Guidance Is Sparse for Nonmotor PD Symptoms

Nonmotor symptoms of Parkinson's disease remain underdiagnosed despite their widespread occurrence, which is the impetus behind new treatment guidelines from the American Academy of Neurology.

“Nonmotor symptoms are an integral part of this syndrome. These symptoms can be as troublesome as motor symptoms and impact activities of daily living, though they are often underrecognized by health care professionals,” wrote Dr. Theresa A. Zesiewicz, lead author of the guidelines and professor of neurology at the University of South Florida, Tampa (Neurology 2010;74:924–31).

Treatment of depression, dementia, and psychosis in Parkinson's disease (PD) has been addressed in a previous guideline (Neurology 2006;66:996–1002), as has treatment of PD-related sialorrhea with botulinum toxin (Neurology 2008;70:1707–14).

However, there are many other nonmotor symptoms for which there is a paucity of research concerning treatment, wrote Dr. Zesiewicz and her colleagues wrote.

“The disease process of PD certainly contributes to many nonmotor symptoms, including autonomic dysfunction (orthostatic hypotension, gastrointestinal symptoms), depression, sexual dysfunction, and sleep dysfunction,” said Dr. Zesiewicz in an interview. “However, medications used to treat PD can contribute to other nonmotor symptoms. For example, the use of some PD medications can contribute to excessive daytime sleepiness, while others can cause insomnia.”

In general, the treatment of most nonmotor PD symptoms should mirror treatments given to non-PD patients, because “research is not currently available to support or refute their use specifically in PD patients,” she said. The new guidelines provide evidence-based recommendations for the treatment of only four conditions: erectile dysfunction, constipation, restless legs syndrome, and fatigue.

A wide range of nonmotor symptoms were reviewed for the guidelines, including autonomic dysfunction such as gastrointestinal disorders, orthostatic hypotension, sexual dysfunction, and urinary incontinence; sleep disorders, such as restless legs syndrome, periodic limb movements of sleep, excessive daytime somnolence, insomnia, REM sleep behavior disorder; fatigue; and anxiety.

After a literature search to capture articles on these symptoms published in 1966–2008, a panel review deemed 46 papers relevant for the development of evidence-based recommendations, concluding that there was insufficient evidence to make recommendations on the treatment of urinary incontinence, orthostatic hypotension, insomnia, REM sleep behavior disorder, and anxiety.

For the treatment of erectile dysfunction in PD, the authors recommend that sildenafil citrate (50 mg) “is possibly efficacious.” Sexual dysfunction is common in both men and women with PD, they wrote. “Dysautonomia manifests as erectile dysfunction (ED) but also as reduced genital sensitivity and lubrication and difficulties reaching orgasm.” Only one controlled clinical trial for the treatment of ED was available for review, however.

For constipation, they concluded that isosmotic macrogol (polyethylene glycol) “possibly improves constipation in PD.” Four studies evaluating the efficacy of pharmacologic agents for PD-related constipation were reviewed, and the recommendation is based on one class II study.

Regarding PD-related sleep dysfunction, the authors found sufficient evidence to make treatment recommendations for excessive daytime somnolence (EDS), and restless leg syndrome or periodic limb movements of sleep.

Based on the results of two class I studies, they recommend modafinil to improve patients' perceptions of wakefulness, although “it is ineffective in objectively improving EDS as measured by objective tests,” they added.

In addition, they said, levodopa/carbidopa “probably decreases the frequency of spontaneous nighttime leg movements,” based on one class I study and should therefore be considered to treat periodic limb movements of sleep in Parkinson's disease.

And finally, “methylphenidate is possibly useful in treating fatigue in PD,” they concluded, based on one class II study.

However, there is potential for abuse, they warn. “Although there is no current evidence to suggest such a risk in PD, patients with PD do have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction,” they cautioned.

“The same rules for treating PD patients with these medications would apply as when treating any patients, including careful monitoring of drug interactions and taking comorbid conditions into consideration,” Dr. Zesiewicz noted.

“Of course, it is important to recognize that the treatments recommended are not the only available treatments,” commented Dr. Ronald B. Postuma, a PD researcher and assistant professor of neurology at the Montreal General Hospital. “The guidelines focus only on therapies that have good randomized controlled trial evidence. All experienced clinicians will recognize several useful treatments that are not in the recommendations because of incomplete evidence,” he said in an interview.

Disclosures: Dr. Zesiewicz reported receiving funding for travel and for serving on speakers bureaus from Boehringer Ingelheim and Teva Pharmaceutical Industries Ltd. She also reported receiving research support from various pharmaceutical companies.

