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Supplements The Case for Early Initiation of Monotherapies and Delayed Dopaminergic Therapy in Parkinson's Disea

The Impact and Management of Nonmotor Symptoms of Parkinson's Disease

Kelly E. Lyons, PhD and Rajesh Pahwa, MD
Thermodysregulation has been reported in up to 64% of patients with PD and involves intolerance to cold and heat, as well as excessive sweating.39 Excessive sweating occurs most commonly either during the “off” state or when the patient is experiencing dyskinesia, and can also be associated with other autonomic symptoms, particularly constipation. Adjustments to PD medications to reduce motor complications can be beneficial. Botulinum toxin injections may reduce sweating. Deep brain stimulation has also been shown to be beneficial, but likely due to a reduction in levodopainduced motor complications.40

Sexual dysfunction is common in PD, affects both men and women, and can include diminished arousal, drive, or orgasm. However, the most common sexual problem is erectile dysfunction.41 In addition to PD, neuropsychological issues as well as medications for depression and cardiac problems can cause sexual dysfunction. Therefore, all medications should be reviewed, potentially offending agents should be reduced or eliminated if possible, and neuropsychiatric assessments should be completed. In some cases, sexual dysfunction can be worsened during “off” periods, so adjustments of PD medications may be helpful. Finally, phosphodiesterase-5 inhibitors (eg, sildenafil, vardenafil, tadalafil) can be prescribed.

Sleep Disturbances

Sleep disturbances, seen in up to 98% of patients with PD, may manifest as sleep fragmentation, insomnia, excessive daytime sleepiness, altered sleep-wake cycle or rapid eye movement (REM) sleep behavior disorder (RBD), and other sleep disorders.10,22 These sleep problems may be linked to PD symptoms, PD medications, or an actual sleep disorder.42 All patients should be educated on good sleep hygiene and should try to maintain a regular sleep schedule. In addition, neuropsychiatric issues should be evaluated, as depression, anxiety, and dementia can result in sleep disturbances. Fragmented sleep may be a result of “off” symptoms during the night, and therefore a trial of extended-release carbidopa/levodopa or a long-acting dopamine agonist may be considered; however, in some patients, dopamine agonists can cause insomnia.43 If these adjustments are not beneficial, the patient should undergo a formal sleep evaluation to rule out a sleep disorder such as sleep apnea, RBD, periodic limb movements of sleep, or restless legs syndrome. If sleep is interrupted by nocturnal urinary frequency, reduction of liquid intake prior to bedtime may be helpful, or anticholinergic medications may be used (unless patients have memory problems or other contraindications).10 In addition, sleep aids such as hypnotics (eg, zolpidem, zaleplon, eszopiclone, ramelteon, etc) or other sedating medications (mirtazapine, trazodone, nortriptyline, etc) may be helpful.

Higher doses of dopaminergic agents are known to be associated with excessive daytime somnolence, which may be more pronounced with dopamine agonists than with levodopa.7,43 In fact, sudden onset of sleep (sudden sleep during the day without a prodrome) has been reported with pramipexole and ropinirole, and may be especially problematic in younger patients who drive.43 Dopaminergic agents may need to be reduced or discontinued if this occurs.43 In 1 randomized, placebo-controlled trial, modafinil (200 mg daily) improved daytime sleepiness in 35% of evaluated patients with PD without worsening UPDRS scores.44 Methylphenidate may also be considered for daytime sleepiness.43

Summary

Nonmotor symptoms of PD may occur early in the disease process. The impact of nonmotor symptoms on HRQOL can be significant, suggesting that early recognition, diagnosis, and management of PD is critical to improving patient outcomes. It is also important to recognize that the treatments for motor and nonmotor symptoms may impact the disease process, and vice versa. Clinicians must understand the symptoms of PD, the benefits and adverse effects of management strategies, and the impact of regimen changes on symptoms in order to fully contribute to improving patient outcomes.

Acknowledgment: The authors would like to thank A. Scott Mathis, BS, PharmD, for editorial assistance in the preparation of the manuscript. A. Scott Mathis, BS, PharmD has no relevant affiliations or financial relationships to disclose relative to this activity.
Author Affiliations: Department of Neurology, University of Kansas Medical Center, Kansas City, KS (KEL, RP).
Funding Source: This activity is supported by an educational grant from Teva Neuroscience, Inc.
Author Disclosure: Dr Lyons reports serving as an advisory board member for St. Jude Medical and as a consultant for Teva Neuroscience, Inc. She also reports receiving royalties from Oxford University Press and serving as president of the International Essential Tremor Foundation. Dr Pahwa reports serving as an advisory board member and consultant for Adamas, EMD Serono, Impax, Medtronic, Novartis, St. Jude Medical, and Teva Neuroscience, Inc. He also reports serving as a lecturer for GE and Teva Neuroscience, Inc, as well as receiving royalties from Oxford University Press.
Authorship Information: Concept and design (KEL, RP); acquisition of data (KEL, RP); drafting of the manuscript (KEL); and critical revision of the manuscript for important intellectual content (KEL, RP).
Address correspondence to: E-mail: kelly.lyons@att.net.

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