The first one I noticed was a report based upon a journal article, Risk factors for somnolence, edema, and hallucinations in early Parkinson disease. The second was based on a different article (in the same journal), The impact of depressive symptoms in early Parkinson disease. Both are in the journal, Neurology®.
Regarding the first article, there were several news reports, all similar to this one (Forbes):
Patients With Early Parkinson's Exhibit Sleepiness, Hallucinations
07.11.07, 12:00 AM ET
WEDNESDAY, July 11 (HealthDay News) -- Factors such as gender, age and overall health may help predict which people with early Parkinson's disease will experience hallucinations, sleepiness or swelling, a new study says.
These symptoms are reported more frequently by people with early Parkinson's disease than the general population, the study authors said...
This was based upon the following journal article:
Risk factors for somnolence, edema, and hallucinations in early Parkinson disease
Kevin M. Biglan, MD, MPH, Robert G. Holloway, Jr, MD, MPH, Michael P. McDermott, PhD, Irene H. Richard, MD and The Parkinson Study Group CALM-PD Investigators
NEUROLOGY 2007;69:187-195
Background: The CALM-PD trial evaluated the development of motor complications in subjects with early Parkinson disease (PD) randomized to initial treatment with either pramipexole or levodopa. A secondary finding of the trial was a higher than anticipated development or worsening of somnolence and edema and development of hallucinations.
Objectives: To investigate risk factors for somnolence, edema, and hallucinations in patients with early PD initiating dopaminergic therapy.
Methods: This was a secondary analysis of data from the CALM-PD trial. Baseline patient characteristics were evaluated for their associations with the development or worsening of somnolence and edema and the development of hallucinations using Cox proportional hazards regression models.
Results: Kaplan-Meier estimates of the 4-year incidence of the development or worsening of somnolence and edema and the development of hallucinations were 35%, 45%, and 17%. Initial pramipexole treatment (hazard ratio [HR] 2.22, 95% CI 1.41, 3.50, p < 0.001), male gender (HR 1.79, 95% CI 1.09, 2.93, p = 0.02), and >5 systems with a comorbid illness (HR 1.62, 95% CI 1.04, 2.51, p = 0.03) were associated with somnolence. Initial pramipexole treatment (HR 3.18, 95% CI 1.95, 5.18, p < 0.0001), female gender (HR 1.46, 95% CI 0.94, 2.27, p = 0.09), and comorbid cardiac disease (HR 1.59, 95% CI 1.02, 2.47, p = 0.04) were associated with edema. Age ≥65 (HR 2.06, 95% CI 0.98, 4.32, p = 0.06), Mini-Mental State Examination score >28 (HR 0.42, 95% CI 0.19, 0.91, p = 0.03), and >5 systems with a comorbid illness (HR 3.42, 95% CI 1.59, 7.38, p = 0.002) were associated with hallucinations.
Conclusions: Comorbid illnesses are important and overlooked risk factors for the development of somnolence, edema, and hallucinations. When initiating therapy with pramipexole, patients should be counseled about and monitored for somnolence and edema. Slight decrements in cognitive function and older age are associated with an increased risk of hallucinations.
The point of the study was quite different that the point of the news article. The news article focused on the fact that some people with early Parkinson's Disease develop certain symptoms, and that there are some identified risk factors. The point of the journal article was that it is possible to identify certain risk factors for the development of particular symptoms, in the context of treatment with dopaminergic drugs.
The article did not answer the question I had, that led me to look into it in the first place. They did mention that there was an unexpectedly high incidence of somnolence in the patients treated with pramipexole (Mirapex). What I want to know is, how many patients had problems with falling asleep suddenly, without warning? And secondarily, how many developed impulse control problems?
There is a small literature on using pramipexole as an adjunctive treatment for treatment-resistant depression, but I have been reluctant to use it very much because of these cautions:
IMPORTANT SAFETY INFORMATION ABOUT MIRAPEX: MIRAPEX may cause you to fall asleep without any warning, even while doing normal daily activities such as driving. When taking MIRAPEX hallucinations may occur and sometimes you may feel dizzy, sweaty or nauseated upon standing up. The most common side effects in clinical trials for RLS were nausea, headache, and tiredness. You should talk with your doctor if you experience these problems.
Patients and caregivers should be informed that impulse control disorders/compulsive behaviors may occur while taking medicines, including pramipexole, to treat Parkinson's disease and RLS.
It would be nice to get a realistic idea of how big those risks really are.
The other thing I want to know is, of the patients who developed hallucinations, how many had hallucinations that were resistant to treatment. I am accustomed to using quetiapine (Seroquel) or even clozapine (Clozaril) for treating hallucinations. In my limited experience, it is common to get the hallucinations calmed down enough that the patient no longer changes his or her behavior in response to the hallucinations. It is uncommon to get them to go away completely. But I see such a limited subset of the patients that I wonder how typical those outcomes are.
The second article presents different lessons and questions. This instance is from UPI:
Depression untreated in Parkinson's
Published: July 11, 2007
ROCHESTER, N.Y., July 11 (UPI) -- Depression appears to be common in early Parkinson's disease, but it is often not treated or diagnosed, according to a U.S. and Canadian study.
