163 results on '"Meyers BS"'
Search Results
2. D81. Gene Expression as Biomarkers of Tissue Viability in Ex Vivo Normothermic Limb Perfusion (EVNLP)
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Abigail Meyers, BS, Varun Kopparthy, PhD, Payam Sadeghi, MD, Francis Papay, MD, Antonio Rampazzo, MD, PhD, and Bahar Bassiri Gharb, MD, PhD
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Surgery ,RD1-811 - Published
- 2023
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3. 127. Investigation of the Transcriptome as a Predictive Biomarker of Muscle Injury in Ex Vivo Normothermic Limb Perfusion
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Abigail Meyers, BS, Varun Kopparthy, PhD, Payam Sadeghi, MD, Francis Papay, MD, Antonio Rampazzo, MD, PhD, and Bahar Bassiri Gharb, MD, PhD
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Surgery ,RD1-811 - Published
- 2023
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4. 124. Porcine Model for Superior Epigastric Artery Based Perforator Flap in Reconstructive Microsurgery
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Abigail Meyers, BS, Varun Kopparthy, PhD, Payam Sadeghi, MD, Sonia K. Pandey, MD, Robert C. Clark, BS, R’ay Fodor, BS, Ryan Khalaf, BS, Jose Reyes, BS, Daniela Duarte Bateman, MD, Diane Jo, BS, Antonio Rampazzo, MD, PhD, and Bahar Bassiri Gharb, MD, PhD
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Surgery ,RD1-811 - Published
- 2023
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5. D93. Efficacy of Virtual Plastic Surgery Encounters in Establishment of Care and Surgical Conversion
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Ryan Khalaf, BS, Abigail Meyers, BS, Payam Sadeghi, MD, Jose Reyes, BS, R’ay Fodor, BS, Diane Jo, BS, Thomas Xia, MD, Emma Toth, BS, Ali Abbaszadeh-Kasbi, MD, Francis Papay, MD, Antonio Rampazzo, MD, PhD, and Bahar Bassiri Gharb, MD, PhD
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Surgery ,RD1-811 - Published
- 2023
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6. D106. Outcomes of Calvarial and Soft Tissue Reconstruction with Latissimus Dorsi Rib Osteomyocutaneous Free Flap
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Abigail Meyers, BS, Bahar Bassiri Gharb, MD, PhD, Majid Rezaei, DDS, MD, Brian Figueroa, MD, Michael Annunziata, MD, Sean Nagel, MD, Mark Bain, MD, Sudish Murthy, MD, PhD, Francis Papay, MD, and Antonio Rampazzo, MD, PhD
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Surgery ,RD1-811 - Published
- 2023
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7. 89. Platelet-Rich Plasma for Treatment of Hair Loss Improves Patient-Reported Quality of Life
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Abigail Meyers, BS, Alison Jin, BA, Grzegorz J. Kwiecien, MD, James Gatherwright, MD, and James Zins, MD
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Surgery ,RD1-811 - Published
- 2022
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8. QS12. Near-infrared Indocyanine Green Florescence as a Viability Measure During Ex Vivo Normothermic Limb Perfusion
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Robert Craig Clark, BS, Varun Kopparthy, PhD, Payam Sadeghi, MD, Abigail Meyers, BS, Sonia Pandey, MD, Ali Abbaszadeh-Kasbi, MD, Frank Papay, MD, Antonio Rampazzo, MD, and Bahar Bassiri Gharb, MD, PhD
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Surgery ,RD1-811 - Published
- 2022
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9. Vascularized Toe and Nonvascularized Toe Phalangeal Transfer for Reconstruction of Congenital Absence of Digits or Thumb: A Systematic Review of the Literature
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Abigail Meyers, BS, Bahar Bassiri Gharb, MD, PhD, and Antonio Rampazzo, MD, PhD
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Surgery ,RD1-811 - Published
- 2021
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10. P90. WHAT ATTRIBUTES MAKE UNITED STATES PLASTIC SURGERY PROGRAMS DESIRABLE? AN UPDATED PERSPECTIVE FROM MEDICAL STUDENTS AND RESIDENTS
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Magnus Chun, BS, Alisa Girard, MBS, Yichi Zhang, BS, Abigail Meyers, BS, Idean Roohani, BS, Tracey Cook, MD, Ping Song, MD, and Abigail Chaffin, MD
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Surgery ,RD1-811 - Published
- 2022
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11. 4: Peripheral Nerves Engage in Reciprocal Neuro- and Angiogenic Crosstalk With SMCs in Extremity Trauma
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Charles D. Hwang, MD, Chase A. Pagani, BS, Seungyong Lee, PhD, Qizhi Qin, PhD, Simone Marini, PhD, Amanda Huber, PhD, Carolyn A. Meyers, BS, Geoffrey E. Hespe, MD, Amy L. Strong, MD, PhD, David M. Stepien, MD, PhD, Michael Sorkin, MD, Johanna Nunez, MD, Aaron W. James, MD, PhD, and Benjamin Levi, MD
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Surgery ,RD1-811 - Abstract
Purpose: Existing literature describes the interdependence between neurotrophic and vascular signals in the central nervous system. We hypothesize a similar crosstalk important to extremity healing involving the peripheral nervous system and angiogenic cells. Nerves are difficult to capture via axons found in the periphery alone. Thus, we have interrogated from publicly available single-nuclei transcriptomic data of peripheral nerve soma (dorsal root ganglia), injured by physical transection or chemically induced pain. We present a combined analysis of extremity polytrauma (burn/tenotomy HO model) and peripheral nerve (post-injury/pain DRG model) to determine if there is expression of vascular signals by nerves and reciprocal neurotrophic signals by cells local to the injury site. Methods: A 30% dorsal burn and Achilles transection was performed in C57/BL6J mice. The tendon site tissues were harvested from baseline (t0) and day 7, 42 after induction. Samples were prepared for library generation on a 10x Genomics Chromium Controller, sequenced on a Illumina HiSeq 4000, and analyzed with Cell Ranger Software for pre-processing and alignment to the mm10 genome. DRG analyses and clusters were abstracted from NIH-GEO (GSE154659). Downstream analyses including unsupervised clustering downstream analyses were performed with Seurat. Results: We first examined candidate neurotrophins and vascular signals in nerve (DRG), finding robust upregulation of Bdnf and Vegfa. In HO, the site of injury contains many cells that may potentially respond to these signals. Indeed, in sequencing data from the pre-HO anlagen, endothelium and smooth muscle cell populations express upregulation for receptors to the nerve-derived Vegfa via Flt1/VEGFR1. This population in addition to being sensitive to the VEGFA ligand, also demonstrates upregulation of Ngf, signifying a potential vasculo-neuro axis where a vascular signal induces endothelium/SMCs to produce neurotrophic signals. Completing the circuit, the original DRG cells and by logical extension, regenerating peripheral nerves, are highly enriched for the neurotrophin receptors: Ntrk1/TrkA (responsive to the SMC derived NGF), Ntrk2/TrkB (responsive to the nerve-autonomous BDNF), and Ntrk3/TrkC (partial combined NGF/BDNF response). This potentially signifies a feedforward loop where peripheral nerve induces angiogenesis which in return, promotes nascent nerve ingrowth in a cyclical process. Indeed, in targeted knockout of a local VEGFA source (VegfaPrrx1 mice), the injury site demonstrates parallel reduction in vascular density (77%) and reduction in nerve fiber frequency (62%) within the HO site. Conclusions: These findings represent the first work characterizing the coordination between neurogenic and angiogenic transcription programs following extremity trauma. We demonstrate through NextGen sequencing, evidence of neuroangiogenic crosstalk following musculoskeletal/neural injury. This VEGFA/NGF axis involves vascular signaling as a potential source for additional proliferation of NGF expressing pericyte/SMCs. The presented data describe the potential nerve-driven regulation contributing to the formation of HO at the extremity that with antagonism or inhibition may lead to better treatments for aberrant extremity wound healing.
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- 2021
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12. 5: Metacarpal Subsidence Following Trapeziectomy
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Abigail E. Meyers, BS, Jillian P. Krebs, BS, Arvin Smith, BS, Antonio Rampazzo, MD, PhD, and Bahar Bassiri Gharb, MD, PhD
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Surgery ,RD1-811 - Abstract
Purpose: It is controversial whether subsidence after trapeziectomy prognosticates pain, poor outcomes, and need for revision. The aim of this study was to investigate the degree of subsidence following trapeziectomy and whether subsidence contributes to poor outcomes. Methods: An IRB approved retrospective review of all patients who underwent trapeziectomy for osteoarthritis of the first carpometacarpal (CMC) joint was conducted from 2003 to 2019. Patients with available radiographic imaging greater than three months postoperatively were included. Patients with arthritis of the metacarpophalangeal joint of the thumb, arthritis of radiocarpal, distal radioulnar, and midcarpal joints were excluded. Demographic information, pain scores, and revision procedures were recorded. Conolly-Rath patient function scores were determined. Subsidence was measured by the ratio of the difference between the trapezial space (TS = distance from base of thumb metacarpal to scaphoid) preoperatively and TS postoperatively over the TS preoperatively. Patients were divided as having a high degree of subsidence (≥50%) or low degree of subsidence (
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- 2021
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13. Evolution of Metacarpal Subsidence following Trapeziectomy
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Abigail Meyers, BS, Jillian Krebs, BS, Antonio Rampazzo, MD, PhD, and Bahar Bassiri Gharb, MD, PhD
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Surgery ,RD1-811 - Published
- 2021
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14. Abstract 7: Nerve Growth Factor Derives From Pericytes And Smooth Muscle Cells After Extremity Trauma
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Charles Hwang, BS, Simone Marini, PhD, Amanda K. Huber, PhD, Seungyong Lee, PhD, David M. Stepien, MD, PhD, Carrie A. Kubiak, MD, Carolyn Meyers, BS, Michael Sorkin, MD, Chase A. Pagani, BA, Talis Rehse, BS, Noelle D. Visser, MS, Mohamed Ali Garada, Husain Rasheed, Joseph A. Greenstein, Zaid N. Khatib, BS, Prasanth Kotha, Kaetlin Vasquez, Jeffrey Lisiecki, MD, Paul S. Cederna, MD, Stephen W.P. Kemp, PhD, Aaron W. James, MD, PhD, and Benjamin Levi, MD
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Surgery ,RD1-811 - Published
- 2020
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15. Abstract 104: Identification of the Role of Sensory Nerve TrkA Signaling on Progenitor Cell Fate after Extremity Trauma
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Charles Hwang, BS, David M. Stepien, MD, PhD, Carrie Kubiak, MD, Carolyn A. Meyers, BS, Seungyong Lee, PhD, Michael Sorkin, MD, Chase A. Pagani, BA, Talis Rehse, BS, Noelle D. Visser, MS, Mohamed A. Garada, Zaid N. Khatib, BS, Prasanth Kotha, Jeffrey Lisiecki, MD, Kaetlin Vasquez, MS, Paul S. Cederna, MD, Stephen W.P. Kemp, PhD, Thomas L. Clemens, PhD, Aaron W. James, MD, PhD, and Benjamin Levi, MD
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Surgery ,RD1-811 - Published
- 2019
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16. Sustaining remission of psychotic depression: Rationale, design and methodology of STOP-PD II
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Flint, AJ, Meyers, BS, Rothschild, AJ, Whyte, EM, Mulsant, BH, Rudorfer, MV, Marino, P, Flint, AJ, Meyers, BS, Rothschild, AJ, Whyte, EM, Mulsant, BH, Rudorfer, MV, and Marino, P
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Background: Psychotic depression (PD) is a severe disabling disorder with considerable morbidity and mortality. Electroconvulsive therapy and pharmacotherapy are each efficacious in the treatment of PD. Expert guidelines recommend the combination of antidepressant and antipsychotic medications in the acute pharmacologic treatment of PD. However, little is known about the continuation treatment of PD. Of particular concern, it is not known whether antipsychotic medication needs to be continued once an episode of PD responds to pharmacotherapy. This issue has profound clinical importance. On the one hand, the unnecessary continuation of antipsychotic medication exposes a patient to adverse effects, such as weight gain and metabolic disturbance. On the other hand, premature discontinuation of antipsychotic medication has the potential risk of early relapse of a severe disorder.Methods/design: The primary goal of this multicenter randomized placebo-controlled trial is to assess the risks and benefits of continuing antipsychotic medication in persons with PD once the episode of depression has responded to treatment with an antidepressant and an antipsychotic. Secondary goals are to examine age and genetic polymorphisms as predictors or moderators of treatment variability, potentially leading to more personalized treatment of PD. Individuals aged 18-85 years with unipolar psychotic depression receive up to 12 weeks of open-label treatment with sertraline and olanzapine. Participants who achieve remission of psychosis and remission/near-remission of depressive symptoms continue with 8 weeks of open-label treatment to ensure stability of remission. Participants with stability of remission are then randomized to 36 weeks of double-blind treatment with either sertraline and olanzapine or sertraline and placebo. Relapse is the primary outcome. Metabolic changes are a secondary outcome.Discussion: This trial will provide clinicians with much-needed evidence to guide the continu
