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Scovia Nalugo Mbalinda,1 Mark Kaddumukasa,2 Josephine Nambi Najjuma,3 Martin Kaddumukasa,1,4 Jane Nakibuuka,1,4 Christopher J Burant,5 Shirley Moore,6 Carol Blixen,7 Elly T Katabira,1 Martha Sajatovic7 1Department of Nursing, School of Health Sciences, College of Health Sciences, Makerere University, Kampala, Uganda; 2Department of Medicine, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda; 3Department of Nursing, Mbarara University of Science and Technology, Mbarara, Uganda; 4Department of Medicine, Mulago Hospital, Kampala, Uganda; 5Louis Stokes VA Medical Center, Geriatric Research Education, and Clinical Center, Cleveland, OH, 44106, USA; 6Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, 44106, USA; 7Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center & Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USACorrespondence: Scovia Nalugo Mbalinda, Department of Nursing, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda, Tel +256782212151, Email snmbalinda@gmail.comPurpose: Evidence supporting secondary stroke in sub-Saharan Africa is scarce. This study describes the incidence of stroke recurrence and associated risk factors in sub-Saharan Africa.Methods and Materials: Scientific databases were systematically searched from January 2000 to December 2022 for population-based observational studies, case-control or cohort studies of recurrent stroke involving adults aged 18 years and above in sub-Saharan Africa (SSA). We assessed the quality of the eligible studies using the Critical Appraisal Skills Program (CASP) checklist for observational studies.Results: Six studies met the inclusion criteria and were included in this study. Stroke recurrence rates in SSA ranged from 9.4% to 25%. Majority of the studies were conducted from Western Africa and showed that stroke recurrence rates are high within sub-Saharan Africa ranging from 2% to 25%. The known stroke risk factors such as hypertension, chronic alcohol consumption, etc., remained the leading causes of stroke recurrence. The studies reported a higher mortality rate ranging from 20.5 − 23% among those with recurrent strokes compared to primary strokes.Conclusion: This systematic review is an update and summary of the available literature on stroke recurrence within sub-Saharan Africa. Further studies are warranted to assess the outcomes and burden of stroke recurrence in SSA.Keywords: stroke recurrence, sub-Saharan Africa, risk factors, secondary prevention, cardiovascular disease

Martin Kaddumukasa,1 Alyssa M Edwards,2 Josephine Nambi Najjuma,3 Scovia Nalugo Mbalinda,4 Jane Nakibuuka,1 Christopher J Burant,5 Shirley M Moore,6 Carol Blixen,2 Elly T Katabira,1 Martha Sajatovic,2 Mark Kaddumukasa1 1Department of Internal Medicine, College of Health Sciences, Makerere University, Kampala, Uganda; 2Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH, USA; 3Department of Nursing, Mbarara University of Science and Technology, Mbarara, Uganda; 4Department of Nursing, College of Health Sciences, Makerere University, Kampala, Uganda; 5Louis Stokes VA Medical Center, Geriatric Research Education, and Clinical Center, Cleveland, OH, USA; 6Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, USACorrespondence: Martin Kaddumukasa, Email kaddumart@gmail.comAbstract: The study set out to perform a systematic literature review of evidence-based interventions that target the reduction of secondary stroke risk in Africa. The review analyzed longitudinal intervention studies conducted in Sub-Saharan Africa, focusing on adult participants who had suffered a prior stroke. It encompassed publications and peer-reviewed papers sourced from reputable databases, including PubMed, Ovid, Cochrane, and Web of Science. Three randomized clinical trial (RCT) studies were included with sample sizes ranging from 16 to 400 participants, mean age ranged between 50 and 66 years, with 64.5% male participants. All studies applied multidisciplinary team interventions of enhanced patient follow-up involving care givers, nurse educators, physicians, and social workers. Interventions ranged from comprehensive patient education, tracking of medication adherence and enforcing healthy lifestyle behaviors (regular exercise, regular BP checks, and dietary changes). We found a decrease in Systolic Blood Pressure over time in 2 of 3 treatment groups, an improvement in medical adherence in all treatment groups, and a decrease in cholesterol levels in 1 treatment group. Evidence-based interventions involving multidisciplinary teams and comprehensive patient education were found to demonstrate promising results in reducing secondary stroke risk in Africa, leading to significant improvements in medical adherence and reductions in systolic blood pressure in the majority of treatment groups. However, more research is required to confirm the influence of these interventions on cholesterol levels and to establish their lasting advantages in preventing strokes among African communities.Keywords: secondary stroke risk, risk interventions, Sub-Saharan Africa

