IU Indianapolis ScholarWorks :: Browsing by Author "Trzepacz, Paula T."

Browsing by Author "Trzepacz, Paula T."

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A review of the abuse potential assessment of atomoxetine: a nonstimulant medication for attention-deficit/hyperactivity disorder
(Springer, 2013) Upadhyaya, Himanshu P.; Desaiah, Durisala; Schuh, Kory J.; Bymaster, Frank P.; Kallman, Mary J.; Clarke, David O.; Durell, Todd M.; Trzepacz, Paula T.; Calligaro, David O.; Nisenbaum, Eric S.; Emmerson, Paul J.; Schuh, Leslie M.; Bickel, Warren K.; Allen, Albert J.; Psychiatry, School of Medicine
Rationale: Treatment of attention-deficit/hyperactivity disorder (ADHD) has for many years relied on psychostimulants, particularly various formulations of amphetamines and methylphenidate. These are central nervous system stimulants and are scheduled because of their abuse potential. Atomoxetine (atomoxetine hydrochloride; Strattera®) was approved in 2002 for treatment of ADHD, and was the first nonstimulant medication approved for this disorder. It was classified as an unscheduled medication indicating a low potential for abuse. However, the abuse potential of atomoxetine has not been reviewed. Objectives: In this article, we review the evidence regarding abuse potential of atomoxetine, a selective inhibitor of the presynaptic norepinephrine transporter, which is unscheduled/unrestricted in all countries where it is approved. Methods: Results from receptor binding, in vitro electrophysiology, in vivo microdialysis, preclinical behavioral, and human laboratory studies have been reviewed. Results: Atomoxetine has no appreciable affinity for, or action at, central receptors through which drugs of abuse typically act, i.e., dopamine transporters, GABA(A) receptors, and opioid μ receptors. In behavioral experiments in rodents, atomoxetine does not increase locomotor activity, and in drug discrimination studies, its profile is similar to that of drugs without abuse potential. Atomoxetine does not serve as a reinforcer in monkey self-administration studies, and human laboratory studies suggest that atomoxetine does not induce subjective effects indicative of abuse. Conclusion: Neurochemical, preclinical, and early clinical studies predicted and supported a lack of abuse potential of atomoxetine, which is consistent with the clinical trial and postmarketing spontaneous event data in the past 10 years.
Association between Serum IGF-I levels and Postoperative Delirium in Elderly Subjects Undergoing Elective Knee Arthroplasty.
(NPG, 2016) Yen, Timothy E.; Allen, John C.; Rivelli, Sarah K.; Patterson, Stephanie C.; Metcalf, Meredith R.; Flink, Benjamin J.; Mirrakhimov, Aibek E.; Lagoo, Sandhya A.; Vail, Thomas P.; Young, Christopher C.; Moon, Richard E.; Trzepacz, Paula T.; Kwatra, Madan M.; Department of Psychiatry, IU School of Medicine
Evidence is mixed for an association between serum insulin-like growth factor-I (IGF-I) levels and postoperative delirium (POD). The current study assessed preoperative serum IGF-I levels as a predictor of incident delirium in non-demented elderly elective knee arthroplasty patients. Preoperative serum levels of total IGF-I were measured using a commercially available Human IGF-I ELISA kit. POD incidence and severity were determined using DSM-IV criteria and the Delirium Rating Scale-Revised-98 (DRS-R98), respectively. Median IGF-I levels in delirious (62.6 ng/ml) and non-delirious groups (65.9 ng/ml) were not significantly different (p = 0.141). The ratio (95% CI) of geometric means, D/ND, was 0.86 (0.70, 1.06). The Hodges-Lehmann median difference estimate was 7.23 ng/mL with 95% confidence interval (−2.32, 19.9). In multivariate logistic regression analysis IGF-I level was not a significant predictor of incident POD after correcting for medical comorbidities. IGF-I levels did not correlate with
Clinical use of amyloid-positron emission tomography neuroimaging: Practical and bioethical considerations
(Elsevier, 2015-09) Witte, Michael M.; Foster, Norman L.; Fleisher, Adam S.; Williams, Monique M.; Quaid, Kimberly; Wasserman, Michael; Hunt, Gail; Roberts, J. Scott; Rabinovici, Gil D.; Levenson, James L.; Hake, Ann Marie; Hunter, Craig A.; Van Campen, Luann E.; Pontecorvo, Michael J.; Hochstetler, Helen M.; Tabas, Linda B.; Trzepacz, Paula T.; Department of Neurology, IU School of Medicine
Until recently, estimation of β-amyloid plaque density as a key element for identifying Alzheimer's disease (AD) pathology as the cause of cognitive impairment was only possible at autopsy. Now with amyloid-positron emission tomography (amyloid-PET) neuroimaging, this AD hallmark can be detected antemortem. Practitioners and patients need to better understand potential diagnostic benefits and limitations of amyloid-PET and the complex practical, ethical, and social implications surrounding this new technology. To complement the practical considerations, Eli Lilly and Company sponsored a Bioethics Advisory Board to discuss ethical issues that might arise from clinical use of amyloid-PET neuroimaging with patients being evaluated for causes of cognitive decline. To best address the multifaceted issues associated with amyloid-PET neuroimaging, we recommend this technology be used only by experienced imaging and treating physicians in appropriately selected patients and only in the context of a comprehensive clinical evaluation with adequate explanations before and after the scan.