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- 2013
17. Preferences for depression treatment among elderly home health care patients.
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Raue PJ, Weinberger MI, Sirey JA, Meyers BS, Bruce ML, Raue, Patrick J, Weinberger, Mark I, Sirey, Jo Anne, Meyers, Barnett S, and Bruce, Martha L
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Objective: The authors hypothesized that the depression treatment preferences of elderly home care patients would vary by their experience of depression and that preferences for active treatment would be associated with current depression and with antidepressant treatment.Methods: The authors conducted cross-sectional secondary analyses of data from the TRIAD study (Training in the Assessment of Depression) of 256 randomly selected elderly patients newly admitted to home care. The study assessed preference for active treatments (medication or psychotherapy) and nonactive or complementary approaches (such as religious activities or doing nothing). Nondepressed patients were asked to choose as if they had serious depression. Two separate indicators of depression experience were used: a current diagnosis of major or minor depression and current or previous antidepressant treatment.Results: Of the 256 patients, 16% (N=41) met criteria for major or minor depression. Forty-seven percent of the sample (N=121) preferred an active treatment as their first choice, and others preferred nonactive or complementary approaches. Logistic regression indicated that current antidepressant use, previous psychotherapy experience, white or Hispanic race-ethnicity (versus black), greater impairment in instrumental activities of daily living, and less personal stigma about depression were independently associated with preference for an active treatment.Conclusions: Elderly home care patients had a variety of treatment preferences, ranging from active treatments, to religious or spiritual activities, to no treatment. Several factors were associated with a preference for active treatment, including treatment experience, physical impairment, race-ethnicity, and attitudes and beliefs. An understanding of patient preferences may help engage older depressed home care patients in treatment. [ABSTRACT FROM AUTHOR]- Published
- 2011
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18. Effect of age on the frequency of anxiety disorders in major depression with psychotic features.
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Flint AJ, Peasley-Miklus C, Papademetriou E, Meyers BS, Mulsant BH, Rothschild AJ, Whyte EM, STOP-PD Study Group, Flint, Alastair J, Peasley-Miklus, Catherine, Papademetriou, Eros, Meyers, Barnett S, Mulsant, Benoit H, Rothschild, Anthony J, and Whyte, Ellen M
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Objective: To compare the frequency of anxiety disorders in older and younger persons with major depressive disorder with psychotic features.Design: Cross-sectional.Setting: University medical centers.Participants: Two hundred fifty-nine persons (N = 117 aged 18-59 years and N = 142 aged > or =60 years) with major depressive disorder with psychotic features who were enrolled in the Study of the Pharmacotherapy of Psychotic Depression (STOP-PD).Measurements: Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) defined anxiety disorders were determined by Structured Clinical Interview for DSM-IV interview at baseline assessment. Younger and older participants were compared on the frequencies of any current anxiety disorder and any lifetime anxiety disorder, as well as the frequencies of individual anxiety disorders.Results: Older persons had significantly lower frequencies of any current anxiety disorder and any lifetime anxiety disorder, even after controlling for relevant demographic and clinical variables. With respect to specific anxiety disorders, older persons had significantly lower frequencies of current and lifetime panic disorder, current and lifetime social anxiety disorder, and current and lifetime posttraumatic stress disorder.Conclusion: The findings of this study are consistent with those of community-based epidemiologic surveys that anxiety disorders are less prevalent in older than younger adults. Because of the rigorous assessment used in STOP-PD, our findings suggest that the age-related decline in the prevalence of anxiety disorders is not simply due to a failure to detect cases in older people, as has been previously suggested. [ABSTRACT FROM AUTHOR]- Published
- 2010
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19. Transition to home care: quality of mental health, pharmacy, and medical history information.
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Brown EL, Raue PJ, Mlodzianowski AE, Meyers BS, Greenberg RL, and Bruce ML
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OBJECTIVE: To assess the completeness and accuracy of clinical information provided by referral sources to visiting nurses for patients admitted to receive home health care. METHODS: Clinical referral information for a representative sample of 243 older adults admitted to receive skilled home-health nursing was compared to medical record information from home-health charts and in-home research interviews to determine their concordance. Measures used included referral information, home-care chart documentation, in-home nurse review of medications, medication allergies, caregiver contact information, cognitive status, depression status, and follow-up plan. RESULTS: There were medication discrepancies between in-home nurse review and admission information in 215 cases (88.4%). Clinical information on medication allergies was lacking from referrers in 85 cases (34.9%). No information was provided by the referrers about cognitive status in 38 (73%) cases classified as cognitively impaired and in only 2 of 35 cases with major depression identified with the Structured Clinical Interview for Axis I Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID), was depression related information provided by referrers. CONCLUSIONS: The primary finding of this study is that during a transfer of an older adult to the home care service sector, essential clinical information is often missing, and there are significant discrepancies between medication regimens. These findings support the need for both educational initiatives and technology to address the complex care needs of older adults across settings to reduce the risk for medication errors and poor outcomes. [ABSTRACT FROM AUTHOR]
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- 2006
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20. Diagnosis and treatment of depression in late life. Consensus statement update.
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Lebowitz BD, Pearson JL, Schneider LS, Reynolds CF III, Alexopoulos GS, Bruce ML, Conwell Y, Katz IR, Meyers BS, Morrison MF, Mossey J, Niederehe G, Parmelee P, Lebowitz, B D, Pearson, J L, Schneider, L S, Reynolds, C F 3rd, Alexopoulos, G S, Bruce, M L, and Conwell, Y
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Objective: To reexamine the conclusions of the 1991 National Institutes of Health Consensus Panel on Diagnosis and Treatment of Depression in Late Life in light of current scientific evidence.Participants: Participants included National Institutes of Health staff and experts drawn from the Planning Committee and presenters of the 1991 Consensus Development Conference.Evidence: Participants summarized relevant data from the world scientific literature on the original questions posed for the conference.Process: Participants reviewed the original consensus statement and identified areas for update. The list of issues was circulated to all participants and amended to reflect group agreement. Selected participants prepared first drafts of the consensus update for each issue. All drafts were read by all participants and were amended and edited to reflect group consensus.Conclusions: The review concluded that, although the initial consensus statement still holds, there is important new information in a number of areas. These areas include the onset and course of late-life depression; comorbidity and disability; sex and hormonal issues; newer medications, psychotherapies, and approaches to long-term treatment; impact of depression on health services and health care resource use; late-life depression as a risk factor for suicide; and the importance of the heterogeneous forms of depression. Depression in older people remains a significant public health problem. The burden of unrecognized or inadequately treated depression is substantial. Efficacious treatments are available. Aggressive approaches to recognition, diagnosis, and treatment are warranted to minimize suffering, improve overall functioning and quality of life, and limit inappropriate use of health care resources. [ABSTRACT FROM AUTHOR]- Published
- 1997
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21. Predictors of attrition during acute pharmacotherapy of psychotic depression in a clinical trial.
