New 'Multiple-Source' DBS Device Looks Good for Parkinson's

June 26, 2015

The first clinical study with a new-generation system of deep-brain stimulation (DBS) for Parkinson's disease has shown promising results.

The VANTAGE study, published in the July issue of Lancet Neurology, evaluated a new "multiple-source" DBS system (Vercise, Boston Scientific).

"DBS is quite popular now for advanced Parkinson's with motor fluctuations, and has shown particular benefits in younger patients and those who are cognitively well," lead author, Professor Lars Timmermann, MD, University Hospital Cologne, Germany, told Medscape Medical News.

He explained that the current systems in use consist of one electrode implanted in each hemisphere of the brain, with each electrode having four contacts, and a bulky stimulator implanted in the chest. "It is a good workhorse, but this new system that we are now testing is much more sophisticated."

Personalized Configuration

The new system has eight contacts in each hemisphere that can deliver a much higher degree of stimulation with a smaller device. Each contact can be programmed individually to deliver as much current as required, so the electrical field can be configured individually in each patient.

"The first-generation DBS devices are limited somewhat by the potential for side effects caused by electrical stimulation to areas of the brain near to the target zone," Professor Timmermann added. "This limits the dose of electrical stimulation that can be given. With the new system we can minimize current in certain areas and maximize stimulation in other areas to obtain a full clinical effect. In this first-in-man study of the new device, we wanted to see if these refinements would translate into better clinical effects and it looks as though they do."

He noted that the previous DBS clinical trials have shown an improvement in motor symptoms of 25% to 40%. "But the new device showed a 60% improvement in this study, and this was accompanied by considerable improvement in quality of life, and a 50% reduction in medication. Also we didn't have a single nonresponder, which is remarkable. Taken together the results are very exciting — truly motivating."

The new system is CE mark approved in Europe and is offered in about 20 European centers. "This is the first evidence that it really works," Professor Timmermann said. "We are very happy with the results."

For the VANTAGE study, 40 patients received a bilateral implant in the subthalamic nucleus. The primary endpoint — Unified Parkinson's Disease Rating Scale (UPDRS) III motor score 6 months after implantation — showed a significant reduction to 13.5 from 37.4 at baseline. In addition, use of antiparkinsonian drugs was reduced by an average of 58% during the study and on time was extended by a mean of 3.5 hours per day at 52 weeks.

In terms of adverse events, one patient died of pneumonia 24 weeks after implantation; this death was judged to be unrelated to the procedure. There were 125 adverse events reported, the most frequent of which were dystonia, speech disorder, and apathy. Three serious adverse events were attributed to the device or procedure (one case each of infection, migration, and respiratory depression), all of which resolved without residual effects and stimulation remained on during the study.

"Remarkable" Results

In an accompanying editorial, Michele Tagliati, MD, Cedars Sinai Medical Center, Los Angeles, California, describes the results of the study as "remarkable."

He says the 62% average improvement in UPDRS motor scores during the study "is better than in any other reported trial of DBS of the subthalamic nucleus," and "[t]he few serious adverse effects recorded confirm previously accepted levels of surgical safety."

He points out a few limitations of the study, including the small number of patients, the nonrandomized open-label design and unblended assessments.

Both Professor Timmermann and Dr Tagliati suggest that further benefits are likely as this technology continues to evolve.

"We think this is the technique for the future but this is just the beginning — many more fantastic developments are being investigated," Professor Timmermann said. "These include steering the current in different directions to have even more effect and the development of devices that stimulate only when needed. These would read the rhythms in the brain and deliver stimulation only when necessary."

Dr Tagliati concludes: "In the end, the future of DBS as a clinical and translational science will depend on our ability to unravel its mechanisms of action. Only when we better understand and control — versus empirically guess — the effects of DBS on the CNS [central nervous system] will the revolutionary power of this technology fully exert its therapeutic promise."