Concordance between DSM-IV and DSM-5 criteria for delirium diagnosis in a pooled database of 768 prospectively evaluated patients using the delirium rating scale-revised-98
(BioMed Central, 2014-09-30) Meagher, David J.; Morandi, Alessandro; Inouye, Sharon K.; Ely, Wes; Adamis, Dimitrios; Maclullich, Alasdair J.; Rudolph, James L.; Neufeld, Karin; Leonard, Maeve; Bellelli, Giuseppe; Davis, Daniel; Teodorczuk, Andrew; Kreisel, Stefan; Thomas, Christine; Hasemann, Wolfgang; Timmons, Suzanne; O’Regan, Niamh; Grover, Sandeep; Jabbar, Faiza; Cullen, Walter; Dunne, Colum; Kamholz, Barbara; Van Munster, Barbara C.; De Rooij, Sophia E.; De Jonghe, Jos; Trzepacz, Paula T.; Department of Psychiatry, School of Medicine
Background The Diagnostic and Statistical Manual fifth edition (DSM-5) provides new criteria for delirium diagnosis. We examined delirium diagnosis using these new criteria compared with the Diagnostic and Statistical Manual fourth edition (DSM-IV) in a large dataset of patients assessed for delirium and related presentations. Methods Patient data (n = 768) from six prospectively collected cohorts, clinically assessed using DSM-IV and the Delirium Rating Scale-Revised-98 (DRS-R98), were pooled. Post hoc application of DRS-R98 item scores were used to rate DSM-5 criteria. ‘Strict’ and ‘relaxed’ DSM-5 criteria to ascertain delirium were compared to rates determined by DSM-IV. Results Using DSM-IV by clinical assessment, delirium was found in 510/768 patients (66%). Strict DSM-5 criteria categorized 158 as delirious including 155 (30%) with DSM-IV delirium, whereas relaxed DSM-5 criteria identified 466 as delirious, including 455 (89%) diagnosed by DSM-IV (P <0.001). The concordance between the different diagnostic methods was: 53% (ĸ = 0.22) between DSM-IV and the strict DSM-5, 91% (ĸ = 0.82) between the DSM-IV and relaxed DSM-5 criteria and 60% (ĸ = 0.29) between the strict versus relaxed DSM-5 criteria. Only 155 cases were identified as delirium by all three approaches. The 55 (11%) patients with DSM-IV delirium who were not rated as delirious by relaxed criteria had lower mean DRS-R98 total scores than those rated as delirious (13.7 ± 3.9 versus 23.7 ± 6.0; P <0.001). Conversely, mean DRS-R98 score (21.1 ± 6.4) for the 70% not rated as delirious by strict DSM-5 criteria was consistent with suggested cutoff scores for full syndromal delirium. Only 11 cases met DSM-5 criteria that were not deemed to have DSM-IV delirium. Conclusions The concordance between DSM-IV and the new DSM-5 delirium criteria varies considerably depending on the interpretation of criteria. Overly-strict adherence for some new text details in DSM-5 criteria would reduce the number of delirium cases diagnosed; however, a more ‘relaxed’ approach renders DSM-5 criteria comparable to DSM-IV with minimal impact on their actual application and is thus recommended.
