bluuebunny/crossref_metadata_2025_split huggingface dataset:
134 Improvements in Clinical Global Impression of Change With Deutetrabenazine Treatment in Tardive Dyskinesia From the ARM-TD and AIM-TD Studies
Authors: Fernandez Hubert H. , Davis Mat D. , Factor Stewart A. , Hauser Robert A. , Jarskog L. Fredrik , Jimenez-Shahed Joohi , Kumar Rajeev , Ochudlo Stanislaw , Ondo William G. , Anderson Karen E. 
Published: June 2018

AbstractIntroductionTardive dyskinesia (TD) is an involuntary movement disorder that is often irreversible, can affect any body region, and can be debilitating. In the ARM-TDand AIM-TD studies, deutetrabenazine treatment demonstrated statistically and clinically significant reductions in Abnormal Involuntary Movement Scale (AIMS) scores at Week 12 compared with placebo (primary endpoint).ObjectiveTo evaluate the efficacy of deutetrabenazine, as measured by the Clinical Global Impression of Change (CGIC) scale, in patients with TD from the pooled ARM-TDand AIM-TD (24 and 36 mg/day doses) data sets, as compared with the pooled placebo cohort.MethodsARM-TD and AIM-TD were 12-week, randomized, double-blind, placebo-controlled studies that evaluated the safety and efficacy of deutetrabenazine for thetreatment of TD. The key secondary endpoint of each study was the proportion of patients “much improved” or “very much improved” (treatment success) at Week 12 on theCGIC.ResultsAt Week 12, the odds of treatment success among patients treated with deutetrabenazine (n=152) was more than double that of patients given placebo (n=107; odds ratio: 2.12; P=0.005). In a categorical analysis of CGIC ratings, patients treated with deutetrabenazine showed greater improvement than patients given placebo (P=0.003). Patients treated with deutetrabenazine also had a significantly better treatment response than those given placebo (least-squares mean CGIC score treatment difference: –0.4; P=0.006).ConclusionsDeutetrabenazine treatment led to statistically and clinically significant improvements in TD symptoms based on the CGIC result, suggesting that clinicians were able to recognize the benefit in patients treated with deutetrabenazine.Presented at: The International Congress of Parkinson’s Disease and Movement Disorders; June 4–8, 2017; Vancouver, British Columbia, Canada.Funding AcknowledgementsThese studies were funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.
136 CerefolinNAC Therapy-Induced Dizziness
Authors: Nayati Jasir T. , Hirsch Alan R. 
Published: June 2018

AbstractStudy ObjectiveCerefolinNAC (CFLN-NAC) contains L-methylfolate (6 mg), methylcobalamin (2 mg), and N-acetylcysteine [NAC] (600 mg) [Pamlab 2017]. Dizziness and lightheadedness have not heretofore been described with use of CFLN-NAC.MethodsCase Study: A 64 year old right-handed female was started on CFLN-NAC for smell and taste issues. Over a three day period, she experienced a gradual increase in dizziness. This was a non-vertiginous lightheadedness, so severe that she was unable to walk, and would lie down the entire day to alleviate the dizziness. It was associated with nausea, but without any vomiting or falls. The dizziness would come and go, last for several hours, and was 9/10 in severity.She admits to a past history of epochs of vertigo. The vertigo occurred three times with nausea and vomiting 13 years, 11 years, and 4 years prior to presentation. She also developed a constant, bilateral, high-pitched tinnitus 14 years prior to presentation, which obstructs her hearing. It is level 3/10 in intensity during the night and in the quiet. There were no alleviating or aggravating factors. Acupuncture was without effect, and she denies any ear pain. After ceasing CFLN-NAC for three days, a gradual reduction of dizziness to baseline ensued.ResultsAbnormalities in Physical Examination: General: Decreased blink frequency and hypokinesia. Cranial Nerve III, IV, VI: Saccadization of horizontal eye movements. Motor Examination: Tone: 1+ cogwheel rigidity in both upper extremities, left more than right. Drift Test: Bilateral Abductor Digiti Minimi sign with cerebellar spooning. Reflexes: Absent quadriceps femoris and Achilles bilaterally. Positive Hoffman reflex bilaterally. Neuropsychiatric Testing: Go-No-Go Test: 6/6 (normal). Animal Fluency Test: 19 (normal). Reliable Digit Span: 10 (normal). Clock Drawing Test: 4 (normal). Center for Neurologic Study Lability Scale: 10 (normal). Other: Audiometry and Fiberoptic Endoscopy: normal. MRI of the brain with and without contrast was normal.ConclusionNone of the individual components in CFLN-NAC have been reported to precipitate dizziness [Pamlab 2017]. The non-vertiginous nature of the dizziness makes it unlikely to be due to vestibular involvement, raising the spectre of this drug having an impact on the autonomic nervous system. While a nocebo effect could be in action, this is unlikely since dizziness was not presented as a potential side effect on initiation of the medication. In addition, methylcobalamin can cause hyperviscosity syndrome, but due to an absence of visual disturbances and altered mental status, it is also improbable. The relatively rapid onset with initiation and resolution upon discontinuation of this medication strongly suggests that it is not a coincidence, rather an origin for the dizziness. Those who are treated with CFLN-NAC should be queried as to new onset dizziness. For those already dizzy, one should consider other treatment options.Funding AcknowledgementsSmell and Taste Treatment and Research Foundation
137 Menstrual Synchrony of Burning Mouth Syndrome
Authors: Nayati Jasir T. , Hirsch Alan R. 
Published: June 2018