Dr. Bernard Ravina of the University of Rochester and Dr. Richard Camicioli of the University of Alberta found that about 27 percent of Parkinson's disease subjects screened positive for depression, while 40 percent of subjects' depression went untreated, according to the study published in the journal Neurology...
The journal article is not in print yet, but the abstract and PDF are available now.
The impact of depressive symptoms in early Parkinson disease
B. Ravina MD, MSCE*, R. Camicioli MD, P. G. Como PhD, L. Marsh MD, J. Jankovic MD, D. Weintraub MD, and J. Elm MA
Published online before print June 20, 2007 (Neurology 2007, doi:10.1212/01.wnl.0000268695.63392.10)
Background: Depressive disorders may affect up to 50% of patients with Parkinson disease (PD) and are associated with increased disability and reduced quality of life. No previous study has systematically examined the impact of depressive symptoms in early, untreated PD. Methods: We administered the 15-item Geriatric Depression Scale (GDS-15) as part of two NIH-sponsored phase II clinical trials in PD, enrolling 413 early, untreated PD subjects. We used linear mixed models to examine the relationship of depressive symptoms, measured by the GDS-15, with motor function and activities of daily living (ADLs), as measured by the Unified PD Rating Scale (UPDRS). A time-dependent Cox model was used to examine the effect of demographic and clinical outcome measures as predictors of investigator-determined time to need for symptomatic therapy for PD. Results: A total of 114 (27.6%) subjects screened positive for depression during the average 14.6 months of follow-up. Forty percent of these subjects were neither treated with antidepressants nor referred for further psychiatric evaluation. Depression, as assessed by the GDS-15, was a significant predictor of more impairment in ADLs (p < 0.0001) and increased need for symptomatic therapy of PD (hazard ratio = 1.86; 95% CI 1.29, 2.68). Conclusions: Clinically important depressive symptoms are common in early Parkinson disease (PD), but are often not treated. Depressive symptoms are an important contributor to disability and the decision to start symptomatic therapy for motor-related impairment in early PD, highlighting the broad importance of identifying and treating depression in this population.
Again, the popular news article misses the important points. Yes, a high percentage of patients with Parkinson's Disease also have depression. And yes, a lot of them don't get treatment. But there are two critical points left out. One, the depression is associated with earlier use of antiparkinsonian drugs. Now, perhaps the thinking on this has changed since I was in training. Back then, the idea was that the antiparkinsonian drugs could only buy you a certain amount of time. The earlier the drugs were started, the earlier the patient would get to the point that the drugs lost their effectiveness.
So, one of the reasons the journal article is important, is that if there is anything that can be done to delay the initiation of antiparkinsonian drugs, then we want to know about it and make use of it.
The second point I'd like to make about this article, is based on a passage in the text, but not in the abstract:
Of the 114 patients who screened positive for depression, 28 (25%) were already receiving treatment for their depression, but had persistent depressive symptoms.
That 25% is not a terribly high figure, but we want it to be zero. One of the most fundamental principles in the treatment of depression is that you want to treat until remission is achieved. 25% of the patients were being treated, but were not in remission.
There is not any way to tell from the article if that was because the patients were not being treated aggressively enough, or if they were refractory to treatment. If the former, it should serve as a reminder of the importance of treating to remission.
The question that is left unanswered is this: if patients with both Parkinson's Disease and depression are treated adequately for their depression, is it possible to delay the initiation of antiparkinsonian medication. If so, does it improve clinical outcomes to do so? The data suggest that it is likely to be the case, and it certainly would be what I would expect, but we need at least one more study to find out for sure.
When I first started to write this, I was planning on complaining about how the news reports missed the main points of the journal articles. After thinking about it some more, I've decided that would not be appropriate. It probably is not realistic to think that a nonspecialist, working with a tight deadline, could extract the main points every time. Rather, it is more appropriate to stress the need for the scientists to express clearly why their studies are important.
I never know why news organization choose to pick up on some journal articles and not others. Probably it has to do with the investigator's institutions submitting press releases. Perhaps if they do that, they should take one extra step to make sure that the press release makes it clear why the study is really important.
Perhaps the people who write the press releases are focused on trying to take some highly technical information, and translating it into something understandable to the general public. That is a pretty big challenge. In general, I think they do a good job of that. But paying more attention to that one additional step would make the whole process much more useful.
Comments
I think the data suggest that early treatment onset reduces mortality and does not hasten progression.
http://scholar.google.com/scholar?q=parkinson%27s+early+treatment&hl=en&lr=&btnG=Search
http://www.neurology.org/cgi/content/abstract/66/7/976
Psychiatrically, there is a definite concern, and there are some practice parameters out there. This looks useful:
D. Aarsland, M. Emre, A. Lees, W. Poewe, C. Ballard, E. B. Montgomery, J. M. Miyasaki, and G. Gronseth
Practice Parameter: Evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology
Neurology, January 2, 2007; 68(1): 80 - 81.