Delirium diagnosis defined by cluster analysis of symptoms versus diagnosis by DSM and ICD criteria: diagnostic accuracy study
(BioMed Central, 2016-05-26) Sepulveda, Esteban; Franco, Jose G.; Trzepacz, Paula T.; Gaviria, Ana M.; Meagher, David J.; Palma, Jose; Viñuelas, Eva; Grau, Imma; Vilella, Elisabet; de Pablo, Joan; Department of Psychiatry, IU School of Medicine
BACKGROUND: Information on validity and reliability of delirium criteria is necessary for clinicians, researchers, and further developments of DSM or ICD. We compare four DSM and ICD delirium diagnostic criteria versions, which were developed by consensus of experts, with a phenomenology-based natural diagnosis delineated using cluster analysis of delirium features in a sample with a high prevalence of dementia. We also measured inter-rater reliability of each system when applied by two evaluators from distinct disciplines. METHODS: Cross-sectional analysis of 200 consecutive patients admitted to a skilled nursing facility, independently assessed within 24-48 h after admission with the Delirium Rating Scale-Revised-98 (DRS-R98) and for DSM-III-R, DSM-IV, DSM-5, and ICD-10 criteria for delirium. Cluster analysis (CA) delineated natural delirium and nondelirium reference groups using DRS-R98 items and then diagnostic systems' performance were evaluated against the CA-defined groups using logistic regression and crosstabs for discriminant analysis (sensitivity, specificity, percentage of subjects correctly classified by each diagnostic system and their individual criteria, and performance for each system when excluding each individual criterion are reported). Kappa Index (K) was used to report inter-rater reliability for delirium diagnostic systems and their individual criteria. RESULTS: 117 (58.5 %) patients had preexisting dementia according to the Informant Questionnaire on Cognitive Decline in the Elderly. CA delineated 49 delirium subjects and 151 nondelirium. Against these CA groups, delirium diagnosis accuracy was highest using DSM-III-R (87.5 %) followed closely by DSM-IV (86.0 %), ICD-10 (85.5 %) and DSM-5 (84.5 %). ICD-10 had the highest specificity (96.0 %) but lowest sensitivity (53.1 %). DSM-III-R had the best sensitivity (81.6 %) and the best sensitivity-specificity balance. DSM-5 had the highest inter-rater reliability (K =0.73) while DSM-III-R criteria were the least reliable. CONCLUSIONS: Using our CA-defined, phenomenologically-based delirium designations as the reference standard, we found performance discordance among four diagnostic systems when tested in subjects where comorbid dementia was prevalent. The most complex diagnostic systems have higher accuracy and the newer DSM-5 have higher reliability. Our novel phenomenological approach to designing a delirium reference standard may be preferred to guide revisions of diagnostic systems in the future.
Empirically Defining Trajectories of Late-Life Cognitive and Functional Decline
(IOS, 2015-11) Hochstetler, Helen; Trzepacz, Paula T.; Wang, Shufang; Yu, Peng; Case, Michael; Henley, David B.; Degenhardt, Elisabeth; Leoutsakos, Jeannie-Marie; Lyketsos, Constantine G.; Department of Psychiatry, IU School of Medicine
Background: Alzheimer’s disease (AD) is associated with variable cognitive and functional decline, and it is difficult to predict who will develop the disease and how they will progress. Objective: This exploratory study aimed to define latent classes from participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database who had similar growth patterns of both cognitive and functional change using Growth Mixture Modeling (GMM), identify characteristics associated with those trajectories, and develop a decision tree using clinical predictors to determine which trajectory, as determined by GMM, individuals will most likely follow. Methods: We used ADNI early mild cognitive impairment (EMCI), late MCI (LMCI), AD dementia, and healthy control (HC) participants with known amyloid-β status and follow-up assessments on the Alzheimer’s Disease Assessment Scale - Cognitive Subscale or the Functional Activities Questionnaire (FAQ) up to 24 months postbaseline. GMM defined trajectories. Classification and Regression Tree (CART) used certain baseline variables to predict likely trajectory path. Results: GMM identified three trajectory classes (C): C1 (n = 162, 13.6%) highest baseline impairment and steepest pattern of cognitive/functional decline; C3 (n = 819, 68.7%) lowest baseline impairment and minimal change on both; C2 (n = 211, 17.7%) intermediate pattern, worsening on both, but less steep than C1. C3 had fewer amyloid- or apolipoprotein-E ɛ4 (APOE4) positive and more healthy controls (HC) or EMCI cases. CART analysis identified two decision nodes using the FAQ to predict likely class with 82.3% estimated accuracy. Conclusions: Cognitive/functional change followed three trajectories with greater baseline impairment and amyloid and APOE4 positivity associated with greater progression. FAQ may predict trajectory class.
