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OBJECTIVE The clinical response of patients with bipolar disorder to medical treatment is variable. A better understanding of the underlying neural circuitry involved in bipolar treatment responsivity subtypes may provide insight into treatment resistance and aid in identifying an effective surgical target for deep brain stimulation (DBS) specific to the disorder. Despite considerable imaging research related to the disease, a paucity of comparative imaging analyses of treatment responsiveness exists. There are also no DBS targets designed expressly for patients with bipolar disorder. Therefore, the authors analyzed cingulum bundle axonal connectivity in relation to cortico-striatal-thalamo-cortical (CSTC) loops implicated in bipolar disorder across subjects who are responsive to treatment (RSP) and those who are refractory to therapy (REF), compared to healthy controls (HCs). METHODS Twenty-five subjects with bipolar disorder (13 RSP and 12 REF), diagnosed using the Mini International Neuropsychiatric Interview and classified with standardized rating scales, and 14 HCs underwent MRI with diffusion sequences for probabilistic diffusion-weighted tractography analysis. Image processing and tractography were performed using MRTrix. Region of interest (ROI) masks were created manually for 10 anterior cingulum bundle subregions, including surgical targets previously evaluated for the treatment of bipolar disorder (cingulotomy and subgenual cingulate DBS targets). Cortical and subcortical ROIs of brain areas thought to be associated with bipolar disorder and described in animal tract-tracing models were created via FreeSurfer. The number of axonal projections from the cingulum bundle subregion ROIs to cortical/subcortical ROIs for each group was compared. RESULTS Significant differences were found across groups involving cingulum bundle and CSTC loops. Subjects in the RSP group had increased connections from rostral cingulum bundle to medial orbitofrontal cortex, which is part of the limbic CSTC loop, whereas subjects in the REF group had increased connectivity from rostral cingulum bundle to thalamus. Additionally, compared to HCs, both RSP and REF subjects had decreased cingulum bundle dorsal connectivity (dorsal anterior/posterior cingulate, dorsomedial/lateral frontal cortex) and increased cingulum bundle ventral connectivity (subgenual cingulate, frontal pole, lateral orbitofrontal cortex) involving limbic and associative CSTC loops. CONCLUSIONS Findings demonstrate that bipolar treatment responsivity may be associated with significant differences in cingulum bundle connectivity in relation to CSTC loops, which may help identify a surgical target for bipolar disorder treatment via DBS in the future.

Objective To address the fact that Black adults (BAs) experience significantly greater stroke burden than the general population, we conducted a systematic literature review which described evidence-based interventions targeting secondary stroke risk reduction in BAs. Data Source Publications were selected from PubMed, Ovid, Cochrane, and Web of Science databases. We included peer-reviewed, longitudinal, English-language studies performed in the USA which reported results for BAs separately and had adult participants who had experienced stroke-related events. Results Six of the 7 studies employed behavioral interventions which promoted education on stroke risk factors, problem-solving skills, and healthy-coping strategies. These studies demonstrated improvements in one or more biologic outcomes including cholesterol control and systolic blood pressure. Conclusions Existing interventions on secondary stroke risk reduction approaches are effective in reducing secondary stroke risk among BAs, especially in individuals with poorly controlled blood pressure at baseline. However, additional research is needed because the current approaches may limit generalizability.

OBJECTIVES: Antipsychotic drugs (APS) are widely used to treat patients with bipolar disorder (BD), but there is limited information in older-age bipolar disorder (OABD). This analysis of the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) investigated characteristics of OABD patients prescribed APS vs. those not prescribed APS. EXPERIMENTAL DESIGN: The observational analysis used baseline, cross-sectional data from 16 international studies for adults aged ≥ 50 years with BD comprising 1,007 individuals with mean age 63.2 years (SD = 9.0), 57.4% women, and mean age of onset 31.6 years (SD = 15.0). The dependent variable was current APS treatment status. The independent variables included demographic and clinical variables, and a random effect for study, that were included in generalized mixed models. PRINCIPAL OBSERVATIONS: 46.6% of individuals (n = 469) were using APS. The multivariate model results suggest that those treated with APS were younger (p = 0.01), less likely to be employed (p < 0.001), had more psychiatric hospitalizations (p = 0.009) and were less likely to be on lithium (p < 0.001). Of individuals on APS, only 6.6% of those (n = 27) were on first-generation antipsychotics (FGAs) and experienced a greater burden of psychiatric hospitalizations (p = 0.012). CONCLUSIONS: APS are widely prescribed in OABD, observed in nearly half of this sample with great variation across sites. Individuals with OABD on APS have more severe illness, more frequent hospitalizations and are more often unemployed vs. those not on APS. Future studies need to examine longitudinal outcomes in OABD prescribed APS to characterize underlying causal relationships.

