Emotional and Cognitive Aspects of PD

The Parkinson’s Disease Foundation (PDF) hosted a symposia on Parkinson’s on July 18, 2008.  The overall topic is “Mind, Mood and Body: Understanding Nonmotor Symptoms of PD.”  Here’s a link to the archived recording of the symposia:


The second speaker, Dr. Matthew Menza, gave a good presentation on the topic of “Emotional and Cognitive Aspects of Parkinson’s Disease.”

Even though this presentation was focused on PD, some references are made to LBD.  And, of course, there are emotional and cognitive aspects to all of the atypical parkinsonism disorders.

The most important thing I got from Dr. Menza’s presentation is that SSRIs should *not* be considered as the first line treatment in dealing with depression in PD.  A recent study showed that an old antidepressant, nortriptyline (Pamelor), performed better than Paxil, an SSRI.  Other drugs that are similar to nortriptylnie are Cymbalta and Effexor.

Of the atypical parkinsonism disorders, the only antidepressant that has been studied is Elavil (amitriptyline) in PSP.  Otherwise, I’m not aware of any studies.  You might take this recent PD research to your MD to find out if his/her recommendation would change based upon the new info.

Dr. Menza spent some amount of time on antipsychotics.  He explained that there was good data to recommend Clozaril and that in some studies Seroquel performed no better than the placebo.

He did talk about Lewy Body Dementia a couple of times, but I didn’t think his description was very good.  (Dr. Menza is a neurologist and psychiatrist.)

These are my notes from his presentation and his answers to the questions directed to him.  Of course it’s much better to watch the video yourself.


Robin’s notes from:

Emotional and Cognitive Aspects of Parkinson’s Disease
Matthew Menza, M.D., Prof. of Psychiatry and Neurology, Robert Wood Johnson Medical School

Non-motor symptoms of PD include:
* sleep disturbances, fatigue, and excessive daytime sleepiness
* depression
* drug reactions, including psychosis and impulsivity
* mild cognitive impairment to dementia

The non-motor symptoms have become the focus of research because they are so important to how patients feel day to day.

Depression:  about 40% have some.  It has a major impact on quality of life and functioning (faster progression of motor symptoms; greater decline in cognitive skills; greater decline in ability to care for self).  Depression often precedes the PD diagnosis.

Symptoms of depression include:  sadness, lack of appetite, sleep problems, lack of interest and motivation, fatigue, crying spells, etc.  Some of these symptoms are seen in PD without depression.  (6:22)

Depression is very inter-related with anxiety (worrying about things in an excessive way).  Anxiety is a common symptom in PD.

What causes depression in PD?  Probably a mix of neurochemical changes in the brain that accompany PD and the stress of living with an illness.

We encourage people to get involved in support groups.  There’s a lot of knowledge in SGs about handling day to day problems.  SG members may have common wisdom that MDs may not know about.

Try relaxation techniques to help yourself forget worries and get to sleep.  Even counting sheep.

Psycho-therapies are being modified and written expressively for those with PD.  Best to find a psychiatrist or psychologist who has experience with PD.

Exercise is a good treatment for depression.

NIH funded an 8-week trial of PD and paroxetine CR (an SSRI), nortriptyline (a tricyclic), and placebo.  This is the largest and first of placebo-controlled studies on antidepressants and PD.  This study is not yet published.  (Other studies are in the works.)  Big improvement in depression for both anti-depressants but nortriptyline was much better than paroxetine.  [paroxetine CR = Paxil CR; nortriptyline = Pamelor]  Nortriptyline affects both serotonin and norepinephrine in the brain.  Paroxetine affects only serotonin.  This study calls into question the use of SSRIs as first line treatment in PD.  Two other newer drugs that affect both serotonin and norepinephrine are Cymbalta and Effexor.  Paxil was effective for some in the study.  (23:48)

Sleep problems in PD are more common than would be expected from age alone.  50-75% of people with PD have trouble with sleep.  In their current study, sleep was the #1 predictor of quality of life (even more than motor problems).  The most common sleep problem is difficulty staying asleep (74-88% of patients).  Other problems:  poor quality sleep, difficulty falling asleep, muscle movements (PLMS and RLS; up to 15%), sleep apnea (up to 12%), RBD, morning headaches.