Florbetapir F18 PET Amyloid Neuroimaging and Characteristics in Patients With Mild and Moderate Alzheimer Dementia
(Elsevier, 2016-03) Degenhardt, Elisabeth K.; Witte, Michael M.; Case, Michael G.; Yu, Peng; Henley, David B.; Hochstetler, Helen M.; D'Souza, Deborah N.; Trzepacz, Paula T.; Department of Psychiatry, IU School of Medicine
Background Clinical diagnosis of Alzheimer disease (AD) is challenging, with a 70.9%–87.3% sensitivity and 44.3%–70.8% specificity, compared with autopsy diagnosis. Florbetapir F18 positron emission tomography (FBP-PET) estimates beta-amyloid plaque density antemortem. Methods Of 2052 patients (≥55 years old) clinically diagnosed with mild or moderate AD dementia from 2 solanezumab clinical trials, 390 opted to participate in a FBP-PET study addendum. We analyzed baseline prerandomization characteristics. Results A total of 22.4% had negative FBP-PET scans, whereas 72.5% of mild and 86.9% of moderate AD patients had positive results. No baseline clinical variable reliably differentiated negative from positive FBP-PET scan groups. Conclusions These data confirm the challenges of correctly diagnosing AD without using biomarkers. FBP-PET can aid AD dementia differential diagnosis by detecting amyloid pathology antemortem, even when the diagnosis of AD is made by expert clinicians.
Florbetapir positron emission tomography and cerebrospinal fluid biomarkers
(Elsevier, 2015-08) Hake, Ann Marie; Trzepacz, Paula T.; Wang, Shufang; Yu, Peng; Case, Michael; Hochstetler, Helen; Witte, Michael M.; Degenhardt, Elisabeth K.; Dean, Robert A.; Department of Neurology, IU School of Medicine
BACKGROUND: We evaluated the relationship between florbetapir-F18 positron emission tomography (FBP PET) and cerebrospinal fluid (CSF) biomarkers. METHODS: Alzheimer's Disease Neuroimaging Initiative-Grand Opportunity and Alzheimer's Disease Neuroimaging Initiative 2 (GO/2) healthy control (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia subjects with clinical measures and CSF collected ±90 days of FBP PET data were analyzed using correlation and logistic regression. RESULTS: In HC and MCI subjects, FBP PET anterior and posterior cingulate and composite standard uptake value ratios correlated with CSF amyloid beta (Aβ1-42) and tau/Aβ1-42 ratios. Using logistic regression, Aβ1-42, total tau (t-tau), phosphorylated tau181P (p-tau), and FBP PET composite each differentiated HC versus AD. Aβ1-42 and t-tau distinguished MCI versus AD, without additional contribution by FBP PET. Total tau and p-tau added discriminative power to FBP PET when classifying HC versus AD. CONCLUSION: Based on cross-sectional diagnostic groups, both amyloid and tau measures distinguish healthy from demented subjects. Longitudinal analyses are needed.