Jane Namusisi,1,2 Stella Kyoyagala,1 Josephine Nantongo,2 Mike Kyewalyanga,1,3 Stephen Sabiiti,1 Angelique Murorunkwere,1 Josephine Nambi Najjuma,1 Jane Nakibuuka,4 Mark Kaddumukasa,4 Martha Sajatovic,5 Peter Kalubi1 1Department of Pediatrics and Child Health, Mbarara University of Science and Technology (MUST), Mbarara, Uganda; 2Department of Pediatrics and Child Health, Mbarara Regional Referral Hospital (MRRH), Mbarara, Uganda; 3Department of Pediatrics and Child Health, Holy Innocents Children’s Hospital, Mbarara, Uganda; 4Department of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda; 5Neurological and Behavioral Outcomes Center, University Hospital Case Medical Center, Case Western Reserve University, Cleveland, OH, USACorrespondence: Jane Namusisi, Mbarara University of science and technology (MUST), P.O. Box 1410, Mbarara, Uganda, Tel +256784064925, Email janedaizzie@gmail.comBackground: Seizure control among children with epilepsy (CWE) receiving anti-seizure medications (ASMs) remains a challenge in low-resource settings. Uncontrolled seizures are significantly associated with increased morbidity and mortality among CWE. This negatively impacts their quality of life and increases stigma.Aim: This study determined seizure control status and described the factors associated among CWE receiving ASMs at Mbarara Regional Referral Hospital (MRRH).Methods: In a retrospective chart review study, socio-demographic and clinical data were obtained from 112 medical records. CWE receiving ASMs for at least six months and regularly attending the clinic were included in the study. Physical or telephone interviews were conducted with the immediate caregivers of the CWE to establish the current seizure control status of the participants.Results: A total of 112 participants were enrolled. Of these, three-quarters had generalized onset seizures, 23% had focal onset seizures, while 2% had unknown onset motor seizures. About 60.4% of the study participants had poor seizure control. Having a comorbidity (p-value 0.048, AOR 3.2 (95% CI 1.0– 9.9)), history suggestive of birth asphyxia (p-value 0.014, AOR 17.8 (95% CI 1.8– 176.8)), and being an adolescent (p-value 0.006, AOR 6.8 (95% CI 1.8– 26.6)) were significantly associated with poor seizure control.Conclusion: Seizure control among CWE receiving ASMs at MRRH remains poor. Efforts geared to addressing seizure control and optimizing drugs are needed, especially among children with comorbidities, those with history of birth asphyxia, and adolescents.Keywords: epilepsy, anti-seizure medications, children, seizure control, Uganda

Alyssa M Edwards,1 Jordan C Petitt,1 Sanjana Kumar,1 Jennifer B Levin,1,2 Martha Sajatovic1,2 1Case Western Reserve University School of Medicine, Cleveland, OH, USA; 2University Hospitals of Cleveland Medical Center, Department of Psychiatry, Cleveland, OH, USACorrespondence: Martha Sajatovic, University Hospitals of Cleveland Medical Center, Department of Psychiatry, 10524 Euclid Ave, Cleveland, OH, 44106, USA, Email martha.sajatovic@uhhospitals.orgIntroduction: Given the increasing use of telepsychiatry and to serve as a reference point informing future research, our team evaluated the literature on the use of telepsychiatry for medication adherence promotion prior to the COVID-19 pandemic among patients with psychotic disorders.Methods: A search of PubMed, Cochrane, Web of Science, CINAHL, and PsycINFO was conducted using PRISMA guidelines to identify telepsychiatry interventions to enhance medication adherence in patients with primary psychotic disorders. Both quantitative and qualitative data were extracted from the identified articles including study characteristics, interventions, and outcomes.Results: In total, 230 articles were obtained through electronic literature search, and 4 articles were eventually retained that met inclusion criteria. All 4 articles were randomized controlled trials, were adjuncts to in-person usual care, used telephone platforms and targeted medication adherence. Compared to treatment as usual, 3 out of 4 studies found medication adherence was improved and 2 out of 4 studies found improved medication attitudes. Telepsychiatry appeared to be acceptable to patients with psychotic disorders.Discussion: In the pre-Covid-19 literature, telepsychiatry appears promising as an adjunct to usual care for increasing medication adherence among individuals with schizophrenia/schizoaffective disorder. However, given the limited number of papers and exclusive use on telephone-only to deliver telepsychiatry, additional research specific to telepsychiatry for patients with psychosis is needed.Keywords: telemedicine, telehealth, telepsychiatry, remote delivery, virtual delivery, schizophrenia, schizoaffective disorder

Jane Namusisi,1 Mark Kaddumukasa,2 Martha Sajatovic,3 Peter Kalubi1 1Department of Pediatrics and Child Health, Mbarara University of Science and Technology (MUST), Mbarara, Uganda; 2Department of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda; 3Neurological and Behavioral Outcomes Center, University Hospital Case Medical Center, Case Western Reserve University, Cleveland, OH, USACorrespondence: Mark Kaddumukasa, Email kaddumark@yahoo.co.uk

