Movement Disorders Moment: Neuropsychiatric Symptoms in Parkinson Disease

What Are the Nonmotor Symptoms of Parkinson Disease?

Often, when considering Parkinson disease (PD), we focus on tremor, gait, and movement or balance and dexterity issues. This is understandable, considering that diagnostic criteria center around motor symptoms despite discussion about revisiting those criteria.^1,2 Nonmotor symptoms, of which neuro-psychiatric features are just a segment, can be the more troubling symptoms, however. Neuropsychiatric symptoms include depression, apathy, delusions, and hallucinations.

Reported prevalence of depression among people with PD varies broadly, from 3% to 90%.^3,4 Among clinicians who see people with PD regularly, most would agree that depression is not rare. The question that does arise is whether the depression is a result of how PD changes brain chemistry or is a manifestation of having to cope with a chronic illness without a cure, and there are studies providing support for both.^5-10

Apathy arises as a symptom of PD quite frequently, and it is important to distinguish apathy from depression. Apathy may also be associated with a sense of malaise or feeling a lack of energy. Apathy typically appears as disinterest and can manifest as being inattentive to others during family events or not responding to activity around oneself. People with apathy may still take pleasure in specific events, such as physical therapy programs where they see friends, whereas in depression people tend to find it hard to take pleasure in anything.

Also found in PD are delusions and hallucinations, which are often visual but can affect all senses and often are the most troubling symptoms for people with PD and their care partners. The burden of these symptoms is high, in part, because delusions and hallucinations often affect interpersonal relationships. For example, a person with PD psychosis may have delusions of infidelity, thinking their partner is carrying on with a neighbor or hired caregiver. Delusions of harm or threats to their own safety and the safety of their home and their loved ones can also be very problematic, especially when combined with hallucinations, such as, seeing people lurking outside who are not really there. It is estimated that nearly 50% of people with PD may have hallucinations and delusions at some point in their illness.^11-13

How Do You Assess Neuropsychiatric Symptoms?

Neuropsychiatric symptoms should be addressed at every neurology visit, just as motor issues are. We clinicians ask about walking, getting up from a chair or out of car, and activities of daily living (eg, showering, dressing, eating) that require movement. We should also be asking our patients about their mood and their ability to take pleasure in those daily activities. Are they enjoying time with friends and family, and what are they looking forward to doing in the near future?

When an individual does not have something to look forward to or seems not to care about or enjoy things that once were enjoyable, it is appropriate to use screening tools for depression. The Beck Depression Inventory is useful in this regard,¹⁴ although it is also important to use this in context and not become overly reliant on a single number. The goal is to understand if symptoms of depression interfere with quality of life.

Every patient with PD should also be asked about hallucinations and delusions because these can escalate and become disruptive. It is preferable to discuss the possibility that they may occur early and continually assess for these symptoms regularly. The alternative may be receiving a frantic call from a caregiver when a patient is threatening them or preparing to flee their home because of delusions.

It must also be recognized that there may be stigma around neuropsychiatric symptoms, and both patients and caregivers are less likely to bring these symptoms up if the clinician does not ask about them.¹⁵ It may also be helpful to speak with patients alone, without caregivers, because sometimes they are uncomfortable with their spouse or caregiver learning they are having these symptoms. This may be because they are unsure how others will react, what consequences may ensue, and often that they will further burden their care partners.

Additionally, patients may not recognize their experiences are not real, so in addition to asking directly about hallucinations and delusions, I ask other kinds of leading questions that can be used to elucidate symptoms of hallucinations and delusions (Box). For example, asking if anything strange has been happening lately is another way to elicit this information.

Ultimately, neurologists and other clinicians need to initiate conversations about neuropsychiatric symptoms so that, as with any other symptom, we can try to minimize suffering and improve outcomes.¹⁶ In my experience the key to overcoming reluctance from people with PD to share such symptoms is to build a trusting relationship in which talking about these symptoms is routine. If symptoms asked about are not present, there is opportunity to discuss that they may occur eventually. When symptoms are present, it provides the opportunity to assess frequency and severity, evaluate for potential nonPD causes and, when necessary, offer treatment.

How Do You Treat Neuropsychiatric Symptoms?

A number of antidepressants have been reviewed specifically for use in people with PD, and venlafaxine has been found to be effective.¹⁷ The selective serotonin reuptake inhibitors (SSRIs), including sertraline, citalopram, or escitalopram are also options. Pramipexol is a dopamine agonist that not only treats some of the motor symptoms of PD, such as stiffness, tremors, muscle spasms, and poor muscle control but can also improve mood, although it is not a first-line agent for depression and may increase impulsivity.¹⁸ Managing depressive symptoms may decrease the need for emergency department visits and hospitalization and improve quality of life.¹⁹

For apathy, some dopaminergic agonists may be beneficial, but caution for impulsivity and other side effects is warranted. Importantly, the antidepressants are usually not helpful for symptoms of apathy. For malaise, fatigue, and generalized brain fog, as in many neurologic conditions, we do not have established treatment options yet, although physical exercise has been reported by some patients to be helpful.

For hallucinations and delusions, most antipsychotics are contraindicated in PD because of their antidopaminergic effects and are not specifically approved by the FDA for treatment of Parkinson disease psychosis.²⁰

Pimavanserin is approved for treatment of psychosis symptoms in people with PD-related hallucinations and delusions. Before initiating treatment with pimavanserin, it is important to rule out any other possible causes of hallucinations and delusions (eg, bladder infections, head injuries, polypharmacy). As with any treatment decision, it is also important to discuss risks and benefits with patients and caregivers. The discussion of risks is especially important in the case of antipsychotics, because all of them have a prominent caution that “(e)lderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.”

The expanded explanation of this warning describes how the use of antipsychotic drugs increased risk of death from all causes in all types of dementia, most of which were related to heart conditions or infections such as pneumonia. To help patients understand their risks, it is important to discuss these warnings prior to initiating pimavanserin treatment. Reasons for a higher risk of mortality have not been fully elucidated at this time but may reflect people who need antipsychotics being further along in their illness, having more comorbidities, or using more medications overall.²¹ Risks of drug-drug interactions with pimavanserin require a review of medications being used, and patients and caregivers should be advised that swelling of the legs or arms, altered gait, increase in hallucinations, and confusional state can occur.

The pivotal trial of pimavanserin demonstrated the medication reduces the severity and frequency of hallucinations and delusions in the majority of, although not all, individuals with PD psychosis after 6 weeks of treatment. ²² Without treatment, hallucinations and delusions tend to worsen , with loss of insight, and other senses becoming involved. Any provider involved in the care of these patients understands the suffering these symptoms cause. Moreover, the symptoms of PD psychosis have been reported to be the foremost reason patients are placed in a long term care facility.^23,24

Conclusions

Greater recognition and assessment of neuropsychiatric symptoms in PD are needed, and clinicians should initiate conversations to assess these symptoms just as they do for motor symptoms. Our role in serving our patients with PD, and their families, is to do our utmost to reduce the suffering this diagnosis brings, and to optimize quality of life. Addressing neuropsychiatric symptoms in PD is a major part of our task.