tabernero C. Risk factors for levodopa-induced dyskinesias in Parkinson’s disease. J Neurol. 1999;246:1127-1133.
4. Pechevis M, Clarke CE, Vieregge P, et al. Effects of dyskinesias in Parkinson’s disease on quality of life and health-related costs: a prospective European study. Eur J Neurol. 2005;12:956-963.
5. Fabbrini G, Brotchie JM, Grandas F, et al. Levodopa-induced dyskinesias. Mov Disord. 2007;22:1379-1389quiz 1523.
6. Muenter MD. Patterns of dystonia in response to L-Dopa therapy for Parkinson’s disease. Mayo Clin Proc. 1977;52:163-174.
7. Pahwa R, Factor SA, Lyons KE, et al. Practice parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;66:983-995.
8. Goetz CG, Poewe W, Rascol O, et al. Evidence-based medical review update: pharmacological and surgical treatments of Parkinson’s disease: 2001 to 2004. Mov Disord. 2005;20:523-539.
9. Luginger E, Wenning GK, Bosch S, et al. Beneficial effects of amantadine on L-dopa-induced dyskinesias in Parkinson’s disease. Mov Disord. 2000;15:873-878.
10. Metman LV, Del Dotto P, LePoole K, et al. Amantadine for levodopa-induced dyskinesias: a 1-year follow-up study. Arch Neurol. 1999;56:1383-1386.
11. Snow BJ, Macdonald L, McAuley D, et al. The effect of amantadine on levodopa-induced dyskinesias in Parkinson’s disease: a double-blind, placebo-controlled study. Clin Neuropharmacol. 2000;23:82-85.
12. Thomas A, Iacono D, Luciano AL, et al. Duration of amantadine benefit on dyskinesia of severe Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2004;75:141-143.
13. Verhagen Metman L, Del Dotto P, van den Munckhof P, et al. Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson’s disease. Neurology. 1998;50:1323-1326.
14. Durif F, Debilly B, Galitzky M, et al. Clozapine improves dyskinesias in Parkinson disease: a double-blind, placebo-controlled study. Neurology. 2004;62:381-388.
15. Bonifati V, Fabrizio E, Cipriani R, et al. Buspirone in levodopa-induced dyskinesias. Clin Neuropharmacol. 1994;17:73-82.
16. Goetz CG, Damier P, Hicking C, et al. Sarizotan as a treatment for dyskinesias in Parkinson’s disease: a double-blind placebo-controlled trial. Mov Disord. 2007;22:179-186.
17. Deep Brain Stimulation for Parkinson’s Disease Study Group . Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson’s disease. N Engl J Med. 2001;345:956-963.
18. Visser-Vandewalle V, Van der Linden C, Temel Y, et al. Long-term motor effect of unilateral pallidal stimulation in 26 patients with advanced Parkinson disease. J Neurosurg. 2003;99:701-707.
19. Kleiner-Fisman G, Herzog J, Fisman DN, et al. Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes. Mov Disord. 2006;21(Suppl 14):S290-S304.
November 19, 2008 — Dyskinesias, along with motor fluctuations, are the main motor complications of levodopa therapy. A retrospective analysis of studies investigating incidence of dyskinesias with levodopa treatment estimated that slightly more than one third of patients who had PD had dyskinesias after 4 to 6 years [1]. Early-onset PD and higher doses of levodopa are the biggest risk factors for the development of dyskinesias [2,3]. Dyskinesias may affect any part of the body and can be choreic or dystonic. They may manifest when plasma levodopa levels are at their peak (peak-dose dyskinesias), as plasma levodopa levels are rising and falling (diphasic dyskinesias), or when plasma levodopa levels are low (off-state dystonia). Dyskinesias typically are mild but may interfere with quality of life when painful or severe, as seen in advanced PD [4].
One way of treating dyskinesias is to modify the antiparkinsonian regimen. Peak-dose dyskinesias are related directly to the amount of levodopa given per dose, so decreasing individual doses generally reduces dyskinesias. The amount of clinical benefit to motor symptoms in PD may decline, however, and patients may experience increasing “off” periods. Thus, a decrease in individual doses of levodopa often has to be combined with more frequent administration, a practice termed dose fractionation. There are significant limitations to this approach, however, which are detailed in the article by Dewey elsewhere in this issue. Discontinuing catechol-O-methyltransferase (COMT) inhibitors or monoamine oxidase (MAO)-B inhibitors also may be helpful in reducing peak-dose dyskinesias.
Sustained-release formulations in theory could reduce dyskinesias, as they are released slowly throughout the day. In practice, however, they tend to prolong the duration of dyskinesias and increase the severity of dyskinesias in the late afternoon or early evening [5]. Patients who have dyskinesias and are on sustained-release levodopa formulations may benefit from switching to immediate-release levodopa.
Diphasic dyskinesias can be difficult to treat. The same strategies can be tried, but there are no data to support one strategy over the other. Other options include overlapping the doses of levodopa to prevent trough plasma levodopa levels until late in the evening or administering very small doses of levodopa frequently (such as 50 mg of levodopa given hourly while awake) [6].
Strategies for treating off-state dystonias are similar to strategies to reduce motor fluctuations in PD and may include changing the levodopa dosing schedule or adding dopamine agonists, COMT inhibitors, or MAO-B inhibitors.