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Ihaddadene RA, Alexopoulos GS, Marino P, Meyers BS, Mulsant BH, Neufeld NH, Rothschild AJ, Voineskos AN, Whyte EM, Flint AJ, and Bingham KS
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Little is known about factors that contribute to attrition in clinical trials of the pharmacotherapy of psychotic depression. The purpose of this study was to identify factors associated with attrition during acute pharmacotherapy in the Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II) clinical trial. Sociodemographic and clinical variables were assessed at baseline in 269 men and women, aged 18-85 years, who were treated with up to 12 weeks of open-label sertraline plus olanzapine. Univariate analyses examined the association of baseline variables with overall non-completion, as well as reasons for non-completion. Logistic regression was used to model the relationship of the significant univariate predictors with non-completion and its reasons. Seventy-four (27.5 %) participants did not complete the acute treatment phase of STOP-PD II. Male gender, younger age, inpatient status, higher Clinical Global Impression (CGI) severity of illness, and higher severity of psychomotor disturbance were associated with non-completion in univariate analyses. In regression models, higher CGI severity of illness score was the only significant independent predictor of non-completion, explained by withdrawal of consent. Our findings have implications for the retention of persons with psychotic depression in clinical trials., Competing Interests: Declaration of competing interest R. A. Ihaddadene has no competing interests; G.S. Alexopoulos has received NIMH grants and has served in the speakers bureau of Takeda, Lundbeck, Otsuka, Alergan, Astra/Zeneca, Sunovion; P. Marino received research support from the NIMH at the time this work was done; B.S. Meyers received research support from the NIMH at the time this work was done; B.H. Mulsant holds and receives support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto. He currently receives or has received research support during the past three years from Brain Canada, the Canadian Institutes of Health Research, the CAMH Foundation, the Patient-Centered Outcomes Research Institute (PCORI), the US National Institute of Health (NIH), Capital Solution Design LLC (software used in a study founded by CAMH Foundation), and HAPPYneuron (software used in a study founded by Brain Canada). Within the past three years, he has also been an unpaid consultant to Myriad Neuroscience; N.H Neufeld has served on an advisory board for Boehringer Ingelheim; he has received grant support from the Brain and Behavior Research Foundation, Canadian Institutes of Health Research, Physicians' Services Incorporated Foundation, Labatt Family Network for Research on the Biology of Depression and the University of Toronto (including an Academic Scholars Award); A.J. Rothschild has received, in the past three years, grant or research support from Compass Pathways, Janssen, Otsuka, and the Irving S. and Betty Brudnick Endowed Chair in Psychiatry. In the past three years, he has been a consultant to Daiichi Sankyo, Inc., Sage Therapeutics, Xenon Pharmaceuticals, Neumora Therapeutics, Zydus Pharmaceuticals (USA), Inc., Sandoz, Inc., and Lupin Pharmaceuticals, Inc. He has received royalties in the past three years for the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT)®, Clinical Manual for the Diagnosis and Treatment of Psychotic Depression, American Psychiatric Press, 2009, The Evidence-Based Guide to Antipsychotic Medications, American Psychiatric Press, 2010, The Evidence-Based Guide to Antidepressant Medications, American Psychiatric Press, 2012, and from UpToDate®; A.N. Voineskos has received funding from the NIMH, Canadian Institutes of Health Research, Canada Foundation for Innovation, CAMH Foundation, and the University of Toronto; E.M. Whyte has received grant support from the NIMH and HRSA; A.J. Flint has received grant support from the U.S. National Institutes of Health, Patient-Centered Outcomes Research Institute, Canadian Institutes of Health Research, Brain Canada, Ontario Brain Institute, Alzheimer's Association, AGE-WELL, the Canadian Foundation for Healthcare Improvement, and the University of Toronto; K.S. Bingham has received grant support from the University of Toronto., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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22. Trajectories of remitted psychotic depression: identification of predictors of worsening by machine learning.
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Banerjee S, Wu Y, Bingham KS, Marino P, Meyers BS, Mulsant BH, Neufeld NH, Oliver LD, Power JD, Rothschild AJ, Sirey JA, Voineskos AN, Whyte EM, Alexopoulos GS, and Flint AJ
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- Adolescent, Adult, Aged, Aged, 80 and over, Humans, Middle Aged, Young Adult, Depression, Olanzapine therapeutic use, Sertraline therapeutic use, Randomized Controlled Trials as Topic, Depressive Disorder, Major diagnosis, Depressive Disorder, Major drug therapy, Psychotic Disorders drug therapy
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Background: Remitted psychotic depression (MDDPsy) has heterogeneity of outcome. The study's aims were to identify subgroups of persons with remitted MDDPsy with distinct trajectories of depression severity during continuation treatment and to detect predictors of membership to the worsening trajectory., Method: One hundred and twenty-six persons aged 18-85 years participated in a 36-week randomized placebo-controlled trial (RCT) that examined the clinical effects of continuing olanzapine once an episode of MDDPsy had remitted with sertraline plus olanzapine. Latent class mixed modeling was used to identify subgroups of participants with distinct trajectories of depression severity during the RCT. Machine learning was used to predict membership to the trajectories based on participant pre-trajectory characteristics., Results: Seventy-one (56.3%) participants belonged to a subgroup with a stable trajectory of depression scores and 55 (43.7%) belonged to a subgroup with a worsening trajectory. A random forest model with high prediction accuracy (AUC of 0.812) found that the strongest predictors of membership to the worsening subgroup were residual depression symptoms at onset of remission, followed by anxiety score at RCT baseline and age of onset of the first lifetime depressive episode. In a logistic regression model that examined depression score at onset of remission as the only predictor variable, the AUC (0.778) was close to that of the machine learning model., Conclusions: Residual depression at onset of remission has high accuracy in predicting membership to worsening outcome of remitted MDDPsy. Research is needed to determine how best to optimize the outcome of psychotic MDDPsy with residual symptoms.
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- 2024
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23. Brain metabolite levels in remitted psychotic depression with consideration of effects of antipsychotic medication.
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Tani H, Moxon-Emre I, Forde NJ, Neufeld NH, Bingham KS, Whyte EM, Meyers BS, Alexopoulos GS, Hoptman MJ, Rothschild AJ, Uchida H, Flint AJ, Mulsant BH, and Voineskos AN
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- Humans, Aspartic Acid, Choline metabolism, Creatine metabolism, Glutamine metabolism, Inositol metabolism, Magnetic Resonance Imaging, Olanzapine pharmacology, Sertraline pharmacology, Antipsychotic Agents pharmacology, Brain diagnostic imaging, Brain metabolism, Depression drug therapy
- Abstract
Background: The neurobiology of psychotic depression is not well understood and can be confounded by antipsychotics. Magnetic resonance spectroscopy (MRS) is an ideal tool to measure brain metabolites non-invasively. We cross-sectionally assessed brain metabolites in patients with remitted psychotic depression and controls. We also longitudinally assessed the effects of olanzapine versus placebo on brain metabolites., Methods: Following remission, patients with psychotic depression were randomized to continue sertraline + olanzapine (n = 15) or switched to sertraline + placebo (n = 18), at which point they completed an MRS scan. Patients completed a second scan either 36 weeks later, relapse, or discontinuation. Where water-scaled metabolite levels were obtained and a Point-RESolved Spectroscopy sequence was utilized, choline, myo-inositol, glutamate + glutamine (Glx), N-acetylaspartate, and creatine were measured in the left dorsolateral prefrontal cortex (L-DLPFC) and dorsal anterior cingulate cortex (dACC). An ANCOVA was used to compare metabolites between patients (n = 40) and controls (n = 46). A linear mixed-model was used to compare olanzapine versus placebo groups., Results: Cross-sectionally, patients (compared to controls) had higher myo-inositol (standardized mean difference [SMD] = 0.84; 95%CI = 0.25-1.44; p = 0.005) in the dACC but not different Glx, choline, N-acetylaspartate, and creatine. Longitudinally, patients randomized to placebo (compared to olanzapine) showed a significantly greater change with a reduction of creatine (SMD = 1.51; 95%CI = 0.71-2.31; p = 0.0002) in the dACC but not glutamate + glutamine, choline, myo-inositol, and N-acetylaspartate., Conclusions: Patients with remitted psychotic depression have higher myo-inositol than controls. Olanzapine may maintain creatine levels. Future studies are needed to further disentangle the mechanisms of action of olanzapine., (© 2023. The Author(s).)
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- 2024
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24. Effects of antipsychotic medication on functional connectivity in major depressive disorder with psychotic features.
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Neufeld NH, Oliver LD, Mulsant BH, Alexopoulos GS, Hoptman MJ, Tani H, Marino P, Meyers BS, Rothschild AJ, Whyte EM, Bingham KS, Flint AJ, and Voineskos AN
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- Humans, Olanzapine therapeutic use, Sertraline therapeutic use, Benzodiazepines, Drug Therapy, Combination, Magnetic Resonance Imaging, Antipsychotic Agents therapeutic use, Depressive Disorder, Major drug therapy
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The effect of antipsychotic medication on resting state functional connectivity in major depressive disorder (MDD) is currently unknown. To address this gap, we examined patients with MDD with psychotic features (MDDPsy) participating in the Study of the Pharmacotherapy of Psychotic Depression II. All participants were treated with sertraline plus olanzapine and were subsequently randomized to continue sertraline plus olanzapine or be switched to sertraline plus placebo. Participants completed an MRI at randomization and at study endpoint (study completion at Week 36, relapse, or early termination). The primary outcome was change in functional connectivity measured within and between specified networks and the rest of the brain. The secondary outcome was change in network topology measured by graph metrics. Eighty-eight participants completed a baseline scan; 73 completed a follow-up scan, of which 58 were usable for analyses. There was a significant treatment X time interaction for functional connectivity between the secondary visual network and rest of the brain (t = -3.684; p = 0.0004; pFDR = 0.0111). There was no significant treatment X time interaction for graph metrics. Overall, functional connectivity between the secondary visual network and the rest of the brain did not change in participants who stayed on olanzapine but decreased in those switched to placebo. There were no differences in changes in network topology measures when patients stayed on olanzapine or switched to placebo. This suggests that olanzapine may stabilize functional connectivity, particularly between the secondary visual network and the rest of the brain., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2023
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25. The relationship of white matter microstructure with psychomotor disturbance and relapse in remitted psychotic depression.