Objectives: Antipsychotic drugs (APS) are widely used to treat patients with bipolar disorder (BD), but there is limited information in older-age bipolar disorder (OABD). This analysis of the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) investigated characteristics of OABD patients prescribed APS vs. those not prescribed APS.Experimental Design: The observational analysis used baseline, cross-sectional data from 16 international studies for adults aged ≥ 50 years with BD comprising 1,007 individuals with mean age 63.2 years (SD = 9.0), 57.4% women, and mean age of onset 31.6 years (SD = 15.0). The dependent variable was current APS treatment status. The independent variables included demographic and clinical variables, and a random effect for study, that were included in generalized mixed models.Principal Observations: 46.6% of individuals (n = 469) were using APS. The multivariate model results suggest that those treated with APS were younger (p = 0.01), less likely to be employed (p < 0.001), had more psychiatric hospitalizations (p = 0.009) and were less likely to be on lithium (p < 0.001). Of individuals on APS, only 6.6% of those (n = 27) were on first-generation antipsychotics (FGAs) and experienced a greater burden of psychiatric hospitalizations (p = 0.012).Conclusions: APS are widely prescribed in OABD, observed in nearly half of this sample with great variation across sites. Individuals with OABD on APS have more severe illness, more frequent hospitalizations and are more often unemployed vs. those not on APS. Future studies need to examine longitudinal outcomes in OABD prescribed APS to characterize underlying causal relationships.

ObjectiveLiterature on older-age bipolar disorder (OABD) is limited. This first-ever analysis of the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) investigated associations among age, BD symptoms, comorbidity, and functioning.MethodsThis analysis used harmonized, baseline, cross-sectional data from 19 international studies (N=1377). Standardized measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Global Assessment of Functioning (GAF).ResultsMean sample age was 60.8years (standard deviation [SD] 12.2years), 55% female, 72% BD I. Mood symptom severity was low: mean total YMRS score of 4.3 (SD 5.4) and moderate-to-severe depression in only 22%. Controlled for sample effects, both manic and depressive symptom severity appeared lower among older individuals (p's&nbsp

Additional file 2.

Additional file 2.

Supplemental Material, sj-pdf-1-ijp-10.1177_00912174211067335 for Mental health comorbidity and youth onset type 2 diabetes: A systematic review of the literature by Molly McVoy , Heather Hardin , Erin Fulchiero , Kate Caforio, Farren Briggs, Mandy Neudecker, and Martha Sajatovic in The International Journal of Psychiatry in Medicine

Additional file 1.

Additional file 1.

Supplemental Material, sj-pdf-1-ijp-10.1177_00912174211067335 for Mental health comorbidity and youth onset type 2 diabetes: A systematic review of the literature by Molly McVoy , Heather Hardin , Erin Fulchiero , Kate Caforio, Farren Briggs, Mandy Neudecker, and Martha Sajatovic in The International Journal of Psychiatry in Medicine

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

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

OBJECTIVES: To identify facilitators and barriers of epilepsy self-management practices among Black children and caregivers. METHODS: Qualitative semi-structured in-depth interviews were conducted with 11 child-caregiver dyads (11 children with epilepsy and 11 caregivers). A deductive-inductive analysis was undertaken to describe the range of barriers and facilitators significant to participants. RESULTS: The barriers and facilitators were classified into 3 management themes: epilepsy-specific knowledge and information, treatment, and lifestyle. Within these themes, several important subthemes were identified. Two subthemes related to knowledge barriers emerged: children and caregivers’ limited understanding and retention of complex written and spoken information and variable training and confidence in seizure first-aid. In contrast, facilitators for introducing and encouraging access to epilepsy self-management concepts were participants’ eagerness to learn about this topic and a keen interest in using educational materials enriched with visual aids on a phone platform as an adjunct to in-person education. The second theme revealed various practical barriers to optimum treatment adherence, including mistrust of the health care system. In comparison, caregivers’ collaborative approach and innovative strategies were identified as facilitators for treatment adherence. Finally, the lifestyle management barriers included a lack of defined processes to adopt healthy behaviors and challenges with disclosing epilepsy. Facilitators of this theme were comprised of building a team around the child to foster wellbeing and making healthy habits a fun and joyful experience for children. DISCUSSION: Qualitative evidence in this study highlights caregivers’ mistrust in the health care system and the lack of community support. Culturally competent interventions may improve access to and quality and utilization of self-management programs in Black children and families while reducing disparities.