Felix Bongomin,1,2 Elly Katabira,1 Martha Sajatovic,3 Mark Kaddumukasa1 1Department of Medicine, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda; 2Department of Medical Microbiology & Immunology, Faculty of Medicine, Gulu University, Gulu, Uganda; 3Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center & Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USACorrespondence: Felix BongominDepartment of Medical Microbiology & Immunology, Faculty of Medicine, Gulu University, P.O. Box 166, Gulu, UgandaEmail drbongomin@gmail.comBackground: Over one-fourth of new onset epilepsy occurs after age 60. However, the burden of epilepsy and other seizure disorders among this special population in Africa is largely unknown, despite a growingnumber of elderly persons on the continent. This study aimed to assess the prevalence and risk factors for epilepsy among persons aged 60 years or older in Africa.Methods: We conducted a systematic review by searching MEDLINE (via) and EMBASE databases from inception to 30th October 2020. Primary researches reporting prevalence or incidence of seizures or epilepsy in older persons (≥ 60 years) were included. Review articles were excluded.Results: We retrieved 107 citations from which 4 studies, recruiting 10, 334 participants were eligible. The studies were conducted between 1999 and 2018 and published between 2005 and 2019. Two of the studies were conducted in the West African countries of Niger and Senegal; meanwhile, the remaining 2 were conducted in East African country of Tanzania. Regarding study design, three were either hospital-based or community-based cross-sectional studies. Meanwhile, 1 was a retrospective hospital-based study. Of the 10,334 participants, 81 (0.78%) had a seizure disorder. The prevalence of seizure ranged from 0.02% to 3.2%.Conclusion: There are limited data on the prevalence of epilepsy in older persons in older adults in most countries in sub-Saharan Africa. Epilepsy among the older adults remains a challenge in Africa and more information is needed to understand the burden to improve care.Keywords: seizure, epilepsy, elderly persons, sub-Saharan Africa

Carolyn H Still,1 Chris Burant,1 Shirley Moore,1 Doug Einstadter,2,3 Cheryl Killion,1 Charles Modlin,4 Sophia Sundararajan,5,6 John D Thornton,3,7 Jackson T Wright Jr,5,6 Martha Sajatovic6,8 1Frances Payne Bolton, School of Nursing, Case Western Reserve University, Cleveland, OH, USA; 2Center for Health Care Research and Policy, Case Western Reserve University, Cleveland, OH, USA; 3The MetroHealth System, Cleveland, OH, USA; 4Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA; 5Case Western Reserve University, School of Medicine, Cleveland, OH, USA; 6University Hospitals Cleveland Medical Center, Cleveland, OH, USA; 7Center for Reducing Health Disparities, Case Western Reserve University, Cleveland, OH, USA; 8Department of Psychiatry and of Neurology, Case Western Reserve University, School of Medicine, Cleveland, OH, USACorrespondence: Carolyn H StillFrances Payne Bolton, School of Nursing, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106, USATel: +1 216 368 6338Email cwh11@case.eduBackground: African American (AA) male survivors of strokes or transient ischemic attacks (TIA) have the highest risk of recurrent stroke when compared to other racial-ethnic men. However, there is a paucity of evidence-based strategies, including organizational, educational, or behavioral interventions, that targets secondary stroke risk reduction in AA men.Methods: Targeted Management for Reducing Stroke Risk (TEAM) is an ongoing, 6-month prospective, randomized controlled trial that will determine whether a curriculum-guided self-management approach, using peer dyads (men who had a stroke or TIA and their care partners) will improve post-stroke care in AA men.Results: The study sample will consist of 160 AA men who have experienced a stroke or TIA within 5 years, randomized to TEAM or Wait-list control group. The primary outcome changes in systolic blood pressure (BP) and high-density lipoprotein (HDL), while secondary outcomes include diastolic BP, total cholesterol, low-density lipoprotein, triglycerides, and glycemic control for diabetics. We hypothesize that AA men in TEAM will have significantly lower systolic BP and higher HDL when compared to AA men in the Wait-list control group at 6-month.Conclusion: Persistent disparities for stroke burden in AA men highlight the need for novel interventions to promote secondary stroke-risk reduction. Building on promising pilot data, TEAM uses a group format, with a nurse and patient co-led intervention focused on AA men and family needs, practice in problem-solving, and attention to emotional and role management. In addition, the TEAM approach may help reduce stroke risk factors and health disparities in AA men.Clinicaltrials.gov Identifier: NCT04402125.Keywords: stroke, transient ischemic attack, stroke prevention, African-Americans, health disparities

Michael J Doane,1 Martha Sajatovic,2 Peter J Weiden,1 Amy K O’Sullivan,1 Stephen Maher,3 Jakob B Bjorner,3 Asia Sikora Kessler,3 Julia Carpenter-Conlin,1 Leona Bessonova,1 Dawn I Velligan4 1Alkermes, Inc, Waltham, MA, USA; 2University Hospitals Cleveland Medical Center, Cleveland, OH, USA; 3Optum, Patient Insights, Johnston, RI, USA; 4The University of Texas Health Science Center at San Antonio, San Antonio, TX, USACorrespondence: Leona BessonovaAlkermes, Inc, 852 Winter Street, Waltham, MA, USATel +1 781 609 6439Email Leona.Bessonova@alkermes.comBackground: This survey examined the experiences of people living with schizophrenia who have used oral antipsychotics (APs).Methods: Adults with self-reported physician-diagnosed schizophrenia (N=200), who were members of an online research participation panel and reported taking one or more oral APs within the last year, completed a cross-sectional online survey that focused on direct report of their experiences regarding APs (eg, symptoms, side effects, adherence). Descriptive analyses were conducted for the total survey sample and for subgroups defined a priori by experience with specific, prevalent side effects.Results: The mean age of the sample was 41.9 (SD=11.0) years, 50% of participants were female, and 32% were nonwhite. Overall ratings were positive for medication effectiveness and convenience but negative for side effects. While most participants reported that APs improved schizophrenia symptoms (92%), 27% reported APs as having done “more harm than good.” Almost all participants (98%) reported experiencing side effects of APs, with the most common being anxiety (88%), feeling drowsy/tired (86%), and trouble concentrating (85%). Side effects frequently cited as either “extremely” or “very” bothersome were weight gain (56%), sexual dysfunction (55%), and trouble concentrating (54%). Over 80% reported that side effects had negatively impacted their work and social functioning (eg, social activities or family/romantic relationships). Since initiating treatment, 56% of respondents had stopped taking APs at some point (65% of these due to side effects). Side effects commonly reported as having led to stopping AP treatment were “feeling like a ‘zombie’” (22%), feeling drowsy/tired (21%), and weight gain (20%).Conclusion: Most participants reported improvements in schizophrenia symptoms associated with the use of APs. However, most participants also reported experiencing numerous bothersome side effects that negatively impacted their work, social functioning, and treatment adherence. Results highlight the unmet need for new APs with favorable benefit-risk profiles.Keywords: schizophrenia, antipsychotics, side effects, adherence, efficacy, preference

