James Beck 0:00
Hi there, and welcome to our very first webinar of the 10th Expert Briefing series from the Parkinson's Foundation. Today's topic is Mental Health and PD. I'm Dr. James Beck, Chief Scientific Officer at the Parkinson's Foundation and your host for today's discussion.
I always like to mention when I introduce these webinars that they are not created in isolation. This is really a community effort that we have put together here, and I'm really pleased to call out that we have a number of independent regional Parkinson's organizations as part of our Alliance of Independent Regional Parkinson Organizations, called AIRPO, who really work with their members and our community to help put these together. I really want to acknowledge their help and support and thank them.
I also want to say that for those of you who are viewing the slides, these slides can be downloaded. If you're on the viewing page right now, look in the bottom left-hand side and there's a button that says download slides. You can download a PDF file at any time during this webinar if you'd like for later reference.
If you're a health professional and you're listening to this webinar, you can earn one free CEU through the American Society on Aging. If you're registered as a health professional and indicated you wanted one of these CEUs, then you will receive an email by the end of today with steps on how to collect that. You have just 30 days, though, so that's until October 18 to collect your free CEU. I encourage you to do it.
Now it's my distinct pleasure to introduce our guest speaker, Laura Marsh, MD, professor of psychiatry and neurology at Baylor College of Medicine. She's also the director of the Mental Health Care Line at the Michael E. DeBakey VA Medical Center, and she's a geriatric neuropsychiatrist. Dr. Marsh's clinical and research expertise focuses on the recognition and treatment of psychiatric disturbances in people with Parkinson's disease.
Since 2009, she's been executive director of the mental health services at the VA, and previously she was director and principal investigator of the clinical research program of the NIH-funded Morris K. Udall Parkinson's Disease Research Center at Johns Hopkins University in Baltimore.
Dr. Marsh is also a member of our Scientific Advisory Board and is someone we've worked with extensively in the past for questions we've had regarding mental health and people with Parkinson's disease. She's an excellent psychiatrist, excellent speaker, and we're really pleased to have her today. Dr. Marsh, I'm going to turn it over to you.
Laura Marsh 2:29
Thank you, Jim. It's a pleasure to be here, and it's a pleasure to be speaking with those out in this internet audience. I know that there are friends and colleagues and people I've taken care of, as well as some watch parties out there. I think that's just wonderful that there's all this interest in mental health and Parkinson's. Obviously, it's something that's important to me. We have a lot to talk about, and we'll move on with the slides. These are my disclosures.
What has been most significant to me and, I think, important for individuals with Parkinson's and their families, is to understand how Parkinson's is more than just a movement disorder and how those motor aspects of the condition interact and evolve over time with the cognitive and psychiatric issues that also occur over the course of Parkinson's disease. My main focus today will be on the common psychiatric diagnoses that occur, and then we'll be talking about some treatments.
We have about 35 minutes to talk about this, so obviously we won't get into all the details, but you'll have some time for questions, and there are many more resources out there as well. I also want to say that some of the slides have quite a bit of detail on them. I won't be going through all of those. You have those for your reference.
James Parkinson, when he first wrote about the condition that took on his name, was looking at six patients who he wrote about. Four of them he examined in person, and two of them he actually just observed on the street. In the lower corner of the slide, you see a picture of a townhome, which is actually James Parkinson's house in London. Apparently it's now a cafe or bistro. What he described in terms of the physical features of Parkinson's really still rings true today.
The involuntary tremulous motion in parts not in action, that's the rest tremor. The tendency to bend the trunk forward, that hunched posture, and to pass from a walking to a running pace, what's called festination. These features that we observe in Parkinson's, you can even spot them from the second floor of James Parkinson's house when you're looking at people walking down the street, as he did. In Europe, they call these kinds of conditions a spot diagnosis because you can spot someone across the room who has that condition.
What he didn't see, however, was that the senses and intellect were actually affected. He said categorically that they were uninjured. But we know over time that it is quite apparent that people are affected psychiatrically and intellectually as a result of the disease process itself. There are many reasons why we have come to recognize that, but still there's a situation where we have under-recognition of psychiatric problems in Parkinson's disease.
While there's this complex face of Parkinson's disease with many celebrities who've been diagnosed, what we still don't hear enough about from those celebrity representatives is the psychiatric aspects. I do find that this presentation is one opportunity for me to encourage people to talk about the psychiatric problems in a forthright fashion so that more attention is paid to them in terms of how we care for Parkinson's comprehensively.
Laura Marsh 6:30
We know that Parkinson's affects quite a number of people, seven to 10 million people globally, with higher rates as people get older, but all races, ethnicities, men, women, et cetera. It's a very complex disease. It's dynamic. Every person is different. It varies over its course. Although it's defined by its motor features, it has what we call pre-motor features before the motor disorder is actually diagnosed or evident. Then there are a whole host of non-motor phenomena that occur, and it tells us that this is a systemic disease.
It affects many, many parts of the body, including the lining of the gut and nerve cells in the digestive system, skin, et cetera, not just in the brain. This is a systemic disease that impacts disability and quality of life in addition to having these motor features.
In fact, what we find over time, and sometimes even early in the disease, is that the psychiatric and the cognitive disturbances are actually much more burdensome and have a greater negative effect on quality of life than the motor, which really encourages us all to make sure we get them recognized and treated.
We can see this even in the early descriptions of Parkinson's disease when they were doing research. Yahr in 1967 looked at 183 people with Parkinson's, and although the majority, 70%, presented with a tremor, at their very first doctor's visit, up to about 10% of the time people were showing features that could be seen in a person who has a depressive disorder: slowness, problems with muscle pain, cramps and aching.
Pain is very common in depression: depression and nervousness itself, fatigue, weakness, and then there's facial masking or decreased facial expression. If you were to see someone cross-sectionally and you weren't looking for Parkinson's disease, you might actually think that person just had depression. We see other evidence of signs and features of psychiatric disturbances, and particularly mood and anxiety problems, even much longer before Parkinson's is diagnosed, not just at the initial evaluation. We see that in particular in the case of anxiety.
