New Classification Scheme for Alzheimer’s Biomarkers

NeuroThe American Academy of Neurology is proposing a new classification scheme to describe Alzheimer’s biomarkers. Biomarkers have become an essential component of Alzheimer disease (AD) research and also in cognitive aging research. A number of current issues suggest that a new descriptive classification scheme for these biomarkers would be useful.

The proposed format is called  the “A/T/N” system in which 7 major AD biomarkers are divided into 3 binary categories based on the nature of the pathophysiology that each measures. “A” refers to the value of a b-amyloid biomarker (amyloid PET or CSF Ab42); “T,” the value of a tau biomarker (CSF phospho tau, or tau PET); and “N,” biomarkers of neurodegeneration or neuronal injury ([18F]-fluorodeoxyglucose–PET, structural MRI, or CSF total tau). Each biomarker category is rated as positive or negative. An individual score might appear as A+/T+/N-, or A+/T-/N-, etc.

Temporal ordering of mechanisms underlying AD pathogenesis are ignored. It includes all individuals in any population regardless of the mix of biomarker findings and therefore is suited to population studies of cognitive aging. It does not specify disease labels and thus is not a diagnostic classification system. It is a descriptive system for categorizing multidomain biomarker findings at the individual person level in a format that is easy to understand and use. Given the present lack of consensus among AD specialists on terminology across the clinically normal to dementia spectrum, a biomarker classification scheme will have broadest acceptance if it is independent from any one clinically defined diagnostic scheme.

Source: Neurology® 2016;87:1–9

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Natural Molecule Can Improve Parkinson’s Disease

PLOS-ONEResearchers from the Departments of Integrative Medicine, Neurology, and Radiology, at Thomas Jefferson University have demonstrated that the natural molecule, n-acetylcysteine (NAC), with strong antioxidant effects, shows potential benefit as part of the management for patients with Parkinson’s disease. Published in PLOS ONE, the combination clinical evaluations of a patient’s mental and physical abilities along with brain imaging studies that tracked the levels of dopamine,  both improved in patients receiving NAC.

Recent research has shown that oxidative stress in the brain may play a critical role in the Parkinson’s disease process, and that this stress also lowers levels of glutathione, a chemical produced by the brain to counteract oxidative stress. Studies in brain cells showed that NAC helps reduce oxidative damage to neurons by helping restore the levels of the antioxidant glutathione. NAC is an oral supplement that can be obtained at most nutrition stores, and interestingly also comes in an intravenous form which is used to protect the liver in acetaminophen overdose.

In the study, compared to controls, the patients receiving NAC had improvements of 4-9 percent in dopamine transporter binding and also had improvements in their Unified Parkinson’s Disease Rating Scale (UPDRS) score of about 13 percent. According to the researchers “we have not previously seen an intervention for Parkinson’s disease have this kind of effect on the brain.” The investigators hope that this research will open up new avenues of treatment for Parkinson’s disease patients.

Monti, DA, et al. PLoS One. 2016 Jun 16;11(6):e0157602.


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New Practice Guidelines on the Use of Antipsychotics in Dementia

A new guideline from the American Psychiatric Association is designed to improve the care of patients with dementia who are exhibiting agitation or psychosis. More specifically, this guideline focuses on the judicious use of antipsychotic medications when agitation or psychosis occurs in association with dementia. It does not review the evidence for other pharmacological interventions. The guideline is intended to apply to individuals with dementia in all settings of care as well as to care delivered by generalist and specialist clinicians. Recommendations regarding treatment with antipsychotic medications are not intended to apply to individuals who are receiving antipsychotic medication for another indication (e.g., chronic psychotic illness) or individuals who are receiving an antipsychotic medication in an urgent context.

The guideline is available online.