Zaira Khalid,1 Hasina Momotaz,2 Farren Briggs,3 Kristin A Cassidy,1,2 Naomi S Chaytor,4 Robert T Fraser,5 Mary R Janevic,6 Barbara Jobst,7 Erica K Johnson,8 Peter Scal,9 Tanya M Spruill,10 Betsy K Wilson,2 Martha Sajatovic1,2 1Department of Psychiatry, Case Western Reserve University School of Medicine, University Hospitals Cleveland Medical Center , Cleveland, OH, USA; 2Department of Neurology, Case Western Reserve University School of Medicine, Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; 3Department of Population Health and Quantitative Science, School of Medicine, Case Western Reserve University, Cleveland, OH, USA; 4Department of Medical Education and Clinical Sciences, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA; 5Department of Rehabilitation Medicine, University of Washington, Seattle, WA, USA; 6Center for Managing Chronic Disease, University of Michigan School of Public Health, Ann Arbor, MI, USA; 7Department of Neurology, Geisel School of Medicine at Dartmouth, Dartmouth College, Lebanon, NH, USA; 8Health Promotion Research Center, University of Washington, Seattle, WA, USA; 9Department of Pediatrics and Adolescent Health, University of Minnesota, Minneapolis, MN, USA; 10Department of Population Health, NYU School of Medicine, New York, NY, USACorrespondence: Martha SajatovicPrevention Research Center, Case Western Reserve University School of Medicine, University Hospitals Cleveland Medical Center, 10524 Euclid Avenue, Cleveland, OH 44106, USATel +1 216 844-2808Fax +1 216 844-2742Email Martha.sajatovic@uhhospitals.orgAim: There are limited data on psychological outcomes in older people with epilepsy (PWE). This analysis, from a large pooled dataset of clinical studies from the Managing Epilepsy Well (MEW) Network, examined clinical variables including depressive symptom severity, quality of life and epilepsy self-management competency among older (age 55+) vs younger (

Martha Sajatovic,1,2 Ruth Ross,3 Susan N Legacy,4 Matthew Byerly,5 John M Kane,6,7 Faith DiBiasi,8 Heather Fitzgerald,9 Christoph U Correll6,7 1Department of Psychiatry, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; 2Departments of Psychiatry and Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; 3Ross Editorial, Port Townsend, WA, USA; 4US Medical Affairs Neuroscience, Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA; 5Cell Biology and Neuroscience, Center for Mental Health Research and Recovery, Montana State University, Bozeman, MT, USA; 6Psychiatry, The Zucker Hillside Hospital, Glen Oaks, NY, USA; 7Psychiatry, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Glen Oaks, NY, USA; 8Scientific Communications, Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, MD, USA; 9Medical Affairs, Lundbeck LLC, Deerfield, IL, USA Objective: The aim of this study was to provide recommendations on initiating and maintaining long-acting injectable antipsychotics (LAIs) in individuals with schizophrenia/schizoaffective or bipolar disorder. Methods: A 50-question survey comprising 916 response options was completed by 34 expert researchers and high prescribers with extensive LAI experience, rating relative appropriateness/importance on a 9-point scale. Consensus was determined using chi-square test of score distributions. Results of 21 questions comprising 339 response options regarding LAI initiation, maintenance treatment, adequate trial definition, identifying treatment nonresponse, and switching are reported. Results: Experts agreed that the most important LAI selection factor was patient response/tolerability to previous antipsychotics. An adequate therapeutic LAI trial was defined as the time to steady state ± 1–2 injection cycles. Experts suggested that oral efficacy and tolerability should be established before switching to an LAI, without consensus on the required time, and that the time for oral supplementation and next injection interval should be determined by the time to attainment of therapeutic LAI levels. Most experts agreed that ≥1 adequate LAI trial is needed to identify the lack of efficacy. There was little agreement about strategies for switching between LAIs. Conclusion: Expert guidance may aid clinicians in their decisions regarding initiating/maintaining LAIs in individuals with schizophrenia/schizoaffective or bipolar disorder. Keywords: expert consensus, schizophrenia, schizoaffective disorder, bipolar disorder, long-acting injectable antipsychotics