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Bingham KS, Calarco N, Dickie EW, Alexopoulos GS, Butters MA, Meyers BS, Marino P, Neufeld NH, Rothschild AJ, Whyte EM, Mulsant BH, Flint AJ, and Voineskos AN
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- Humans, Sertraline therapeutic use, Depression, Brain, Anisotropy, White Matter diagnostic imaging, Depressive Disorder, Major diagnostic imaging, Depressive Disorder, Major drug therapy, Psychotic Disorders diagnostic imaging, Psychotic Disorders drug therapy
- Abstract
Background: Psychomotor disturbance is common in psychotic depression and is associated with relapse. In this analysis, we examined whether white matter microstructure is associated with relapse probability in psychotic depression and, if so, whether white matter microstructure accounts for the association between psychomotor disturbance and relapse., Methods: We used tractography to characterize diffusion-weighted MRI data in 80 participants enrolled in a randomized clinical trial that compared efficacy and tolerability of sertraline plus olanzapine with sertraline plus placebo in the continuation treatment of remitted psychotic depression. Cox proportional hazard models tested the relationships between psychomotor disturbance (processing speed and CORE score) at baseline, white matter microstructure (fractional anisotropy [FA] and mean diffusivity [MD]) in 15 selected tracts at baseline, and relapse probability., Results: CORE was significantly associated with relapse. Higher mean MD was significantly associated with relapse in the each of the following tracts: corpus callosum, left striato-frontal, left thalamo-frontal, and right thalamo-frontal. CORE and MD were each associated with relapse in the final models., Limitations: As a secondary analysis with a small sample size, this study was not powered for its aims, and is vulnerable to types I and II statistical errors. Further, the sample size was not sufficient to test the interaction of the independent variables and randomized treatment group with relapse probability., Conclusions: While both psychomotor disturbance and MD were associated with psychotic depression relapse, MD did not account for the relationship between psychomotor disturbance and relapse. The mechanism by which of psychomotor disturbance increases the risk of relapse requires further investigation., Clinical Trial Registration: Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II); NCT01427608. URL: https://clinicaltrials.gov/ct2/show/NCT01427608., Competing Interests: Declaration of competing interest K.S. Bingham receives grant support from the University of Toronto. N. Calarco has no disclosures. E.W. Dickie receives grant support from the Brain and Behavior Research Foundation. G.S. Alexopoulos has received NIMH grants and has served in the speakers' bureau of Takeda, Lundbeck, Otsuka, Alergan, Astra/Zeneca, Sunovion. M.A. Butters receives research financial support from NIH. P. Marino received research support from the NIMH at the time this work was done. B.S. Meyers received research support from the NIMH at the time this work was done. B.H. Mulsant holds and receives support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto. He currently receives research support from Brain Canada, the Canadian Institutes of Health Research, the CAMH Foundation, the Patient-Centered Outcomes Research Institute (PCORI), the US National Institute of Health (NIH), Capital Solution Design LLC (software used in a study founded by CAMH Foundation), and HAPPYneuron (software used in a study founded by Brain Canada). He has been an unpaid consultant to Myriad Neuroscience. N.H. Neufeld has received grant support from the Brain and Behavior Research Foundation, Canadian Institutes of Health Research, Physicians' Services Incorporated Foundation, and the University of Toronto. A.J. Rothschild has received grant or research support from Janssen, the National Institute of Mental Health, Otsuka, Praxis, Eli-Lilly (medications for a NIH-funded clinical trial), Pfizer (medications for a NIH-funded clinical trial), and the Irving S. and Betty Brudnick Endowed Chair in Psychiatry, is a consultant to Alkermes, Janssen, Sage Therapeutics, Xenon Pharmaceuticals and several generic medication companies, has received royalties for the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT)®; Clinical Manual for the Diagnosis and Treatment of Psychotic Depression, American Psychiatric Press, 2009; The Evidence-Based Guide to Antipsychotic Medications, American Psychiatric Press, 2010; The Evidence-Based Guide to Antidepressant Medications, American Psychiatric Press, 2012; and, UpToDate® and has received honorarium from Wolters Kluwer (Journal Editor). E.M. Whyte received grant support from the NIMH and HRSA at the time that this study was completed. A.J. Flint has received grant support from the U.S. National Institutes of Health, Patient-Centered Outcomes Research Institute, Canadian Institutes of Health Research, Brain Canada, Ontario Brain Institute, Alzheimer's Association, AGE-WELL, and the Canadian Foundation for Healthcare Improvement. A.N. Voineskos has receives funding from the NIMH, Canadian Institutes of Health Research, Canada Foundation for Innovation, CAMH Foundation, and the University of Toronto., (Copyright © 2023 Elsevier B.V. All rights reserved.)
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- 2023
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26. Residual or re-emergent impaired insight into delusions following remission is unrelated to later relapse during a randomized clinical trial of continuation pharmacotherapy for psychotic depression - The STOP-PD II Study.
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Song J, Mulsant BH, Sanches M, Alexopoulos GS, Marino P, Meyers BS, Rothschild AJ, Voineskos AN, Whyte EM, Flint AJ, and Gerretsen P
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- Humans, Olanzapine therapeutic use, Sertraline therapeutic use, Delusions drug therapy, Delusions etiology, Depression, Benzodiazepines therapeutic use, Drug Therapy, Combination, Treatment Outcome, Antipsychotic Agents therapeutic use, Psychotic Disorders complications, Psychotic Disorders drug therapy
- Abstract
Background: Impaired insight into delusions is associated with a lower probability of remission of psychotic depression, independent of illness severity. The relationship between participant characteristics and impaired insight into delusions in remitted psychotic depression, and whether impaired insight is associated with risk of relapse of psychotic depression during continuation pharmacotherapy were examined., Methods: Data were analyzed from 126 participants in the STOP-PD II study who experienced sustained remission of psychotic depression during 8-week stabilization treatment with sertraline plus olanzapine and were then randomized to 36 weeks of continuation treatment with sertraline plus either olanzapine or placebo. Insight into delusions was assessed with the Resolution of Delusions Scale (RODS). Linear regression analyses examined the associations between participant characteristics and insight into delusions. Cox proportional-hazards models examined whether i) change in RODS during stabilization treatment; or ii) RODS at the end of stabilization treatment predicted risk of relapse during 36 weeks of continuation treatment., Results: Severity of psychosis before initiation of treatment was the only participant characteristic associated with the change in insight during stabilization treatment. Neither change in insight during stabilization treatment nor insight at the end of stabilization treatment was associated with risk of relapse., Limitations: Insufficient statistical power and the lack of variability in RODS scores at the time of randomization may have contributed to the absence of a relationship between RODS and risk of relapse., Conclusion: Residual or reemergent insight impairment following acute treatment does not preclude patients from sustaining remission of psychotic depression in a randomized placebo-controlled trial., Competing Interests: Conflict of interest J. Song has no disclosures. B.H. Mulsant holds and receives support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto. He currently receives research support from Brain Canada, the Canadian Institutes of Health Research, the CAMH Foundation, the Patient-Centered Outcomes Research Institute (PCORI), the US National Institute of Health (NIH), Capital Solution Design LLC (software used in a study founded by CAMH Foundation), and HAPPYneuron (software used in a study founded by Brain Canada). He has been an unpaid consultant to Myriad Neuroscience. M. Sanches has no disclosures. G.S. Alexopoulos has received NIMH grants and has served in the speakers bureau of Takeda, Lundbeck, Otsuka, Alergan, and participated in advisory boards of Eisai and Janssen. P. Marino received research support from the NIMH at the time this work was done. B.S. Meyers received research support from the NIMH at the time this work was done. A.J. Rothschild has received grant or research support from Janssen, the National Institute of Mental Health, Otsuka, and Praxis, and the Irving S. and Betty Brudnick Endowed Chair in Psychiatry, is a consultant to Alkermes, Sage Therapeutics, Xenon Pharmaceuticals, and several generic medication companies, has received royalties for the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT)®; Clinical Manual for the Diagnosis and Treatment of Psychotic Depression, American Psychiatric Press, 2009; The Evidence-Based Guide to Antipsychotic Medications, American Psychiatric Press, 2010; The Evidence-Based Guide to Antidepressant Medications, American Psychiatric Press, 2012; and, UpToDate® and has received honorarium from Wolters Kluwer (Journal Editor). A.N. Voineskos has received funding from the NIMH, Canadian Institutes of Health Research, Canada Foundation for Innovation, CAMH Foundation, and the University of Toronto. E.M. Whyte received grant support from the NIMH and HRSA at the time that this work was done. A.J. Flint has received grant support from the U.S. National Institutes of Health, Patient-Centered Outcomes Research Institute, Canadian Institutes of Health Research, Brain Canada, Ontario Brain Institute, Alzheimer's Association, AGE-WELL, and the Canadian Foundation for Healthcare Improvement. P. Gerretsen reports receiving research support from the Canadian Institute of Health Research (CIHR), Ontario Ministry of Health and Long-Term Care, Ontario Mental Health Foundation (OMHF), the Centre for Addiction and Mental Health (CAMH), CAMH Foundation, and an Academic Scholars Award from the Department of Psychiatry, University of Toronto., (Copyright © 2022. Published by Elsevier B.V.)
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- 2023
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27. Genomic Investigation of Remission and Relapse of Psychotic Depression Treated with Sertraline plus Olanzapine: The STOP-PD II Study.
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Men X, Marshe V, Elsheikh SS, Alexopoulos GS, Marino P, Meyers BS, Mulsant BH, Rothschild AJ, Voineskos AN, Whyte EM, Kennedy JL, Flint AJ, and Müller DJ
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- Male, Humans, Female, Olanzapine therapeutic use, Depression, Benzodiazepines therapeutic use, Drug Therapy, Combination, Treatment Outcome, Genomics, Double-Blind Method, Sertraline therapeutic use, Antipsychotic Agents therapeutic use
- Abstract
Introduction: Little is known regarding genetic factors associated with treatment outcome of psychotic depression. We explored genomic associations of remission and relapse of psychotic depression treated with pharmacotherapy., Methods: Genomic analyses were performed in 171 men and women aged 18-85 years with an episode of psychotic depression who participated in the Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II). Participants were treated with open-label sertraline plus olanzapine for up to 12 weeks; those who achieved remission or near-remission and maintained it following 8 weeks of stabilization were eligible to participate in a 36-week randomized controlled trial that compared sertraline plus olanzapine with sertraline plus placebo in preventing relapse., Results: There were no genome-wide significant associations with either remission or relapse. However, at a suggestive threshold, SNP rs1026501 (31 kb from SYNPO2) in the whole sample and rs6844137 (within the intronic region of SYNPO2) in the European ancestry subsample were associated with a decreased likelihood of remission. In polygenic risk analyses, participants who had greater improvement after antidepressant treatments showed a higher likelihood of reaching remission. Those who achieved remission and had a higher polygenic risk for Alzheimer's disease had a significantly decreased likelihood of relapse., Conclusion: Our analyses provide preliminary insights into the genetic architecture of remission and relapse in a well-characterized group of patients with psychotic depression., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
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- 2023
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28. Predictors of relapse of psychotic depression: Findings from the STOP-PD II randomized clinical trial.