RBD (REM behavior disorder) is a particular concern.  PD accounts for 27% of RBD cases.  32% had injured themselves and 64% had assaulted their spouse.  Acting out dreams.  Can be a few vocalizations or something more dramatic.  People are reluctant to talk to MDs about this.  There’s a good treatment for RBD that works most of the time.

Excessive daytime sleepiness (EDS) occurs in up to 51% of PD patients.

Sleep attacks (sudden onset of sleep, usually without much warning) are associated with nearly every dopaminergic medication but especially Mirapex and Requip.  3.8% of PD patients had sudden attacks while driving.  Some still debate whether these attacks are caused by these drugs or EDS.

Sleep disturbances in PD may be related to nocturia (frequent need to urinate at night), pain, dystonia, akinesia, difficulty turning, etc.  Sleep is regulated by adrenergic, serotonergic, cholinergic, and various peptidergic symptoms which are disrupted (variably) in PD.  Depression is a major risk factor.  Dopaminergics can also worsen sleep (produce arousal and suppress REM).  (33:00)

Treatment of sleep disturbances includes:  exercise, sleep hygiene, intermittent use of sleep meds (Lunesta, Ambien, etc).  Some medications may help daytime sleepiness including Provigil, Ritalin (an older stimulant), and sometimes amantadine (Symmetrel).

Sleep hygiene:  regular sleep hours; avoid excess time in bed; regular get-up time regardless of sleep quality; avoid daytime naps (of 2 hours in length; 15 minutes is OK); use bed for sleep or sex; relaxation; physical activity; sunlight in morning; bedroom quality (noise, temperature, humidity); avoid evening stimulants; avoid large evening meals.  If you are worrying, get out of bed.  (36:34)

Two categories of unusual behaviors that sometimes accompany meds given for PD:  psychosis (hallucinations and delusions); impulse control disorders (including gambling, binge eating, buying, hypersexuality).

Psychosis is rare in untreated PD.  Can be caused by all PD meds though psychosis is somewhat more frequent with dopaminergic receptor agonists.  Biggest risk factor for developing psychosis is memory impairment.

Hallucinations (seeing something that isn’t really there) occurs in approximately 30% of PD patients.  Usually these are mild.  The problem is when hallucinations are frightening.

Delusions (belief that isn’t shared by other people in your world) occur in 3-17% of patients.  Can cause major problems and be very disruptive.  Generally later in illness when memory begins to fail.  Typically persecutory (eg, fear of being poisoned, infidelity).  Please bring these up with your MD.

There was just a large study on impulse control behaviors just discussed.  Seem to occur more frequently with Mirapex and Requip but can also occur with Sinemet.  (42:03)

In the face of these problems (psychosis or impulse control disorders), the first thing MDs do is reduce the dopamine medication.  “Motion-emotion conundrum.”  If reducing the parkinson meds doesn’t solve the problem, then MDs look to antipsychotics.  (43:08)  The first antipsychotic given is Seroquel.  If that doesn’t work, then Clozaril is tried.  Clozaril requires a weekly blood sample.  Clozaril is very effective.  (43:42)

In early PD, most develop a little of what could be described as “mild cognitive impairment.”  This is impairment of tasks requiring the frontal lobe of the brain — planning, judgment, and recall memory.  This doesn’t cause major problems.  Dopamine replacement leads to some improvement.  (44:39)

The more difficult thing is the more serious memory impairment that happens later in the disease.  Quite a few people develop this.  This is not Alzheimer’s.  This is much, much slower in development than Alzheimer’s, and generally less severe.  There are trials out there looking at the typical AD drugs (such as Exelon) in PD.  In one study, Exelon had a slightly positive response, and some with PD can take this drug.  It’s worth trying.  There is a question if Namenda will work.