How do delirium motor subtypes differ in phenomenology and contributory aetiology? a cross-sectional, multisite study of liaison psychiatry and palliative care patients
(BMJ, 2021-04-14) Glynn, Kevin; McKenna, Frank; Lally, Kevin; O’Donnell, Muireann; Grover, Sandeep; Chakrabarti, Subho; Avasthi, Ajit; Mattoo, Surendra K.; Sharma, Akhilesh; Ghosh, Abhishek; Shah, Ruchita; Hickey, David; Fitzgerald, James; Davis, Brid; O'Regan, Niamh; Adamis, Dimitrious; Williams, Olugbenja; Awan, Fahad; Dunne, C.; Cullen, Walter; McInerney, Shane; McFarland, John; Jabbar, Faiza; O'Connell, Henry; Trzepacz, Paula T.; Leonard, Maeve; Meagher, David; Psychiatry, School of Medicine
Objectives: To investigate whether delirium motor subtypes differ in terms of phenomenology and contributory aetiology. Design: Cross-sectional study. Setting: International study incorporating data from Ireland and India across palliative care, old age liaison psychiatry and general adult liaison psychiatry settings. Participants: 1757 patients diagnosed with delirium using criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition (DSM IV). Primary and secondary outcome measures: Hyperactive, mixed and hypoactive delirium subtypes were identified using the abbreviated version of the Delirium Motor Subtype Scale. Phenomenology was assessed using the Delirium Rating Scale Revised. Contributory aetiologies were assessed using the Delirium Aetiology Checklist (DEC), with a score >2 indicating that the aetiology was likely or definitely contributory. Results: Hypoactive delirium was associated with dementia, cerebrovascular and systemic infection aetiologies (p<0.001) and had a lower overall burden of delirium symptoms than the other motor subtypes. Hyperactive delirium was associated with younger age, drug withdrawal and the DEC category other systemic aetiologies (p<0.001). Mixed delirium showed the greatest symptom burden and was more often associated with drug intoxication and metabolic disturbance (p<0.001). All three delirium motor subtypes had similar levels of impairment in attention and visuospatial functioning but differed significantly when compared with no subtype (p<0.001). Conclusions: This study indicates a pattern of aetiology and symptomatology of delirium motor subtypes across a large international sample that had previously been lacking. It serves to improve our understanding of this complex condition and has implications in terms of early detection and management of delirium.
Performance of the Delirium Rating Scale-Revised-98 Against Different Delirium Diagnostic Criteria in a Population With a High Prevalence of Dementia
(Elsevier, 2015-09) Sepulveda, Esteban; Franco, Jose G.; Trzepacz, Paula T.; Gaviria, Ana M.; Viñuelas, Eva; Palma, Jose; Ferré, Gisela; Grau, Imma; Vilella, Elisabet; Department of Psychiatry, IU School of Medicine
Background Delirium diagnosis in elderly is often complicated by underlying dementia. Objective We evaluated performance of the Delirium Rating Scale-Revised-98 (DRS-R98) in patients with high dementia prevalence and also assessed concordance among past and current diagnostic criteria for delirium. Methods Cross-sectional analysis of newly admitted patients to a skilled nursing facility over 6 months, who were rated within 24–48 hours after admission. Interview for Diagnostic and Statistical Manual of Mental Disorders, 3rd edition-R (DSM)-III-R, DSM-IV, DSM-5, and International Classification of Diseases 10th edition delirium ratings, administration of the DRS-R98, and assessment of dementia using the Informant Questionnaire on Cognitive Decline in the Elderly were independently performed by 3 researchers. Discriminant analyses (receiver operating characteristics curves) were used to study DRS-R98 accuracy against different diagnostic criteria. Hanley and McNeil test compared the area under the curve for DRS-R98’s discriminant performance for all diagnostic criteria. Results Dementia was present in 85/125 (68.0%) subjects, and 36/125 (28.8%) met criteria for delirium by at least 1 classification system, whereas only 19/36 (52.8%) did by all. DSM-III-R diagnosed the most as delirious (27.2%), followed by DSM-5 (24.8%), DSM-IV-TR (22.4%), and International Classification of Diseases 10th edition (16%). DRS-R98 had the highest AUC when discriminating DSM-III-R delirium (92.9%), followed by DSM-IV (92.4%), DSM-5 (91%), and International Classification of Diseases 10th edition (90.5%), without statistical differences among them. The best DRS-R98 cutoff score was ≥14.5 for all diagnostic systems except International Classification of Diseases 10th edition (≥15.5). Conclusions There is a low concordance across diagnostic systems for identification of delirium. The DRS-R98 performs well despite differences across classification systems perhaps because it broadly assesses phenomenology, even in this population with a high prevalence of dementia.

Browsing by Author "Trzepacz, Paula T."

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