The VANTAGE study was funded by Boston Scientific, and three of the coauthors are employees of the company. Professor Timmermann has received research grants; personal fees for consultancy, travel, and speaking; and nonfinancial support from Boston Scientific. Dr Tagliati has received consulting fees and research support to his institution from Boston Scientific.

http://www.medscape.com/viewarticle/847093?src=wnl_edit_tpal

App to prevent fatal falls in Parkinson's patients

London, June 26:

A smartphone app can prevent dangerous freezing of gait in people suffering from Parkinson's disease.

Many patients in the latter stage of Parkinson's disease are at high risk of dangerous falls.

One major reason is the disabling symptom referred to as freezing of gait -- inability to step forward that typically occurs during gait initiation or when turning while walking.

The app called CuPID utilises small sensors placed on a patients' shoes that measure a person's gait in "real-time".

If certain deviations emerge, an audio message alerts the patient to change his or her walking pattern immediately to avoid a dangerous situation.

"Freezing of gait is a leading cause of disability in patients with Parkinson's disease. Recognising fall is a very powerful key for prevention and this is one of the features of this app," said professor Jeffrey Hausdorff from Tel Aviv University.

Freezing of gait often occurs during "walking transitions" associated with turning, starting, stopping and moving in open spaces.

It can also occur when people approach narrow spaces such as doors or elevators and in crowded places.

Hausdorff and his team conducted a pilot study on 20 patients with Parkinson's disease who used the CuPid app and 20 patients who did not use the app.

The results are promising and the examiners are currently exploring the possibility of a larger follow-up study to further demonstrate the app's efficacy.

The CuPID app has completed its pilot run and is being fine-tuned for more widespread use, the team said.

http://health.einnews.com/article/272893188/NT3-oPp-EY5dJr81

VA Expands Disability Benefits for Air Force Personnel Exposed to Contaminated C-123 Aircraft

June 18, 2015, 11:10:00 AM

WASHINGTON – The Department of Veterans Affairs (VA) today published a new regulation that expands eligibility for some benefits for a select group of Air Force Veterans and Air Force Reserve personnel who were exposed to the herbicide Agent Orange through regular and repeated contact with contaminated C-123 aircraft that had been used in Vietnam as part of Operation Ranch Hand (ORH).

VA published this regulation as an interim final rule so that it could immediately begin providing benefits to eligible Air Force veterans and Air Force Reserve personnel who submit a disability compensation claim for any of the 14 medical conditions that have been determined by VA to be related to exposure to Agent Orange.

Secretary of Veterans Affairs Robert A. McDonald made the decision to expand benefits following receipt of a 2015 report by the National Academy of Sciences Institute of Medicine (IOM) on Post-Vietnam Dioxin Exposure in Agent Orange-Contaminated C-123 Aircraft. This VA-requested report found evidence that as many as 1,500 to 2,100 Air Force and Air Force Reserve personnel who served as flight, medical and ground maintenance crew members on ORH C-123 aircraft previously used to spray Agent Orange in Vietnam were exposed to the herbicide.

“Opening up eligibility for this deserving group of Air Force veterans and reservists is the right thing to do,” said Secretary McDonald. “We thank the IOM for its thorough review that provided the supporting evidence needed to ensure we can now fully compensate any former crew member who develops an Agent Orange-related disability.”

Under this new rule, Air Force and Air Force Reserve flight, medical and ground maintenance crewmembers who served on the contaminated ORH C-123s are presumed to have been exposed to herbicides during their service, thus making it easier for them to establish entitlement for some VA benefits if they develop an Agent Orange-related presumptive condition. In addition, for affected Air Force Reserve crew members, VA will presume that their Agent Orange-related condition had its onset during their Reserve training. This change ensures that these reservists are eligible for VA disability compensation and medical care for any Agent Orange-related presumptive condition, and that their surviving dependents are eligible for dependency and indemnity compensation and burial benefits.

The interim final rule can be found on the Federal Register: www.federalregister.gov/public-inspection. VA will immediately begin processing claims and issuing benefits to eligible Air Force crew members.

