Neuropsychiatric symptoms are common in newly diagnosed, untreated patients with Parkinson's disease (PD), but they remain relatively stable over a 2-year follow-up, initial longitudinal data show.
Patricia de la Riva, MD, University Hospital Donostia, San Sebastian, Spain, and colleagues found that patients with PD experienced more depression, fatigue, apathy, and anxiety than healthy controls at baseline and at 12 months and 24 months of follow-up. Apathy and psychosis both significantly increased over time in patients with PD as well.
"The point to make clinically is that there is always a range of nonmotor symptoms that can occur in PD, and they can occur early in the disease course at the time of diagnosis," senior author, Daniel Weintraub, MD, associate professor of psychiatry and neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, told Medscape Medical News.
"And really, the take-home message is that there needs to be some kind of routine and ongoing monitoring of nonmotor symptoms — psychiatric symptoms, cognitive symptoms — from the time of diagnosis and on a regular basis to identify clinically significant symptoms that might need treatment."
The study was published online August 15 in Neurology.
Parkinson's Progression Markers Initiative
The Parkinson's Progression Markers Initiative (PPMI) is a prospective longitudinal study designed to identify biomarkers PD progression. For this analysis, investigators evaluated 423 newly diagnosed, untreated patients with PD and 196 healthy controls at study onset.
Of this group, 261 patients with PD and 145 healthy controls were again evaluated 12 months later while 96 patients PD and 83 healthy controls were evaluated at 24-month follow-up.
At baseline, 13.9% of patients with PD screened positive for depression compared with 6.6% of healthy controls. Over the 24-month follow-up, depression increased in frequency to 18.7% in the PD group, but the difference between baseline and follow-up was not significant.
Among health controls, the frequency of depression slightly decreased over the same follow-up interval. At baseline, more patients with PD were taking an antidepressant, at 16.1%, than those who screened positive for depression, the researchers note.
At 24 months of follow-up, 25% of patients with PD were taking an antidepressant. Despite the increase in antidepressant use over time, at least two thirds of patients with PD who screened positive for depression at a given visit were not being treated with an antidepressant, "suggesting that depression is undertreated in early PD," the authors note.
As for cognition, the Montreal Cognitive Assessment score decreased significantly over time in patients with PD (P < .001) but the change in cognition seen in the PD group was similar to that in healthy controls, the investigators report.
At the 24-month follow-up visit, 81% of patients had started dopamine replacement therapy and close to 44% of them had been receiving treatment for a minimum of 1 year. At baseline, 21% of patients with PD also screened positive for impulse control disorder (ICD) or related behavior symptoms.
Interestingly, the proportion of patients with PD who have ICD symptoms did not increase significantly over the 24-month follow-up. There was also no significant difference in the frequency of ICD symptoms at any time point between patients with PD and healthy controls.
However, as Dr. Weintraub explained to Medscape Medical News, when investigators removed the group of patients with PD who screened positive for ICD symptoms at baseline and compared patients who started dopamine replacement therapy at some point during the 24-month follow-up to those who did not, "people who started medication over that 2-year period were more likely to report new ICD symptoms compared with patients who did not start a medication," he observed.
Specifically, at the 2-year time point, there were 6 incident cases of ICD or related behavior symptoms in the dopamine replacement group vs none in the untreated group (P = .009).
There were also more incident cases of excessive daytime sleepiness in the medication group (31%) than in the untreated group (10.6%) (P = .03). The frequency of new-onset psychosis, although not statistically significant, was nearly 3 times higher in the medication group compared with patients who remained untreated.
As investigators note, one third of patients reporting fatigue at baseline reported an improvement in fatigue following initiation of dopamine replacement therapy. Fatigue improved in only 11% of patients not taking antiparkinsonian medication.
However, dopamine replacement therapy had no effect on depression, anxiety, apathy, or cognition.
Asked to comment on the study, Michele Tagliati, director of the Movement Disorders Program at Cedars-Sinai Medical Center, Los Angeles, California, underscored the importance of early detection and treatment of these symptoms.
"This is a very interesting study, highlighting the early occurrence of neuropsychiatric symptoms in Parkinson's disease," Dr. Tagliati told Medscape Medical News. "Despite being classically considered a late evolution of the disease, almost 20% of patients with early, untreated Parkinson's disease had clinical signs of depression. Most importantly, two thirds of them were untreated.