The American Psychiatric Association Practice Guideline on the Use of Antipsychotics to Treat Agitation or Psychosis in Patients With Dementia

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Mixed Depression May Be More Common Than Previously Thought

AJPMixed states are characterized by concurrent manic and depressive symptoms. The concept of a “with mixed features” specifier for major depressive episodes was introduced in DSM-5 and defined by the presence of at least three nonoverlapping opposite-pole symptoms in the context of a syndromal depressive, hypomanic, or manic episode. There has been growing interest in the phenomenology and clinical implications of the opposing mixed state—that is, manic or hypomanic symptoms during a depressive episode. A study published in the American Journal of Psychiatry assessed the prevalence and features of mixed depression among bipolar disorder patients and qualitatively compared a range of diagnostic thresholds for mixed depression.

Visit outcomes of adult outpatients (N=907) with bipolar disorder across 14,310 visits between 1995 and 2002 were analyzed. At each visit, mania and depression symptoms were assessed using the Inventory of Depressive Symptomatology–Clinician-Rated Version (IDS-C) and the Young Mania Rating Scale (YMRS). Patients with an IDS-C score of greater or equal to 15 and a YMRS score between 2 and 12 at the same visit were classified as having mixed depression. The presence of mixed depression was observed in 2,139 visits (14.9% of total) and among 584 patients (64.4% of total). Those classified as having one or more mixed depression visits also had more symptomatic visits and fewer non-depressed visits compared with those with no mixed depression visits.

The authors concluded that among the patient population studied, depressive symptoms were common, and subthreshold hypomania occurred in almost half of all visits with depression. The study revealed that women were more likely than men to experience hypomanic symptoms concurrently with depression across a range of diagnostic criteria for mixed depression. “The presence of mixed depression appears to be a marker of vulnerability to mixed depression features in general and may portend a more symptomatic course of illness over time. The stability of our mixed depression construct across a range of definitions supports the possibility that broader diagnostic criteria for mixed depression may improve sensitivity while preserving clinical meaningfulness.”

Source: American Journal of Psychiatry
Published Online April 15, 2016


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No Changes to Maintenance Of Certification for Psychiatry, Neurology

A number of medical boards are in the process of reviewing their maintenance of certification (MOC) requirements and steps.  Jeffrey Lyness, MD, psychiatry director for the American Board of Psychiatry and Neurology (ABPN), professor of psychiatry and neurology, and senior associate dean for academic affairs at the University of Rochester School of Medicine and Dentistry, in New York, presented at the American Association for Geriatric Psychiatry (AAGP) 2016 Annual Meeting this month and reported that the ABPN is not likely to make any major changes anytime soon to the MOC process. There were some minor changes for 2016 making the requirements for Part IV, the Improvement in Medical Practice module, which is also known as the Performance in Practice (PIP) module, more flexible.

For the PIP this year, ABPN diplomates can choose either a clinical or a feedback module. In 2015, the clinical module was required, and in 2014, diplomates were expected to do both. Psychiatrists can receive clinical module credit for a wide variety of activities, including completing institutional quality improvement (QI) activities, completing professional QI activities, such as participating in registries, and through meaningful participation in the American Board of Medical Specialties’ (ABMS’) Portfolio Project. Completion of the “Feedback module” requirements can be met through patient or peer surveys, for example, institutional peer review and supervisor evaluation.

Part IV is a three-step process that includes initial assessment, identifying areas that need improvement and implementing an improvement process, and then undertaking a reassessment. Another new requirement beginning in 2016 is that psychiatrists who are being certified or recertified must take a patient safety course. The ABPN will be listing approved courses on its website.


Lyness JM. Update On Geriatric Psychiatry Maintenance Of Certification Program. Journal of the American Association For Geriatric Psychiatry.2016;24(3) Supl 1. Abstracts from the 2016 AAGP Annual Meeting. Washington, DC. March 17–20, 2016. Session 207.

Ault A. MOC: No Changes for Psychiatry, Neurology Anytime Soon. Medscape Medical News. Website Published March 22, 2016. Accessed March 22, 2016

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Antipsychotic Use in Parkinson’s Disease Associated With Mortality Risk

JNA new study by researchers at the Perelman School of Medicine at the University of Pennsylvania, the University of Michigan Medical School, and the Philadelphia and Ann Arbor Veterans Affairs (VA) Medical Centers and suggests that antipsychotic drugs may do significantly more harm in a subset of Parkinson’s patients.