VA encourages reservists who were assigned to flight, ground or medical crew duties at Lockbourne/Rickenbacker Air Force Base in Ohio (906th  and 907th Tactical Air Groups or 355th and 356thTactical Airlift Squadron), Westover Air Force Base in Massachusetts (731st Tactical Air Squadron and 74thAeromedical Evacuation Squadron) or Pittsburgh, Pennsylvania, International Airport ( 758th Airlift Squadron) during the period 1969 to 1986, and developed an Agent Orange-related disability to file a disability compensation claim online through the joint VA-Department of Defense web portal, eBenefits (https://www.ebenefits.va.gov/).

VA also has identified several active duty locations where ORH C-123 aircraft may have been used following their service in Vietnam. Active duty personnel who served in a regular USAF unit location where a contaminated C-123 was assigned and who had regular and repeated contact with the aircraft through flight, ground or medical duties during the period 1969 to 1986, and who develop an Agent Orange-related disability, also are encouraged to apply for benefits. For more information on applying for these benefits, including the affected units, Air Force Specialty Codes and dates of service for affected crew members, and a listing of Agent Orange-related conditions, visit www.benefits.va.gov/compensation/agentorange-c123.asp.

In order to avoid unnecessary delay of benefits, claimants should annotate “(C-123)” after each Agent Orange related disability in Part II, Block 14 of VA Form 21-526 or Section I, Block 11 of VA

Form VA Form 21-526EZ when filing on eBenefits.  Example: Diabetes (C-123).  If claimants have any of the following documents, they should be attached to their application:

• Discharge, separation papers,  (DD214 or equivalent)
• USAF Form 2096 (unit where assigned at the time of the training action)
• USAF Form 5 (aircraft flight duties)
• USAF Form 781 (aircraft maintenance duties)
• Dependency records (marriage & children's birth certificates)
• Medical evidence (doctor & hospital reports)

VA will process all claims related to C-123 exposure at the St. Paul, Minnesota, VA Regional Office.  Claims not filed through eBenefits should be mailed to the following address (or faxed to 608-373-6694):

Department of Veterans Affairs

Claims Intake Center

Attention: C123 Claims

PO Box 5088

Janesville, WI 53547-5088

Individuals with specific benefit questions related to herbicide exposure on C-123s may call VA’s special C-123 Hotline at 1-800-749-8387 (available 8 a.m. – 9 p.m. EST) or e-mail VSCC123.VAVBASPL@va.gov.

http://www.va.gov/opa/pressrel/pressrelease.cfm?id=2714

Partnering of PD researchers with patient groups needed to improve effectiveness of clinical trials

Published: Thursday 25 June 2015 

Survey of Parkinson's disease researchers, patients, and caregivers discloses strategies for eliminating inherent barriers, as reported in the Journal of Parkinson's Disease

Despite an urgent need for new medications, clinical trials in Parkinson's disease (PD) have a relatively low rate of success. The reasons for this are complex, prompting a group of investigators from PD advocacy groups to conduct a survey of the principle stakeholders, PD scientists, patients, and caregivers, to determine some of the underlying barriers. Their results are published in the Journal of Parkinson's Disease.

"With development of a new drug estimated to cost between $1 and $3 billion and taking as long as 15 years, the successful execution of clinical trials is essential," explained lead investigator Tom Isaacs, Co-Founder of The Cure Parkinson's Trust, London, UK. "Our findings identified the most significant obstacles to carrying out effective clinical trials for those involved in conducting research as lack of funding and support. For those with Parkinson's, the principal barriers to their participation in medical research were found to be fear of potential adverse consequences, interruption of their ongoing medical regimen, and concern about receiving placebos."

Lack of funding was cited by 66% of researchers surveyed, with the administrative burden to managing the trials noted by 46%. Recruitment of subjects was viewed as a barrier by 43%.

In most clinical trials, recruiting study subjects takes substantial effort and time and often results in significant delays in drug development. From the point of view of 240 potential study subjects and care partners, the authors found that 56% of the respondents were concerned with potential adverse consequences or side effects from the trial, while 53% did not want to disrupt their current medication. Fully 38% were worried that they might receive the placebo.