Nonmotor symptoms of Parkinson's disease remain underdiagnosed despite their widespread occurrence, which is the impetus behind new treatment guidelines from the American Academy of Neurology.

“Nonmotor symptoms are an integral part of this syndrome. These symptoms can be as troublesome as motor symptoms and impact activities of daily living, though they are often underrecognized by health care professionals,” wrote Dr. Theresa A. Zesiewicz, lead author of the guidelines and professor of neurology at the University of South Florida, Tampa (Neurology 2010;74:924–31).

Treatment of depression, dementia, and psychosis in Parkinson's disease (PD) has been addressed in a previous guideline (Neurology 2006;66:996–1002), as has treatment of PD-related sialorrhea with botulinum toxin (Neurology 2008;70:1707–14).

However, there are many other nonmotor symptoms for which there is a paucity of research concerning treatment, wrote Dr. Zesiewicz and her colleagues wrote.

“The disease process of PD certainly contributes to many nonmotor symptoms, including autonomic dysfunction (orthostatic hypotension, gastrointestinal symptoms), depression, sexual dysfunction, and sleep dysfunction,” said Dr. Zesiewicz in an interview. “However, medications used to treat PD can contribute to other nonmotor symptoms. For example, the use of some PD medications can contribute to excessive daytime sleepiness, while others can cause insomnia.”

In general, the treatment of most nonmotor PD symptoms should mirror treatments given to non-PD patients, because “research is not currently available to support or refute their use specifically in PD patients,” she said. The new guidelines provide evidence-based recommendations for the treatment of only four conditions: erectile dysfunction, constipation, restless legs syndrome, and fatigue.

A wide range of nonmotor symptoms were reviewed for the guidelines, including autonomic dysfunction such as gastrointestinal disorders, orthostatic hypotension, sexual dysfunction, and urinary incontinence; sleep disorders, such as restless legs syndrome, periodic limb movements of sleep, excessive daytime somnolence, insomnia, REM sleep behavior disorder; fatigue; and anxiety.

After a literature search to capture articles on these symptoms published in 1966–2008, a panel review deemed 46 papers relevant for the development of evidence-based recommendations, concluding that there was insufficient evidence to make recommendations on the treatment of urinary incontinence, orthostatic hypotension, insomnia, REM sleep behavior disorder, and anxiety.

For the treatment of erectile dysfunction in PD, the authors recommend that sildenafil citrate (50 mg) “is possibly efficacious.” Sexual dysfunction is common in both men and women with PD, they wrote. “Dysautonomia manifests as erectile dysfunction (ED) but also as reduced genital sensitivity and lubrication and difficulties reaching orgasm.” Only one controlled clinical trial for the treatment of ED was available for review, however.

For constipation, they concluded that isosmotic macrogol (polyethylene glycol) “possibly improves constipation in PD.” Four studies evaluating the efficacy of pharmacologic agents for PD-related constipation were reviewed, and the recommendation is based on one class II study.

Regarding PD-related sleep dysfunction, the authors found sufficient evidence to make treatment recommendations for excessive daytime somnolence (EDS), and restless leg syndrome or periodic limb movements of sleep.

Based on the results of two class I studies, they recommend modafinil to improve patients' perceptions of wakefulness, although “it is ineffective in objectively improving EDS as measured by objective tests,” they added.

In addition, they said, levodopa/carbidopa “probably decreases the frequency of spontaneous nighttime leg movements,” based on one class I study and should therefore be considered to treat periodic limb movements of sleep in Parkinson's disease.

And finally, “methylphenidate is possibly useful in treating fatigue in PD,” they concluded, based on one class II study.

However, there is potential for abuse, they warn. “Although there is no current evidence to suggest such a risk in PD, patients with PD do have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction,” they cautioned.

“The same rules for treating PD patients with these medications would apply as when treating any patients, including careful monitoring of drug interactions and taking comorbid conditions into consideration,” Dr. Zesiewicz noted.

“Of course, it is important to recognize that the treatments recommended are not the only available treatments,” commented Dr. Ronald B. Postuma, a PD researcher and assistant professor of neurology at the Montreal General Hospital. “The guidelines focus only on therapies that have good randomized controlled trial evidence. All experienced clinicians will recognize several useful treatments that are not in the recommendations because of incomplete evidence,” he said in an interview.

Disclosures: Dr. Zesiewicz reported receiving funding for travel and for serving on speakers bureaus from Boehringer Ingelheim and Teva Pharmaceutical Industries Ltd. She also reported receiving research support from various pharmaceutical companies.