It's a big need, and underidentified. There's also the concern with medications interacting with each other - antipsychotics and l-dopa potentiate and diminish motor and psychotic symptoms, so it's a messy balancing act.
Posted by: stewart | July 14, 2007 10:00 AM
I look at many of these kinds of articles as coming from the desire for recognition by getting something published in the literature. Things that people throw at you when you first meet, challenging your competence before they've even had any demonstration of it. Someone reads these, patient or family member, then comes in armed as if they are an expert on this, and they just want to make sure you're considering these things. As if all the years you spend in training, out in practice, reading these articles and others on your own, have insufficiently prepared you to make good decisions without their help and supervision.
So you figuratively bite your tongue, take a deep breath, and go on. I will usually make some effort to address some issues, but I make it clear I'm not there to stand up to the media-based Inquisition or pass some layman's test of my neurologic prowess. If that's what the visit is all about, let's part ways while you search for some other "whippin' boy."
I don't doubt the absolute validity of these articles about compulsive gambling, but surely they're overblown, since I have yet to see an example in my practice. And while there is something to be said about depression as an associated feature, it's important to be careful and not perceive the motor signs of parkinsonism as definite signs of depression, since they're quite similar. Furthermore, there is a definite sensitivity to medications of all sorts that patients with parkinsonism have, so trying to limit unnecessary polypharmacy for every little stinking symptom they have is also in our minds.
Posted by: Greg P | July 15, 2007 10:29 AM
Yes, and sometimes people see an article about, say, Mirapex and gambling, they they try to blame the problem on the drug. Never mind that the problem began before the drug was even invented.
Posted by: Joseph j7uy5 | July 16, 2007 1:19 AM
Hi all,
I thought, based on the subject matter at hand, you might be interested in some of my research on the gambling/dopamine agonist question. This issue has not just been overhyped by the press, the first three studies themselves are, at very best, incredibly flimsy, and, at worst, simply do not present sufficient evidence to support their conclusions - and in one case, highly relevant information was omitted.
Here is the link to my blog overall:
http://anukets-crusade.blogspot.com/
And here are the links to specific gambling-related entries:
http://anukets-crusade.blogspot.com/2006/09/gambling-and-dopamine-agonists-wheres.html
http://anukets-crusade.blogspot.com/2007/02/pathological-gambling-associated-with.html
http://anukets-crusade.blogspot.com/2007/02/letter-to-fda-alleging-research.html
Finally, to Greg P, while i can imagine that it could become tedious to continually have to correct the erroneous information patients "arm" themselves with, i hope that most neurologists will keep in mind that where they have seen both what the patient is going through and the info they bring with them thousands of times, this is all new for each individual patient.
I would bet that, while there are doubtless some people out there who do actually want to see their neurologist jump through hoops, the vast majority are just terrified at what is happening to them and are simply trying to educate themselves in an effort to feel at least a little bit less out of control. They no doubt truly believe that they have found some piece of info that is relevant to their medical care and that is why they present it to you - not, in the vast majority of cases i would wager, in order to challenge your prowess as a neurologist.
Unfortunately, all too often the outlets people rely on for their education are inaccurate.
I would welcome any thoughts anyone might have, including criticism (constructively offered, preferably) of anything in my blog. I am not interested in thinking I am right if I am not.
Posted by: anuket | July 16, 2007 10:59 AM
A note to those who think Mirapex and gambling are NOT related. I am proof they are. I am 54 years old and Never gambled in my life or had any other compulsive behaviour before taking Mirapex. I almost destroyed my life before finding out it could be the drug. I stopped the drug and the urge to gamble went away. It is sad that people can accept a side effect that involves your digestive system, blood pressure, heart, ect...but can't accept that it could affect your brain, reasoning and logic. This is a very real problem that Mirapex users should be made aware of. Of course all gamblers do not take Mirapex. But it is a real side affect and should be treated as such.
Posted by: Rebecca Bandon | August 13, 2007 5:02 AM
i started requip back in 9/06 for RLS and it was a miracle. Stopped working six months later and made symptoms worse. Started mirapex last week. only other drug taken was protonix. took mirapex as usual 6 p.m. on friday night. Sat am went to Lowe's with my husband and i was fine. Took him home around 9 am and then proceeded to fast food for breakfast. Stopped at red light at an extremely busy intersection near my home. Reachedh over to get money out of middle compartment in car. Took out $7.00 and the next thing I knew, I was going straight through the intersection right into oncoming traffic. it was as if i was in the middle of a bad dream. i looked to the left, saw cars coming and could not react. felt the impact and was then tossed across 4 lanes of traffic. I "woke up" when someone was yelling at me to pull my car out of traffic. At that point I realized just what had happened but had no clue as to why. I was trying to figure out what to say to the police as to what had just happened. thank God no one was seriously hurt but every time i close my eyes I see that car coming at me and it was as if it had been a horrific night mare. did not equate it to mirapex until being up all night thinking of nothing else. i knew not to drive when taking prescription drugs and I didn't. no one told me that i could be affecte 14 hours later. I don't know what happened to me, but i don't know what else it could have been. someone please help that could explain
Posted by: Dottie Davis | August 27, 2007 4:01 PM