"It seems likely that the gap between the willingness of people living with Parkinson's to participate in clinical trials and the reality of the shortfall in recruitment numbers could be closed if there were better understanding, information, and communication between those conducting the trials and the participants," commented Isaacs. He and his co-authors further noted that Involvement of the patient community from the outset contributes to a culture of partnership and collaboration.

The results of the survey of more than 300 people with a connection to PD were presented at the Rallying to the Challenge meeting of Parkinson's patients held in September 2014 at the Van Andel Research Institute, an independent biomedical research and science education organization in Grand Rapids, Michigan, USA. Based on discussions of these results at the meeting, recommendations in the areas of communication, education, funding, recruitment and compliance were developed.

As a result of the Rallying to the Challenge meeting, a steering committee will be formed, comprised of both scientists and patients, to draft a Clinical Trials Charter to help bridge the gaps uncovered in the survey. The authors remind us that the "Parkinson's Movement seeks to develop and deliver stronger partnerships between the research and patient communities, and in so doing, expedite the search for better treatments and ultimately a cure."

http://www.medicalnewstoday.com/releases/295898.php?tw

New Zealand blackcurrants good for the brain

New Zealand blackcurrants

Published: Thursday 25 June 2015

Research has shown that New Zealand blackcurrants are good for keeping us mentally young and agile, a finding that could have potential in managing the mental decline associated with aging populations, or helping people with brain disorders such as Parkinson's disease or depression.

The research, conducted by scientists at Plant & Food Research (New Zealand) in collaboration with Northumbria University (UK), showed that compounds found in New Zealand blackcurrants increased mental performance indicators, such as accuracy, attention and mood. The study also showed that juice from a specific New Zealand blackcurrant cultivar, 'Blackadder', also reduced the activity of a family of enzymes called monoamine oxidases, which regulate serotonin and dopamine concentrations in the brain. These chemicals are known to affect mood and cognition, and are the focus for treatments of both neurodegenerative symptoms associated with Parkinson's disease and mood disorders, including stressand anxiety.

Results of the research have been published online in the Journal of Functional Foods, a leading journal in the field.

"This study is the first to look at the effects of berry consumption on the cognitive performance of healthy young adults," says Dr. Arjan Scheepens, the Plant & Food Research scientist who led the study. "Our previous research has suggested that compounds found in certain berryfruit may act like monoamine oxidase inhibitors, similar to a class of pharmaceuticals commonly used in the treatment of both mood disorders and neurodegenerative diseases like Parkinson's disease. This research has shown that New Zealand-grown blackcurrants not only increase mental performance, but also reduce the activity of monoamine oxidases."

"One of the key trends in the food industry is the development of ingredients and foods that have beneficial effects on human health," says professor Roger Hurst, Science Group Leader Food & Wellness at Plant & Food Research. "Understanding what, and how, foods affect mental performance could lead to the development of new foods designed for populations or situations where mental performance or mental decline is a factor, such as older people or those suffering from stress, anxiety or other mood disorders. This research shows how New Zealand blackcurrants can potentially add value, both for the food industry and for people looking for foods that naturally support their own health aspirations."

Participants in the study -- 36 healthy adults aged between 18 and 35 years -- consumed a 250ml drink prior to conducting a set of demanding mental performance assessments. The participants consumed either a sugar and taste-matched placebo (no blackcurrant), an anthocyanin-enriched New Zealand blackcurrant extract (Delcyan™ from Just the Berries) or a cold-pressed juice from the New Zealand blackcurrant cultivar 'Blackadder', bred by Plant & Food Research. The assessments showed that after consuming the Delcyan™ and 'Blackadder' drinks, attention and mood were improved while mental fatigue was reduced. In addition, blood tests showed that the activity of the monoamine oxidase enzymes (MAO) was strongly decreased after consuming the 'Blackadder' juice, indicating the potential for compounds found in 'Blackadder' blackcurrants as a functional food ingredient to support brain health or managing the symptoms of disorders like Parkinson's disease.

http://www.medicalnewstoday.com/releases/295879.php?tw

Future Science Group showcases UK Parkinson's Excellence Network

PUBLIC RELEASE: 25-JUN-2015

A new effort to improve treatment

The newly launched UK Parkinson's Excellence Network can transform care for those affected by Parkinson's, according to an article in Neurodegenerative Disease Management. The journal, published by Future Science Group, features a detailed review of the multi-disciplinary effort, which brings together health professionals, social care experts, Parkinson's UK, and patients, to develop and advocate for more patient-centered care for those affected by Parkinson's in the United Kingdom.