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Flint AJ, Bingham KS, Alexopoulos GS, Marino P, Mulsant BH, Neufeld NH, Rothschild AJ, Voineskos AN, Whyte EM, and Meyers BS
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- Male, Female, Humans, Olanzapine therapeutic use, Depression, Benzodiazepines, Drug Therapy, Combination, Double-Blind Method, Chronic Disease, Treatment Outcome, Sertraline therapeutic use, Sertraline adverse effects, Antipsychotic Agents adverse effects
- Abstract
Psychotic depression has a high rate of relapse. The study aims were to identify a prediction model of risk of relapse of psychotic depression and examine whether predictors moderated the effect of treatment on relapse. One hundred and twenty-six men and women aged 18-85 years, who experienced sustained remission or near-remission of psychotic depression with sertraline plus olanzapine, participated in a 36-week randomized controlled trial that compared sertraline plus olanzapine with sertraline plus placebo in preventing relapse (NCT01427608). Cox regression analyses were performed to identify significant predictors of relapse and to model the combined role of significant predictors. Concordance statistic was calculated to determine the accuracy of the best fit multivariable models in predicting relapse. Finally, interaction terms were tested for each significant predictor to examine whether they moderated the effect of treatment on risk of relapse. Lifetime number of depressive episodes, severity of residual depressive symptoms at the time of randomization, and psychomotor disturbance both at acute enrollment when participants were depressed and at the time of randomization predicted risk of relapse. Multivariable models had 69-70% accuracy in predicting relapse. Psychomotor disturbance was associated with increased risk of relapse in the sertraline plus olanzapine group compared with sertraline plus placebo, whereas the other predictors did not moderate the effect of treatment on relapse. Future research is needed to determine whether a combination of clinical and biological variables can further increase the accuracy of prediction of relapse of psychotic depression., Competing Interests: Declaration of competing interest A.J. Flint has received grant support from the U.S. National Institutes of Health, Patient-Centered Outcomes Research Institute, Canadian Institutes of Health Research, Brain Canada, Ontario Brain Institute, Alzheimer's Association, AGE-WELL, and the Canadian Foundation for Healthcare Improvement. K.S. Bingham receives grant support from the University of Toronto. N.H Neufeld has received grant support from the Brain and Behavior Research Foundation, Canadian Institutes of Health Research, Physicians' Services Incorporated Foundation, and University of Toronto. G.S. Alexopoulos has received NIMH grants and has served in the speakers bureau of Takeda, Lundbeck, Otsuka, Alergan, Astra/Zeneca, Sunovion. P. Marino received research support from the NIMH at the time this work was done. B.H. Mulsant holds and receives support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto. He currently receives or has received research support during the past three years from Brain Canada, the Canadian Institutes of Health Research, the CAMH Foundation, the Patient-Centered Outcomes Research Institute (PCORI), the US National Institute of Health (NIH), Capital Solution Design LLC (software used in a study founded by CAMH Foundation), and HAPPYneuron (software used in a study founded by Brain Canada). Within the past three years, he has also been an unpaid consultant to Myriad Neuroscience. A.J. Rothschild has received grant or research support from Allergan, Janssen, the National Institute of Mental Health, Otsuka, Praxis, Eli-Lilly (medications for a NIH-funded clinical trial), Pfizer (medications for a NIH-funded clinical trial), and the Irving S. and Betty Brudnick Endowed Chair in Psychiatry, is a consultant to Alkermes, Janssen, Sage Therapeutics, Xenon Pharmaceuticals, and several generic medication companies; has received royalties for the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT)®; Clinical Manual for the Diagnosis and Treatment of Psychotic Depression, American Psychiatric Press, 2009; The Evidence-Based Guide to Antipsychotic Medications, American Psychiatric Press, 2010; The Evidence-Based Guide to Antidepressant Medications, American Psychiatric Press, 2012; and, UpToDate® and has received honorarium from Wolters Kluwer (Journal Editor). E.M. Whyte receives grant support from the NIMH and HRSA. A.N. Voineskos has received funding from the NIMH, Canadian Institutes of Health Research, Canada Foundation for Innovation, CAMH Foundation, and the University of Toronto. B.S. Meyers received research support from the NIMH at the time this work was done., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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- 2023
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29. Severe Familial Exudative Vitreoretinopathy, Congenital Hearing Loss, and Developmental Delay in a Child With Biallelic Variants in FZD4.
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van der Ende SR, Meyers BS, Capasso JE, Sasongko M, Yonekawa Y, Pihlblad M, Huey J, Bedoukian EC, Krantz ID, Ngo MH, McMaster CR, Levin AV, and Robitaille JM
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- DNA genetics, DNA Mutational Analysis, Familial Exudative Vitreoretinopathies, Female, Frizzled Receptors genetics, Humans, Mutation, Pedigree, Biological Products, Eye Diseases, Hereditary diagnosis, Eye Diseases, Hereditary genetics, Hearing Loss, Sensorineural diagnosis, Hearing Loss, Sensorineural genetics, Retinal Diseases diagnosis
- Abstract
Importance: Familial exudative vitreoretinopathy (FEVR) is a nonsyndromic autosomal dominant retinal disorder commonly caused by variants in the FZD4 gene. This study investigates the potential role beyond ocular abnormalities for FZD4 gene variants in patients with FEVR., Objective: To evaluate the role of FZD4 in symptoms beyond those associated with FEVR through a patient with biallelic variants in FZD4., Design, Setting, and Participants: This case series included the DNA testing and phenotyping of 1 patient proband and her parents, combined with signaling assays, to determine the association of patient-derived compound heterozygous variants on FZD4 signaling and biologic function., Main Outcomes and Measures: FZD4 genes were tested using next-generation sequencing and Sanger sequencing. Cell-based assays measured the effect of the variants on FZD4 signaling., Results: The proband presented with absent red reflexes from complete tractional retinal detachments diagnosed at 3 days of age and failed the newborn screening hearing test. Auditory brainstem response at 6 months of age showed bilateral mild to moderate high-frequency sensorineural hearing loss. The patient manifested developmental delays in speech and walking. Intravenous fluorescein angiography (IVFA) of the patient's parents detected stage 1 FEVR. Genetic testing revealed 2 FZD4 variants in the patient, each variant found in 1 parent. Signaling assays confirmed that the presence of both variants was associated with significantly worse signaling activity compared with the heterozygous state., Conclusions and Relevance: Results of this case series suggest that extraocular syndromic FEVR was associated with FZD4 variants. The decrease in FZD4 signaling owing to the biallelic nature of the disease resulted in hearing deficits, developmental delays, and a more severe retinal phenotype.
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- 2022
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30. Factor analysis of the CORE measure of psychomotor disturbance in psychotic depression: Findings from the STOP-PD II study.
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Bingham KS, Neufeld NH, Alexopoulos GS, Marino P, Mulsant BH, Rothschild AJ, Voineskos AN, Whyte EM, Meyers BS, and Flint AJ
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- Adult, Depression, Factor Analysis, Statistical, Humans, Bipolar Disorder, Depressive Disorder, Major complications, Psychotic Disorders complications
- Abstract
The CORE instrument is commonly used to measure psychomotor disturbance. We examined the factor structure of the CORE in 266 adults with an acute episode psychotic depression, a disorder with a high rate of psychomotor disturbance. Exploratory factor analysis identified a two-factor solution: Factor 1 corresponded to the CORE's retardation and non-interactiveness items and Factor 2 corresponded to its agitation items. Internal consistency was excellent for Factor 1 but questionable for Factor 2. These findings suggest that the CORE's retardation and non-interactiveness items should be combined in one subscale when assessing patients with an acute episode of psychotic depression., (Copyright © 2022. Published by Elsevier B.V.)
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- 2022
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31. Trends in drug revenue among major pharmaceutical companies: A 2010-2019 cohort study.
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Meyers DE, Meyers BS, Chisamore TM, Wright K, Gyawali B, Prasad V, Sullivan R, and Booth CM
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- Cohort Studies, Commerce, Humans, Retrospective Studies, Drug Costs, Drug Industry, Pharmaceutical Preparations
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Background: Over the past 2 decades there has been a substantial increase in the number of new cancer medicines; this has been accompanied by a dramatic rise in drug costs. It is unknown how these trends impact the revenue of the pharmaceutical sector., Methods: Retrospective cohort study to characterize temporal trends of revenue generated from cancer medicines as a proportion of total drug revenue among 10 large pharmaceutical companies from 2010 to 2019. Itemized product-sales data publicly available through company websites or annual filings were used to identify annual drug revenue. Revenue data were adjusted for inflation and converted to 2019 US dollars., Results: During the study period, cumulative annual revenue generated from cancer drugs increased by 70%: from $55.8 billion to $95.1 billion, while cumulative revenue from nononcology drugs decreased 18%: from $342.2 billion to $281.5 billion. The proportion of total drug revenue generated from oncology drugs increased substantially over the study period: from 14% in 2010 to 25% in 2019 (τ = 1.0, P < .001)., Conclusions: Among 10 of the world's largest pharmaceutical companies, revenues generated from the sale of cancer drugs have increased by 70% over the past decade, while revenues from other medicines have decreased by 18%. Revenues from cancer drugs now account for one-quarter of the net revenues from these companies. Further work is needed to understand if this increase in sales revenue reflects industry profit, and to what extent increased spending has translated into improvements in patient and population outcomes., (© 2021 American Cancer Society.)
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- 2022
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32. Effect of Older vs Younger Age on Anthropometric and Metabolic Variables During Treatment of Psychotic Depression With Sertraline Plus Olanzapine: The STOP-PD II Study.
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Flint AJ, Rothschild AJ, Whyte EM, Alexopoulos GS, Mulsant BH, Marino P, Banerjee S, Pollari CD, Wu Y, Voineskos AN, and Meyers BS
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- Adolescent, Adult, Aged, Aged, 80 and over, Benzodiazepines adverse effects, Depression, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Olanzapine adverse effects, Treatment Outcome, Young Adult, Antipsychotic Agents adverse effects, Sertraline adverse effects
- Abstract
Objective: To examine the effect of older versus younger age on change in anthropometric and metabolic measures during extended treatment of psychotic depression with sertraline plus olanzapine., Methods: Two hundred and sixty-nine men and women aged 18-85 years with an episode of psychotic depression were treated with open-label sertraline plus olanzapine for up to 12 weeks. Participants who remained in remission following an 8-week stabilization phase were eligible to participate in a 36-week randomized controlled trial (RCT) that compared the efficacy and tolerability of sertraline plus olanzapine with sertraline plus placebo. Weight, waist circumference and plasma lipids, glucose, HbA1c, and insulin were measured at regular intervals during the acute, stabilization and randomized phases of the study. Linear mixed models were used to analyze the trajectories of anthropometric and metabolic measures., Results: Participants aged 60 years or older experienced less weight gain and less increase in cholesterol during the combined acute and stabilization phases of the study compared with those aged 18-59 years. At the acute-stabilization termination visit, mean weight in older participants was 6.5 lb. less than premorbid weight, whereas it was 17.9 lb. more than premorbid weight in younger participants. In the RCT, there was a significant interaction of treatment and age group for the trajectory of weight, but the post hoc tests that compared age groups within each treatment arm were not statistically significant. There were no clinically significant differences between younger and older participants in glycemic measures., Conclusion: Older patients with psychotic depression experienced less increase in weight and total cholesterol than their younger counterparts during acute and stabilization treatment with sertraline plus olanzapine. In the older group, weight gained during the acute and stabilization phases appeared to be partial restoration of weight lost during the index episode of depression, whereas weight gain in younger participants was not., (Copyright © 2020 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)
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- 2021
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33. Association between psychomotor disturbance and treatment outcome in psychotic depression: a STOP-PD II report.
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Flint AJ, Bingham KS, Neufeld NH, Alexopoulos GS, Mulsant BH, Rothschild AJ, Whyte EM, Voineskos AN, Marino P, and Meyers BS
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Background: Little is known about the relationship between psychomotor disturbance (PMD) and treatment outcome of psychotic depression. This study examined the association between PMD and subsequent remission and relapse of treated psychotic depression., Methods: Two hundred and sixty-nine men and women aged 18-85 years with an episode of psychotic depression were treated with open-label sertraline plus olanzapine for up to 12 weeks. Participants who remained in remission or near-remission following an 8-week stabilization phase were eligible to participate in a 36-week randomized controlled trial (RCT) that compared the efficacy and tolerability of sertraline plus olanzapine (n = 64) with sertraline plus placebo (n = 62). PMD was measured with the psychiatrist-rated sign-based CORE at acute phase baseline and at RCT baseline. Spearman's correlations and logistic regression analyses were used to analyze the association between CORE total score at acute phase baseline and remission/near-remission and CORE total score at RCT baseline and relapse., Results: Higher CORE total score at acute phase baseline was associated with lower frequency of remission/near-remission. Higher CORE total score at RCT baseline was associated with higher frequency of relapse, in the RCT sample as a whole, as well as in each of the two randomized groups., Conclusions: PMD is associated with poorer outcome of psychotic depression treated with sertraline plus olanzapine. Future research needs to examine the neurobiology of PMD in psychotic depression in relation to treatment outcome.
