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Background: Given the importance of medication adherence among individuals with bipolar disorder (BD), this analysis from an ongoing randomized controlled trial (RCT) examined the relationship between BD symptoms, functioning and adherence in 69 poorly adherent adults with BD., Method: Study inclusion criteria included being ≥ 18 years old with BD Type 1 or 2, difficulties with medication adherence and actively symptomatic as measured by Brief Psychiatric Rating Scale (BPRS) score ≥ 36, Young Mania Rating Scale (YMRS) > 8 or Montgomery Asberg Depression Rating Scale (MADRS) > 8. Adherence was measured in 2 ways: 1) the self-reported Tablets Routine Questionnaire (TRQ) and 2) electronic pill container monitoring (eCap pillbox). BD symptoms and functioning were measured with the MADRS, YMRS, Clinical Global Impressions Scale (CGI), and Global Assessment of Functioning (GAF). Only screening and baseline data were examined., Results: Mean age was 42.32 (SD = 12.99) years, with 72.46% (n = 50) female and 43.48% (n = 30) non-white. Mean past 7-day percentage of days with missed BD medications using TRQ was 40.63% (SD = 32.61) and 30.30% (SD = 30.41) at screening and baseline, respectively. Baseline adherence using eCap was 42.16% (SD = 35.85) in those with available eCap data (n = 41). Worse adherence based on TRQ was significantly associated with higher MADRS (p = 0.04) and CGI (p = .03) but lower GAF (p = 0.02). eCAP measured adherence was not significantly associated with clinical variables., Conclusion: While depression and functioning were approximate markers of adherence, reliance on patient self-report or BD symptom presentation may give an incomplete picture of medication-taking behaviors., (Copyright © 1964–2024 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

Background: Cognitive deficits in bipolar disorder (BD) impact functioning and are main contributors to disability in older age BD (OABD). We investigated the difference between OABD and age-comparable healthy comparison (HC) participants and, among those with BD, the associations between age, global cognitive performance, symptom severity and functioning using a large, cross-sectional, archival dataset harmonized from 7 international OABD studies., Methods: Data from the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) database, spanning various standardized measures of cognition, functioning and clinical characteristics, were analyzed. The sample included 662 euthymic to mildly symptomatic participants aged minimum 50years (509 BD, 153 HC), able to undergo extensive cognitive testing. Linear mixed models estimated associations between diagnosis and global cognitive performance (g-score, harmonized across studies), and within OABD between g-score and severity of mania and depressive symptoms, duration of illness and lithium use and of global functioning., Results: After adjustment for study cohort, age, gender and employment status, there was no significant difference in g-score between OABD and HC, while a significant interaction emerged between employment status and diagnostic group (better global cognition associated with working) in BD. Within OABD, better g-scores were associated with fewer manic symptoms, higher education and better functioning., Limitations: Cross-sectional design and loss of granularity due to harmonization., Conclusion: More research is needed to understand heterogenous longitudinal patterns of cognitive change in BD and understand whether particular cognitive domains might be affected in OABD in order to develop new therapeutic efforts for cognitive dysfunction OABD., Competing Interests: Declaration of competing interest FK reports no conflict of interest. Dr. Sajatovic has research grants from Otsuka, the International Society for Bipolar Disorders (ISBD), NIH, and the Centers for Disease Control and Prevention (CDC). She is a consultant to Otsuka, Janssen, Lundbeck, Teva, Neurelis and has received publication royalties from Springer Press, Johns Hopkins University Press, Oxford Press and UpToDate. Dr. Rej has salary support from the Fonds de Recherche Quebec - Sante, Grant from Mitacs, Steering Committee for Abbvie, Shareholder of Aifred Health. Dr. Mulsant holds and receives support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto. During the past five years, he has received research support from Brain Canada, the Canadian Institutes of Health Research, the CAMH Foundation, the Patient-Centered Outcomes Research Institute (PCORI), the US National Institute of Health (NIH), Capital Solution Design LLC (software used in a study founded by CAMH Foundation), and HAPPYneuron (software used in a study founded by Brain Canada). He has also been an unpaid consultant to Myriad Neuroscience., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of