Several lines of evidence, and more recent data even than what I show here, have shown that up to even 20 years before the onset of motor signs, there are higher rates of anxiety disorders or anxiety symptoms that either coincide with or are associated with eventually an increased risk of developing PD. All of those suggest that there are signs of the illness perhaps being evident, but just not in the form of a motor or movement abnormality. Instead, they're in terms of mood regulation.
In some data we looked at when I was in Baltimore at Johns Hopkins, we looked at 250 individuals, volunteers, who took part in very detailed psychiatric assessments. In this slide, what we're looking at in the blue are people who had the diagnosis of depression after the diagnosis of Parkinson's disease. In red, it's people who had a major depressive diagnosis before their Parkinson's disease. In this case, there are about 111 people out of the 250 who had major depression at some point.
Laura Marsh 10:26
Half of those essentially had the depressive diagnosis even up to 40 years, 50 years before the diagnosis, but you see a real increase in the frequency in that 10-year period before the disease is diagnosed. What you see here on this slide is the left side is the frequency or the number of people who are affected, and on the x-axis, the bottom line, it's the duration between your earliest major depressive episode onset and then your Parkinson's diagnosis. Those are years, with time zero being when you were diagnosed. This data wasn't just shown by us. There are others who have also shown that, on average, depression precedes the diagnosis of Parkinson's disease by about four to six years.
When it comes to the treatments of Parkinson's disease, we also see very positive benefits from taking these medicines on motor aspects of the disease. Compared to many other neurodegenerative disorders, Parkinson's really has very definitive treatments for its motor aspects: levodopa/carbidopa, the dopamine agonists, MAO inhibitors, as well as a number of non-pharmacologic treatments, things that are very helpful to people, exercise, but also surgical procedures like deep brain stimulation, anticholinergics, although their use is controversial because of their impact on cognition, and then amantadine.
However, there's no free lunch. Over time, despite their efficacy, as the person's Parkinson's progresses and the years pass on, there is a loss of efficacy of that initial dose of, say, for example, levodopa. Whereas it normally lasted four to six hours in the beginning, it might not last as long, or it might not pack as big of a punch in terms of the impact on one's motor symptoms. Also, what we see is, toward the end of the dose, that deterioration in its effectiveness.
We see what is called on-off phenomenon, which is where you're on and the medicine's working, and then the medicine wears off and someone can become unable to move and actually, in some cases, become what we call akinesic, or unable to move or initiate their movements. We also see these dose-limiting side effects.
The hyperkinesias or dyskinesias, the writhing kinds of movements, hyperactive movements of the limbs, the neck, and then dystonias, or sustained muscle contractions of the hands or limbs, or perhaps of the jaw. They can be quite painful, and they may be occurring at the peak of the dose when the Sinemet or levodopa level is high, or they could occur actually as someone is wearing off. They can be very disabling and painful and limiting in terms of function.
But in addition to all these motor consequences, these fluctuating motor effects, we also see fluctuating psychiatric and cognitive symptoms that go along with that. I'll show a little bit more about that in a couple slides.
Laura Marsh 13:49
In addition, there are other neuropsychiatric effects. The Parkinson's medicines can cause mood changes, for the better or for the worse. They can be associated with psychosis, confusion, delirium, where one has decreased attention and awareness, difficulty concentrating, disinhibition, impulse control disorders such as gambling or hypersexuality, or repetitive behaviors. We see that in particular with dopamine agonists. And then there are these fluctuating neuropsychiatric, non-motor symptoms.
These non-motor fluctuations are really quite striking in many patients. The dysautonomic symptoms are features that go along with the dysregulation of the autonomic nervous system. The kinds of symptoms you see are things like sweating, drenching sweats, hot sensations, flushing, cold sensations, hot sensations. One of my male patients with Parkinson's disease came to me and said, "Dr. Marsh, I never expected to go through menopause with my Parkinson's."
Our goal was to try to reduce those fluctuations so he didn't have those symptoms, but he was quite sympathetic to others as a result. Other problems that are related to autonomic dysfunction are visual complaints, palpitations, things that can resemble what you might experience with a panic attack. In some cases, people do have very psychiatric symptoms like extreme anxiety associated with those autonomic symptoms, and we call that off-anxiety, or they can have off-depression. Sometimes people have an elevated mood as part of their fluctuations, and their mood goes down when the medicine wears off.
They can have psychosis, or they can have slowed thinking when the medicine's not working, when the medicine is in the off state. Or they can have rushed thinking and speak too fast, et cetera, when the medicine's at its peak. Then other kinds of symptoms: fatigue, restlessness or akathisia, where you have to walk and you can't sit down, pain, et cetera. These are very striking symptoms that can be quite bothersome, especially if you don't know what's happening.
When you recognize them and you say, oh, this is what this is, then you can begin to work with them and work on treatment. This is just a slide that gives an example of what it's like when someone has levodopa-related fluctuations. Every time you see a little yellow arrow, that's where someone takes their Sinemet on the bottom, on the horizontal axis. On the vertical axis, you're looking at someone being off versus on, or even dyskinetic. If they wake up at 6:00 a.m. and they take their Sinemet, they're in an off state. They have trouble moving. They're slow.
By 7:00 a.m., they're doing just fine, on, moving around, getting their breakfast, and then the dyskinesias, hyperactive movements, begin to kick in. By the end of the dose at 9:00 a.m., it's worn off, and they're back down into the off state. Along with that, there are changes in their moods. They start off as anxious, and when they're moving normally, their mood is back to a neutral state.
Laura Marsh 17:26
This goes on throughout the day for someone who has fluctuations. If I were to examine a person at 3:00 p.m., when they were in a relative off state, they might be quite anxious, whereas if I saw them at noon, they would be in a relatively neutral state. Often individuals who have this kind of fluctuation don't have a good recollection of how they were even the three hours before because they're experiencing this intense anxiety, say at 3 p.m., and that's all that's on their mind.