"We formed this network to fundamentally improve the care provided to people with Parkinson's, from the point of diagnosis onwards," said Professor David Burn, Consultant Neurologist, author of the article and clinical director of the Excellence Network. "By bringing together patients, their caregivers, experts in both the clinical treatment and social services, and the resources of Parkinson's UK, the largest charity funder of Parkinson's research in Europe, we believe we can drive a fundamental change in patient care."

The article provides details on the Excellence Network's six themed working groups, which focus on leading improvement in subject areas such as education or service development. The Excellence Network also supports 20 regional working groups, which seek to empower and support both patients and professionals to build awareness and drive changes in their local area.

"The aim is to raise our voices so the need for better care is recognized, and to raise the level of service consistency, so that every person with Parkinson's receives a high-quality standard of care, and every professional can make better use of their time and effort," said Professor Burn.

"Prof. Burn provides extensive detail on this new effort, developed in direct response to the requests of those living with Parkinson's disease, to disseminate successful Parkinson's care strategies throughout the UK," said Daphne Boulicault, Editor of Neurodegenerative Disease Management. "This is a practical first step towards a nationwide, multidisciplinary and patient-centered Parkinson's service."

Parkinson's is a progressive neurological condition for which there is currently no cure. In the UK, one person in every 500, or about 127,000 people, has Parkinson's.

###

To view the articles:

- http://www.futuremedicine.com/doi/full/10.2217/nmt.15.18

- http://www.futuremedicine.com/doi/full/10.2217/nmt.15.15

Additional articles and cancer content can be found on Neurology Central, Future Science Group's free eCommunity for neurology professionals. The membership-based portal offers free access to breaking neurology news and peer-reviewed journal articles, with content selected by fellow clinicians.

About Parkinson's UK 

Parkinson's UK is the UK's leading charity supporting those with the condition. Its mission is to find a cure and improve life for everyone affected by Parkinson's through cutting edge research, information, support and campaigning.

For advice, information and support, visit http://www.parkinsons.org.uk or call our free, confidential helpline on 0808 800 0303.

About Future Science Group 

Founded in 2001, Future Science Group (FSG) is a progressive publisher focused on breakthrough medical, biotechnological, and scientific research. FSG's portfolio includes two imprints, Future Science and Future Medicine. Both publish eBooks and journals. In addition to this core publishing business FSG develops specialist eCommunities. Key titles and sites includes Bioanalysis Zone, Epigenomics, Nanomedicine and the award-winning Regenerative Medicine.

The aim of FSG is to service the advancement of clinical practice and drug research by enhancing the efficiency of communications among clinicians, researchers and decision-makers, and by providing innovative solutions to their information needs. This is achieved through a customer-centric approach, use of new technologies, products that deliver value-for-money and uncompromisingly high standards.  http://www.future-science-group.com

http://health.einnews.com/article/272713929/k8xZ7GC4xxGQIbeA

Threshold for Quick Diagnosis of Sleep Issues in PD

Pauline Anderson

June 23, 2015

BERLIN, Germany — German researchers have come up with a quick and easy way to determine a need for referral for serious sleep problems in patients with Parkinson's disease (PD).

They have determined that a score of 18 or above on the Parkinson's Disease Sleep Scale-2 (PDSS-2) indicates sleep-related issues severe enough for referral to a specialist, according to Maria-Lucia Muntean, MD, PhD, Paracelsus Elena Klinik, Kassel, Germany.

The cutoff of 18 on the PDSS "will allow clinicians to easily evaluate sleep problems in PD patients and to decide quickly whether further investigations are needed in order to determine the exact nature of the sleep disturbance," said Dr Muntean.

