NeuroVoices: Lucia Ricciardi, MD, PhD, on Addressing Neuropsychiatric Symptom Management in Parkinson Disease

Lucia Ricciardi, MD, PhD

Credit: St. Georges Hospital

Parkinson disease (PD) is diagnosed based on the presence of motor symptoms, but the high prevalence of numerous neuropsychiatric symptoms and cognitive impairment suggests that it is more accurately conceptualized as a neuropsychiatric disorder. Over the years, clinicians have begun to understand the broad scope of neuropsychiatric manifestations, including depression, anxiety, apathy, psychosis, and cognitive impairment. Patients with the disease are more predisposed to delirium, and PD treatments give rise to specific syndromes, including impulse control disorders, dopamine agonist withdrawal syndrome, and dopamine dysregulation.

At the 2024 International Congress of Parkinson’s Disease and Movement Disorders (MDS), held September 27-October 1, in Philadelphia, Pennsylvania, a session focused on the neuropsychiatric symptoms and cognitive dysfunction in PD. One of the speakers, Lucia Ricciardi, MD, PhD, focused on the clinical manifestations of neuropsychiatric symptoms of the disease, highlighting ways clinicians can identify and manage them. Ricciardi, a consultant neurologist and senior lecturer at St. Georges Hospital in London, United Kingdom, has worked numerous years in research, focusing on the biological, behavioral, and psychological experiences of non-motor symptoms in patients with PD and other movement disorders.

As part of a new iteration of NeuroVoices, Ricciardi gave an overview of her presentation and the clinical utility behind what she discussed. She spoke on the multifactorial nature of how neuropsychiatric symptoms arise and some the research efforts that need greater focus, such as improved understanding of the underlying mechanisms of these symptoms. Furthermore, she gave clinical perspective on the ways to reduce neuropsychiatric risk in patients with PD, highlighting ways to tailor treatment approaches and incorporating nonpharmacological methods.

NeurologyLive: Why was this topic of interest to you?

Lucia Ricciardi, MD, PhD: My presentation at MDS was part of a teaching course on neuropsychiatric and cognitive dysfunction in Parkinson’s disease. We had a surprisingly large number of attendees, which was very encouraging. The focus was mostly on understanding the clinical manifestations, but also giving an update on what we know and how we manage the treatment. Specifically, my presentation was on neuropsychiatric symptoms, with a focus on depression, anxiety, apathy, impulse control disorders, and psychosis.

This topic is of great interest to me. I’m a consultant neurologist working with Parkinson's patients, and my clinical research focuses on non-motor symptoms. I’m particularly interested in neuropsychiatric symptoms because we still don’t know enough about them, yet they have a huge impact on the quality of life for both patients and their families. There's also a significant social aspect to this. In my presentation, I guided the audience through diagnosing these symptoms, their clinical presentations, and how we manage them.

Neuropsychiatric symptoms have received more attention over the last 10 years, and many are interested in the topic now. However, these symptoms are still often overlooked in clinical settings. Although we are making progress, we’re still not doing enough.

Where do the neuropsychiatric symptoms of PD stem from?

Neuropsychiatric symptoms in Parkinson’s are multifactorial, and many factors contribute to their worsening. There are disease-related factors, medication-related factors, and social factors. The disease itself, as part of the neurodegenerative process, affects circuits and networks that control mood, cognition, and behavior. As the disease progresses, these symptoms tend to worsen or appear more frequently.

Other non-motor and motor symptoms, like sleep disturbances and autonomic dysfunction, also have a big impact on mood and anxiety. Medications can play a role as well. For example, some neuropsychiatric symptoms are triggered by medications, particularly dopamine agonists. Impulsive-compulsive behaviors, for instance, are often triggered in predisposed patients by dopamine agonists, and hallucinations can be induced by increasing medication dosage or having too much dopaminergic stimulation.

On the other hand, we know these symptoms can also be part of neuropsychiatric fluctuations, such as hypo-dopaminergic states. When patients are in the "wearing off" phase, they are more prone to anxiety, depression, and apathy. But when they’re "on" and overstimulated, they can become impulsive. So, dopaminergic medication—especially dopamine agonists—can certainly contribute, but there are many factors involved. Additionally, social and environmental factors, like isolation and caregiver stress, also worsen the symptoms.

For experts treating patients with PD, what should they focus on to reduce the burden of neuropsychiatric symptoms?

That’s a very good question. Until recently, we thought some symptoms—like impulsive-compulsive behaviors—were purely drug-related. But that’s not entirely true. It’s not just the medication itself but also the increased dopamine load in predisposed individuals that triggers these symptoms. Medications certainly play a role, though.

For example, in patients with cognitive impairment, we should be cautious about using dopamine agonists or prescribing high doses of dopamine, as these patients are more prone to hallucinations and impulse control disorders. It’s important to tailor dopaminergic treatment carefully, especially in patients with cognitive impairment, advanced Parkinson’s, or older age, as these are risk factors for neuropsychiatric symptoms.

At the same time, for patients experiencing non-motor fluctuations or neuropsychiatric changes, we should adjust their dopaminergic medication based on those mood and behavioral shifts throughout the day. Additionally, we need to consider non-dopaminergic medications, like SSRIs or SNRIs, for patients who might benefit from them.

Finally, we must not overlook non-pharmacological approaches, which are underused. Interventions like mindfulness meditation and cognitive behavioral therapy can have a wonderful effect on these patients.

In terms of understanding and treating the neuropsychiatric aspects of PD, where should research be directed?

That’s a great question. Yes, I believe research needs to focus more on neuropsychiatric symptoms. Although this has been a growing field in recent years, we still need more research. These symptoms are very common, highly disabling, and should be a top research priority.

We need to clarify the underlying mechanisms of these symptoms. For example, we need to investigate the role of neurotransmitters other than dopamine, such as serotonergic, noradrenergic, and cholinergic systems. Better understanding the networks and circuits involved, using techniques like non-invasive neuromodulation or intracranial neurophysiology, will also be invaluable.

Another research priority is improving how we identify and track these symptoms. Digital medicine has become a big topic in recent years, and I think developing objective biomarkers is key. Tools like wearables, mobile apps, or other digital approaches could help us predict who is at risk of developing these symptoms.

Lastly, my research focuses on holistic management, involving multidisciplinary care. Too often, neurologists, psychiatrists, and psychologists work in silos. We need to integrate these fields and work together to create holistic treatment plans. This should include non-pharmacological interventions but also promote self-management. Patients need to be involved and empowered in their care. This could involve educating them about diet, sleep, and what they can do daily to improve their condition.