Notes

Coping with an MPN inside Eire: patients' and caregivers' viewpoints.
Median time to CSWG was 14 weeks. CSWG results were numerically similar among patients with SZ and BD-I.Over 96% of patients had TIs during follow-up (median time of 12 [SZ] and 13 [BD-I] weeks). Among patients with CSWG and subsequent TIs and weight measurements, 74% did not return to baseline weight after interrupting treatment; the remainder returned to baseline weight with median times of 38 (SZ) and 39 (BD-I) weeks. Results suggest that most patients with CSWG do not return to baseline weight after stopping treatment with oral SGAs of moderate-to-high weight gain risk.Funding. Alkermes, Inc.
Carbamazepine, an anticonvulsant also used as a mood stabilizer and for trigeminal neuralgia, is associated with serious, sometimes fatal cutaneous adverse drug reactions, including Stevens Johnson Syndrome and toxic epidermal necrolysis1. Current literature demonstrates a genetic predisposition linked to specific class I and II human leukocyte antigen (HLA) types in various ethnic populations2. HLA-A*3101 is one such HLA type, and is routinely identified by the tag SNP rs1061235. However, rs1061235 has poor specificity for HLA*3101 due to interference of HLA-A*33 types3. We investigated the false positive rate in our population and developed a novel real-time PCR assay that distinguishes HLA-A*3101 from other HLA-A types including HLA-A*33.

120 unique samples were tested in triplicate during the validation of this assay and were sent to a reference lab for HLA next generation sequencing (NGS) typing, including 89 in-house samples and 31 Coriell samples with documented HLA typing results. The results fromd are expected to occur rarely in our patient population; we expect these HLA types make up less than 0.003% of the our population. Our assay specificity for the validation is >99%.

Our custom real-time PCR assay for detection of HLA-A*3101 is significantly more specific than the commonly used tag SNP rs1061235. Clinicians considering carbamazepine therapy for their patients will have a better understanding of cutaneous adverse reaction risk and can make improved personalized treatment decisions. This quick, cost effective assay allows more patients in need of carbamazepine treatment to benefit from its use.

Genomind, Inc.
Genomind, Inc.
Tardive dyskinesia (TD) is an involuntary movement disorder that is more prevalent in older patients. However, there is limited information on TD treatment for this population. In two 12-week pivotal trials (ARM-TD and AIM-TD), TD patients demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) score with deutetrabenazine versus placebo.

Patients who completed ARM-TD or AIM-TD enrolled in an open-label extension (OLE) study. This post hoc analysis assessed change and percent change from baseline in AIMS score, response rates for ≥50% AIMS improvement, Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and safety in younger (<55years) and older (≥55 years) patients.

This analysis included 119 younger and 218 older patients enrolled in the OLE. Data presented at Week 145 (mean±SE) total deutetrabenazine dose was 39.4±1.39mg/day and 39.5±1.04mg/day in younger and older patients, respectively. Changes from baseline in AIMS score were -6.7±0.62 and -6.5±0.47, respectively (percent changes of -61.4%±4.10% and -54.6%±3.01%). The majority of younger and older patients achieved treatment success per CGIC (67% and 76%) and PGIC (64% and 63%) and achieved ≥50% AIMS response (76% and 62%). Deutetrabenazine was generally well tolerated in both groups. Exposure-adjusted incidence rates (incidence/patient-years) were <0.01 and 0.02 for akathisia, 0.07 (both) for somnolence and sedation, 0.04 and 0.11 for parkinson-like events, and 0.06 and 0.09 for depression in younger and older patients, respectively.

Deutetrabenazine treatment was associated with sustained improvements in AIMS score and was well tolerated in both younger and older TD patients.

Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel.
Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel.
There is a plethora of drugs available to psychiatrists for treatment of mental illness, which can vary in efficacy, tolerability, metabolic pathways and drug-drug interactions. Psychotropics are the second most commonly listed therapeutic class mentioned in the FDA's Table of Pharmacogenomic Biomarkers in Drug Labeling. Pharmacogenomic (PGx) assays are increasingly used in psychiatry to help select safe and appropriate medication for a variety of mental illnesses. Our commercial laboratory offers PGx expert consultations by PharmDs and PhDs to clinician-users. Our database contains valuable information regarding the treatment of a diverse and challenging population.

Genomind offers a PGx assay currently measuring variants of 24 genes relevant for selection of drugs with a mental illness indication. Since 2012 we have analyzed > 250,000 DNA samples. Between 10/18 - 8/20 6,401 reports received a consult. The data contained herein are derived from those consults. Consultants record information on prior ml". In addition, 94% reported that these consults were superior to PGx consults provided through other laboratories. Patient characteristics captured during consults via a Clinical Global Impressions-Severity (CGI-S) scale revealed that the majority of patients were moderately (54%) or markedly ill (23%). The most frequent symptoms reported were depression, anxiety, insomnia and inattentiveness.