competing interest AD reports no conflicts of interest. MS reports research grants from Intra-Cellular, Merck, Otsuka, Alkermes, International Society for Bipolar Disorders (ISBD), National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC), Patient-Centered Outcomes Research Institute (PCORI). MS has been a consultant to Alkermes, Otsuka, Janssen, Lundbeck, Teva, Neurelis and has received publicaiton royalties from Springer Press, Johns Hopkins University Press, Oxford Press and UpToDate. MS has also received compensation for preparation of/participation in CME activities from American Physician's Institute (CMEtoGo), Psychopharmacology Institute, American Epilepsy Society, Clinical Care Options, American Academy of Child and Adolescent Psychiatry, Neurocrine

Objective: Sex-specific research in adult bipolar disorder (BD) is sparse and even more so among those with older age bipolar disorder (OABD). Knowledge about sex differences across the bipolar lifespan is urgently needed to target and improve treatment. To address this gap, the current study examined sex differences in the domains of clinical presentation, general functioning, and mood symptoms among individuals with OABD., Methods: This Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) study used data from 19 international studies including BD patients aged ≥50 years (N = 1,185: 645 women, 540 men).A comparison of mood symptoms between women and men was conducted initially using two-tailed t tests and then accounting for systematic differences between the contributing cohorts by performing generalized linear mixed models (GLMMs). Associations between sex and other clinical characteristics were examined using GLMM including: age, BD subtype, rapid cycling, psychiatric hospitalization, lifetime psychiatric comorbidity, and physical health comorbidity, with study cohort as a random intercept., Results: Regarding depressive mood symptoms, women had higher scores on anxiety and hypochondriasis items. Female sex was associated with more psychiatric hospitalizations and male sex with lifetime substance abuse disorders., Conclusion: Our findings show important clinical sex differences and provide support that older age women experience a more severe course of BD, with higher rates of psychiatric hospitalization. The reasons for this may be biological, psychological, or social. These differences as well as underlying mechanisms should be a focus for healthcare professionals and need to be studied further., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project pools archival datasets on older age bipolar disorder (OABD). An initial Wave 1 (W1; n = 1369) analysis found both manic and depressive symptoms reduced among older patients. To replicate this finding, we gathered an independent Wave 2 (W2; n = 1232, mean ± standard deviation age 47.2 ± 13.5, 65% women, 49% aged over 50) dataset., Design/methods: Using mixed models with random effects for cohort, we examined associations between BD symptoms, somatic burden and age and the contribution of these to functioning in W2 and the combined W1 + W2 sample (n = 2601)., Results: Compared to W1, the W2 sample was younger (p < 0.001), less educated (p < 0.001), more symptomatic (p < 0.001), lower functioning (p < 0.001) and had fewer somatic conditions (p < 0.001). In the full W2, older individuals had reduced manic symptom severity, but age was not associated with depression severity. Age was not associated with functioning in W2. More severe BD symptoms (mania p ≤ 0.001, depression p ≤ 0.001) were associated with worse functioning. Older age was significantly associated with higher somatic burden in the W2 and the W1 + W2 samples, but this burden was not associated with poorer functioning., Conclusions: In a large, independent sample, older age was associated with less severe mania and more somatic burden (consistent with previous findings), but there was no association of depression with age (different from previous findings). Similar to previous findings, worse BD symptom severity was associated with worse functioning, emphasizing the need for symptom relief in OABD to promote better functioning., (© 2024 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Objects: Studies of older age bipolar disorder (OABD) have mostly focused on "younger old" individuals. Little is known about the oldest OABD (OOABD) individuals aged ≥70 years old. The Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) project provides an opportunity to evaluate the OOABD group to understand their characteristics compared to younger groups., Methods: We conducted cross-sectional analyses of the GAGE-BD database, an integrated, harmonized dataset from 19 international studies. We compared the sociodemographic and clinical characteristics of those aged <50 (YABD, n = 184), 50-69 (OABD, n = 881), and ≥70 (OOABD, n = 304). To standardize the comparisons between age categories and all characteristics, we used multinomial logistic regression models with age category as the dependent variable, with each characteristic as the independent variable, and clustering of standard errors to account for the correlation between observations from each of the studies., Results: OOABD and OABD had lower severity of manic symptoms (Mean YMRS = 3.3, 3.8 respectively) than YABD (YMRS = 7.6), and lower depressive symptoms (% of absent = 65.4%, and 59.5% respectively) than YABD (18.3%). OOABD and OABD had higher physical burden than YABD, especially in the cardiovascular domain (prevalence = 65% in OOABD, 41% in OABD and 17% in YABD); OOABD had the highest prevalence (56%) in the musculoskeletal domain (significantly differed from 39% in OABD and 31% in YABD which didn't differ from each other). Overall, OOABD had significant cumulative physical burden in numbers of domains (mean = 4) compared to both OABD (mean = 2) and YABD (mean = 1). OOABD had the lowest rates of suicidal thoughts (10%), which significantly differed from YABD (26%) though didn't differ from OABD (21%). Functional status was higher in both OOABD (GAF = 63) and OABD (GAF = 64), though only OABD had significantly higher function than YABD (GAF = 59)., Conclusions: OOABD have unique features, suggesting that (1) OOABD individuals may be easier to manage psychiatrically, but require more attention to comorbid physical conditions; (2) OOABD is a survivor cohort associated with resilience despite high medical burden, warranting both qualitative and quantitative methods to better understand how to advance clinical care and ways to age successfully with BD., (© 2024 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Background: Bipolar disorder type 1 (BD-1) is a serious episodic mental illness whose severity can be impacted by social determinants of health (SDOH). To date the relationship of social and economic factors with health care utilization has not been formally analyzed using real-world data., Objective: To describe patient characteristics and assess the influence of SDOH on hospitalizations and costs in patients with BD-1 insured with commercial and managed Medicaid health plans., Methods: This retrospective observational study used data from the Medical Outcomes Research for Effectiveness and Economics (MORE 2 ) Registry to identify patients aged 18 years and older with evidence of BD-1 between July 1, 2016, and December 31, 2018. SDOH were linked to patients at the "near neighborhood" level (based on ZIP9 area). Multivariable models assessed the relationship between patient characteristics and hospitalizations (incidence rate ratios [95% CI]) and costs (cost ratios [95% CI])., Results: Of 243,286 patients with BD-1, 62,148 were covered by commercial insurance and 181,138 by Medicaid. Mean ages [±SD] were similar (commercial 39.8 [±14.8]; Medicaid 40.1 [±13.6]), with more female patients in both cohorts (commercial 59.8%; Medicaid 65.4%). All-cause hospitalization rates were 21.6% for commercial and 35.1% for Medicaid patients; emergency department visits were 39.7% and 64.3%, respectively. All-cause costs were $15,379 [±$27,929] for commercial and $21,474 [±$37,600] for Medicaid. Older age was a significant predictor of fewer hospitalizations compared with those aged younger than 30 years, particularly ages 40-49 for both commercial (0.60 [0.57-0.64]) and Medicaid (0.82 [0.80-0.85]). Increasing age was associated with significantly higher costs, especially age 65 and older (commercial 1.37 [1.31-1.44]); (Medicaid 1.43 [1.38-1.49]). Initial treatment with antipsychotics plus antianxiety medications was a significant predictor of higher hospitalizations (commercial 2.12 [1.98-2.27]; Medicaid 1.62 [1.57-1.68]) and higher costs (commercial 1.86 [1.80-1.92]); Medicaid 1.80 [1.76-1.84]). Household income was inversely associated with hospitalizations for Medicaid (<$30,000 [1.16 (1.12-1.19)]; $30,000-$39,999 [1.11 (1.07-1.15)]; $40,000-$49,999 [1.08 (1.05-1.12)]; $50,000-$74,999 [1.06 (1.02-1.09)]). Not speaking English well or at all was associated with 90% higher hospitalizations for commercial patients (1.93 [1.36-2.76]) but 40% fewer hospitalizations for Medicaid patients (0.59 [0.53-0.67]). Low English language proficiency was associated with significantly higher costs for commercial patients (2.22 [1.86-2.64]) but lower costs for Medicaid patients (0.57 [0.53-0.61])., Conclusions: Medicaid patients with BD-1 had high SDOH burden, hospitalizations, and costs. The association of lower English proficiency with fewer hospitalizations and lower costs in Medicaid patients suggests a potential disparity in access to care. These findings highlight the importance of addressing social risk factors to advance health equity in treatment of mental illness.