ObjectivesIndividuals with serious mental illnesses such as bipolar disorder (BD) are at an increased risk for poor medication adherence compared to the general population. Individuals with BD also have high rates of chronic comorbid medical conditions like hypertension (HTN), diabetes, and cardiovascular disease. Cognitive-behavioral therapies often integrate strategies to improve medication adherence by targeting medication attitudes and self-efficacy, but the pathway toward behavior change needs further investigation.MethodsThis 3-month prospective, single-arm cohort study tested an automated SMS intervention entitled Individualized Texting for Adherence Building- Cardiovascular (iTAB-CV) in 38 participants with BD and HTN. The Tablets Routine Questionnaire (TRQ) measures the percentage of BD and HTN non-adherence over the past week and the past month. Attitudinal and habit measures including the Brief Illness Perception Questionnaire (Brief IPQ), the Medication Adherence Self-Efficacy Scale-Revised (MASES-R), the Self-Report Habit Index (SRHI), the Beliefs about Medicines Questionnaire (BMQ), and the Attitudes toward Mood Stabilizers Questionnaire (AMSQ) were given for BD and HTN medications. Correlational analyses were run to determine the associations between BD and HTN attitudinal and habit indices. Additionally, longitudinal analyses were conducted to determine if attitudes changed over time as a function of a 2-month mobile-health intervention.ResultsIllness attitudes towards BD were worse than towards HTN at the start of the study. Attitudes toward BD and towards mood-stabilizing drugs as well as antihypertensives improved following a mHealth intervention aimed at improving adherence. Furthermore, self-efficacy and habit strength for both BD and HTN drugs were correlated and were responsive to the intervention, with most of the change occurring after the first month of the intervention and not requiring the addition of the explicit reminders.ConclusionParticipants who received iTAB-CV showed improved attitudes towards BD and mood-stabilizing medication, and had an improvement in self-efficacy and habit strength towards taking both BD and HTN medications. Increased attention to mechanisms of change in mHealth interventions for adherence may facilitate impact. It should be noted that the methodology of the study limits drawing causal conclusions and suggests the need for a randomized control trial.

Self-management techniques that assist patients with chronic conditions, such as epilepsy, diabetes, and arthritis, play an important role in managing and caring for their conditions. The US Center for Disease Control and Prevention (CDC)-funded Managing Epilepsy Well (MEW) Network consists of 11 study sites across the US that aims to develop and disseminate self-management techniques for epilepsy patients. Epilepsy affects more than 65 million patients worldwide with serious negative impact on their own as well as their family member's quality of life. Taking advantage of advances in biomedical informatics, the MEW Network has created an integrated database (MEW DB) using a common data model and two tiers of study variables. The MEW DB consists of 1680 patient data records covering a wide range of patient population nationwide. Therefore, there is growing interest in the use of the MEW DB for different cohort query analysis. To address the challenges in: (1) selecting appropriate MEW research studies based on inclusion/exclusion criteria; (2) creating a patient cohort for given research hypothesis; and (3) performing appropriate statistical tests; we have developed an integrated data query and statistical analysis informatics tool called Insight. The Insight platform features an intuitive user interface to support the three phases of study selection, patient cohort creation, and statistical testing with the use of an epilepsy domain ontology to support ontology-driven query expansion. We evaluate the Insight platform using two user evaluation methods of "first click testing" and "user satisfaction survey". In addition, we performed a time performance test of the Insight platform using four patient datasets and three statistical test. The results of the user evaluation show that Insight platform is strongly approved by the users and the results of the time performance show that there is marginal difference in performance as the volume of patient data increases in the MEW DB.

Additional file 1. Original survey items.