AbstractStudy ObjectiveBurning mouth syndrome (BMS) is characterized by oral mucosal burning sensations, with normal clinical and laboratory results. Menstrual synchrony of migraines and epilepsy have been discussed; however, menstrual synchrony of BMS has not heretofore been described.MethodsCase Study: A 29 year old right-handed female exhibited intermittent BMS symptoms, one month after suffering a left parietal infarction. She describes the pain as a burningsensation, localized to the bilateral and anterior aspects of her tongue. It lasts for four days, starts three days prior to her menses, and occurs twice a month. She is unable to correlate any patterns or triggers that may cause to exacerbate her BMS. She denies any taste disturbances, hot-flashes, night sweats, and perspiration.ResultsAbnormalities during neurological examination were noted. Cranial nerves (CN) III, IV, and VI showed bilateral lateral first degree end-gaze unsustained nystagmus. CN IX and X showed decreased bilateral gag reflex. A right pronator drift with a right abductor digiti minimi sign was seen in the motor examination. The cerebellar examination was positive for bilateral dysmetria during the Finger-To-Nose examination, and exhibited Holmes rebound phenomena, right more than left. Sensory examination showed decreased light touch in the lower extremities, right more than left. Hoffman reflex was bilaterally positive. Mental status examinations demonstrated poor similarity interpretation and calculation ability. Her neuropsychiatric testing was normal, and included the Go-No-Go and Animal Fluency Testing. MRI of the brain exhibited gliosis/laminar necrosis in the left inferior parietal lobe, and an 8mm descent of cerebellar tonsils below the foramen magnum.ConclusionThe potential mechanism for catamenial BMS is manyfold. Estrogen and progesterone both have nociceptive properties. Premenstrual drop or reduction of estrogen and progesterone may act to disinhibit pain [Vincent 2008], with pain modulation being more effective during the ovulatory phase (high estrogen and low progesterone) [Rezaii 2012]. Depression in the presence of Late Luteal Phase Dysphoric Disorder may function to exacerbate the perception of underlying pain throughout the body, including the mouth and tongue. Decrease in estrogen and progesterone levels may also alter salivary output and composition. This may allow baseline reduction of proprioceptive input on the tongue, thus acting through Melzack and Wall’s Gate Control Theory of Pain to disinhibit small C fibers, which is perceived as burning pain [Melzack 1978]. Along with menses, olfactory ability drops, and food preferences are often reported to change [Keller 2013]. A decrease in estrogen and progesterone can also enhance trigeminal nerve sensitivity [Martin 2007], which exacerbates pain. This may indirectly influence or be associated with her BMS. Such observations justifies a trial of hormonal agents for therapy of BMS.Funding AcknowledgementsSmell and Taste Treatment and Research Foundation
141 The Effects of Valbenazine on Tardive Dyskinesia: Subgroup Analyses of 3 Randomized, Double-Blind, Placebo-Controlled Trials
Authors: Meyer Jonathan , Remington Gary , Norbash Ali , Burke Joshua , Siegert Scott , Liang Grace S. 
Published: June 2018