Martha Sajatovic,1,2 Ruth Ross,3 Susan N Legacy,4 Christoph U Correll,5,6 John M Kane,5,6 Faith DiBiasi,7 Heather Fitzgerald,8 Matthew Byerly9 1Department of Psychiatry, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; 2Departments of Psychiatry and Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; 3Ross Editorial, Port Townsend, WA, USA; 4US Medical Affairs Neuroscience, Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA; 5Psychiatry, The Zucker Hillside Hospital, Glen Oaks, NY, USA; 6Psychiatry, The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Glen Oaks, NY, USA; 7Scientific Communications, Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, MD, USA; 8Medical Affairs, Lundbeck LLC, Deerfield, IL, USA; 9Cell Biology and Neuroscience, Center for Mental Health Research and Recovery, Montana State University, Bozeman, MT, USA Objective: To assess expert consensus on barriers and facilitators for long-acting injectable antipsychotic (LAI) use and provide clinical recommendations on issues where clinical evidence is lacking, including identifying appropriate clinical situations for LAI use. Methods: A 50-question survey comprising 916 response options was distributed to 42 research experts and high prescribers with extensive LAI experience. Respondents rated options on relative appropriateness/importance using a 9-point scale. Consensus was determined using chi-square test of score distributions. Mean (standard deviation) ratings were calculated. Responses to 29 questions (577 options) relating to appropriate patients and clinical scenarios for LAI use are reported. Results: Recommendations aligned with research on risk factors for nonadherence and poor outcomes for patients with schizophrenia/schizoaffective or bipolar disorder. Findings suggested, contrary to general practice patterns, that LAI use may be appropriate earlier in the disease course and in younger patients. Results for bipolar disorder were similar to those for schizophrenia but with less consensus. Numerous facilitators of LAI prescribing were considered important, particularly that LAIs may reduce relapses and improve outcomes. Conclusion: Findings support wider use of LAIs in patients with schizophrenia/schizoaffective and bipolar disorders beyond the setting of poor adherence and earlier use in the disease course. Keywords: expert consensus, schizophrenia, schizoaffective disorder, bipolar disorder, long-acting injectable antipsychotics

Martha Sajatovic,1 Faith DiBiasi,2 Susan N Legacy3 1Departments of Psychiatry and Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, USA; 2US Medical Affairs, Neuroscience, Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, MD, USA; 3US Medical Affairs, Neuroscience, Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA Introduction: Antipsychotics are recommended as first-line therapy for acute mania and maintenance treatment of bipolar disorder; however, published literature suggests their real-world use remains limited. Understanding attitudes toward these medications may help identify barriers and inform personalized therapy. This literature review evaluated patient and clinician attitudes toward the use of antipsychotics for treating bipolar disorder. Materials and methods: A systematic search of the Cochrane Library, Ovid MEDLINE, Embase, and BIOSIS Previews identified English language articles published between January 1, 2000, and June 15, 2016, that reported attitudinal data from patients, health care professionals, or caregivers; treatment decision-making; or patient characteristics that predicted antipsychotic use for bipolar disorder. Results were analyzed descriptively. Results: Of the 209 references identified, 11 met the inclusion criteria and were evaluated. These articles provided attitudinal information from 1,418 patients with bipolar disorder and 1,282 treating clinicians. Patients’ attitudes toward antipsychotics were generally positive. Longer duration of clinical stability was associated with positive attitudes. Implementation of psychoeducational and adherence enhancement strategies could improve patient attitudes. Limited data suggest clinicians’ perceptions of antipsychotic efficacy and tolerability may have the greatest impact on their prescribing patterns. Because the current real-world evidence base is inadequate, clinician attitudes may reflect a relative lack of experience using antipsychotics in patients with bipolar disorder. Conclusion: Although data are very limited, perceived tolerability and efficacy concerns shape both patient and clinician attitudes toward use of antipsychotic drugs in bipolar disorder. Additional studies are warranted. Keywords: bipolar disorder, antipsychotics, systematic review, attitudes

Martha Sajatovic,1,2 Angela L Ridgel,3 Ellen M Walter,1,4 Curtis M Tatsuoka,1,2 Kari Colón-Zimmermann,2 Riane K Ramsey,2 Elisabeth Welter,2 Steven A Gunzler,1,4 Christina M Whitney,1,4 Benjamin L Walter1,4 1Department of Neurology, Case Western Reserve University School of Medicine, 2Neurological and Behavioral Outcomes Center, University Hospitals Cleveland Medical Center, Cleveland, 3Department of Exercise Physiology, Kent State University, Kent, 4Movement Disorders Center, University Hospitals Cleveland Medical Center, Cleveland, OH, USA Background: Depression is common in people with Parkinson’s disease (PD), and exercise is known to improve depression and PD. However, lack of motivation and low self-efficacy can make exercise difficult for people with PD and comorbid depression (PD-Dep). A combined group exercise and chronic disease self-management (CDSM) program may improve the likelihood that individuals will engage in exercise and will show a reduction in depression symptoms. The purpose of this study was to compare changes in depression in PD-Dep between individual versus group exercise plus CDSM and to examine participant adherence and perception of the interventions.Methods: Participants (N=30) were randomized to either Enhanced EXerCisE thErapy for PD (EXCEED; group CDSM and exercise) or self-guided CDSM plus exercise. Outcomes were change in depression assessed with the Montgomery–Asberg Depression Rating Scale (MADRS), cognition, apathy, anxiety, sleep, quality of life, motor function, self-efficacy, and patient satisfaction.Results: Both groups showed significant improvement in MADRS (P