Additional file 2. Supplementary tables and figures.

Additional file 1. SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents.

Additional file 1. SPIRIT 2013 Checklist: Recommended items to address in a clinical trial protocol and related documents.

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 (

OBJECTIVE: This study evaluated the feasibility, acceptability, and preliminary efficacy of psychoeducation plus an automated text-messaging intervention (iTAB-CV) to improve adherence for antihypertensives and bipolar disorder medication. METHODS: Following a psychoeducation program, iTAB-CV was administered for two months. In month one, participants received one educational/motivational and one mood rating text daily. In month two, medication reminders were added. RESULTS: The sample (n=38) was 74% African-Americans, 53% women, with a mean age of 51.53±9.06. Antihypertensive non-adherence decreased from 43%±23% to 21%±26% at 12 weeks [χ(2) = 34.6, df= 3, p< 0.001]. SBP decreased from 144.8±15.5 mmHg to 136.0±17.8 mmHg (χ(2) = 17.6, df=3, p< 0.001). Retention was 100%. CONCLUSIONS: In this uncontrolled trial, participants were highly engaged and medication adherence and reduced SBP were sustained following psychoeducation plus iTAB-CV. Since iTAB-CV is automated and delivered remotely, it has potential to reach a large and challenging population.

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 January1, 2000,and June15,2016, 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

The evidence base regarding characteristics of older adults with bipolar disorder (BD) remains limited. The NIH-funded multicenter study Acute Pharmacotherapy of Late-Life Mania (GERI-BD) assessed various clinical domains before and during mood stabilizer treatment in older adults participating in a 9-week, double-blind randomized controlled trial. We describe the rationale for selecting these instruments.Domains and instruments were selected on the basis of the study design and the participants. The investigators' experience in clinical trials involving young adults with BD or older adults with major depressive disorder, along with open studies of older adults with BD, contributed to the selection process.We identified domains and selected instruments that could be used to assess the participants given their diagnostic, treatment history, and medical and mood state characteristics. They were also intended to measure tolerability and efficacy and permit examination of potential moderating and mediating factors.Decisions regarding the assessment domains to be included in the clinical trial highlight the challenges facing researchers studying drug treatments for older adults with BD, or more generally, mood disorders. We suggest that the domains and instruments selected by GERI-BD investigators constitute a "toolbox" that can be customized for other investigators. Copyright © 2017 John WileySons, Ltd.

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

Screening questions. (DOCX 157Â kb)

Recruitment and retention of individuals with serious mental illness (SMI) and comorbid diabetes mellitus (DM) in research studies can be challenging with major impediments being difficulties reaching participants via telephone contact, logistic difficulties due to lack of transportation, ongoing psychiatric symptoms, and significant medical complications. Research staff directly involved in recruitment and retention processes of this study reviewed their experiences. The largest barriers at the macro, mediator, and micro levels identified in this study were inclement weather, transportation difficulties, and intermittent and inaccessible telephone contact. Barrier work-around practices included using the health system's EHR to obtain current phone numbers, providing transportation assistance (bus passes or parking reimbursement), and flexible scheduling of appointments. Suggestions are intended to assist in planning for recruitment and retention strategies.

Background: Major depression disorder (MDD) is one of the most common mental disorders world-wide and is prevalent throughout the lifespan, with prevalence estimates of 1-5% in those 65 years of age and older. Methods: The aim of this mini-review is to briefly summarize clinically relevant topics within the domain of later-life MDD. Results: The mini-review presents an overview of epidemiology, complications of late life MDD, risk factors and clinical presentation, clinical assessment, general issues relevant to the treatment of the older adult with MDD, drug treatments, discussion of how medical complexity affects drug treatment and other treatment modalities. Conclusion: The mini-review concludes with a short discussion of clinical and research implications. Treatment of depression in the geriatric population is a complex endeavor and clinicians often are faced with medical, social, and environmental issues which can impede the treatment process. Antidepressant drugs, particularly the SSRI and SNRI antidepressants are helpful, but dosing titration needs to be considered against the backdrop of comorbidity and concomitant medications. Psychotherapy and other approaches are additional avenues to consider in the older individuals with MDD. Future research in particular needs to address older people with more extensive medical complexity as well as the “oldest-old”, individuals in their 80’s and beyond.