An analysis of approximately 15,000 patient records in a VA database found that Parkinson’s patients who began using antipsychotic drugs were more than twice as likely to die during the following six months, compared to a matched set of Parkinson’s patients who did not use such drugs. Over a decade ago the FDA has mandated “black box” warnings on antipsychotic medications, noting that there is an increased risk of death when these drugs are used in dementia patients. In the new study, researchers examined the possibility that antipsychotic drug use is associated with higher mortality not just in Parkinson’s dementia patients, but in all Parkinson’s disease patients. The analysis revealed that in the 180 days after they first took antipsychotic drugs, patients in the first group died in much larger numbers, compared with the matched control patients during the same periods. Overall the Parkinson’s patients who used antipsychotics had 2.35 times the mortality of the non-users.

Antipsychotics have been used to manage psychosis that can accompany Parkinson’s disease. The underlying causes of psychosis in Parkinson’s are not well understood, but are thought be the result of the spread of the neurodegenerative disease process to certain brain areas, as well as from higher doses of Parkinson’s drugs that enhance dopamine function. The researchers recommend that for the present, neurologists and other physicians should prescribe antipsychotics to Parkinson’s patients only after looking for other possible solutions, such as treating any co-morbid medical conditions associated with psychosis, reducing the dosage of dopamine replacement therapies, and simply managing the psychosis without antipsychotics.


Weintraub D, et al. Association of Antipsychotic Use With Mortality Risk in Patients With Parkinson Disease. JAMA Neurol. 2016 Mar 21.[Epub ahead of print] PMID:26999262

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Intranasal Formulation Studied for Seizure Cluster Patients

Increased seizure activity including seizure clusters (SCs) and acute repetitive seizures (ARS) are seizure emergencies that require prompt medical attention. Immediate and effective treatment is needed or these seizures may progress to status epilepticus. Treatment in a hospital setting is generally with intravenous  benzodiazepines; this requires a trained professional to administer an intravenous medication. Since most seizures occur out of a hospital, novel approaches to clinical management are needed.

According to Bancke and colleagues, “the ideal out-of-hospital medication for SC/ARS would be highly effective, have rapid onset (minutes) along with a prolonged duration of action (hours), and be quick and easy to administer, with little or no monitoring required.” Alternate routes of seizure rescue medication administration have been explored and currently, the only FDA approved rescue treatment for patients with intermittent episodes of increased seizure activity that can be administered by non-health care professionals is rectal diazepam gel. Although this has been used successfully in both home settings and in hospitals, “there re some drawbacks regarding rectal dosing” and it can be difficult to administer rectal medication to a convulsing patient; in addition, rectally administered drugs may be socially embarrassing.

A recent study of midazolam, which is a potent anticonvulsant that has been used in Europe for decades, evaluated a new formulation. It has been formulated as a nasal spray and is being evaluated as a potential rescue treatment for seizures in patients who require control of intermittent episodes of increased seizure activity. The study evaluated 3 doses of the midazolam nasal spray against midazolam intravenous (IV) and midazolam IV administered intranasally (Inj-IN). Results showed  that the intranasal (IN) spray absorption was rapid and consistent, and that the IN formulation had 36% greater relative bioavailability than the injectable formulation. Treatment emergent adverse effects were evaluated as mild. While this is a phase I study, it demonstrates a potential treatment approach and offers hope for patients who suffer from seizure clusters and acute repetitive seizures.

A number of pediatric studies have evaluated intranasal midazolam for seizures and found it to be efficacious and reasonably safe for treatment of acute seizures in the pediatric population. Various studies have demonstrated a shorter time to seizure cessation with intranasal midazolam versus rectal diazepam in children in the community, prehospital, and ED settings. Many first responders, including caregivers, prefer intranasal midazolam and believe that it is less invasive for patients.