The large variety of psychotropic drugs available to providers, and their highly variable response rates, tolerability, capacity for drug-drug interactions and metabolic pathways present a challenge for even expert psychopharmacologists. Consultation with experts in PGx provides additional useful information that may improve outcomes and decrease healthcare resource utilization. This database may provide future opportunities for machine learning algorithms to further inform implications of included gene variants.

Genomind, Inc.
Genomind, Inc.The National Poison Data System (NPDS), is the data warehouse for the 55 US regional poison centers. While the primary role of a poison center is to provide medical management to the public and healthcare providers, a standardized database is used to collect case data. These data are routinely used to evaluate drug safety, including characterization of prescription medication misuse and abuse. While an effective therapy for attention deficit/hyperactivity disorder (ADHD), prescription stimulant medications (RxStim) may be misused and abused, a behavior that has been noted as an emerging public health concern particularly in relation to polysubstance abuse. The objective of this study was to characterize intentional exposures to RxStim in patients age >12 y of age as managed by US poison centers from Jan 2015- 31 Dec 2019.NPDS cases of intentional exposure to a RxStim in a patient >12 y managed from Jan 2015-Dec 2019 were included for analysis. Intentional exposures are defined in the NPDS manual as exposures nd 14.0% lost to follow-up but judged as a potentially toxic exposure. Another 22.4% reported minimally bothersome effects. Admission to a healthcare facility was reported for 1 out of 3 cases and another 36.3% were treated/evaluated/released from a healthcare service. An average of 2.3 clinical effects were reported per exposure, the most common being neurological effects (53.2%; examples include agitation, drowsiness/lethargy, confusion, hallucinations/delusions, tremor), cardiovascular effects (50.8%; examples include tachycardia, hypertension), and gastrointestinal effects (9.4%; examples include vomiting, nausea).RxStim misuse and abuse cases managed by US poison centers most often leads to significant medical outcomes which require medical attention. The role of these medications in polysubstance abuse is concerning and suggestive of needed strategies to address this increasingly important public health concern.Funding Arbor Pharmaceuticals, LLC.Perampanel is an anti-epileptic drug reported to exert its effects in the central never system (CNS) by inhibiting post-synaptic glutamate receptors. The most commonly reported neuropsychiatric side effects are affective dysregulation with some reports of psychosis. GDC-0879 However, the precise therapeutic mechanism is unknown. We report on a 32-year-old African American male with recurring generalized tonic-clonic (GTC) seizures, who presented to our hospital with onset of mood lability for several months, subsequent to adding perampanel to his antiepileptic medications. On presentation, perampanel administration was temporarily withheld, and subsequently, noted to be coincident with neuropsychiatric symptomatology, including motor weakness in emotional contexts. The mechanisms underlying cataplexy are complex and, in our patient, most likely induced by an interaction between perampanel and the wakeful inhibition of the sublaterodorsal nucleus projections.
The internet allows easy access for the sales of psychoactive agents that are not regulated by the FDA. Some of those agents are used to help manage anxiety, depression and sleep, such as tianeptine, etizolam, and phenibut. These medications have the potential for abuse and potentially leading to altered mental status when intoxicated or withdrawing. This presents a challenge to clinicians who may not be aware of availability of such substances. Available literature has discussed the use of above substances individually, but how do you treat if there is use of more than one substance with different mechanisms of actions? Here we present a case of an adult male who has used all three agents simultaneously, leading to a hospital admission.

A 32-year-old male presented to the emergency department (ED) for altered mental status (AMS). He has a documented history of anxiety but was never treated with prescription medications. No history of substance use was documented. He was self-medicating with concurrent usty managing poly-substance use/abuse and stresses the importance for physicians to screen for psychoactive agents purchased over the internet or over the counter to improve treatment outcomes. Continued discussions with patients regarding risks/benefits of use of such substances would be beneficial and help increase awareness.
The 12-week ARM-TD and AIM-TD studies in tardive dyskinesia (TD) patients showed statistically significant improvements in TD symptoms with deutetrabenazine. The completed open-label extension (OLE) study (SD-809-C-20) evaluated long-term efficacy and safety of deutetrabenazine in TD.

Patients who completed ARM-TD or AIM-TD enrolled in the OLE study, with deutetrabenazine dose titrated based on dyskinesia control and tolerability. Change from baseline in Abnormal Involuntary Movement Scale (AIMS) score was assessed by local site raters. Treatment success was evaluated locally as patients being "much improved" or "very much improved" on Clinical Global Impression of Change (CGIC).

343 patients enrolled in the OLE study; 6 patients were excluded from analyses. At Week 54 (n=249; dose [mean±SE] 38.7±0.66mg/day), mean change from baseline in AIMS score was -4.8±0.28; 66% of patients experienced treatment success. At Week 106 (n=194; dose 39.3±0.75mg/day), mean change from baseline in AIMS score was -5.4±0.33; 65% of patients experienced treatment success.
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