It can be very helpful if one is experiencing these to keep an hourly calendar every day, midnight, 1 a.m., 2 a.m., et cetera, through the whole day, so that you can track these fluctuations and begin to see if there are any patterns in terms of when you take your medicines, whether you're having fluctuations, and whether they are motor, cognitive or psychiatric. You can also track what else might be going on in terms of even social things that might be happening or circumstantial issues.
We know that in Parkinson's there's the main primary dopamine deficiency, and this also influences the psychiatric symptoms that can occur. Not only does Parkinson's affect what's called the mesostriatal or the nigrostriatal system, but it also affects the mesolimbic system, which is involved in mood regulation, and the mesocortical system that is involved in higher-order intellectual functions, executive functions in particular that are affected in Parkinson's.
Then it's even more complicated than that. Parkinson's, the degenerative process, affects non-dopaminergic neurons. We see changes in the locus coeruleus, which makes norepinephrine, or midbrain raphe, which makes serotonin, and the nucleus basalis that affects acetylcholine, all of which are involved in mood, sleep, thinking abilities, et cetera.
We also see Alzheimer-type changes in the brain, plaques and tangles, not in everyone, and then varying degrees of Lewy body pathology. Obviously, by definition, someone with Parkinson's has Lewy bodies, but some people have more of them outside of the nigrostriatal system, and that can be associated with additional cognitive difficulties.
Given all this, the rich pathology, what you have is a whole host of symptoms that we refer to as the PD non-motor symptom complex: the neuropsychiatric symptoms, which all focus on these various autonomic symptoms; sleep disorders, which are quite prominent in Parkinson's; as well as other symptoms, fatigue, changes in skin, blurred vision, et cetera, that can occur. It's lots of things to think about with Parkinson's.
Laura Marsh 20:03
Again, it can seem overwhelming, but I think that when you know to look for these, you can begin to chip away at the block in terms of what is a salient problem for you, and then begin to treat that. This slide is just an example of how the motor symptoms progress from early to late, and then how, at any given time, there might be treatment of non-motor symptoms as well as non-pharmacologic treatments.
Thinking about the impact of psychiatric disturbances, although Robin Williams did not ultimately have the diagnosis of Parkinson's disease, he did have a synucleinopathy, was diagnosed with dementia with Lewy bodies, and his death certainly called attention to the problem of depression and suicidality in these conditions, and one that I think we can all remind ourselves to make sure we attend to these.
The neuropsychiatric disturbances have a broad negative impact. It's bad enough to be depressed or to have hallucinations, and in fact that really cuts into lots of positive experiences. Some people are reluctant or uncomfortable talking about their psychiatric symptoms. But when they hear that these psychiatric problems also affect their motor symptoms of Parkinson's, that kind of inspires them to go ahead and say, okay, I can help my Parkinson's motor symptoms. I'll go for it. I'll treat that depression.
Whatever it takes to get someone to practice a whole health approach, that's good enough for me. But we see worsening motor deficits, increased even perceived need for motor therapy. If you're more anxious, you're going to think you need more. Cognitive deficits, greater healthcare costs, et cetera, and then decreased quality of life.
When you look at it over the disease course, what's most disabling in this study that was done longitudinally in Australia, with up to 20 years of follow-up, most people had, everyone essentially had, some degree of cognitive decline. Many people had hallucinations and depression, and those were actually the most disabling to people, much more so than their dyskinesias or their on-off, et cetera.
We also saw early in the disease how the depressive symptoms can influence even when someone starts taking the anti-Parkinsonian treatment. We saw that when Yahr was examining patients, they had depressive phenomena in that slide I showed early on.
Laura Marsh 22:38
This is a study by the NET-PD study that was done back in around 2004 or so, and many individuals with Parkinson's who had never been treated with any dopaminergic or PD meds took the medicines. The question they were asking is, at what point does someone need to start on anti-Parkinson's therapy? The thought was that the motor symptoms are going to predict when people would start taking the anti-Parkinson's therapy.
But what actually was the most prominent effect was the depressive symptoms that someone had. Depressive symptoms predicted deficits in activities of daily living as well as the need for symptomatic PD therapy. I think in many cases, we've had individuals who haven't started on Parkinson's therapy but they have depression early on in the disease, and we'll actually treat their depression before they start on anti-Parkinson's therapy.
We see this example even in the longitudinal study that we did in Baltimore, where if you're following people at any given time over six years, at some points, zero, two, four, six years, they might have had features of a major depression, which is where they needed additional treatment. Other times, at the two-year mark, they were in remission. Their depression was treated. There was nothing more that needed to be done for them in terms of that depression.
At any given time on this disability scale, which is the vertical axis, called the Northwestern Disability Scale, the higher your score, the less disabled you are. The blue line is the people who are depressed. Over time, whether you were depressed or not, the Parkinson's progressed, and there was some increase in your disability. But if you were treated for your depression and you had depression remission, you were about four points on average better, less disabled, than you were if you had an active depression. Again, treating depression helps those symptoms of Parkinson's.
Despite all this impact, what we see is that many times Parkinson's depressive disturbances are under-recognized or under-treated. I won't go into all these details of the various studies, but the bottom line is, even when we're looking for it, such as in the study by Shulman, where the patients were filling out a self-report form of whether they had depressive symptoms, anxiety symptoms, fatigue or sleep problems, and in this case, you can see, and that's in the orange and the blue or purple, that was whether the physician thought that the person had depression, anxiety, fatigue or sleep problems. You can see the patients and the physicians are pretty good at recognizing if there was a sleep problem present.
Laura Marsh 00:25:34
But there were a lot of discrepancies between the patient’s experience versus what the clinicians saw. In clinical practice, we see about a third of patients at any given time having depressive disorders, but they’re often not recognized.
When they’re not recognized, they’re also not treated. Even when they are recognized, as you see in Dr. Weintraub’s study, two-thirds of people often are not getting treatment for it. We have a problem of underrecognition, but also undertreatment.
What can we do to improve recognition? The first is to be aware of just how prevalent they are and how prevalent other psychiatric problems are altogether in Parkinson’s. Again, this is looking at our study from Baltimore. It’s called the MOOD-PD Study, or Methods of Optimal Depression Detection in Parkinson’s. We looked at these 250 people, and at any given time over their life, over 80% had at least one psychiatric diagnosis. I refer to the 17% who had nothing as the unscathed.