Molly Howland,1 Kevin C Allan,1 Caitlin E Carlton,1 Curtis Tatsuoka,2–4 Kathleen A Smyth,3 Martha Sajatovic1,2,4,5 1Case Western Reserve University School of Medicine, 2Neurological and Behavioral Outcomes Center, University Hospitals Case Medical Center, 3Department of Epidemiology and Biostatistics, 4Department of Neurology, 5Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, OH, USA Objectives: Patients with cognitive impairment may have difficulty reporting their functional and cognitive abilities, which are important clinical outcomes. Health care proxies may be able to corroborate patient self-reports. Several studies reported discrepancy between patient and proxy ratings, though the literature is sparse on changes over time of these ratings. Our goals in this 12-month study were to compare patient and proxy reports on functioning, cognition, and everyday executive function, and to further elucidate correlates of patient–proxy discrepancy. Methods: This was a prospective cohort study of individuals older than 70 years who ranged from having no cognitive impairment to having moderate dementia who had a proxy available to complete instruments at baseline (N=76). Measurements included Alzheimer’s Disease Cooperative Study–Activities of Daily Living Inventory (ADCS-ADLI), Neuro-QOL Executive Function, PROMIS Applied Cognition (PROMIS-Cog), Mini-Mental State Examination (MMSE), and Geriatric Depression Scale. Results: Patient- and proxy-rated ADCS-ADLI were correlated at baseline and at 1-year follow-up. Patient and proxy ratings were discrepant on Neuro-QOL Executive Function and PROMIS-Cog. Greater patient–proxy discrepancy on PROMIS-Cog was associated with younger age and less depression, and greater patient–proxy discrepancy on Neuro-QOL Executive Function was associated with less depression and worse cognitive impairment. Patient–proxy discrepancy increased over time for everyday executive function. Changes in proxy-rated but not patient-rated ADCS-ADLI correlated with MMSE changes. Conclusion: Patients and proxies generally agree in reporting on activities of daily living. Patient and proxy reports differ in their respective evaluation of cognitive functioning and everyday executive function. Ratings from both sources may be preferred for these two domains, though studies using gold standard measures are necessary. It is important that clinicians are aware of the differences between patient and proxy perspective to create an accurate clinical picture and guide treatment. Keywords: agreement, activities of daily living, dementia, executive function, caregiver

Dawn I Velligan,1 Martha Sajatovic,2 Ainslie Hatch,3 Pavel Kramata,4 John P Docherty3 1Department of Psychiatry, The University of Texas Health Science Center, San Antonio, TX, 2Departments of Psychiatry and Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, 3Medical Affairs, ODH, Inc., Princeton, NJ, 4C4 MedSolutions LLC, Yardley, PA, USA Background: Antipsychotic medication reduces the severity of serious mental illness (SMI) and improves patient outcomes only when medicines were taken as prescribed. Nonadherence to the treatment of SMI increases the risk of relapse and hospitalization and reduces the quality of life. It is necessary to understand the factors influencing nonadherence to medication in order to identify appropriate interventions. This systematic review assessed the published evidence on modifiable reasons for nonadherence to antipsychotic medication in patients with SMI. Methods: Articles published between January 1, 2005, and September 10, 2015, were searched on MEDLINE through PubMed. Abstracts were independently screened by 2 randomly assigned authors for inclusion, and disagreement was resolved by another author. Selected full-text articles were divided among all authors for review. Results: A qualitative analysis of data from 36 articles identified 11 categories of reasons for nonadherence. Poor insight was identified as a reason for nonadherence in 55.6% (20/36) of studies, followed by substance abuse (36.1%, 13/36), a negative attitude toward medication (30.5%, 11/36), medication side effects (27.8%, 10/36), and cognitive impairments (13.4%, 7/36). A key reason directly associated with intentional nonadherence was a negative attitude toward medication, a mediator of effects of insight and therapeutic alliance. Substance abuse was the only reason consistently associated with unintentional nonadherence, regardless of type and stage of SMI. Discussion: Although adherence research is inherently biased because of numerous methodological limitations and specific reasons under investigation, reasons for nonadherence consistently identified as significant across studies likely reflect valid existing associations with important clinical implications. Conclusion: This systematic review suggests that a negative attitude toward medication and substance abuse are consistent reasons for nonadherence to antipsychotic medication among people with SMI. Adherence enhancement approaches that specifically target these reasons may improve adherence in a high-risk group. However, it is also important to identify drivers of poor adherence specific to each patient in selecting and implementing intervention strategies. Keywords: adherence, antipsychotics, attitude toward medication, bipolar disorder, schizophrenia, substance abuse