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- 2021
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34. Pharmacotherapy Prescriptions for Relapse Prevention of Psychotic Depression After Electroconvulsive Therapy.
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Patel DA, Flint AJ, Rothschild AJ, Whyte EM, Meyers BS, Mulsant BH, Voineskos AN, Marino P, and Alexopoulos GS
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- Adult, Aged, Aged, 80 and over, Antidepressive Agents administration & dosage, Antipsychotic Agents administration & dosage, Depression therapy, Drug Therapy, Combination, Female, Humans, Lithium Compounds administration & dosage, Male, Middle Aged, Psychotic Disorders psychology, Recurrence, Retrospective Studies, Secondary Prevention methods, Depression prevention & control, Electroconvulsive Therapy methods, Psychotic Disorders therapy
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Purpose/background: Electroconvulsive therapy (ECT) is effective in the treatment of acute episodes of psychotic depression. However, no adequately powered studies have directly investigated the efficacy of antipsychotic pharmacotherapy in relapse prevention of psychotic depression after ECT. In the absence of such literature, we reviewed the clinical practice of 4 academic medical centers that have made research contributions in the treatment of psychotic depression over the past 20 years., Methods/procedures: We reviewed medical records of patients with a diagnosis of psychotic depression who received 1 or more acute courses of ECT over the span of 3 years. Chi-square tests were used to compare pharmacotherapy prescribed at the time of completion of ECT., Findings/results: A total of 163 patients received 176 courses of ECT for separate episodes of psychotic depression. The combination of an antidepressant plus an antipsychotic was the most common regimen, ranging from 61.9% to 85.5% of all prescriptions. One center added lithium in 45.5% of cases treated with the combination of an antidepressant plus an antipsychotic. An antipsychotic alone was prescribed in less than 10% of cases. An antidepressant alone or other drug combinations were rare., Implications/conclusions: The combination of an antidepressant plus an antipsychotic was the most commonly prescribed regimen at the completion of ECT for relapse prevention in patients with psychotic depression acutely treated with ECT. Although this report offers a view of the clinical practice of 4 academic medical centers, it also points to the need of randomized controlled trials on continuation pharmacotherapy after treatment of psychotic depression with ECT., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2021
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35. Effects of Antipsychotic Medication on Brain Structure in Patients With Major Depressive Disorder and Psychotic Features: Neuroimaging Findings in the Context of a Randomized Placebo-Controlled Clinical Trial.
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Voineskos AN, Mulsant BH, Dickie EW, Neufeld NH, Rothschild AJ, Whyte EM, Meyers BS, Alexopoulos GS, Hoptman MJ, Lerch JP, and Flint AJ
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- Adolescent, Adult, Aged, Aged, 80 and over, Diffusion Tensor Imaging, Double-Blind Method, Female, Follow-Up Studies, Humans, Male, Middle Aged, Young Adult, Antipsychotic Agents pharmacology, Cerebral Cortex diagnostic imaging, Cerebral Cortex drug effects, Cerebral Cortex pathology, Depressive Disorder, Major diagnostic imaging, Depressive Disorder, Major drug therapy, Depressive Disorder, Major pathology, Olanzapine pharmacology, Outcome Assessment, Health Care, Psychotic Disorders diagnostic imaging, Psychotic Disorders drug therapy, Psychotic Disorders pathology, Sertraline pharmacology, White Matter diagnostic imaging, White Matter drug effects, White Matter pathology
- Abstract
Importance: Prescriptions for antipsychotic medications continue to increase across many brain disorders, including off-label use in children and elderly individuals. Concerning animal and uncontrolled human data suggest antipsychotics are associated with change in brain structure, but to our knowledge, there are no controlled human studies that have yet addressed this question., Objective: To assess the effects of antipsychotics on brain structure in humans., Design, Setting, and Participants: Prespecified secondary analysis of a double-blind, randomized, placebo-controlled trial over a 36-week period at 5 academic centers. All participants, aged 18 to 85 years, were recruited from the multicenter Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II). All participants had major depressive disorder with psychotic features (psychotic depression) and were prescribed olanzapine and sertraline for a period of 12 to 20 weeks, which included 8 weeks of remission of psychosis and remission/near remission of depression. Participants were then were randomized to continue receiving this regimen or to be switched to placebo and sertraline for a subsequent 36-week period. Data were analyzed between October 2018 and February 2019., Interventions: Those who consented to the imaging study completed a magnetic resonance imaging (MRI) scan at the time of randomization and a second MRI scan at the end of the 36-week period or at time of relapse., Main Outcomes and Measures: The primary outcome measure was cortical thickness in gray matter and the secondary outcome measure was microstructural integrity of white matter., Results: Eighty-eight participants (age range, 18-85 years) completed a baseline scan; 75 completed a follow-up scan, of which 72 (32 men and 40 women) were useable for final analyses. There was a significant treatment-group by time interaction in cortical thickness (left, t = 3.3; P = .001; right, t = 3.6; P < .001) but not surface area. No significant interaction was found for fractional anisotropy, but one for mean diffusivity of the white matter skeleton was present (t = -2.6, P = .01). When the analysis was restricted to those who sustained remission, exposure to olanzapine compared with placebo was associated with significant decreases in cortical thickness in the left hemisphere (β [SE], 0.04 [0.009]; t34.4 = 4.7; P <.001), and the right hemisphere (β [SE], 0.03 [0.009]; t35.1 = 3.6; P <.001). Post hoc analyses showed that those who relapsed receiving placebo experienced decreases in cortical thickness compared with those who sustained remission., Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, antipsychotic medication was shown to change brain structure. This information is important for prescribing in psychiatric conditions where alternatives are present. However, adverse effects of relapse on brain structure support antipsychotic treatment during active illness., Trial Registration: ClinicalTrials.gov Identifier: NCT01427608.
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- 2020
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36. Structural brain networks in remitted psychotic depression.
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Neufeld NH, Kaczkurkin AN, Sotiras A, Mulsant BH, Dickie EW, Flint AJ, Meyers BS, Alexopoulos GS, Rothschild AJ, Whyte EM, Mah L, Nierenberg J, Hoptman MJ, Davatzikos C, Satterthwaite TD, and Voineskos AN
- Subjects
- Cross-Sectional Studies, Depression, Female, Humans, Magnetic Resonance Imaging, Male, Brain diagnostic imaging, Depressive Disorder, Major diagnostic imaging, Depressive Disorder, Major drug therapy, Psychotic Disorders diagnostic imaging, Psychotic Disorders drug therapy
- Abstract
Major depressive disorder with psychotic features (psychotic depression) is a severe disorder. Compared with other psychotic disorders such as schizophrenia, relatively few studies on the neurobiology of psychotic depression have been pursued. Neuroimaging studies investigating psychotic depression have provided evidence for distributed structural brain abnormalities implicating the insular cortex and limbic system. We examined structural brain networks in participants (N = 245) using magnetic resonance imaging. This sample included healthy controls (n = 159) and the largest cross-sectional sample of patients with remitted psychotic depression (n = 86) collected to date. All patients participated in the Study of Pharmacotherapy of Psychotic Depression II randomized controlled trial. We used a novel, whole-brain, data-driven parcellation technique-non-negative matrix factorization-and applied it to cortical thickness data to derive structural covariance networks. We compared patients with remitted psychotic depression to healthy controls and found that patients had significantly thinner cortex in five structural covariance networks (insular-limbic, occipito-temporal, temporal, parahippocampal-limbic, and inferior fronto-temporal), confirming our hypothesis that affected brain networks would incorporate cortico-limbic regions. We also found that cross-sectional depression and severity scores at the time of scanning were associated with the insular-limbic network. Furthermore, the insular-limbic network predicted future severity scores that were collected at the time of recurrence of psychotic depression or sustained remission. Overall, decreased cortical thickness was found in five structural brain networks in patients with remitted psychotic depression and brain-behavior relationships were observed, particularly between the insular-limbic network and illness severity.
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- 2020
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37. Cognitive Impairment in Geriatric Psychotic Depression: Unanswered Questions.
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Meyers BS
- Subjects
- Aged, Cognition, Depression, Humans, Cognition Disorders, Cognitive Dysfunction, Psychotic Disorders
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- 2019
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38. Health-related quality of life in remitted psychotic depression ✰ .
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Bingham KS, Whyte EM, Mulsant BH, Rothschild AJ, Rudorfer MV, Marino P, Banerjee S, Butters MA, Alexopoulos GS, Meyers BS, and Flint AJ
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- Age Factors, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Randomized Controlled Trials as Topic psychology, Remission Induction, Sex Factors, Cost of Illness, Depressive Disorder, Major psychology, Quality of Life psychology
- Abstract
Background: Some patients with major depression continue to demonstrate deficits in health-related quality of life (HRQL) following remission. No data exist, however, regarding HRQL in remitted psychotic depression. In this study, we aimed to characterize HRQL in patients with psychotic depression receiving controlled pharmacotherapy., Methods: This is a secondary analysis of a randomized controlled trial studying continuation pharmacotherapy of psychotic depression. We compared participants' HRQL (measured using the SF-36) between baseline and remission and to population norms. We also compared SF-36 scores stratified by age and gender and examined the correlation between SF-36 scores and medical burden, depression score and neuropsychological performance in remission., Results: SF-36 scores were significantly lower than population norms at baseline, but improved following remission to the level of population norms. Neither SF-36 scores nor magnitude of SF-36 improvement differed substantially between genders or between younger and older participants. In remission, depression scores were correlated with most SF-36 scales and medical burden was correlated with SF-36 scales measuring physical symptoms. Neuropsychological measures were generally not correlated with SF-36 scores., Limitations: This study was a secondary analysis not powered specifically to measure HRQL as an outcome variable and the SF-36 was the only HRQL measure used., Conclusions: Participants with remitted psychotic depression demonstrated levels of HRQL comparable to population norms, despite marked impairment in HRQL when acutely ill. This finding suggests that, when treated in a rigorous manner, many patients with this severe illness improve significantly from a clinical and HRQL perspective., (Copyright © 2019. Published by Elsevier B.V.)
- Published
- 2019
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39. Effect of Continuing Olanzapine vs Placebo on Relapse Among Patients With Psychotic Depression in Remission: The STOP-PD II Randomized Clinical Trial.