AbstractStudy ObjectivesThe approval of valbenazine (INGREZZA; VBZ) for the treatment of tardive dyskinesia (TD) in adults was based on results from double-blind, placebo (PBO)-controlled trials. These studies demonstrated the efficacy of once-daily VBZ based on intent-to-treat analyses. However, because many different types ofpatients can develop TD, subgroup analyses describing treatment outcomes by various patient factors were also conducted.MethodsData were pooled from three 6-week trials: KINECT (NCT01688037), KINECT 2 (NCT01733121), KINECT 3 (NCT02274558), with outcomes analyzed by VBZ dose (80 mg, 40 mg) and PBO. Descriptive analyses conducted using the Abnormal Involuntary Movement Scale (AIMS) total score included: mean change from baseline to Week 6; and AIMS response, defined as 50% improvement from baseline to Week 6. Subgroups were defined as follows: age (<55 years, ≥55 years), sex (male, female), psychiatric diagnosis (schizophrenia/schizoaffective disorder, mood disorder), CYP2D6 genotype (poor metabolizer [PM], non-PM), body mass index (BMI) (<18.5, 18.5 to <25, 25 to <30, ≥30 kg/m2), concomitant antipsychotic (yes, no); type of antipsychotic (atypical, typical/both); lifetime history of suicidality (yes, no); concomitant anticholinergic (yes, no); TD duration (<7 years, ≥7 years).ResultsThe pooled population included 373 participants (VBZ 80 mg, n=101; VBZ 40 mg, n=114; PBO, n=158). Mean improvements from baseline to Week 6 in AIMS total score were greater overall with VBZ compared to PBO. Within subgroup categories, AIMS score improvement with VBZ 80 mg (recommended dose) was greater in CYP2D6 PMs (n=17; 80 mg, -6.8; 40 mg, 2.4; PBO, 0.5), participants taking no concomitant antipsychotics (n=64; 80 mg, -4.9; 40 mg, -3.0; PBO, 0.0), and overweight participants (BMI 25 to <30 kg/m2, n=115; 80 mg, -4.2; 40 mg, 2.7; PBO, -0.7). Overweight participants also had the highest AIMS response rates at Week 6 (80 mg, 57.7%; 40 mg, 31.6%; PBO, 11.8%), followed by participants taking typical/both antipsychotics (n=67; 80 mg, 57.1%; 40 mg, 20.0%; PBO, 25.0%), and those taking anticholinergics (n=126; 80 mg, 52.9%; 40 mg, 22.7%; PBO, 6.3%).ConclusionThese preliminary analyses indicate that TD improvements were generally greater with VBZ than PBO across most subgroups. However, the small sizes of some subgroups may need to be considered when interpreting results. Additional analyses within subgroup categories are ongoing and will be presented at the meeting.Funding AcknowledgementsThis study was funded by Neurocrine Biosciences, Inc.
143 Effect of Tardive Dyskinesia on Quality of Life: Patient-Reported Symptom Severity Is Associated With Deficits in Physical, Mental, and Social Functioning
Authors: McEvoy Joseph , Carroll Benjamin , Gandhi Sanjay , Rizio Avery , Maher Stephen , Kosinski Mark , Bjorner Jakob 
Published: June 2018

AbstractIntroductionTardive dyskinesia (TD), an often-irreversible movement disorder typically caused by exposure to antipsychotics, most commonly affects the face, mouth, and tongue and may be debilitatingObjectiveTo investigate TD burden on patients’ quality of life and functionalityMethodsAdults with clinician-confirmed schizophrenia, bipolar disorder, or major depressive disorder participated in an observational study. Approximately half (47%) ofparticipants had a clinician-confirmed TD diagnosis. Participants completed the SF-12v2 Health Survey® (SF-12v2), Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF), social withdrawal subscale of the Internalized Stigma of Mental Illness scale (SW-ISMI), and rated the severity of their TD symptoms. Group differences in SF-12v2 physical and mental component summaries (PCS and MCS), Q-LES-Q-SF, and SW-ISMI scores were analyzed.ResultsTD (n=79) and non-TD (n=90) groups were similar in age, gender, and number of patients with schizophrenia, bipolar disorder, and major depressive disorder. TD patients reported significantly worse scores on PCS (P=0.003), Q-LES-Q-SF (P<0.001) and SW-ISMI (P<0.001) than non-TD patients. The difference in PCS exceeded the established minimal clinically important difference (MCID) of 3 points. When stratified by TD severity, those with more severe symptoms had significantly worse Q-LES-Q-SF (P<0.001) and SW-ISMI (P=0.006) scores than those with less severe symptoms. Differences in PCS (P=0.12) and MCS (P=0.89) were in the expected direction and exceeded the MCID.ConclusionsAmong patients with psychiatric disorders, TD is associated with significant physical health burden and incremental mental health burden. TD severity is also associated with lower overall quality of life and greater social withdrawal.Presented at: Psych Congress; September 16–19, 2017; New Orleans, Louisiana, USA.Funding AcknowledgementsThis study was funded by Teva Pharmaceutical Industries, Petach Tikva, Israel.
144 A Clinical Practice Assessment In Tardive Dyskinesia: Are Physicians Up-to-Date?
Authors: Lubarda Jovana , Hughes Stacey , Correll Christoph U. 
Published: June 2018