Most people had at least something that had occurred in their life, and currently, at the time they were examined, 80% had at least one psychiatric diagnosis, with the most common being a mood disorder, the next most common being an anxiety disorder, and the third most common being psychosis. There were impulse control problems and substance use problems that are overall lower than we see in the general population, and they were less so at the time that the people were examined.
What we see is that when you have one psychiatric problem, there is some increased risk of having more than one. We need to be looking where there’s depression. You also want to make sure whether there’s presence of anxiety or whether there’s presence of psychosis. Again, in this MOOD-PD sample where 60% had a mood disorder, 21% of those people with a mood disorder also had an anxiety disorder, and 7.6% had also had psychosis. Then there’s about 8% who had all three of those conditions.
We want to make sure that we’re thorough and looking at all of those phenomena at the same time, so we can make sure we provide the best and most comprehensive treatment.
There are some other psychiatric diagnoses that occur independently or may occur, again, with depression. One is apathy. Another is emotionalism or pathological crying, anxiety, psychosis, impulse control disorders and then cognitive impairment. I won’t be talking about cognitive impairment today.
Laura Marsh 00:28:22
Depressive disorders, in general, occur in about 40% overall when you look at all the various studies. It was 60% in our study, but that might have been because of the people who chose to be in the study, so we had more of a selection bias or recruitment bias. We see several types of disturbances. Some are mild, what we call minor depression, and those may just get better on their own. But 50% of those may actually get worse and develop what we call clinically significant major depression, more severe symptoms.
In my experience, most times when someone has major depression once, they tend to keep having it. It needs to be treated and managed, and they tend to need to stay on antidepressants. Some people can come off medicines and they don’t ever need to go back on, so I don’t know what the recurrence rate is absolutely. We know that there aren’t clear data on that. In general, we know that the older someone is, the longer the Parkinson’s has been around, that it can be associated with that. I’ve already mentioned how the onset can be before the overt signs of Parkinson’s.
In other words, the onset or the explanation of depression in Parkinson’s is not because of how progressed your disease is or because of your disability. It’s because of the depressive disorder.
One way that people can get confused about recognizing Parkinson’s depression is because depression and Parkinson’s have so many overlapping features. In terms of the motor symptoms, you often see this hunched posture in Parkinson’s, the slow movements, and you see the same thing in people with depression, which is why I have a picture there of Eeyore, who I believe also has a depressive disorder. He moves slowly. He’s very negativistic and doesn’t really have much energy. Lots of complaints. We see both of those in Parkinson’s, whether you have depression or not.
What we have to look for are other more specific features of depression. When we look at the diagnostic criteria for depression, of course you’ll be looking for depressed or sad mood, but many people don’t actually experience sadness or cheerfulness. They might have what we call anhedonia or decreased interest. They don’t get pleasure out of things that they normally took pleasure in.
They can have sleep disturbances and appetite changes, but more on the mood end of things, these feelings of worthlessness or excessive guilt, thoughts of death or suicide or suicidal thoughts, even attempts or making plans, and then some decreased ability to think or concentrate. Even when someone has depression, they may think their cognition is much worse than it actually is, if the depression weren’t treated. I look for persistent emotional features.
Laura Marsh 00:31:19
If you’re able to enjoy yourself and get out, but you’re discouraged at times or sometimes demoralized because of your Parkinson’s, but you get out and you do things and you can maintain that mood, and you don’t have a pervasive change in your mood or at least it’s not that recurrent, you might just need to be doing other kinds of things. You don’t necessarily need treatment for a frank major depressive disorder. We’re looking for persistent sadness and inability to enjoy those previously enjoyable experiences. You don’t have to get down to where you’re absolutely enjoying nothing.
If you get to the point, as some have said, “Well, I don’t even enjoy my grandchildren anymore,” there are probably a lot of other activities that one stopped doing and stopped enjoying way before that. Pessimism, hopelessness, negative rumination, thinking that things aren’t going as well even when they’re going quite well. People who think their Parkinson’s isn’t better after DBS, when yet they’re actually walking better and doing better in all accounts, but their depression gives them that sort of mud-colored lens to look through. Inappropriate guilt and so forth.
What many patients have said to me is, I can cope with Parkinson’s as long as I’m not depressed. Because when you’re depressed, you’re looking at the world through mud-colored glasses.
Some people have said, well, Parkinson’s depression is not the same as regular depression that you see without Parkinson’s. But that’s really a very subtle statistical difference. That’s why I think it’s important to remember depression is depression. It’s not good whenever you have it. People do get to the point where they feel that their life is not worth living. They can have suicidal thoughts, and those are treatable.
Depression is treatable, and people need to be reaching out and getting help for that because people do get better. I’ve taken care of so many patients who get back to the point where they say, I can cope with this disease as long as I’m not depressed.
I’m going to move on to some of the other conditions. Anxiety is certainly common in Parkinson’s. We see several types. Some are episodic, like panic attacks. Phobias are more situational, depending on what you’re doing. Generalized anxiety is more continuous, and then we have the wearing-off phenomena. Again, it’s important: these are not understandable reactions to the motor symptoms. These can occur before the onset of Parkinson’s. Then you can also see anxiety with the non-motor fluctuations.
What we see here on the bottom row is that up to 20% of people have anxiety symptoms that really don’t fall into any of the usual categories of anxiety disorders like PTSD or panic disorder, phobias, etc. We often think of those as being somewhat specific to Parkinson’s itself. We call those PD-specific conditions. We can see, again, those non-motor fluctuations or off anxiety and the fluctuating motor symptoms. Then we can also see this psychiatric impact of anxiety disorders. Patients who are feeling anxious about getting to a doctor’s appointment or going to an event, their motor symptoms can increase.
Laura Marsh 00:34:30
They can have more freezing or on-off fluctuations and gait difficulties. Sometimes managing the anxiety isn’t about taking a medicine. It’s realizing, oh, I’m just getting anxious about whether I’m going to get out of the house on time.