- Author
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Flint AJ, Meyers BS, Rothschild AJ, Whyte EM, Alexopoulos GS, Rudorfer MV, Marino P, Banerjee S, Pollari CD, Wu Y, Voineskos AN, and Mulsant BH
- Subjects
- Adolescent, Adult, Aged, Antidepressive Agents therapeutic use, Antipsychotic Agents adverse effects, Depressive Disorder, Major psychology, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Olanzapine adverse effects, Proportional Hazards Models, Secondary Prevention, Sertraline therapeutic use, Young Adult, Affective Disorders, Psychotic drug therapy, Antipsychotic Agents therapeutic use, Depressive Disorder, Major drug therapy, Olanzapine therapeutic use
- Abstract
Importance: Psychotic depression is a severely disabling and potentially lethal disorder. Little is known about the efficacy and tolerability of continuing antipsychotic medication for patients with psychotic depression in remission., Objective: To determine the clinical effects of continuing antipsychotic medication once an episode of psychotic depression has responded to combination treatment with an antidepressant and antipsychotic agent., Design, Setting, and Participants: Thirty-six week randomized clinical trial conducted at 4 academic medical centers. Patients aged 18 years or older had an episode of psychotic depression acutely treated with sertraline plus olanzapine for up to 12 weeks and met criteria for remission of psychosis and remission or near-remission of depressive symptoms for 8 weeks before entering the clinical trial. The study was conducted from November 2011 to June 2017, and the final date of follow-up was June 13, 2017., Interventions: Participants were randomized either to continue olanzapine (n = 64) or switch from olanzapine to placebo (n = 62). All participants continued sertraline., Main Outcomes and Measures: The primary outcome was risk of relapse. Main secondary outcomes were change in weight, waist circumference, lipids, serum glucose, and hemoglobin A1c (HbA1c)., Results: Among 126 participants who were randomized (mean [SD] age, 55.3 years [14.9 years]; 78 women [61.9%]), 114 (90.5%) completed the trial. At the time of randomization, the median dosage of sertraline was 150 mg/d (interquartile range [IQR], 150-200 mg/d) and the median dosage of olanzapine was 15 mg/d (IQR, 10-20 mg/d). Thirteen participants (20.3%) randomized to olanzapine and 34 (54.8%) to placebo experienced a relapse (hazard ratio, 0.25; 95% CI, 0.13 to 0.48; P < .001). The effect of olanzapine on the daily rate of anthropometric and metabolic measures significantly differed from placebo for weight (0.13 lb; 95% CI, 0.11 to 0.15), waist circumference (0.009 inches; 95% CI, 0.004 to 0.014), and total cholesterol (0.29 mg/dL; 95% CI, 0.13 to 0.45) but was not significantly different for low-density lipoprotein cholesterol (0.04 mg/dL; 95% CI, -0.01 to 0.10), high-density lipoprotein cholesterol (-0.01 mg/dL; 95% CI, -0.03 to 0.01), triglyceride (-0.153 mg/dL; 95% CI, -0.306 to 0.004), glucose (-0.02 mg/dL; 95% CI, -0.12 to 0.08), or HbA1c levels (-0.0002 mg/dL; 95% CI, -0.0021 to 0.0016)., Conclusions and Relevance: Among patients with psychotic depression in remission, continuing sertraline plus olanzapine compared with sertraline plus placebo reduced the risk of relapse over 36 weeks. This benefit needs to be balanced against potential adverse effects of olanzapine, including weight gain., Trial Registration: ClinicalTrials.gov Identifier: NCT01427608.
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- 2019
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40. Resting state functional connectivity in patients with remitted psychotic depression: A multi-centre STOP-PD study.
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Neufeld NH, Mulsant BH, Dickie EW, Meyers BS, Alexopoulos GS, Rothschild AJ, Whyte EM, Hoptman MJ, Nazeri A, Downar J, Flint AJ, and Voineskos AN
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- Adult, Aged, Brain Mapping, Case-Control Studies, Depressive Disorder, Major physiopathology, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Ontario, Brain physiopathology, Connectome, Depression psychology, Depressive Disorder, Major psychology, Rest psychology
- Abstract
Background: There is paucity of neurobiological knowledge about major depressive disorder with psychotic features ("psychotic depression"). This study addresses this knowledge gap by using resting state functional magnetic resonance imaging (R-fMRI) to compare functional connectivity in patients with psychotic depression and healthy controls., Methods: We scanned patients who participated in a randomized controlled trial as well as healthy controls. All patients achieved remission from depressive and psychotic symptoms with sertraline and olanzapine. We employed Independent Component Analysis in independent samples to isolate the default mode network (DMN) and compared patients and controls., Findings: The Toronto sample included 28 patients (mean [SD], age 56·2 [13·7]) and 39 controls (age 55·1 [13·5]). The Replication sample included 29 patients (age 56·1 [17·7]) and 36 controls (age 48·3 [17·9]). Patients in the Toronto sample demonstrated decreased between-network functional connectivity between the DMN and bilateral insular, somatosensory/motor, and auditory cortices with peak activity in the right planum polare (t = 4·831; p = 0·001, Family Wise Error (FWE) corrected). A similar pattern of between-network functional connectivity was present in our Replication sample with peak activity in the right precentral gyrus (t = 4·144; p = 0·003, FWE corrected)., Interpretation: Remission from psychotic depression is consistently associated with an absence of increased DMN-related functional connectivity and presence of decreased between-network functional connectivity. Future research will evaluate this abnormal DMN-related functional connectivity as a potential biomarker for treatment trajectories., Funding: National Institute of Mental Health., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2018
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41. Stabilization treatment of remitted psychotic depression: the STOP-PD study.
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Bingham KS, Meyers BS, Mulsant BH, Rothschild AJ, Whyte EM, Banerjee S, Artis AS, Alexopoulos GS, and Flint AJ
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- Adult, Aged, Antidepressive Agents therapeutic use, Antipsychotic Agents therapeutic use, Blood Glucose analysis, Blood Glucose drug effects, Body Weight drug effects, Cholesterol blood, Depressive Disorder, Major diagnosis, Diagnostic and Statistical Manual of Mental Disorders, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Male, Middle Aged, Olanzapine administration & dosage, Placebos administration & dosage, Remission Induction methods, Sertraline administration & dosage, Triglycerides blood, Depressive Disorder, Major drug therapy, Olanzapine therapeutic use, Psychotic Disorders drug therapy, Sertraline therapeutic use
- Abstract
Objective: We conducted a 12-week double-blind study of stabilization pharmacotherapy in patients with remitted psychotic depression (PD)., Methods: Seventy-one persons aged 18 years or older who had achieved remission of PD when randomized to either olanzapine plus sertraline or olanzapine plus placebo were continued on the double-blind treatment associated with remission. Symptoms of depression and psychosis, and weight, were measured once every 4 weeks. Cholesterol, triglycerides, and glucose were measured at stabilization phase baseline and Week 12/termination., Results: The effect of treatment did not significantly change with time for depression, weight, or metabolic measures in the stabilization phase. Eight of the 71 participants (11.3%; 95% CI: 5.8, 20.7) experienced a relapse of major depression, psychosis, or both. Treatment groups did not differ in the frequency of relapse. In the entire study group, the adjusted estimate for change in weight was an increase of 1.66 kg (95% CI: 0.83, 2.48) and the adjusted estimate for change in total cholesterol was a decrease of 14.8 mg/dL (95% CI: 3.5, 26.1) during the 12-week stabilization phase; the remaining metabolic measures did not significantly change., Conclusion: Continuation of acute treatment was associated with stability of remission., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2018
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42. Combating Stigma Against Dementia: A Role for Geriatric Psychiatry.
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Avari JN and Meyers BS
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- Humans, Dementia, Geriatric Psychiatry, Social Stigma
- Published
- 2018
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43. The Association of Baseline Suicidality With Treatment Outcome in Psychotic Depression.
- Author
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Bingham KS, Rothschild AJ, Mulsant BH, Whyte EM, Meyers BS, Banerjee S, Szanto K, and Flint AJ
- Subjects
- Adult, Antipsychotic Agents administration & dosage, Antipsychotic Agents adverse effects, Diagnostic and Statistical Manual of Mental Disorders, Double-Blind Method, Drug Monitoring methods, Drug Therapy, Combination methods, Female, Humans, Male, Middle Aged, Olanzapine, Psychiatric Status Rating Scales, Treatment Outcome, Benzodiazepines administration & dosage, Benzodiazepines adverse effects, Depressive Disorder, Major diagnosis, Depressive Disorder, Major drug therapy, Depressive Disorder, Major psychology, Sertraline administration & dosage, Sertraline adverse effects, Suicidal Ideation, Suicide, Attempted prevention & control, Suicide, Attempted psychology
- Abstract
Objective: To examine the association between baseline suicidality and outcome of major depression in a randomized controlled trial of the pharmacotherapy of psychotic depression and to explore the interaction of suicidality, randomized treatment assignment, and depression outcome., Methods: This study was a secondary analysis of data from 258 persons aged 18 years or older with DSM-IV-defined major depressive disorder with psychotic features who participated in a 12-week randomized controlled trial (RCT) comparing olanzapine plus sertraline with olanzapine plus placebo (the Study of the Pharmacotherapy of Psychotic Depression [STOP-PD], which ran from 2002 to 2007). The independent variable was baseline suicidality, defined by 4 groups (suicide attempt in the current episode, active suicidal ideation, passive suicidal ideation, and no suicidality). The outcome variables were change in 16-item Hamilton Depression Rating Scale (HDRS₁₆) total score (excluding the suicide item) over time and remission of psychotic depression over time., Results: Suicidality groups did not significantly differ on baseline HDRS₁₆ total score. Baseline suicidality group was significantly associated with change in HDRS₁₆ score over time in the sample as a whole (F₃,₁₃₉₄ = 8.17; P < .0001), but was not significantly associated with probability of remission over time. Among participants assigned to olanzapine and placebo, persons with no suicidality had a significantly greater reduction in HDRS₁₆ total score compared to those with passive suicidal ideation (7.5-point difference in change scores between the 2 groups; 95% CI, 4.3-10.7 t₁₃₉₄ = 4.61, P < .0001), active suicidal ideation (4.4 points; 95% CI, 1.4-7.4; t₁₃₉₄ = 2.85, P = .0176), or suicide attempts (6.1 points; 95% CI, 2.8-9.4; t₁₃₉₄ = 3.66, P = .0015). The 12-week change from baseline in HDRS₁₆ score for patients with no suicidality was not significantly different between the 2 treatment arms. However, the 12-week HDRS₁₆ improvement was significantly greater in the olanzapine plus sertraline arm, compared with the olanzapine plus placebo arm, for patients with suicide attempts (8.7-point difference in change scores between the 2 groups; 95% CI, 5.1-12.4; t₁₃₉₄ = 4.75, P < .0001), active suicidal ideation (8.1 points; 95% CI, 4.5-11.7; t₁₃₉₄ = 4.38, P < .0001), or passive suicidal ideation (5.7 points; 95% CI, 2.2-9.2; t₁₃₉₄ = 3.23, P = .0012), respectively., Conclusions: Baseline suicidality predicted worse acute treatment outcome of psychotic depression. However, participants with suicidality had a better outcome when treated with the combination of olanzapine and sertraline than when treated with olanzapine plus placebo., Trial Registration: ClinicalTrials.gov identifier: NCT00056472., (© Copyright 2017 Physicians Postgraduate Press, Inc.)