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

This study evaluated the utility of Patient-Reported Outcomes Measure Information System Depression Scale (PROMIS-8a) compared with selected "Legacy" depression scales, including the Montgomery-Asberg Depression Rating Scale (MADRS), Geriatric Depression Scale (GDS), and GDS-Short Form (GDS-SF). Additionally, the measures' properties were assessed across levels of cognitive functioning.This cross-sectional analysis was extracted from a prospective cohort study. PROMIS-8a and Legacy depression measures were administered to individuals aged at least 70 years grouped by cognitive status based on the Saint Louis University Mental Status Examination. McNemar tests were run to determine if measures categorized the absence or presence of depression differently and item analysis evaluated classification discrepancies.Sample mean age was 78, and most participants were women (71%), white (79%), with at least a high school education (89%). The percentage of individuals with at least mild depression was similar across measures (20.7% PROMIS-8a, 19.0% MADRS, 17.9% GDS, 13.9% GDS-SF). PROMIS-8a total score correlated moderately with MADRS (r = 0.56, df = 295, p 0.01), GDS (r = 0.68, df = 291, p 0.01), and GDS-SF (r = 0.60, df = 291, p 0.01), and predictive validity of the measures was similar. There were no significant mean differences on depression measures by cognitive status.Although all measures identified a similar percent of depressed individuals, the classification differed by measure. Item analysis showed that PROMIS-8a was more likely to identify feelings of dysphoria while the MADRS and GDS were more likely to identify physiologic aspects of depression. Given the brevity and ease of administration of the PROMIS-8a, it appears to be a useful depression screen for community-dwelling older adults.

Additional file 1. The study questionnaire.

Using the database of the National Institute of Mental Health-sponsored acute treatment of late life mania study (GERI-BD), we assessed the role of social support in the presentation of late life bipolar mania.In the first 100 subjects randomized in geriatric BD, we explored the demographic, clinical, and social support characteristics (assessed using the Duke Social Support Index) and aspects of manic presentation. We selected two dependent variables: symptom severity, as determined by the Young Mania Rating Scale (YMRS) at baseline, and duration of episode. We selected nine potential independent variables on the basis of Pearson correlation coefficients. We derived two final models using multiple regression analysis employing an iterative process.In our severity model, being married was associated with a higher YMRS score (p = 0.05), whereas higher social interaction scores with non-family members were associated with a lower YMRS score (p = 0.011). In the episode duration model, longer duration was associated with a higher Hamilton Depression Rating Scale score (p = 0.03) and higher social interaction scores with non-family members (p = 0.0003), younger age (p = 0.04), higher number of persons in one's family social network (p = 0.017), and higher instrumental support scores (p = 0.0062).In late life mania, more social interaction with one's community appears to be associated with less severe symptoms at presentation for treatment, however, it can also be associated with slightly longer the duration of episode. Two aspects of the Duke Social Support Index are associated with a shorter episode duration prior to seeking treatment: being part of a larger family network and a having a higher level of instrumental support prior to treatment. The Instrumental Support Subscale measures the degree of assistance that is available for the respondent in performing daily tasks. These findings suggest that in older adults with BD, close social interactions and support are important in limiting the length of the illness episode prior to treatment. Social interactions involving non-family members may be less important in moderating the intensity of the symptoms at presentation.

The elderly are the fastest growing segment of the global population with the number of people age 60 or older having doubled since 1980 and the number of people age 80 or older expected to increase more than 4-fold (to 395 million) by the year 2050. While depression is overall less common in older people compared to younger people, there are sub-groups of elderly, such as those with significant medical comorbidity, who are at greatly elevated risk for depression. Negative consequences of late-life depression include functional decline and disability, increased use of non-mental health services, increased mortality rates due to cardiovascular causes, increased cancer rates, and substantially greater risk for suicide. Geriatric suicide is a global epidemic, which is worsened in many countries and cultures by socioeconomic disparities and cultural/social upheaval. Geriatric depression should be carefully assessed and treated. Treatments for geriatric depression include biological modalities such as antidepressant medications and Electroconvulsive therapy (ECT) as well as psychotherapy and psychosocial interventions. When they are prescribed pharmacotherapies for depression, older adults are especially likely to experience adverse drug effects as a result of their multiple chronic diseases, use of multiple concomitant medications, and the pharmacokinetic and pharmacodynamic changes that accompany aging. Antidepressants that minimize side effects are generally preferred in elderly individuals although the expected therapeutic response to drug treatment is generally modest. Psychosocial and psychotherapeutic measures can also be effective in late-life depression. Complexities of assessment and treatment include the risk of missing a bipolar depressive diagnosis, which would contra-indicate the use of antidepressant monotherapy. Given the projected increased proportions and overall numbers of older people with mental disorders there is a need for all clinicians to be familiar with mental health issues in elderly patients.