Recent evidence-based reviews recommend amantadine for treating dyskinesias in PD [7,8]. Amantadine is believed to have an antidyskinetic effect through its action at the N-methyl-D-aspartate receptor. Amantadine can reduce dyskinesias between 24% and 60% [9,10,11,12,13]. In one study, the effect of amantadine was maintained for up to a year. Some patients, however, are reported to have had rebound dyskinesias when amantadine was discontinued [12]. Side effects include confusion, peripheral edema, and livedo reticularis.
A double-blind, placebo-controlled trial of clozapine demonstrates an increase in “on” time without dyskinesias with a corresponding decrease in “on” time with dyskinesias [14]. The potential for agranulocytosis and the frequent blood monitoring required make it an unattractive agent, however. Buspirone is reported effective in one small crossover trial of 10 patients [15], but only seven patients completed the trial, and there are no other large randomized studies. Clinical trials of other drugs reported to be helpful for treating dyskinesias were uncontrolled or failed to show efficacy in large double-blind trials [6,16].
Although pallidotomy commonly was used as a surgical intervention for dyskinesias with good results [8], most surgical centers have turned to deep brain stimulation (DBS) to treat patients who have motor fluctuations and dyskinesias. There are two main targets for DBS in patients who have PD: the globus pallidus interna (GPi) and the subthalamic nucleus (STN). Although DBS of the GPi reduces dyskinesias in open-label reports and blinded evaluations of patients on and off stimulation [17,18], a recent practice parameter determined that there was insufficient evidence to determine the efficacy of GPi DBS for dyskinesias [7]. Part of this lack of evidence is because most centers prefer to place electrodes in the STN DBS. In a meta-analysis of outcomes, STN DBS reduced dyskinesias in patients who had PD by an average of 69.1% [19]. This occurs along with a reduction in levodopa dosage, which is mainly responsible for the improvement in dyskinesias. Based on existing studies, STN DBS is considered possibly effective for reducing motor fluctuations, dyskinesias, and antiparkinsonian medications in PD [7]. Adverse effects from DBS surgery may include surgical complications, such as hemorrhage, stroke, infection of the device, seizures, delirium, and stimulation-related effects, such as dystonia, confusion, paresthesias, dysarthria, and diplopia, depending on the stimulation site.
References
1. Ahlskog JE, Muenter MD. Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov Disord. 2001;16:448-458.
2. Schrag A, Schott JM. Epidemiological, clinical, and genetic characteristics of early-onset parkinsonism. Lancet Neurol. 2006;5:355-363.
3. Grandas F, Galiano ML, Tabernero C. Risk factors for levodopa-induced dyskinesias in Parkinson’s disease. J Neurol. 1999;246:1127-1133.
4. Pechevis M, Clarke CE, Vieregge P, et al. Effects of dyskinesias in Parkinson’s disease on quality of life and health-related costs: a prospective European study. Eur J Neurol. 2005;12:956-963.
5. Fabbrini G, Brotchie JM, Grandas F, et al. Levodopa-induced dyskinesias. Mov Disord. 2007;22:1379-1389quiz 1523.
6. Muenter MD. Patterns of dystonia in response to L-Dopa therapy for Parkinson’s disease. Mayo Clin Proc. 1977;52:163-174.
7. Pahwa R, Factor SA, Lyons KE, et al. Practice parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;66:983-995.
8. Goetz CG, Poewe W, Rascol O, et al. Evidence-based medical review update: pharmacological and surgical treatments of Parkinson’s disease: 2001 to 2004. Mov Disord. 2005;20:523-539.
9. Luginger E, Wenning GK, Bosch S, et al. Beneficial effects of amantadine on L-dopa-induced dyskinesias in Parkinson’s disease. Mov Disord. 2000;15:873-878.
10. Metman LV, Del Dotto P, LePoole K, et al. Amantadine for levodopa-induced dyskinesias: a 1-year follow-up study. Arch Neurol. 1999;56:1383-1386.
11. Snow BJ, Macdonald L, McAuley D, et al. The effect of amantadine on levodopa-induced dyskinesias in Parkinson’s disease: a double-blind, placebo-controlled study. Clin Neuropharmacol. 2000;23:82-85.
12. Thomas A, Iacono D, Luciano AL, et al. Duration of amantadine benefit on dyskinesia of severe Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2004;75:141-143.
13. Verhagen Metman L, Del Dotto P, van den Munckhof P, et al. Amantadine as treatment for dyskinesias and motor fluctuations in Parkinson’s disease. Neurology. 1998;50:1323-1326.
14. Durif F, Debilly B, Galitzky M, et al. Clozapine improves dyskinesias in Parkinson disease: a double-blind, placebo-controlled study. Neurology. 2004;62:381-388.
15. Bonifati V, Fabrizio E, Cipriani R, et al. Buspirone in levodopa-induced dyskinesias. Clin Neuropharmacol. 1994;17:73-82.
16. Goetz CG, Damier P, Hicking C, et al. Sarizotan as a treatment for dyskinesias in Parkinson’s disease: a double-blind placebo-controlled trial. Mov Disord. 2007;22:179-186.
17. Deep Brain Stimulation for Parkinson’s Disease Study Group . Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in Parkinson’s disease. N Engl J Med. 2001;345:956-963.
18. Visser-Vandewalle V, Van der Linden C, Temel Y, et al. Long-term motor effect of unilateral pallidal stimulation in 26 patients with advanced Parkinson disease. J Neurosurg. 2003;99:701-707.
19. Kleiner-Fisman G, Herzog J, Fisman DN, et al. Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes. Mov Disord. 2006;21(Suppl 14):S290-S304.
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