Non-Motor Symptoms of Parkinson’s Disease Are More Common Than Most Think

      Graphical abstract

      Non-motor symptoms — and fluctuations in these symptoms — are a surprisingly common and often disabling part of life for residents with Parkinson’s disease (PD), said Julie Gammack, MD, CMD, at the annual conference of AMDA — The Society for Post-Acute and Long-Term Care Medicine in Atlanta, GA.
      Non-motor components of the disease such as dementia and psychosis are often a reason for long-term care placement, and the subsequent morbidity and mortality are significant: The limited body of research available on residents with PD in long-term care has shown a high prevalence of depression, hallucinations, and agitation, for instance, and a 3-year post-placement mortality of 50%.
      More broadly, one-third of patients with PD who experience motor function fluctuations also have non-motor fluctuations. “What I didn’t realize was how prevalent these symptoms can be,” said Dr. Gammack, a professor of medicine in the Division of Geriatric Medicine at Saint Louis University in Missouri. “There’s a suggestion [from the literature] that after having PD for 5 or 10 years, almost everyone will have some non-motor component of the disease.”
      Research indicates, moreover, that cognitive dysfunction and mood disorders, autonomic dysfunction, and other non-motor symptoms can actually precede motor symptoms by up to 10 years in some individuals with PD. “We should think about [such symptoms] as potential precursors, especially in those who are starting to develop some rigidity and gait instability,” she said.
      Non-motor symptoms in patients with PD can be managed as they would in other clinical scenarios, such as managing insomnia with sleep hygiene or constipation with changes in diet and fluid intake. However, in addition, because “on-off phenomena can happen with non-motor symptoms just as with motor symptoms” and because these fluctuations appear to be connected, it is often important to optimize continuous dopaminergic prescribing, she said.
      Increasing dopaminergic administration, optimizing dopaminergic agonists, and adding advanced therapies and nondopaminergic treatment are all therapeutic options, Dr. Gammack explained. “So for non-motor fluctuations, optimizing the total management of their PD [is the goal].”
      PD psychosis, which appears to increase mortality, involves hallucinations, illusions, or delusions that are continuous or recurrent for 1 month or more. “Their psychosis is often visually based,” Dr. Gammack said. “These individuals are clear in their thinking, they have insight and are not delirious, and they’re adamant that what they’re seeing is actually there.”
      The risk of psychosis increases with the use of certain medications (such as dopamine agonists, anticholinergics, amantadine, and serotonin) and in the presence of underlying visual processing deficits and ocular pathology, sleep disorders, and psychiatric conditions. Medication reduction can reduce the symptoms of psychosis, but unfortunately this often comes at the cost of worsened motor symptoms, Dr. Gammack said.
      The antipsychotics clozapine and quetiapine “get the most attention” for PD psychosis (an off-label use), but both can potentially worsen motor symptoms. Clozapine may have more minimal motor side effects, but agranulocytosis is a concern. “And of course, we try to avoid antipsychotics as much as we can,” Dr. Gammack said.
      The drug pimavanserin, a 5-HT2A inverse agonist, was approved in 2016 by the U.S. Food and Drug Administration for PD psychosis. A 6-week randomized, double-blind, placebo-controlled study reported an approximately 3-point decrease in the PD adapted scale for assessment of positive symptoms (SAPS-PD) — a 37% improvement — with use of the drug, although the rating scale used in the study had not been previously validated (Lancet 2014;383:533–540).
      PD dementia is also common, especially with a longer duration of PD (>70% at 5 years), Dr. Gammack noted. Research has looked at stimulants, cholinesterase inhibitors, and memantine in patients with PD (all off-label), and thus far cholinesterase inhibitors have the “best evidence” for a small improvement.
      Christine Kilgore is a freelance writer in Falls Church, VA.