AbstractStudy ObjectivesTo assess physicians’ current knowledge, skills, competence, and practice barriers regarding tardive dyskinesia (TD) and assess continuing medical education (CME) needs.Assessment MethodsA 29-question clinical practice assessment survey instrument consisting of multiple-choice knowledge and case-based questions was administered online to gather abaseline “snapshot” of knowledge, skills, attitudes, and competence on TD epidemiology, risk factors, diagnosis, current guideline-based management, and emerging management strategiesThe survey launched online on a website dedicated to continuous professional development on July 25, 2016, and was made available to healthcare providers without monetary compensation or charge. Data were collected through August 28, 2016Confidentiality was maintained and responses were de-identified and aggregated prior to analysesResultsData were collected for the 1157 psychiatrists and 177 neurologists who responded to all survey questions during the study period. The findings were:∙Epidemiology: 62% of psychiatrists and 68% of neurologists were aware that TD affects approximately 20% of patients treated with neuroleptic agents∙Risk factors: 63% of psychiatrists and 67% of neurologists were aware of risk factors for TD, such as older age∙Diagnosis: 93% of psychiatrists and 71% of neurologists were aware that Abnormal Involuntary Movement Scale (AIMS) can be used to support diagnosis of TD∙Guidelines: 21% of psychiatrists and 11% of neurologists were aware of the American Psychiatric Association guidelines for monitoring of TD, and 56% of psychiatrists and 42% of neurologists were aware of the American Academy of Neurology guidelines on treatment of TDNew/emerging treatments: 24% of psychiatrists and 34% of neurologists were aware of the mechanisms of action of new/emerging treatments for TD, and 54% and 44%, respectively, were aware of the clinical data for valbenazineConclusionsThis educational research yielded important insights into clinical practice gaps in TD, indicating that both psychiatrists and neurologists would benefit from continuing medical education on epidemiology, risk factors, diagnosis, guideline-based care, and information on how to incorporate new/emerging treatments for TD into practice.Funding AcknowledgementsThe educational activity and outcomes measurement were funded through an independent educational grant from Neurocrine Biosciences, Inc.
148 Visual Snow Defeats Guardians of the Galaxy Volume 2: Unremitting Pixelation Despite Three-Dimentional Stereoscopic Film
Authors: Prashar Kanchan S , Titus Abraham M , Kinkhabwala Vishal , Hirsch Alan R 
Published: June 2018

AbstractIntroductionPixelated vision or visual snow has been associated with schizophrenia (Silverstein 2011). The impact of viewing a 3D motion picture on such a visualphenomenon has not heretofore been described.MethodCase Study: A 28 year old right handed single male three years prior to presentation noticed that all his vision was pixelated. The pixelated vision is panoramic, involving the entire visual field. The pixels are characterized by 10,000 flat white and gray dots measuring 1mm x 1mm. No changes in color, shape, or size were noted in high and low intensity light. White, dark, gray, or multicolored backgrounds had no effect on his vision. The visual distortions are not impacted by head movements, emotions, degree of tiredness, driving, or his hedonic perception of the object being visualized. The pixels were noted to disappear upon closure of both eyes but persisted during monocular vision with either eye. These visual hallucinations were sporadic during the first year and became continuous over the following two years. Two weeks after onset ofpixelated vision he developed auditory hallucinations and hyperacusis. These increased in intensity and frequency to 500-600 times per day. He denied palinopsia, migraines, tinnitus, and photophobia. These hallucinations persisted despite treatment with aripiprazole, paliperidone, lurasidone, olanzapine, clozapine, ziprasidone, benztropine, bupropion, lamotrigine, modafinil, trazodone, atomoxetine, and amphetamine.ResultsAbnormalities in Examination: Hypoverbal, blunted affect, impaired concentration, preoccupied with racing thoughts. Admitted to actively having auditory and visualhallucinations, without suicidal or homicidal ideations. Memory testing: Able to recall 2 out of 4 objects in 3 minutes and 3 out of 4 with reinforcement. Similarities interpreted concretely. Visual Acuity: 20/20 OU. Retinal examination: Normal. Intraocular Pressure: 19 mm OD, 20 mm OS (normal). Automotive Perimetry Testing: Normal. Cover/Uncover: Normal. Near Convergence: 3 inches (normal). Lens or filtered prism have no effect on visual snow. MRI of his brain, EEG, BAER, liver function tests, CBC, vitamin B12, folate, and thyroid function tests were normal. MRA: mild hypoplasia of distal right vertebral artery.DiscussionVisual snow has been anecdotally described as static, continuous, and independent of the specific visual environment (McKendrick, 2017). However, thepersistence of visual snow in the presence of 3D movies has never been reported. The visual snow paralleled auditory hallucinations and hyperacusis in frequency and intensity, which suggests there may be generalized hyperexcitability of the brain inducing both auditory and visual hallucinations. Agents that reduce cortical hyperexcitability (i.e., anticonvulsants, anxiolytics) may have efficacy. Treatment with these agents has been described (Ghannam, 2017), warrants further investigation.Funding AcknowledgementsNo funding.
156 Improvement in Disease Severity in Patients With Treatment-Resistant Depression Following Treatment With Intranasal Esketamine
Authors: Nash Abigail , Shawi May , Singh Jaskaran , Daly Ella , Copper Kimberly , Lim Pilar , Lane Rosanne , Gogate Jagadish , DiBernardo Allitia , Hough David , Alphs Larry 
Published: June 2018

