By MARILYNN LARKIN
Dr Irene Richard, a movement disorder neurologist and researcher at the University of Rochester, is an investigating senior medical adviser to The Michael J. Fox Foundation, an organization committed to improving the lives of people with Parkinson’s disease. Dr. Richard is an expert on the mental and emotional aspects of the illness and is leading a national study looking into whether medications might help treat depression related to Parkinson’s disease.
Q. You investigate the links between mood disorders and Parkinson’s disease. Isn’t it normal to be depressed after a diagnosis of Parkinson’s?
A. Feeling sad after a diagnosis is understandable. But that’s not the same as depression, which is actually a syndrome with many facets. Up to 40 percent of people with Parkinson’s disease develop this syndrome and experience symptoms that may include depressed mood; decreased interest in people and activities; and problems with sleep, appetite and sex. In contrast to sadness, which usually dissipates as people come to accept their diagnosis, depression may continue for weeks or even years. And there’s increasing evidence that although the symptoms are similar, depression related to Parkinson’s disease may be different from regular depression.
Q. How is depression in Parkinson’s disease different?
A. Research has shown us that in some cases, depression may be the first sign of Parkinson’s disease, appearing well before any motor symptoms, and so we think it may be part of the underlying disease process. But not everyone who has Parkinson’s gets depressed, so there’s probably something going on that makes certain people vulnerable and others not — and this vulnerability doesn’t seem to be related to the severity of the disease or how disabled the person is. So a person with mild Parkinson’s symptoms might become severely depressed, whereas someone with worse symptoms doesn’t.
That said, it can be difficult to diagnose depression in Parkinson’s because other symptoms may mask the depression. For example, people with Parkinson’s tend to move slowly and speak softly, without a lot of inflection. These are also signs of major depression. But when individuals with Parkinson’s behave that way, most people don’t think depression — they just chalk it up to the disease. But if the depression can be appropriately treated, the person’s quality of life will improve, as may some of the symptoms.
So the bottom line is at this point is we don’t know if depression is fundamentally different in Parkinson’s or just looks different because of the company it keeps. But either way, it should be treated.
Q. Can doctors just prescribe antidepressants?
A. It’s not that simple. We can’t just transfer information we know based on the brains of people without Parkinson’s and assume that these drugs will work the same way in people who do. We’ve actually embarked on the first large, multi-center, placebo-controlled clinical trial to see whether antidepressants work and can be tolerated by people with Parkinson’s. Nobody has tried to test this until now.
We’ll also try to see whether antidepressants might affect Parkinson’s motor symptoms. We know that certain types of antidepressants can actually induce Parkinson’s-type symptoms in some people who don’t have the disease. And there’s some evidence that selective serotonin reuptake inhibitors and medications with anticholinergic properties, such as tricyclic antidepressants and norepinephrine reuptake inhibitors, may actually help symptoms of Parkinson’s.
But patients with Parkinson’s generally are on a number of other medications, so we don’t know how well the side effects would be tolerated. For example, a person who doesn’t have Parkinson’s disease might not get dizzy or sedated, but someone with Parkinson’s might. We’ll be trying to answer these questions in our study, which is funded by the National Institute of Neurological Diseases and Stroke and compares venlafaxine (Effexor) or paroxetine (Paxil) to placebo.
Q. What stage has the study reached?
A. Recruitment has been difficult, in part because, as is the case for many mood disorders, doctors don’t recognize when their patients are depressed. And if they do recognize it, there’s a stigma attached to having a “mental” disorder, so people don’t want to admit it. And even if they recognize and admit it, many of the people we want to enroll are tired and apathetic because of their disease, so they don’t want to join clinical trials. So we really have a lot of strikes against us.
On the positive side, anyone who enrolls will get in-depth attention from movement disorder specialists, and they’ll also be contributing to knowledge that will help others.
Q. Are other mental or emotional symptoms common in Parkinson’s?
A. We’ve known for a while that some anti-Parkinson’s medications can trigger hallucinations or delusions in some patients. But more recently, we’ve realized that because Parkinson’s affects multiple domains of brain function, you can get mood fluctuations similar to motor fluctuations, where your brain no longer responds to medication by producing dopamine in a steady state. Instead, you have peaks and valleys that can lead to too much motor activity (“on”) or, at the other extreme, rigidity (“off”).
With mood fluctuations, an individual can transition from being sad and suicidal to euphoric within minutes. The change is very dramatic and disconcerting to the person and the people around him or her.
Not everyone experiences these rapid mood swings, but in those who do, they tend to correlate, time-wise, with motor fluctuations. This means someone may be depressed when “off” and normal mood or euphoric when “on.” But having said that, my group has done some research looking at diaries in which patients documented their motor state and their mood hourly for seven days. We found wide variations in mood and motor fluctuations, even for the same individual, over the course of a week. And although the two types of fluctuations correlated in the majority of patients, there was a subset in which they did not.
So it appears there are two independent fluctuations going on in the brain, one for mood and one for motor. This can be very upsetting; it’s like bipolar disorder on a daily basis — you just go from one extreme to another. So we and others are looking into the mechanisms behind these fluctuations, and hopefully at some point, we’ll have a treatment.
Q. What is the most challenging part of your work?
A. Getting people to pay attention to the emotional aspects of the disease. In my work with patients, I’ve been really struck by the way they struggle not only with motor symptoms, but also from emotional symptoms. This has really motivated me to work on these conditions and help raise awareness.
Q. Is awareness of the emotional aspects of Parkinson’s disease increasing?
A. I have to say it’s finally starting to happen. Society’s awareness about mental illness over all is being raised and, hopefully, there will be less stigma attached to it. And in the setting of Parkinson’s disease, these conditions are now on the radar screen. The Michael J. Fox Foundation has asked researchers to apply for grants looking at psychiatric outcomes in Parkinson’s, which is great. We’re also trying to interest researchers involved in emotional and
mental disorders in other neurological diseases, like Alzheimer’s, to also focus on Parkinson’s
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