She presented her study here at the Congress of the European Academy of Neurology (EAN).

Time Constraints

From 60% to 98% of patients with PD experience some sleep problems, including insomnia, sleep fragmentation, sleep apnea, restless legs syndrome (RLS), and daytime sleepiness, the authors note. Such problems can seriously affect quality of life.

Clinicians can evaluate patients with PD for sleep problems through a detailed interview, but time and financial constraints limit doing this use in everyday practice, said Dr Muntean.

Several questionnaires evaluate sleep in patients with PD, including the Pittsburgh Sleep Quality Index (PSQI) and the PDSS-2. The PDSS-2 includes 15 questions, each with a value of 0 to 4 for a maximum total score of 60.

The study included 93 patients (52 men and 41 women) with idiopathic PD who were inpatients at the movement disorders clinic at the Paracelsus Elena Hospital Kassel, Germany, and were enrolled consecutively from December 2013 to February 2014.

The analysis included only inpatients because, as Dr Muntean explained, it was important for physicians to observe the patients directly.

The mean patient age was just over 69 years. While all patients had Hoehn and Yahr stages 1 to 5, more than half were stage 3 to 4. The patients continued to take their regular PD medication.

Two Questions

All patients completed the PDSS-2. The attending physician answered two questions:

1. Does the patient suffer from sleep problems which are not related to Parkinson's disease (for example, sleep onset or sleep maintenance problems, daytime somnolence)?
2. Does the patient suffer from Parkinson specific sleep disorders in the night (for example, REM behavior sleep disorder, RLS, tremor, akinesia)?

If the answer was "yes," the physician then classified the sleep problem as mild, moderate, or severe.

The researchers found that 56.98% of patients were considered to have sleep problems not related to PD, while 62.26% patients were deemed to have sleep problems related to PD.

The statistical analysis showed that 83% of patients with a PDSS-2 total score of 18 or more had clinically relevant sleep disturbances compared with 33% of the patients who had a score of less than 18.

PDSS-2 scores were positively related to the severity of the sleep problems, added Dr Muntean.

The results suggest that a score of 18 or more "represents an optimal combination of sensitivity and specificity" to constitute a "cutoff" warranting referral to a sleep specialist or center specializing in sleep disorders, she said.

This is, to Dr Muntean's knowledge, the first time that researchers have determined a cutoff for sleep problems in European patients with PD. Japanese researchers came up with evidence that a PDSS-2 score higher than15 indicated a poor sleeper.

The different cutoff was due to the Japanese researchers' correlating the PDSS-2 total scores with those of the PSQI and not to a questionnaire completed by a clinician. However, the cutoffs might not be that different.

"If we take into account that the PDSS-2 total scores vary between 0 and 60, the cutoff values from the two studies could be considered similar," said Dr Muntean. "Due to ethnic and sleep habit differences, it's difficult to make a one-to-one comparison between the European and Japanese PD population."

Session co-chair Claudio Bassetti, MD, professor and chair, Department of Neurology, University Hospital (Inselspital), Bern, Switzerland, questioned how physicians actually answered the "crucial" questions upon which the prediction depends. "How did they get the answer to those questions at the end of workup? Was it just based on clinical judgment?"

Dr Muntean replied that the attending physicians were expert in movement disorders and had the opportunity to observe the patients for a few days and to interview them, before determining the presence and severity of sleep problems.

Dr Muntean has disclosed no relevant financial relationships.

Congress of the European Academy of Neurology (EAN). Abstract 01226. Presented June 20, 2015.

http://www.medscape.com/viewarticle/846875?src=wnl_edit_tpal&uac=140844CK

Antipsychotic Use Increases Mortality in Parkinson's

Medscape Medical News > Conference News

Daniel M. Keller, PhD

June 23, 2015

SAN DIEGO — The use of antipsychotic (AP) medication to treat psychosis in Parkinson's disease (PD) increases the risk for all-cause death, and the risk varies with the AP class and the specific drugs within a class, a study shows.