AbstractBackgroundRecognizing the importance not only of the clinician’s opinion but also of the patient’s experience and perspective, Sequenced Treatment Alternatives to Relieve Depression (STAR*D) utilized both clinician-reported and patient-reported outcomes in a large-scale multi-step study on antidepressant effectiveness in real-world settings. Both approaches indicate that <17% of Major Depressive Disorder (MDD) patients respond to novel oral treatments after two prior antidepressant failures. To address this low response rate and continue to investigate the use of patient-rated outcomes in clinical trials, an antidepressant with a new mechanism of action is being investigated for efficacy and safety utilizing both clinician-rated and patient-reported scales.MethodsThis is a post-hoc analysis of a Janssen R&D Phase 2a clinical trial (ESKETINTRD2003). Subjects aged 20-64 withMDD without psychotic features (DSM IV) and a history of inadequate response to ≥2 antidepressants were randomized [3:1:1:1] to 1 week of twice-weekly treatment with intranasal placebo (n=33), esketamine 28 mg (n=11), 56 mg (n=11), or 84 mg (n=12). Participants taking oral antidepressants at study entry continued treatment during the study. Changes in depression severitywere measured using the Clinical Global Impression Severity (CGI-S) and the Patient Global Impression Severity (PGI-S) scales.ResultsAt all esketamine doses (28 mg, 56 mg, 84 mg), subjects reported a one-point mean change in PGI-S from baseline to week one compared to no change on placebo (p-values 0.005, 0.001, 0.032 respectively). Similarly, mean CGI-S scores improved for subjects receiving esketamine at all doses (p-values 0.028, 0.004, 0.049 respectively) compared to no change inplacebo subjects. These data are consistent with previously reported data based on the Montgomery Åsberg Depression Rating Scale (MADRS) and support positive correlation between patient-reported and clinician-reported outcomes.DiscussionInitial results from this Phase 2a study suggest clinically relevant improvement in depression symptoms in as early as one week when treated with twice-weekly intranasal esketamine as reported by both clinicians and patients. This work will help guide future investigations of esketamine in larger populations to provide better therapeutic options for treatment resistantMDD patients.Funding AcknowledgementsJanssen
177 Management of Treatment-Resistant Schizophrenia With Clozapine Augmentation
Authors: Phyu Pwint , Arocha Emelina , Oms Juan D. , Gunaseelan Luxhman , Foroughi Golbon , Rizvi Syed A. A. 
Published: June 2018

AbstractA 44-year-old woman with a history of chronic schizoaffective disorder, epilepsy, social phobia, anxiety, and panic attacks presented with concern for “feeling anxious.” After a history, physical examination, and laboratory tests, the woman received a diagnosis of treatment-resistant schizophrenia. While clozapine is the standard therapy for schizophrenia, certain patients such as the woman in this case do not respond well to clozapine monotherapy, requiring clozapine to be augmented with other antipsychotics or antidepressants. This case outlines the unique challenges of managing patients with treatment-resistant schizophrenia, especially when they present with comorbid conditions such as epilepsy that can limit treatment options. A multipronged approach, including pharmacologic therapy as well as cognitive behavioral therapy, should also be considered.Funding AcknowledgementsNo funding.