"Interestingly, the introduction of dopaminergic therapy — the mainstay for parkinsonian motor symptoms treatment — did not fundamentally improve and possibly increased the incidence of neuropsychiatric symptoms, suggesting that neurotransmitter abnormalities other than dopamine must already play a role early in the course of the illness," he pointed out.
"Fortunately, the early progression of neuropsychiatric problems seems to be fairly mild, at least in the first 2 years of follow-up," he added. "Therefore, early detection and treatment of these symptoms can substantially improve our ability of improving the quality of life of patients with Parkinson's disease."
Also commenting, Matthew Menza, MD, professor and chair, Department of Psychiatry, Rutgers University, New Brunswick, New Jersey, told Medscape Medical News that the PPMI study is the specialty's first really good longitudinal prospective study of psychiatric symptoms in PD.
"Many of these symptoms are probably more important to quality of life at least early on in the disorder," Dr. Menza added, "and we don't really know a lot about progression of these kinds of symptoms that are incredibly important to patients — if they are depressed, if they are fatigued — these are the things that disrupt their life more than the actual movement disorder which can be pretty well managed. So it's a very important study and as we've seen just recently with Robin Williams, how critical these kinds of symptoms can be."
Susan Schneider, Williams' wife, released a recent statement saying that Williams was struggling with early stages of PD along with anxiety and depression but that he was not ready to share this information publicly. His wife did not draw a connection between Williams' suicide and the diagnosis of PD.
Nevertheless, as Dr. Menza pointed out, "many people have depression before they know they have PD." In the PPMI study, 1 in 5 patients with newly diagnosed PD had significant depression and two thirds of those identified as depressed over the course of follow-up did not receive antidepressant therapy.
"While this doesn't mean that the depression wasn't being treated — there are other treatments for depression — in general previous studies have shown that depression is very underrecognized in PD and very undertreated," Dr. Menza noted.
In a separate study published online July 17 in the Journal of Parkinson's Disease, researchers led by Danny Bega, MD, from the Department of Neurology at Northwestern University Feinberg School of Medicine in Chicago, Illinois, used data from the National Parkinson's Foundation's (NPF's) quality improvement initiative project dataset to examined the prevalence of depressive symptoms among patients enrolled, the largest cohort of PD patients reported to date, they note. "Our study confirms the high prevalence (23% of 7031 patients) in a large cohort of PD patients," the authors write. Although rates of physician recognition of depressive symptoms were higher in this report than in previous findings in this population, even at these NPF Centers of Excellence participating in an NPF quality improvement project, 46% of patients who scored in the "depressed" range according to a tool called the Parkinson's Disease Questionnaire were untreated.
Further longitudinal data will be necessary to determine the effect of antidepressant use and mental health services on depression, to compare the relative efficacy of treatments in this population, and to determine whether there may be a synergistic effect of medication and mental health services, they write.
"In the interim, physicians should be vigilant about systematic screening for depression as part of the routine assessment of all PD patients," the authors conclude.
Less "Doom" Than "Gloom"
After news of Williams' death and the subsequent disclosure that he was living with PD, the PDF released a statement discussing issues relative to suicide in PD.
The statement noted that:
"Research, although limited, has consistently shown that suicide rates for people with Parkinson's disease are the same if not significantly lower (up to 10 times lower according to a study found here) than the rates for the general population."
Medications prescribed for Parkinson's have very safe profiles, "with no evidence linking them to suicide risk." Dopamine agonists have been linked to impulse control disorders, the statement notes. "However, these side effects are pleasure seeking and suicide is not one of them. In fact, dopamine agonists have a documented antidepressant effect."
If patients or their loved ones notice any signs of depression, they should contact a healthcare professional. Any questions about suicide and PD can be directed to the PDF's HelpLine at 800-457-6676 or firstname.lastname@example.org.
"Although a Parkinson's diagnosis is full of doom and gloom, it is, fortunately, more gloom than doom," said James Beck, PhD, PDF's vice president, scientific affairs, in the release. "People are more likely to face depression than to commit suicide. Awareness of depression and Parkinson's, combined with prompt treatment, can help go a long way to alleviate that gloom."
The PPMI is a public-private partnership and is funded by the Michael J. Fox Foundation for Parkinson's Research. Dr. Weintraub has also received funding support from the Michael J. Fox Foundation for Parkinson's Research. The study authors, Dr. Menza, and Dr. Bega have disclosed no relevant financial relationships.
Neurology. Published online August 15, 2014. Abstract
J Parkinson Dis. Published online July 17, 2014. Full text
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Cite this: Depression, Anxiety Common in New PD Patients - Medscape - Aug 26, 2014.