How do you distinguish between depression and anxiety in Parkinson’s disease? Often, it’s hard to know. There’s a lot of overlap, again, in terms of the motor symptoms and the comorbidities of psychiatric problems. You’ve got to again look specifically at these psychological or mood features. In anxiety, what you see is not just apprehension and worry, but also this avoidance tendency.
The best way to manage your anxiety about something is to avoid what makes you anxious. If you’re anxious about going out of the house, stay in. When I see a patient who stays in all the time, they say, “No, I’m not anxious.” Of course, it’s because they’re not going out.
Often the way to treat anxiety is to focus on what you’re actually avoiding, and that’s how you can overcome that. We see emotional reactivity, being overly detailed, et cetera. What you don’t see in anxiety in the absence of depression is guilt or decreased self-worth, et cetera, those morbid thoughts that people can have.
Apathy is another problem. It’s quite common. It can be a part of depression. What you see in apathy is this loss of motivation, not a loss of interest, but a loss of motivation as well as this indifference, not pursuing activities, especially ones that require thinking things through. The big problem with apathy is that those patients don’t complain. It’s usually the families and others around them that complain about that lack of initiative.
Another common problem is something called emotionalism or pathological crying. We see that in up to 50% of patients, where they have this excessive sentimentality. It’s inappropriate. It’s involuntary, very sudden tearfulness that might occur when thinking about the love for one’s family.
It can be present in depression, but some people have it just on their own, and they think they might be depressed because they’re crying all the time. But it could just be emotionalism, especially when it’s very fleeting and doesn’t have the other mood symptoms. It can be quite embarrassing at times, and people can avoid going out.
Laura Marsh 00:36:29
Psychosis is a very problematic condition. Its prevalence depends on how you define psychosis, which was debated for many years. We came up with some consistent criteria. But the rates will vary up to about 40% in general, up to 80% when someone has a significant dementia. There tends to be greater prevalence as time goes on with Parkinson’s, but not everyone is affected. Again, a major clinical challenge, a source of caregiver burden.
We’ve had a better improvement in management with the use of antipsychotics that can be tolerated in Parkinson’s. We have three general categories. There are these minor hallucinations. Some of them aren’t really hallucinations. Some are a sense of presence or a vivid sensation. Others are what we call passive hallucinations, brief visions in your peripheral field or illusions, sensory distortions. Sometimes they’re highly formed complex visions of people or children, animals, or they can be just puff balls. They can occur in any sensory domain, but most commonly they’re visual.
The important point is that often they’ve been called minor hallucinations, but even if they’re minor, that’s not always the case. If they’re occurring, it’s important to let your clinicians know because they can be associated with greater physical disability, more severe symptoms and reduced quality of life.
These are how we define Parkinson’s psychosis, which is used as a basis for developing treatments and approaches to treat psychosis.
The last I’m going to talk about are some of the PD-specific disturbances. In particular, we’ve all heard about the risk factors for Parkinson’s psychosis and for the impulse control disorders.
There are the intrinsic factors, such as things like cognitive impairment or older age, things they can’t control, other psychiatric pathology. But some of the biggest risk factors for impulse control disorders and psychosis are these extrinsic factors. One, the dopaminergic medications, especially the dopamine agonists. Anticholinergics, things like benzodiazepines, opiates, all big no-nos from a geriatric psychiatrist perspective, and then polypharmacy with multiple psychoactive drugs.
Laura Marsh 00:39:22
Some other conditions we see are what are called early morning off emotional states: low mood in the morning, anxiety, or dopamine agonist withdrawal states. Again, for the sake of time, I won’t go over that. Then on-off or the non-motor fluctuations, as we talked about.
The impulse control disorders are quite problematic. It’s still remarkable to me that some patients with Parkinson’s or their clinicians haven’t heard of these, and they will present with these symptoms completely uncontrolled and taking medicines that certainly can feed into having those kinds of symptoms. We can see great problems as a result of gambling or other sexual behaviors, overspending, et cetera. This is just a slide that gives you some information on factors that are associated with impulse control disorders.
Now I want to move on to finish up with treatment. There are general approaches. The first general sentiment that you must remember: treatment works. People recover. When we treat your psychiatric disorder or your problems, we’re not going to get rid of your Parkinson’s disease. But again, it’s a lot easier to cope, and it’s a lot easier for your family to cope when you have your psychiatric problems addressed assertively.
Take a targeted and individualized approach. What I like to use is this little acronym. I call it MESS. This came about because a patient was telling me he just was focusing on the medications one day. He says, “Doctor Marsh, I want to take this medicine. I need to adjust this medicine.” I said, no, you’re just focusing on the medicine. You need the whole MESS: medication or medical conditions addressed, education, skills and support. Because if you don’t get the whole MESS as part of your treatment, you feel like a mess.
First, medications. Adjust, optimize, make sure you’re actually taking your anti-Parkinson’s medicines as you’re supposed to. If you’re having bad side effects from them, talk to the doctor who’s prescribing them and get them adjusted.
Identify and treat medical conditions. As a psychiatrist, we often identify urinary tract infections and other conditions that are making our patients worse from a mood and cognitive standpoint, and adjust these medications that are causing any kind of cognitive or psychiatric problem.
Laura Marsh 00:41:22
As far as the ESS, we use these non-pharmacologic approaches: educational programs like what you’re doing today, learning about your disease and all the things that can happen in it, as well as what you can do about it. It is one of the most powerful things that you can do.
Skills. Psychotherapy is about skills. It’s not just about listening and having someone hear you. It’s also about learning the skills to manage the emotions and difficulties that you have. Occupational therapy and physical therapy, they all teach you skills. Speech therapy, recreational therapy, self-support, support groups. Why even more important to have these watch parties? This is fantastic for you. Do things that give you support plus exercise plus fun. Then, of course, addressing our caregiver needs. Sometimes it’s caregivers who also need treatment.