Bancke, et al. Epilepsia.2015;56(11):1723-1731. PMID: 26332539.
Humphries, et al. J Pediatr Pharmacol Ther. 2013 Apr;18(2):79-87. PMID: 23798902
Thakker, et al. J Neurol. 2013;260(2):470-474. PMID:22983456

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Non-invasive Vagus Nerve Stimulation For Depression

BPsyA new study published in the current issue of Biological Psychiatry describes successful reduction of depressive symptoms in patients using a novel non-invasive method of vagus nerve stimulation (VNS).
Traditional vagus nerve stimulation (VNS) is a neurostimulation technique that has been used to alleviate treatment-resistant symptoms of depression. However, it was also costly and requires neurosurgery to implant the vagal nerve stimulators.

In this new study, researchers from the China Academy of Chinese Medical Sciences in collaboration with Harvard Medical School investigated a new, modified form of VNS called transcutaneous VNS (tVNS), which instead stimulates the vagus nerve through electrodes clipped onto the ear. Compared to patients who received sham VNS, the patients who received real VNS (N=34) showed significant improvement of their depressive symptoms as measured by the Hamilton Depression Rating Scale.

The safe and low-cost characteristics of tVNS have the potential to significantly expand the clinical application of VNS.

Source: Biological Psychiatry


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Task Force Calls for Depression Screening During and After Pregnancy

This week the US Preventive Services Task Force (USPSTF) updated their recommendations on screening for depression in adults. Included in the recommendations is the screening of women for depression during pregnancy and after giving birth. This is the first time the Task Force has recommended screening for maternal mental illness.

The USPSTF reviewed the evidence on the benefits and harms of screening for depression in adult populations, including older adults and pregnant and postpartum women. It also reviewed the accuracy of depression screening instruments; and the benefits and harms of depression treatment in these populations. The task force added that  “Screening should be implemented with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up. The USPSTF reviewed the evidence on the benefits and harms of screening for depression in adult populations, including older adults and pregnant and postpartum women; the accuracy of depression screening instruments; and the benefits and harms of depression treatment in these populations.”

The USPSTF also describes the benefits of early detection and intervention and treatment. They found adequate evidence that programs combining depression screening with adequate support systems in place improve clinical outcomes (ie, reduction or remission of depression symptoms) in adults, including pregnant and postpartum women. It also supports treatment of adults and older adults with depression identified through screening in primary care settings with antidepressants, psychotherapy, or both decreases clinical morbidity.

The USPSTF also found adequate evidence that treatment with cognitive behavioral therapy (CBT) improves clinical outcomes in pregnant and postpartum women with depression.


NY Times


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Antipsychotic Discontinuation in Recovered First-Episode Psychosis Results in Relapse

jcp-logoA study published in the Journal of Clinical Psychiatry evaluated the risk of symptom recurrence over 3 years after antipsychotic discontinuation in a sample of functionally recovered first-episode nonaffective psychosis (FEP) patients with schizophrenia spectrum disorder.

When to discontinue antipsychotic medication in patients who have fully recovered from their initial episode of psychosis has been discussed and debated over the years. A prospective, open-label, nonrandomized study evaluated patients from an FEP intervention program at a university hospital setting. Forty-six individuals agreed to discontinue medication while 22 chose to be the control group and remain on antipsychotics. Criteria for participation in the study was: (1) a minimum of 18 months on antipsychotic treatment, (2) clinical remission for at least 12 months, (3) functional recovery for at least 6 months, and (4) stabilization at the lowest effective doses for at least 3 months. Forty-six individuals who were willing to discontinue medication were included in the discontinuation group (target group). The rates of relapse over the 3-year period were 67.4% in the discontinuation group and 31.8% in the maintenance group. The mean time to relapse was 209 (median = 122) days and 608 (median = 607) days, respectively

According to the researchers, a comparison of the two groups demonstrated that rate of symptom recurrence in functionally recovered FEP patients following the self-elected discontinuation of treatment was very high. The relapsed individuals demonstrated significant differences (P < .05) in the Assessment of Negative Symptoms scale, the Clinical Global Impressions scale, and the Disability Assessment Schedule from those who did not relapse.

Source: Journal of Clinical Psychiatry

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