Nonmotor symptoms of Parkinson's disease remain underdiagnosed despite their widespread occurrence, which is the impetus behind new treatment guidelines from the American Academy of Neurology.

“Nonmotor symptoms are an integral part of this syndrome. These symptoms can be as troublesome as motor symptoms and impact activities of daily living, though they are often underrecognized by health care professionals,” wrote Dr. Theresa A. Zesiewicz, lead author of the guidelines and professor of neurology at the University of South Florida, Tampa (Neurology 2010;74:924–31).

Treatment of depression, dementia, and psychosis in Parkinson's disease (PD) has been addressed in a previous guideline (Neurology 2006;66:996–1002), as has treatment of PD-related sialorrhea with botulinum toxin (Neurology 2008;70:1707–14).

However, there are many other nonmotor symptoms for which there is a paucity of research concerning treatment, wrote Dr. Zesiewicz and her colleagues wrote.

“The disease process of PD certainly contributes to many nonmotor symptoms, including autonomic dysfunction (orthostatic hypotension, gastrointestinal symptoms), depression, sexual dysfunction, and sleep dysfunction,” said Dr. Zesiewicz in an interview. “However, medications used to treat PD can contribute to other nonmotor symptoms. For example, the use of some PD medications can contribute to excessive daytime sleepiness, while others can cause insomnia.”

In general, the treatment of most nonmotor PD symptoms should mirror treatments given to non-PD patients, because “research is not currently available to support or refute their use specifically in PD patients,” she said. The new guidelines provide evidence-based recommendations for the treatment of only four conditions: erectile dysfunction, constipation, restless legs syndrome, and fatigue.

A wide range of nonmotor symptoms were reviewed for the guidelines, including autonomic dysfunction such as gastrointestinal disorders, orthostatic hypotension, sexual dysfunction, and urinary incontinence; sleep disorders, such as restless legs syndrome, periodic limb movements of sleep, excessive daytime somnolence, insomnia, REM sleep behavior disorder; fatigue; and anxiety.

After a literature search to capture articles on these symptoms published in 1966–2008, a panel review deemed 46 papers relevant for the development of evidence-based recommendations, concluding that there was insufficient evidence to make recommendations on the treatment of urinary incontinence, orthostatic hypotension, insomnia, REM sleep behavior disorder, and anxiety.

For the treatment of erectile dysfunction in PD, the authors recommend that sildenafil citrate (50 mg) “is possibly efficacious.” Sexual dysfunction is common in both men and women with PD, they wrote. “Dysautonomia manifests as erectile dysfunction (ED) but also as reduced genital sensitivity and lubrication and difficulties reaching orgasm.” Only one controlled clinical trial for the treatment of ED was available for review, however.

For constipation, they concluded that isosmotic macrogol (polyethylene glycol) “possibly improves constipation in PD.” Four studies evaluating the efficacy of pharmacologic agents for PD-related constipation were reviewed, and the recommendation is based on one class II study.

Regarding PD-related sleep dysfunction, the authors found sufficient evidence to make treatment recommendations for excessive daytime somnolence (EDS), and restless leg syndrome or periodic limb movements of sleep.

Based on the results of two class I studies, they recommend modafinil to improve patients' perceptions of wakefulness, although “it is ineffective in objectively improving EDS as measured by objective tests,” they added.

In addition, they said, levodopa/carbidopa “probably decreases the frequency of spontaneous nighttime leg movements,” based on one class I study and should therefore be considered to treat periodic limb movements of sleep in Parkinson's disease.

And finally, “methylphenidate is possibly useful in treating fatigue in PD,” they concluded, based on one class II study.

However, there is potential for abuse, they warn. “Although there is no current evidence to suggest such a risk in PD, patients with PD do have a risk for dopamine dysregulation syndrome and impulse control disorders that share many clinical and functional imaging features with addiction,” they cautioned.

“The same rules for treating PD patients with these medications would apply as when treating any patients, including careful monitoring of drug interactions and taking comorbid conditions into consideration,” Dr. Zesiewicz noted.

“Of course, it is important to recognize that the treatments recommended are not the only available treatments,” commented Dr. Ronald B. Postuma, a PD researcher and assistant professor of neurology at the Montreal General Hospital. “The guidelines focus only on therapies that have good randomized controlled trial evidence. All experienced clinicians will recognize several useful treatments that are not in the recommendations because of incomplete evidence,” he said in an interview.

Disclosures: Dr. Zesiewicz reported receiving funding for travel and for serving on speakers bureaus from Boehringer Ingelheim and Teva Pharmaceutical Industries Ltd. She also reported receiving research support from various pharmaceutical companies.