Again, when you start doing the targeted individualized treatment for the psychiatric aspects, then we begin to look at specific psychiatric medications: antidepressants, sleep medicines, anti-anxiety, et cetera. Consider other somatic treatments. Electroconvulsive therapy is a very effective treatment for depression, especially in Parkinson’s, and it improves the Parkinson’s as well as the motor symptoms and the mood. Transcranial magnetic stimulation and deep brain stimulation are also used for treatment of depression.
I’m not going to go over this slide, but it’s just showing that if you look at the SMD for all interventions and then for antidepressants alone, the 0.30 and the 0.56 are about the overall effect size. These medicines and these treatments are effective for people over the various studies that have been conducted. They all work. There’s not one that’s necessarily better than the other. The important thing is that you take the medicine for an adequate amount of dose for a long enough time.
Sometimes these medicines take four weeks to begin to really have an effect. Maybe you might feel something different within the first week or so, but you’re not going to feel changes or feel completely well even at eight weeks, as we see in this particular study. Residual symptoms can persist. In this trial, we had 16 responders out of the 52 people taking it, but they still had residual symptoms: some depressed mood, some lack of interest. If you kept going on up to 16 weeks, 20 weeks, et cetera, a lot of those symptoms continue to dissipate.
Laura Marsh 00:44:14
What also helps, and this is in regular depression without Parkinson’s, is the combination of antidepressant treatment plus psychotherapies. This is data showing how the effect size with the psychotherapy treatment was actually 0.87 versus 0.5 with the antidepressant medications. I noted about a year ago in November, Dr. Roseanne Dobkin spoke about psychotherapy treatments in Parkinson’s. You might want to go back to those slides and take a look at those and what she had to say.
The psychotherapies are extremely useful. They can be done individually with antidepressants, or on their own. On their own or in combination, excuse me.
Psychosis, the first thing you want to do is get rid of medicines that are making it worse: anticholinergics, et cetera, dopamine agonists. The last thing you do is discontinue, obviously, the levodopa, but sometimes you have to reduce the levodopa dosage.
What we do then is add antipsychotic medications, which can allow for an increase in Parkinson’s meds. There are several types of antipsychotics. Obviously, the traditional ones we don’t use because they block the dopamine receptor, and they cause parkinsonism and can be very dangerous in patients.
The atypical agents can be helpful. The ones that people use are clozapine, which is the gold standard, but it has some side effects and requires blood monitoring that make it less likely to be used. Pimavanserin has been shown to be efficacious, as well as quetiapine, which is fairly well tolerated and helps with sleep. But it actually hasn’t been shown to have the efficacy in trials, though it’s still used often as a first choice by people. This is just a slide looking at the different antipsychotic treatments. The only medication that is FDA approved for Parkinson’s psychosis is pimavanserin.
Laura Marsh 00:46:17
The other strategies we use to treat psychosis are cognitive-enhancing agents: memantine, as well as galantamine, et cetera, rivastigmine. Then electroconvulsive therapy can be helpful, especially for psychotic depression. Ondansetron, or Zofran, has sometimes been used by people postoperatively to help after surgery when people are having some confusion.
In conclusion, looking just at mental health and Parkinson’s, remember, psychiatric disturbances are common. They overlap with the motor features of PD. They’re related to the disease as well as to its treatment, and they develop before the diagnosis as well as over the course. They have such a negative impact across multiple domains, it’s so important to have them recognized and treated because treatment works.
But you need the full MESS, and you need to treat them assiduously and to remission, or as much as possible, to reduce excess disability. I encourage you to address caregiver burden, as well as work in interdisciplinary coordinated teams. Thank you.
I’ll close there.
James Beck 00:47:33
Thank you very much, Doctor.
That was fantastic. Had lots of shout-outs, people really appreciating the detail you’re going into. I’d like to just mention a couple folks who are on the call. We’ve got over 2,500 registered users from 23 different countries. Really, a large number of allied health professionals are joining us, nearly 315. A lot of care partners and people with Parkinson’s disease as well, not surprisingly.
I want to give a shout-out to a couple of our viewing parties, which are a great way for people to get together to listen to our Expert Briefings and then be able to talk about them afterwards amongst yourselves. We have a large viewing party in the Heartland in Kansas City, 28 people, and 24 at the Westwood Lutheran Church in Minnesota. In Ohio, we’ve got another 15 who are at the Parkside Village Senior Living Center. Say hi to all of them.
I just want to ask a few questions that have been coming in that you touched on, but I think we could maybe go into a little bit more depth on, if you don’t mind, Dr. Marsh. Okay. Sleep. This is a real problem that people with PD experience, and this is from a care partner in Massachusetts.
How do we deal with the issue of sleep, which can exacerbate some of these issues that people may have? It can maybe be symptoms of depression, but it can also exacerbate not getting enough of it, some of the other cognitive issues that people may experience during the day. Is this something that’s within your bailiwick as a psychiatrist to address, or who would someone go to and how do you deal with it? I guess maybe that’s the best way to go.
Laura Marsh 00:49:16
One point I’ve made to patients or in presentations over the years is when people see me for a clinical appointment, or your neurologist or whoever, you see them for a half hour or an hour, you have an initial maybe two-hour assessment, and then you see them again in three months. Over the course of a year, maybe you see them for four hours. The rest of the year, you’re kind of on your own. You need to, but you have a lot of resources. As far as that goes, you start with your primary care and your neurologist, presumably. When things start to get more complicated, it’s important often to go to a specialized movement disorder center.
Different regions of the country and the world have different resources available in terms of how they’re working with folks with neurodegenerative diseases and looking at these comorbid psychiatric problems. Depression is most commonly treated by primary care doctors, and I think it’s important to, one can start there. But the important thing is to monitor how someone’s doing. If you’re not getting better and if you’re looking at target symptoms, I think what is challenging for people is everything seems all sort of overlapping with one another, and there’s a big mishmash.
But if you know you’re looking at something specific, this is my depression, or you’ve been evaluated at least by someone who says, okay, these are kind of the features of depression, you can follow that and say, okay, I’m sleeping better, I’m having more interest, but I’m still not enjoying anything. I still feel guilty. Then you can begin to say, this is still like, I think I need to go to someone with a little bit higher level of expertise.