- Published
- 2017
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44. Improvement in Depression is Associated with Improvement in Cognition in Late-Life Psychotic Depression.
- Author
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Victoria LW, Whyte EM, Butters MA, Meyers BS, Alexopoulos GS, Mulsant BH, Rothschild AJ, Banerjee S, and Flint AJ
- Subjects
- Aged, Aged, 80 and over, Aging drug effects, Aging psychology, Antidepressive Agents therapeutic use, Antipsychotic Agents therapeutic use, Depressive Disorder, Major complications, Double-Blind Method, Drug Therapy, Combination, Humans, Late Onset Disorders complications, Late Onset Disorders drug therapy, Middle Aged, Olanzapine, Psychotic Disorders complications, Treatment Outcome, Benzodiazepines therapeutic use, Cognition drug effects, Depressive Disorder, Major drug therapy, Psychotic Disorders drug therapy, Sertraline therapeutic use
- Abstract
Objective: To characterize cognitive function at baseline and investigate the relationship between change in cognition, depression, and psychosis after treatment among older adults with major depressive disorder with psychotic features., Methods: This was a secondary analysis of a double-blind, randomized, controlled treatment trial at inpatient and outpatient settings at four academic health centers on "Young Old" (aged 60-71 years, N = 71) and "Older" (aged 72-86 years, N = 71) participants diagnosed with psychotic depression. Olanzapine plus sertraline or olanzapine plus placebo were given until week 12 or termination., Results: At baseline, Young Old and Older participants did not differ on measures of depression severity or global cognition, information processing speed, and executive function. Improvement in depressive and psychotic symptoms from baseline to treatment end was similar in both the Young Old and Older groups. However, improvement in depressive symptoms was significantly associated with improvement in global cognitive function in Young Old participants but not in Older participants., Conclusion: Cognitive dysfunction was not a detriment to improvement in symptoms of psychotic major depression in our geriatric patients. Young Old and Older patients improved to a similar degree on measures of depression and delusions from baseline to treatment end. However, improvement in cognition over the course of treatment was more prominent in the Young Old group than in the Older group., (Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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45. Geriatric Psychiatry: Is There a Future?
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Avari JN and Meyers BS
- Subjects
- Fellowships and Scholarships statistics & numerical data, Fellowships and Scholarships trends, Humans, Forecasting, Geriatric Psychiatry trends, Health Workforce trends
- Published
- 2017
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46. Assessing Late Life Major Depression: Does Brain Disease Affect Measurement of Severity and Treatment Response?
- Author
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Meyers BS
- Subjects
- Appetite, Depression, Depressive Disorder, Major, Humans, Weight Loss, Brain Diseases, Dementia
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- 2016
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47. SSRI-antipsychotic combination in psychotic depression: sertraline pharmacokinetics in the presence of olanzapine, a brief report from the STOP-PD study.
- Author
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Davies SJ, Mulsant BH, Flint AJ, Meyers BS, Rothschild AJ, Whyte EM, Kirshner MM, Sorisio D, Pollock BG, and Bies RR
- Subjects
- Adult, Age Factors, Antipsychotic Agents administration & dosage, Antipsychotic Agents therapeutic use, Benzodiazepines therapeutic use, Drug Interactions, Drug Therapy, Combination, Female, Half-Life, Humans, Male, Middle Aged, Models, Biological, Nonlinear Dynamics, Olanzapine, Selective Serotonin Reuptake Inhibitors administration & dosage, Selective Serotonin Reuptake Inhibitors pharmacokinetics, Selective Serotonin Reuptake Inhibitors therapeutic use, Sertraline administration & dosage, Sertraline therapeutic use, Sex Factors, Benzodiazepines administration & dosage, Depressive Disorder, Major drug therapy, Psychotic Disorders drug therapy, Sertraline pharmacokinetics
- Abstract
Objective: We recently reported an unexpected interaction between olanzapine and sertraline in a population being treated for psychotic depression. Contrary to knowledge of cytochrome p450 interactions sertraline increased apparent clearance of olanzapine by 30%. Here we examined the pharmacokinetics of sertraline in the same population. Existing studies suggest that sertraline apparent clearance is significantly increased in male subjects and suggested an age/sex interaction., Methods: We studied subjects undergoing combination of sertraline/olanzapine treatment for psychotic depression in the Study of the Pharmacotherapy of Psychotic Depression. Nonlinear mixed effect modelling software was used to examine the sertraline pharmacokinetics, evaluating age, sex, race, and olanzapine exposure as covariates., Results: Eighty-seven subjects (median age 62 years, 28 male subjects, 11 African-Americans) provided 138 samples for sertraline concentration. Olanzapine exposure had a 14.8-fold range. A one compartment model with combined residual error described the sertraline concentration data adequately. Half-life and sex effect on sertraline apparent clearance (males averaging 50% higher (p < 0.005); 96.6 l/h vs 64.8 in female subjects) were similar to previous reports. No other covariate (age, race or olanzapine exposure) had a significant impact on apparent clearance, and no age/sex interaction emerged., Conclusion: Sertraline pharmacokinetics were similar to historical descriptions in populations not taking antipsychotics. Unlike our unexpected finding that sertraline increases olanzapine apparent clearance, olanzapine exposure had no impact on sertraline pharmacokinetics. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)
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- 2016
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48. Establishing the cut-off score for remission and severity-ranges on the Psychotic Depression Assessment Scale (PDAS).
- Author
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Østergaard SD, Rothschild AJ, Flint AJ, Mulsant BH, Whyte EM, Vermeulen T, Bech P, and Meyers BS
- Subjects
- Antidepressive Agents administration & dosage, Antidepressive Agents therapeutic use, Antipsychotic Agents administration & dosage, Antipsychotic Agents therapeutic use, Benzodiazepines administration & dosage, Benzodiazepines therapeutic use, Depressive Disorder, Major drug therapy, Drug Therapy, Combination, Female, Humans, Olanzapine, ROC Curve, Randomized Controlled Trials as Topic, Sertraline administration & dosage, Sertraline therapeutic use, Depressive Disorder, Major diagnosis, Psychiatric Status Rating Scales, Remission Induction, Severity of Illness Index
- Abstract
Background: The Psychotic Depression Assessment Scale (PDAS) is a rating scale dedicated to the measurement of severity in psychotic depression (PD). The aim of this study was to establish the PDAS cut-off for remission of PD as well as PDAS score-ranges for mild, moderate, and severe PD. The secondary aim was to test how remission, as defined by the PDAS, would perform as outcome measure when applied to the data from a large randomized controlled trial (RCT) in PD., Methods: The study was based on data from the Study of Pharmacotherapy in Psychotic Depression (STOP-PD). The cut-off for remission on the PDAS and the severity-ranges for mild, moderate, and severe PD were defined using the Clinical Global Impression - Severity scale (CGI-S) as reference by means of pair-wise receiver operating characteristic (ROC) analyses. Subsequently, it was tested whether remission on the PDAS could separate the effects of Olanzapine+Sertraline vs. Olanzapine+Placebo through an intention-to-treat, mixed-effects logistic regression of the data from STOP-PD., Results: According to the ROC analyses, the ideal cut-off for remission of PD was a PDAS total score <8, while the severity-ranges for mild, moderate and severe PD were 8-15, 16-23, and >23 respectively. When applying the PDAS total score <8 (remission) as outcome on the STOP-PD data, treatment with Olanzapine+Sertraline performed significantly better than Olanzapine+Placebo (p<0.001)., Limitations: The STOP-PD was not designed specifically to answer the research questions of the present study., Conclusions: According to this study, a total score <8 on the PDAS corresponds to remission of PD., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2016
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49. Relationship Between Cerebrovascular Risk, Cognition, and Treatment Outcome in Late-Life Psychotic Depression.
- Author
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Bingham KS, Whyte EM, Meyers BS, Mulsant BH, Rothschild AJ, Banerjee S, and Flint AJ
- Subjects
- Adolescent, Adult, Aged, Antidepressive Agents therapeutic use, Antipsychotic Agents therapeutic use, Cerebrovascular Disorders psychology, Cognition drug effects, Cognition Disorders psychology, Depressive Disorder, Major psychology, Double-Blind Method, Executive Function drug effects, Humans, Mental Processes drug effects, Middle Aged, Neuropsychological Tests, Olanzapine, Psychiatric Status Rating Scales, Psychotic Disorders complications, Psychotic Disorders drug therapy, Psychotic Disorders psychology, Reaction Time drug effects, Risk, Severity of Illness Index, Stroop Test, Treatment Outcome, Young Adult, Benzodiazepines therapeutic use, Cerebrovascular Disorders complications, Cognition Disorders complications, Depressive Disorder, Major complications, Depressive Disorder, Major drug therapy, Sertraline therapeutic use
- Abstract
Objective: To examine whether cerebrovascular risk, executive function, and processing speed are associated with acute treatment outcome of psychotic depression in older adults., Methods: The authors analyzed data from 142 persons aged 60 years or older with major depression with psychotic features who participated in a 12-week randomized controlled trial (RCT) comparing olanzapine plus sertraline with olanzapine plus placebo. The independent variables were baseline cerebrovascular risk (Framingham Stroke Risk Score), baseline executive function (Stroop interference score and the initiation/perseveration subscale of the Mattis Dementia Rating Scale), and baseline processing speed (color and word reading components of the Stroop). The outcome variable was change in severity of depression, measured by the 17-item Hamilton Depression Rating Scale total score, during the course of the RCT., Results: Greater baseline cerebrovascular risk was significantly associated with less improvement in depression severity over time, after controlling for pertinent covariates. Neither executive function nor processing speed predicted outcome., Conclusion: This study suggests an association of cerebrovascular risk, but not executive function or processing speed, with treatment outcome of major depression with psychotic features in older adults., (Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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50. All Spiking, Sustained ON Displaced Amacrine Cells Receive Gap-Junction Input from Melanopsin Ganglion Cells.
- Author
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Reifler AN, Chervenak AP, Dolikian ME, Benenati BA, Li BY, Wachter RD, Lynch AM, Demertzis ZD, Meyers BS, Abufarha FS, Jaeckel ER, Flannery MP, and Wong KY
- Published
- 2015
- Full Text
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