Annemiek Dols,1 Welmoed Krudop,2 Christiane Möller,2 Kenneth Shulman,3 Martha Sajatovic,4 Yolande AL Pijnenburg2 1Department of Old Age Psychiatry, GGZInGeest, 2Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Centre, Amsterdam, the Netherlands; 3Department of Geriatric Psychiatry, Sunnybrook Health Science Centre, Faculty of Medicine, University of Toronto, Toronto, Canada; 4Department of Psychiatry and Neurology, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, OH, USA Objectives: Although bipolar disorder has been understood classically as a cyclic disease with full recovery between mood episodes, in the last decade, evidence has accumulated supporting progressive features. The clinical picture of advanced or end-stage bipolar disorder is heterogeneous with possible deficits in cognition and behavior, as illustrated by our case series.Cases: From our neuropsychiatric outpatient clinic, we describe four cases with bipolar disorder gradually developing a clinical syndrome, including apathy, disinhibition, loss of empathy, stereotypical behavior, and compulsiveness, fulfilling the criteria for possible behavioral variant frontotemporal dementia. All cases were diagnosed with bipolar 1 disorder at least 10 years before the onset of the current symptoms, which were not due to recent mood episodes or switches of medication. In all cases, 3–7 years of follow-up yielded no progression. Repeated neuroimaging was within normal limits. Cerebrospinal fluid biomarker studies were not supportive of underlying neurodegenerative pathology. C9orf72 mutation status was negative in all cases.Conclusion: Symptoms fitting the criteria for possible behavioral variant frontotemporal dementia may be present in end-stage of bipolar disorder. An alternative neurodegenerative nature seems unlikely based on repeated normal neuroimaging and the absence of clinical progression. Functional involvement of the frontal-subcortical networks might play a role. Keywords: bipolar disorder, older, staging, bvFTD, benign phenocopy syndrome

Carol Blixen,1,2 Jennifer B Levin,2 Kristin A Cassidy,2 Adam T Perzynski,1 Martha Sajatovic2–4 1Center for Health Care Research and Policy, MetroHealth Medical Center, 2Department of Psychiatry, 3Department of Neurology, Neurological Institute, 4Department of Biostatistics & Epidemiology, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA Background: Bipolar disorder (BD) is a chronic mental illness associated with reduced quality of life, high rates of suicide, and high financial costs. Evidence indicates that psychosocial stress might play an important role in the onset and course of BD. Objective: The objective of this study was to address the gap between coping theory and the clinical use of coping strategies used to self-manage BD.Methods: In-depth interviews were conducted with a sample of 21 poorly adherent patients with BD. All interviews were audiotaped, transcribed verbatim, and analyzed using content analysis with an emphasis on dominant themes.Results: Transcript-based analysis generated two major domains of coping strategies used to self-manage BD: 1) problem focused (altering eating habits, managing mood-stabilizing medications, keeping psychiatric appointments, seeking knowledge, self-monitoring, and socializing) and 2) emotion focused (distracting activities, denial, isolation, modifying/avoiding, helping others, and seeking social support). Participants used both types of coping strategies to deal with stressful situations brought about by the internal and external demands associated with self-management of BD.Conclusion: This qualitative study provided a first step in evaluating coping strategies as a possible mediator in the self-management of BD and has implications for health care providers. Being able to characterize an individual’s coping behaviors can help patients modify or replace more maladaptive coping with better coping strategies in the self-management of this chronic mental illness. Keywords: bipolar disorder, coping strategies, self-management

Thomas Scheidemantel,1 Irina Korobkova,2 Soham Rej,3,4 Martha Sajatovic1,2 1University Hospitals Case Medical Center, 2Case Western Reserve University School of Medicine, Cleveland, OH, USA; 3Department of Psychiatry, University of Toronto, Toronto, ON, 4Geri PARTy Research Group, Jewish General Hospital, Montreal, QC, Canada Abstract: Asenapine (Saphris®) is an atypical antipsychotic drug which has been approved by the US Food and Drug Administration for the treatment of schizophrenia in adults, as well as the treatment of acute manic or mixed episodes of bipolar I in both adult and pediatric populations. Asenapine is a tetracyclic drug with antidopaminergic and antiserotonergic activity with a unique sublingual route of administration. In this review, we examine and summarize the available literature on the safety, efficacy, and tolerability of asenapine in the treatment of bipolar disorder (BD). Data from randomized, double-blind trials comparing asenapine to placebo or olanzapine in the treatment of acute manic or mixed episodes showed asenapine to be an effective monotherapy treatment in clinical settings; asenapine outperformed placebo and showed noninferior performance to olanzapine based on improvement in the Young Mania Rating Scale scores. There are limited data available on the use of asenapine in the treatment of depressive symptoms of BD, or in the maintenance phase of BD. The available data are inconclusive, suggesting the need for more robust data from prospective trials in these clinical domains. The most commonly reported adverse effect associated with use of asenapine is somnolence. However, the somnolence associated with asenapine use did not cause significant rates of discontinuation. While asenapine was associated with weight gain when compared to placebo, it appeared to be modest when compared to other atypical antipsychotics, and its propensity to cause increases in hemoglobin A1c or serum lipid levels appeared to be similarly modest. Asenapine does not appear to cause any clinically significant QTc prolongation. The most commonly reported extra-pyramidal symptom associated with asenapine was akathisia. Overall, asenapine appears to be a relatively well-tolerated atypical antipsychotic, effective in the treatment of acute manic and mixed episodes of BD. Keywords: asenapine, bipolar, manic episode, mixed episode, depressive features, safety, tolerability