Again, when things are still relatively mild, getting that support, doing that whole MESS, getting education, learning some skills. It’s not uncommon if I start treating someone for depression, but they’re worried about, they’re anxious about falling, I’m going to get them to physical therapy. I’m going to get them to occupational therapy so they can really work at their maximum, have those skills that help them cope and feel less anxious, feel more confident.
So they can, when they actually feel better and want to do things, they’re going to be able to go out there and have confidence to do them. It’s a combination. But the question is, do I do this as a psychiatrist? Yes, I do that as a psychiatrist, but so do a lot of other clinicians as well as nurses, social workers, therapists. We all really try to work together, and I think that would be that you try to get your team for any given patient and as a caregiver.
James Beck 00:52:05
Yeah, absolutely. I think that’s a really good point. I love your methodology, and I think it’s really good. One of the key takeaways I hope everyone in the audience is getting is how little depression is treated and recognized in PD yet how tractable it seems to be from a clinical standpoint to be able to treat and really potentially impact someone’s quality of life and their symptoms if it gets addressed.
I think that’s really a key message here: get those depression symptoms examined and get started on some kind of help along those lines. One of the things that people are asking is, and I think you touched on it, this balance between medication and psychotherapy. It seems there’s certainly advocacy, if I may summarize it, that getting the medication is important, but it seems like the psychotherapy is equally important as well. Is that a fair assessment?
Laura Marsh 00:53:06
I think so, especially these cognitive behavioral therapies. They’re wonderful skills that people learn that often can be helpful even if you don’t have a prominent mood disorder. There are several trials as well as ongoing use of cognitive behavioral therapy for anxiety and depression. We modify them based on what works for that person, as well as we’ve modified them in Parkinson’s so that the caregiver or another person can work with the patient who has Parkinson’s.
When people look at the kinds of things you can do in cognitive behavioral therapy, what people like the most are breathing exercises. Learning to breathe slowly, calm down, and, you know, breathing is absolutely free. There are no drug-drug interactions. It’s extremely helpful for people with Parkinson’s as a way to begin to manage. Once someone sort of settles down, their brain begins to work again, and they can then begin to think about other things that they can do to help themselves feel better and engage in what they want to be doing.
James Beck 00:54:16
It’s interesting when you talk about these breathing exercises and whatnot. A question came in from Minnesota. This is an interesting one, and you could probably have a whole Expert Briefing on this, but just loosely, how is it that when we talk about depression or even Parkinson’s, dealing with brain changes, differences in chemical imbalance, if you will, how is something like psychotherapy helpful when we’re just talking about breathing or these other types of cognitive behavioral therapy exercises?
Laura Marsh 00:54:47
Well, we do know from studies that have looked just at psychotherapy and interventions in individuals who don’t have other neurodegenerative disorders, for example, in OCD or depression, that there are brain changes that actually occur when people have psychotherapy. If they’ve improved, or when you treat depression, it doesn’t matter how you treat it, if you’re better, your brain’s going to look different than if you’re actively ill.
This is why in Parkinson’s I often find that most of the patients who I’ve treated will need more than just psychotherapy. They often need an antidepressant. I think that’s because we know that the serotonergic neurons have decreased in number. We know that the noradrenergic neurons have decreased along with dopamine. We probably have to replace those to some extent.
That sort of gets someone out of that trench and gets you so well, but then you’ve still got to function in the world. The things you do are often what psychotherapy can help you with. The medicine’s just kind of an end, but it’s what you do with your life when you’re feeling better that helps you feel better. If you have some additional skills and education, you’ll do things that are different than if you’re just worried about what’s going to happen to you or in a state of panic.
James Beck 00:56:13
Sure. Absolutely. Speaking of panic, we had several questions coming in about anxiety. We talked a little bit about this with anxiety. It seems that it’s something that could be managed well without medication. For people who are worried about developing Parkinson’s disease, we’ve talked about how depression happens a lot beforehand. Is anxiety another one of the symptoms that seems to precede PD? And certainly not indicative that someone will develop PD if they already have an anxious personality.
Laura Marsh 00:56:49
Right. It is associated with an increased relative risk. This is an area that we’re very interested in. If someone has certain genetic markers and there’s evidence of other anxiety phenomena, are these sort of pre-PD signs? Then those would be people we’d want to make sure had neuroprotective approaches being used in addition to exercise, if there were medications that were effective in that way.
Yes, anxiety can occur before. It seems to be associated with it. Many times when someone has anxiety in the general population, most mood disorders and anxiety disorders occur in adolescence or young adulthood. That’s when conditions begin psychiatrically. We’re very much all about chronic disorders that begin in youth. Whereas when someone with Parkinson’s has developed anxiety, I’ve had many patients who suddenly at the age of 50 developed a phobia or panic attacks, and they never had any problems before.
That was very striking to me when I first examined patients and met people telling me that story. It coincided with other data suggesting it wasn’t just what I was observing, that others were getting data looking at that as well.
James Beck 00:58:16
Interesting. Thinking big picture, some questions are coming in from a variety of sources, one from Florida and one from Vermont. I think they’re both approaching the same question from different angles. One is just talking about young-onset PD. Young-onset PD seems to often be a slightly different flavor than Parkinson’s disease. Do you see any differences with mental health issues for this group who may not be taking medication at the particular time? It seems like evidence would suggest they experience similar issues, but what do you know?
Laura Marsh 00:58:52
Well, of course there’s the context in which someone’s experiencing young-onset Parkinson’s. They might have family often, or they have kids that they may be responsible for. They’re working, or they may be the primary breadwinner, so there are many other consequences that occur. The impact is potentially broader.
Where we do see particular differences are in the onset of impulse control disorders. Often, people who are younger will be started on dopamine agonists, and so you see higher rates of impulse control disorders, the gambling, the hypersexuality. Again, those have often been sort of explained away. Well, they’re just feeling upset about their Parkinson’s, so they’re going out and having this last hurrah. That’s not it. It’s the drug.