Aims To identify clinical factors associated with disability in depressed older adults with bipolar disorder (BPD) receiving lamotrigine. Methods Secondary analysis of a multi-site, 12-week, open-label, uncontrolled study of addon lamotrigine in 57 adults 60 years and older with BD I or II depression. Measures included the Montgomery Asberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS), Cumulative Illness Rating Scale for Geriatrics (CIRS-G), Dementia Rating Scale (DRS), and WHO-Disability Assessment Scale II (WHO-DAS II). Results Medical comorbidiy in this group of elders was substantial, with roughly 60% of subjects having disorders of the vascular, musculoskeletal/integument, and endodrine/metabolic/breast systems. We found significant relationships among mood (MADRS), medical comorbidity (CIRS-G), cognition (DRS), and disability (WHO-DAS II). More severe BPD depression, more medical comorbidity and more impaired cognition were all associated with lower functioning in BPD elders. Conclusions Our findings fit the paradigm shift that has been occurring in BPD, supporting the notion that BPD is not solely an illness of mood but that it affects multiple domains impacting overall functioning.

Given resource constraints in conducting clinical trials, it is critical that rater training focuses on scale items wherein standardization is most challenging. This analysis examined mood disorder symptom ratings submitted in an online rater training program conducted preparatory to the initiation of a multi-site, international mood disorder treatment trial. Ratings were entered online and analyzed for consistency and variability, and compared to established standards (Gold Consensus Ratings/ GCRs).Raters participated in web-based rater training on the Hamilton Depression Rating Scale (HAM-D), Montgomery Asberg Rating Scale (MADRS), and Young Mania Rating Scale (YMRS). Training included integration of didactic materials and videos of two bipolar depressed patients interviewed by two U.S. clinicians. Raters viewed the videos and rated the mood scales. Inter-rater agreement was assessed using Kappa statistics. Ratings between the raters and the GCRs for individual scale items were assessed using McNemar test for paired binomial proportions.194 raters from 16 countries, 80 sites and speaking 20 different languages participated. Interrater agreement on videos ratings ranged from substantial to moderate (HAM-D, Kappa video A = 0.72, video B = 0.65, p0.001), (MADRS, Kappa = 0.65 and 0.47, p0.001), (YMRS, Kappa = 0.75, and 0.64, p0.001). There was no significant difference on agreement based upon on English proficiency, clinical experience, or by country. Scale items that differed from the GCR on the HAM-D were depressed mood, delayed insomnia, retardation, and anxiety (psychic). Items that differed on the MADRS were apparent sadness, inner tension, concentration difficulties, lassitude and inability to feel. Items that differed on the YMRS were irritability and disruptive behavior.Identification of specific rating scale items in which rater variability is greatest may facilitate training approaches that target these areas for more efficient training in international clinical trials.