Martha Sajatovic,1 Michael S Davis,2 Kristin A Cassidy,3 Joseph Nestor,2 Johnny Sams,3 Edna Fuentes-Casiano3 1Department of Psychiatry and Neurological and Behavioral Outcomes Center, Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, OH, USA; 2MedicaSafe, New York, NY, USA; 3Department of Psychiatry, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, OH, USA Objective: As poor medication adherence is common in bipolar disorder (BD), technology-assisted approaches may help to monitor and enhance adherence. This study evaluated preliminary feasibility, patient satisfaction and effects on adherence, BD knowledge, and BD symptoms associated with the use of a multicomponent technology-assisted adherence enhancement system. Methods: This prospective study tested the system in five BD patients over a 15-day period. System components included: 1) an automated pill cap with remote monitoring sensor; 2) a multimedia adherence enhancement program; and 3) a treatment incentive program. This study evaluated system usability, patient satisfaction and effects on adherence (Morisky scale), knowledge (treatment knowledge test [TKT]), and symptoms (internal state scale [ISS]). Results: Mean age of the sample was 62 years, 4/5 (80%) Caucasian, and 4/5 (80%) single/divorced or widowed. Most participants (4/5, 80%) were on a single BD medication. Participants had BD for an average of 21 years. Challenges included attaching the pill sensor to standard pharmacy bottles for individuals using very large pill containers or those with multiday pill boxes. Three of five (60%) individuals completed the full 15-day period. Usability scores were high overall. Mean Morisky scores improved. Means on all four subscales of the ISS were all in the direction of improvement. On the TKT, there was a 40% increase in mean scores. Conclusion: A multicomponent technology-assisted BD adherence enhancement system is feasible. Challenges include accommodating multiple types of pill containers and monitoring multiple drugs simultaneously. The system can also generate adherence information that is potentially useful for treatment planning. Keywords: adherence, compliance, bipolar disorder, manic depressive disorder, mood stabilizers

Martha Sajatovic,1,2 Curtis Tatsuoka,2 Philipp Dines,1 Christopher S Bialko,1 Melanie Athey,1 Tiffany Williams,1 Kristin A Cassidy11Department of Psychiatry, 2Department of Neurology, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, Cleveland, OH, USAObjective: Psychotropic-related weight gain is a common concern among patients with bipolar disorder (BD). This concern affects satisfaction with treatment and may lead to non-adherence and relapse. This was a 12-week, uncontrolled prospective trial of patient-choice–facilitated ziprasidone switching among non-adherent BD patients with weight concerns. This study was conducted from January 2011 to July 2012.Method: Patients were asked to identify the “offending” BD medication which they believed was causing weight problems, and this agent was replaced with ziprasidone. The primary outcome was change in adherence as measured with the Tablets Routine Questionnaire (TRQ). Secondary outcomes included medication attitudes, BD symptoms, global psychopathology, social functioning, and quality of life.Results: The most common agents causing weight concerns were quetiapine (N=7, 23%), aripiprazole (N=4, 13%), olanzapine, lithium, and divalproex (all N=3, 10%). Adherence improved from a baseline of missing 48.6% of prescribed BD medication in the past week (44.9% in the past month) to missing 25.3% (P=0.002) of prescribed BD medication in the past week (P

Martha Sajatovic,1 Thomas R Thompson,2 Kevin Nanry,3 Suzanne Edwards,2 Ranjani Manjunath21Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH, 2GlaxoSmithKline, Research Triangle Park, NC; 3Quintiles, Durham, NC, USABackground: Lamotrigine is an anticonvulsant drug indicated for the maintenance treatment of bipolar I disorder and for various types of epilepsy. An orally disintegrating tablet (ODT) of lamotrigine was developed to provide a formulation option that might increase patient convenience and satisfaction.Methods: Subjects with mood disorders who reported difficulty swallowing currently prescribed lamotrigine immediate-release medication (baseline) were enrolled and treated with lamotrigine ODT for three weeks (end of treatment). Subject satisfaction and convenience were measured using the Treatment Satisfaction Questionnaire for Medication (TSQM). Also measured were global psychopathology using the Clinical Global Impression severity index (CGI-S) and depressive symptoms using the Beck Depression Inventory (BDI-II).Results: Lamotrigine ODT was found to be significantly more convenient to use than lamotrigine immediate-release (change in baseline TSQM convenience score: 23.3, n = 97, P < 0.001). The mean TSQM global satisfaction score was similar at baseline (76.3) and after treatment with lamotrigine ODT (76.0). There were no significant changes on CGI-S and BDI-II.Conclusion: Subjects reported that lamotrigine ODT was significantly more convenient than lamotrigine immediate-release, while both formulations were associated with good satisfaction. Lamotrigine ODT may be a treatment option for patients who have difficulty swallowing medication.Keywords: lamotrigine, epilepsy, antiepileptic drug, bipolar disorder, mood disorder