"The antipsychotics users had a hazards ratio between 2 and 3 compared with non–antipsychotic users in terms of 6-month mortality, so they were that much more likely to die," Daniel Weintraub, MD, from the Philadelphia Veterans Affairs Medical Center and associate professor of psychiatry in the Perelman School of Medicine of the University of Pennsylvania in Philadelphia, told Medscape Medical News.

He presented the study findings here at the International Parkinson and Movement Disorder Society (MDS) 19th International Congress.

The study included data on patients with PD in the national Veterans Affairs administrative database between 1999 and 2010. The cohort was largely male.

Using 31 exclusion criteria, matching factors, and covariates, the researchers formed a matched control cohort of non–AP users. They compared 180-day mortality of AP users with that of nonusers, from which hazard ratios were calculated. There were 7877 matched pairs.

All APs Raised Mortality Risk

No class of AP (typical vs atypical) or specific drug was without risk for death.

"Some people might assume [the newer, atypical ones] have a lower risk, and yes, they did have a lower risk, but the risk for atypical antipsychotics was elevated as well, compared with nonusers," Dr Weintraub said.

Table. Mortality Risks by Antipsychotic Class and Specific Drug (Intention-to-Treat Analysis)

Class or Drug	Hazard Ratio	P Value
No antipsychotic use	1.0	–
Atypical antipsychotic	2.26	<.001
Typical antipsychotic	3.65	<.001
Haloperidol	5.08
Other typical	1.82	.07
Olanzapine	2.79	<.001
Quetiapine	2.16	<.001
Risperidone	2.46	<.001
Other atypical	1.19	.62

Whether the analysis was done by intention to treat or by exposure to drug, the patterns were largely the same. Adjustments were made for measurable confounders related to PD severity and comorbidities.

The only typical AP relatively commonly prescribed was haloperidol. Three atypical APs commonly prescribed were quetiapine, olanzapine, and risperidone.

Quetiapine represented almost 70% of AP prescriptions in the cohort, and although the mortality risk was lowest with quetiapine, it was still about double the risk compared with no AP use.

Haloperidol, olanzapine, and risperidone were all associated with higher mortality risks than quetiapine.

The researchers found similar results when they excluded patients who died within the first 2 weeks or 4 weeks of AP exposure to eliminate patients who were at imminent risk for death when therapy was initiated.

Dr Weintraub next plans to look at National Death Index data for causes of death and also to examine hospitalization and outpatient visit data to see whether there was increased morbidity associated with AP use.

Psychosis in PD is common, affecting 60% of patients, with half of them receiving treatment with APs. The study did not include any patients who had psychosis but were not treated for it in order to investigate the mortality risk of PD psychosis alone. Psychosis was included as a covariate here to control for it; however, there was no strict matching of treated vs nontreated patients with PD psychosis.

The value of treating psychosis in PD needs to be balanced against the mortality risk.

Calling it "a very important study in Parkinson's disease," Michael Okun, MD, professor of neurology and co-director of the Center for Movement Disorders and Neurorestoration at the University of Florida in Gainesville and national medical director of the National Parkinson Foundation, commented to Medscape Medical News that "patients should be aware that treatment of Parkinson's related psychosis can be life-changing and life-saving in some cases."

He said clinicians "tend to use drugs such as clozapine, quetiapine, and possibly a new agent, pimavanserin. If you can preserve optimal treatment of the motor symptoms of Parkinson's and also suppress psychosis, the risk-benefit ratio usually favors treatment."

Dr Okun noted that the increased mortality with AP use in patients with PD psychosis parallels findings of their use in non-PD patients with psychosis.

Dr Weintraub and colleagues recommend developing and testing new APs as well as nonpharmacologic strategies for managing psychosis in PD.

The research was federally funded through the Department of Veterans Affairs. Dr Weintraub and Dr Okun have disclosed no relevant financial relationships.

International Parkinson and Movement Disorder Society (MDS) 19th International Congress. Abstract 482. Presented June 16, 2015.

http://www.medscape.com/viewarticle/846898?src=wnl_edit_tpal&uac=140844CK#vp_1