This is a multisite, 12-week, open-label trial of lamotrigine augmentation in 57 older adults (≥ 60 years; mean ± SD age = 66.5 ± 6.7 years) with either type I or type II bipolar depression.Primary outcome measure was change from baseline on the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary outcome measures included Hamilton Depression Rating Scale (HAM-D), Clinical Global Impression-Bipolar version (CGI-BP), and the WHO-Disability Assessment Schedule II (WHO-DAS II). The Udvalg for Kliniske Undersøgelser (UKU) was used to assess side effects.A total of 77.2% of the study subjects had bipolar I disorder. The mean (SD) lamotrigine dose was 150.9 (68.5) mg/day. There was significant improvement in the MADRS, HAM-D, CGI-BP, and in most domains on the WHO-DAS II. For patients for whom final MADRS score was available: 31 (57.4%) met remission criteria and 35 (64.8%) met response criteria. There were 19/57 (33.3%) who dropped out of the study prematurely, with 6 dropouts due to adverse events (4 cases of rash, 1 manic switch, and 1 hyponatremia). Two cases of rash were possibly drug related and were resolved with drug discontinuation. The most common UKU adverse effects were reduced sleep duration (n = 14, 24.6%), weight loss (n = 12, 21.1%), increased dream activity (n = 12, 21.1%), polyuria/polydipsia (n = 11, 19.3%), weight gain (n = 9, 15.8%), diminished sexual desire (n = 9, 15.8%), increased sleep (n = 9, 15.8%), lassitude/fatigue (n = 8, 14%), and unsteady gait (n = 8, 14%). No significant changes in electrocardiogram or laboratory tests were observed.In bipolar depressed elders, lamotrigine was associated with improvement in depression, psychopathology, and functional status. There was a moderate number of adverse events, although relationship of adverse events (particularly falls) to study medication could not be clearly determined in this uncontrolled trial. Controlled studies are needed to further evaluate efficacy and tolerability of lamotrigine therapy in geriatric bipolar depression.

We describe the cognitive function of older adults presenting with bipolar disorder (BD) and mania and examine whether longer lifetime duration of BD is associated with greater cognitive dysfunction. We also examine whether there are negative, synergistic effects between lifetime duration of BD and vascular disease burden on cognition. A total of 87 nondemented individuals with bipolar I disorder, age 60 years and older, experiencing manic, hypomanic, or mixed episodes, were assessed with the Dementia Rating Scale (DRS) and the Framingham Stroke Risk Profile (FSRP) as a measure of vascular disease burden. Subjects had a mean (SD) age of 68.7 (7.1) years and 13.6 (3.1) years of education; 50.6% (n = 44) were females, 89.7% (n = 78) were white, and 10.3% (n = 9) were black. They presented with overall and domain-specific cognitive impairment in memory, visuospatial ability, and executive function compared to age-adjusted norms. Lifetime duration of BD was not related to DRS total score, any other subscale scores, or vascular disease burden. FSRP scores were related to the DRS memory subscale scores, but not total scores or any other domain scores. A negative interactive effect between lifetime duration of BD and FSRP was only observed with the DRS construction subscale. In this study, lifetime duration of BD had no significant relationship with overall cognitive function in older nondemented adults. Greater vascular disease burden was associated with worse memory function. There was no synergistic relationship between lifetime duration of BD and vascular disease burden on overall cognition function. Addressing vascular disease, especially early in the course of BD, may mitigate cognitive impairment in older age.

Rayan K Al Jurdi1,2, Lena A Dixit1, Martha Sajatovic3 1Baylor College of Medicine, Department of Psychiatry, Houston, Texas, USA; 2South Central Mental Illness Research and Clinical Core, Department of Veterans Affairs, Houston, Texas; 3Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USAAbstract: Atypical antipsychotics have become a widely utilized component of the bipolar disorder treatment armamentarium, with approximately 45% of bipolar patients prescribed atypicals. Over the last decade all atypical drugs except for clozapine have received a Food and Drug Administration (FDA) bipolar indication. In October 2008, the FDA approved quetiapine XR monotherapy for the treatment of acute depressive episodes of bipolar disorder and acute manic or mixed episodes in bipolar I disorder based on two placebo-control trials. Quetiapine was also approved as adjunct therapy with lithium and divalproex for the treatment of acute manic or mixed episodes as well as maintenance of bipolar I disorder. In contrast to immediate release quetiapine which may require a twice-daily regimen, the XR formulation is intended for once-daily administration. This drug profile of quetiapine XR will address chemistry, pharmacodynamics, pharmacokinetics, metabolism, safety and tolerability and clinical trials in bipolar disorder.Keywords: quetiapine XR, bipolar disorder

We describe the increasing prevalence of chronic illnesses such as obesity and type 2 diabetes have markedly increased in both developed and developing countries. We describe the relationship between type 2 diabetes and mental illness. The extant literature suggests a critical need for innovative treatments targeted to individuals with comorbid diabetes and mental illness. Given the complexity and challenge of both of these disorders in tandem with the interactive challenges and burdens of psychiatric and medical comorbidity, it is essential that interventions address the issue of mental and medical health from the perspective of the individual with the disorder, engage individuals to actively participate in illness self-management, and include consideration of the multiple barriers to care.