Dealing with cognitive impairment includes:  household safety (and preventing wandering), reminders as to the structure of the house, day care, in-home help.

It’s important to educate yourself about psychiatric issues.  Sometimes you have to educate your physician about psychiatric issues in PD.  (46:39)

Question: Is bipolar a precursor to PD?
Answer:  I don’t think so but on the other hand certainly people with PD can develop bipolar disorder (though this would be unusual).  Bipolar disorder hits people early in life.  (48:00)

Question:  Can you elaborate on Lewy bodies?
Answer:  In Lewy body disease, there is wide distribution of Parkinson’s pathology across the brain.  This is a variant of PD where the cognitive impairment and memory impairment progresses much, much more rapidly than in normal PD.  And the individuals are much more sensitive to the adverse side effects of PD.  It’s a much more rapidly progressive illness than normal PD.  Not much is known about LBD.  It can be quite a trial.  (49:10)

Question:  What were the side effects related to nortriptyline?  (50:06)
Answer:  The newer antidepressants are better tolerated.  Surprisingly, nortriptyline (an older med) was well tolerated.  There was more constipation in the nortriptyline group.  Our lesson from the study:  don’t start with an SSRI.  (51:13)

Question:  When will a cure happen?
Answer:  Someday there will be a cure.  But what do you do now?  We need research on the problems we are having right now.  (51:56)

Question:  Can you comment on the French clozapine study?
Answer:  There have been two well-controlled Clozaril trials showing Clozaril is better than placebo for psychosis.  Weekly blood draws for six months can be a problem for some.  Some of the Seroquel trials did not show that Seroquel was any better than placebo.

Question:  Can we view panic reactions as a behavioral equivalent of a motor tremor?
Answer:  I suppose you could look at them that way.  Sometimes those with anxiety have panic attacks.  I don’t know if it’s the same neurochemically.

Question:  Depression vs. anger.  Can anger be a stimulus?
Answer:  Anger can motivate people to make changes in behavior.  If people are having a lot of anger, it’s usually based on relationships and chronic problems.  Counseling may be helpful in determining cause of anger.  Is the anger a personality change?

Question:  What determines sexual dysfunction?  Compared to what you used to do?  Frequency?
Answer:  These problems are happening in people who are older, some of whom have less interest in sex.  Autonomic dysfunction can contribute.  There are also relationship issues.  If something has dramatically changed compared to the past, then we look to some cause (medication?) for the problem.  (56:09)

Question:  If a person with PD is on bipolar meds, and needs an antidepressant, is there a conflict?  Are they more likely to become manic?  Any connection?
Answer:  This is complicated.  Lithium (a bipolar med) can sometimes not be at all well-tolerated in PD.  Med changes have to be made.  But there are some bipolar meds that those with PD can take.  Depression would be seen as a function of bipolar disorder.  In bipolar disorder, we generally try not to use antidepressants because this can worsen the mania.  But we do use them in conjunction with a mood stabilizer.  (58:10)

Question:  My husband becomes agitated and anxious.
Answer:  Agitation can be many things.  Impulsivity can be a personality change.  Is there a change in impulsivity?

Question:  How effective is Remeron for depression in PD?
Answer:  We have no idea.  Remeron is a new kind of antidepressant.  It works differently than Paxil, Prozac, that class.  Remeron tends to be very helpful with sleep.  It has a lot of antihistaminic and anticholinergic effects so it can make constipation worse.  Each antidepressant needs to be studied individually:  does this drug work in this person?

Question:  Is depression in PD hereditary?  (00:48)
Answer:  We don’t know.  We think that in non-PD depression has a hereditary component (“somewhat more likely” to develop PD).  Many people, however, with no family history develop depression, and many people with a family history of depression who never develop it.  Is there something different about PD and depression compared to PD without depression?  We don’t know but it’s a good question.