That tends to occur more in people who’ve had some impulsivity issues or family history of such. Along with that, there can be psychosis occurring in those individuals and some of these conditions like the extreme fluctuations or even these dopamine agonist withdrawal syndromes. Those tend to be the kinds of problems that we see in terms of the specific conditions. But then there are, as I said, the psychosocial social functioning kinds of issues that are different and that need to be addressed as well.
I would say the main caveat is, if you’re depressed, it’s pretty hard to cope with all that, and it’s going to be hard for your family. We want to make sure that gets treated as a first step.
James Beck 01:00:32
Absolutely. Another thing we talked a little bit about was psychosis and hallucinations that come with it. A couple questions from folks in Utah, North Carolina, and an allied health professional in California. They’re trying to understand this sense of delusions and paranoia. One person is saying her husband has obsessive thoughts of her having an affair, which she thinks may be Parkinson’s related.
Then there are other aspects of delusions where people see things that are just not there or know something that’s just absolutely not true and will not believe otherwise. What are your observations on that?
Laura Marsh 01:01:11
Again, I did not talk enough about delusions in here for the sake of time, unfortunately. One of the more common delusions is this belief, delusional jealousy, or the belief that someone’s having an affair, especially someone who’s with you 24/7 and it’s completely impossible. But nonetheless, it’s a common paranoid thought. Others can have more involved paranoid ideas, thinking that there are plots or other issues that someone may have, or more mood-elevated-type delusions where they feel they have extra powers, et cetera.
It can be the whole gamut of potential kinds of delusions that we see in psychiatry. Some are just general paranoia. Again, the first thing is always look at the medicines, look at the medicines, look at the medications and the medical conditions, and make sure they’re treated. Often people with paranoia need to be treated because it’s so disruptive when people have delusions.
Sometimes with minor hallucinations, people can get away with it. Often I try to, again, manipulate the medicine. Often we’ll use an antidepressant, help people get sleep, so getting good sleep at night, treating depression, keeping a regular schedule during the day, staying awake so you sleep better at night, exercising, socializing, getting people where they can have all those other activities. If they can do that, then that may reduce the impact of those psychotic symptoms.
But medicine still may be needed, and many, many patients are prescribed, for good reason, antipsychotics. We give those carefully. Again, pimavanserin is available. Quetiapine is often used. Even just tiny bits can help people sleep better. Clozapine is an excellent drug for treating psychosis. Even though it’s a nuisance to have to go get your blood drawn every week, the benefits, if you need it, are far greater than any nuisance of getting your blood drawn.
James Beck 01:03:25
Absolutely. I’ve got one more question to ask in just a second, but I just want to mention that we had a resources page up there a little while ago, and I didn’t get a chance to mention it. Anybody who’s got persistent questions about this issue or other issues related to Parkinson’s disease, I really encourage them to reach out and call our excellent Helpline, which we’ve just recently extended the hours of. Now we go to 5 p.m. Pacific Time, that’s 8 p.m. Eastern Time. That number is 1-800-4PD-INFO. That’s 1-800-4PD-INFO.
Right now on the screen is the survey that we have, asking you questions about what you thought of today’s Expert Briefing. I’m sure everyone thinks it’s fantastic, but if you don’t, we also want to hear that as well because we use the survey results to really help improve and provide feedback, and try to make certain that we’re always having the best Expert Briefings available.
If you have friends who missed today’s event, or if you want to go back and just listen to it again, we’re going to have an archive made available next week on Tuesday, September 25. You can go to our website, which is Parkinson.org, to download that.
Laura, my last question for you is regarding executive function. This is something we don’t always think about as a mental health issue, but I think it can be disruptive nevertheless. This one person phrased this issue in the realm of discussions and arguments that they may have with emotional conversations. They lose their train of thought, and they become a wreck as a result of it.
How do people cope with that? Is there a strategy for ensuring that they can maintain a track on this? This is something that many people with PD, I imagine, experience.
Laura Marsh 01:05:12
The more one gets anxious about it or worries about it, the more it snowballs and gets worse. The first thing is, one, recognize that it’s happening. That’s a good start. Then you have to sort of study yourself. When does it occur? What’s happening at those times? Are there too many people around? Multitasking is a frontal function. It’s an executive function, so it’s best to have one-on-one conversations and not try to hold court. Look at the things that precipitate it and make it worse, what makes it better, what makes it worse, and how you can handle it.
If there are times of day when it’s worse, if your medicine’s wearing off, does it tend to be worse then? If you’re going to have to do something like pay your bills, which requires executive function, do that at a time when your medicine’s working well, when you’re not distracted by other things. Avoid the multitasking. Look at what the emotional triggers are of it, and then assess what might be happening and how you can handle those specifically.
There are many different processes that are occurring, but people who can work often with this, one is cognitive rehabilitation that people sometimes have. Speech therapists are wonderful for working on the specific problem that the person with the question described. They can work with someone both on the other ways that Parkinson’s affects speech, but also in terms of discourse and engagement, and then keeping one’s thoughts online so that you can continue in a conversation and the back-and-forth.
Sometimes occupational therapy also, because it helps you to simplify your environment and use these skills, and see how you can do things differently to make your life easier. What you do in 2018 might not be what you should be doing in 2020, so you’d have to go in and do a reboot. I would encourage that, whether it’s physical therapy, speech, et cetera.
James Beck 01:07:24
Fantastic. Thank you very much, Dr. Marsh. This has been a really wonderful Expert Briefing, and I know that everyone who’s listening has really enjoyed it thoroughly. I just want to let people know that if you enjoyed this Expert Briefing, I think you’ll really enjoy our next one. We have a webinar coming up on Tuesday, November 27, same time, 1 to 2 p.m. Eastern Time. The topic is going to be Advanced PD and Palliative Care in the 21st Century.
Our presenter is going to be Dr. Janis Miyasaki, who’s at the University of Alberta, and she is a real leader in this field and someone who’s really another excellent presenter, as Dr. Marsh was. I bid everyone adieu until we have a chance to talk again in November. Thank you very much.
Laura Marsh 01:08:08
Thank you.