Objective: The current literature on employment in older adults with bipolar disorder (OABD) is limited. Using the Global Aging and Geriatric Experiments in Bipolar Disorder Database (GAGE-BD), we examined the relationship of occupational status in OABD to other demographic and clinical characteristics., Methods: Seven hundred and thirty-eight participants from 11 international samples with data on educational level and occupational status were included. Employment status was dichotomized as employed versus unemployed. Generalized linear mixed models with random intercepts for the study cohort were used to examine the relationship between baseline characteristics and employment. Predictors in the models included baseline demographics, education, psychiatric symptom severity, psychiatric comorbidity, somatic comorbidity, and prior psychiatric hospitalizations., Results: In the sample, 23.6% (n = 174) were employed, while 76.4% were unemployed (n = 564). In multivariable logistic regression models, less education, older age, a history of both anxiety and substance/alcohol use disorders, more prior psychiatric hospitalizations, and higher levels of BD depression severity were associated with greater odds of unemployment. In the subsample of individuals less than 65 years of age, findings were similar. No significant association between manic symptoms, gender, age of onset, or employment status was observed., Conclusion: Results suggest an association between educational level, age, psychiatric severity and comorbidity in relation to employment in OABD. Implications include the need for management of psychiatric symptoms and comorbidity across the lifespan, as well as improving educational access for people with BD and skills training or other support for those with work-life breaks to re-enter employment and optimize the overall outcome., (© 2023 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Background: By 2030, over 50% of individuals living with bipolar disorder (BD) are expected to be aged ≥50 years. However, older age bipolar disorder (OABD) remains understudied. There are limited large-scale prospectively collected data organized in key dimensions capable of addressing several fundamental questions about BD affecting this subgroup of patients., Methods: We developed initial recommendations for the essential dimensions for OABD data collection, based on (1) a systematic review of measures used in OABD studies, (2) a Delphi consensus of international OABD experts, (3) experience with harmonizing OABD data in the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD, n ≥ 4500 participants), and (4) critical feedback from 34 global experts in geriatric mental health., Results: We identified 15 key dimensions and variables within each that are relevant for the investigation of OABD: (1) demographics, (2) core symptoms of depression and (3) mania, (4) cognition screening and subjective cognitive function, (5) elements for BD diagnosis, (6) descriptors of course of illness, (7) treatment, (8) suicidality, (9) current medication, (10) psychiatric comorbidity, (11) psychotic symptoms, (12) general medical comorbidities, (13) functioning, (14) family history, and (15) other. We also recommend particular instruments for capturing some of the dimensions and variables., Conclusion: The essential data dimensions we present should be of use to guide future international data collection in OABD and clinical practice. In the longer term, we aim to establish a prospective consortium using this core set of dimensions and associated variables to answer research questions relevant to OABD., (© 2023 John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objective: Inflammation has received increasing attention as a contributor to the pathophysiology of bipolar disorder (BD) and cardiac hypertrophy into heart failure (HF). Accordingly, we chose BD-related inflammatory markers to investigate their relationships with cardiac left ventricular function and structure in BD., Methods: Sixty physically healthy and euthymic patients with bipolar I disorder were recruited to compare with 50 healthy normal controls. The echocardiography was performed to estimate left ventricular mass index (LVMI) as a parameter of LV hypertrophy (LVH) and left ventricle ejection fraction (LVEF) as a parameter of systolic function. An LVEF above the normal range (>70%) was defined as a hyperdynamic heart. Participants' levels of inflammatory and atherosclerosis-related parameters were measured., Results: Compared with normal controls, BD group had significantly higher rates of LVH (63% vs. 42%) and hyperdynamic heart (32% vs. 2%) and higher mean values of LVMI and LVEF. After adjustment for the effects of BMI and age, multiple regression analyses of BD group showed that the peripheral level of interleukin-8 was positively associated with LVMI and the level of soluble tumor necrosis factor receptor 1 (sTNF-R1) was positively associated with LVEF., Conclusions: Patients with BD from young adulthood are likely to have LVH with normal LV function and hyperdynamic heart associated with diastolic dysfunction. Low-grade inflammation may underlie the mechanisms of LV hypertrophy and cardiac dysfunction in BD patients., Competing Interests: Declaration of Competing Interest Author Sajatovic has the following conflicts of interest to disclose: In the last 3 years she has received research grants from Nuromate, Otsuka, Alkermes, International Society for Bipolar Disorders (ISBD), National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC), Patient-Centered Outcomes Research Institute (PCORI); Consultant: Alkermes, Otsuka, Janssen, Myriad, Health Analytics, Frontline Medical Communications; Royalties: Springer Press, Johns Hopkins University Press, Oxford Press, UpToDate; Compensation for preparation of CME activities: American Physician's Institute, MCM Education, CMEology, Potomac Center for Medical Education, Global Medical Education, Creative Educational Concepts, Psychopharmacology Institute. The other authors have no potential conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: While medication non-adherence is common in bipolar disorder (BD), few studies have specifically assessed non-adherent BD adolescents and young adults (AYAs). This analysis, using screening and baseline data from an ongoing randomized controlled trial, examined the relationship between BD symptoms and adherence in poorly adherent AYAs., Methods: AYAs ages 13-21 had sub-optimal adherence defined as missing ⩾ 20% of prescribed BD medication. Mean sample (N = 36) age was 19.1 years (SD = 2.0), 66.7 % (N = 24) female, 25.0 % (n = 9) non-white. Adherence was measured via: 1) self-reported Tablets Routine Questionnaire (TRQ) and 2) electronic monitoring (SimpleMed pillbox). Symptoms were measured with the Hamilton Depression Rating Scale (HAM-D), the Young Mania Rating Scale (YMRS), and the Clinical Global Impression Scale (CGI)., Results: Mean percentage of missed BD medications using TRQ was 34.9 (SD = 28.9) at screening and 30.6 (SD = 33.0) at baseline. Mean percentage of missed medication using SimpleMed at baseline was 42.1 (SD = 37.0). The correlation between TRQ and SimpleMed was r = 0.36 (p = 0. 13). Neither CGI nor age were correlated with adherence. Neither TRQ nor SimpleMed were significantly related to HAM-D. YMRS was positively associated with worse adherence for TRQ (r = 0.36, p = 0.03), but not significantly associated with SimpleMed. Adherence did not differ by other demographic attributes., Conclusion: Adherence levels varied widely in AYA with BD. Adherence monitoring increased adherence by approximately 4.5%, and use of electronic pill monitoring identified a greater proportion of missed medication vs. self-report. BD symptoms may not consistently identify AYA with adherence challenges., (Copyright © 1964–2023 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

Background: Schizophrenia (SZ) and bipolar I disorder (BD-I) are chronic mental health disorders often treated with antipsychotic medications. This qualitative study sought to better understand disease burden and treatment experiences with oral antipsychotic medications in participants living with SZ or BD-I., Methods: Six 90-min focus groups were conducted with participants diagnosed with SZ or BD-I. Trained moderators facilitated discussions using a semistructured guide. Participants described symptoms, impacts of disease, and experiences with oral antipsychotic medications, whether favourable or unfavourable., Results: Among participants with SZ (n = 15; 3 groups, 5 per group), 53% were male and 33% were white, with a mean of 18.6 years since diagnosis. Of participants with BD-I (n = 24; 3 groups, 8 per group), 33% were male and 42% were white, with a mean of 13.0 years since diagnosis. Participants described numerous symptoms of their illnesses that impacted relationships and daily life, including effects on emotional health, the ability to work, and encounters with law enforcement. Previous antipsychotic medications were deemed effective by 14/15 (93%) participants with SZ and 12/16 (75%) participants with BD-I. Most participants with SZ (13/15; 87%) or with BD-I (16/24; 67%) reported discontinuing their antipsychotic medication at some point. Side effects were a common reason for discontinuing or switching medications for participants with SZ (8/15; 53%) and for those with BD-I (11/24; 46%). The most common side effects reported in both cohorts were weight gain, drowsiness, sexual problems, and neurologic symptoms. Side effects negatively affected quality of life, leading to serious health problems and issues with self-esteem., Conclusions: People living with SZ or BD-I cited a range of favourable and unfavourable experiences with oral antipsychotic medications. Most participants reported that their antipsychotics were effective at controlling their symptoms, but multiple side effects impacted their quality of life, caused additional serious health problems, and often led to discontinuation of or switching antipsychotics. Findings from this study contribute to a better understanding of patients' experiences with antipsychotics and highlight a need for new medications with favourable benefit/risk profiles., (© 2023. The Author(s).)

Objectives: The distinction between bipolar I disorder (BD-I) and bipolar II disorder (BD-II) has been a topic of long-lasting debate. This study examined differences between BD-I and BD-II in a large, global sample of OABD, focusing on general functioning, cognition and somatic burden as these domains are often affected in OABD., Methods: Cross-sectional analyses were conducted with data from the Global Aging and Geriatric Experiments in Bipolar Disorder (GAGE-BD) database. The sample included 963 participants aged ≥50 years (714 BD-I, 249 BD-II). Sociodemographic and clinical factors were compared between BD subtypes including adjustment for study cohort. Multivariable analyses were conducted with generalized linear mixed models (GLMMs) and estimated associations between BD subtype and (1) general functioning (GAF), (2) cognitive performance (g-score) and (3) somatic burden, with study cohort as random intercept., Results: After adjustment for study cohort, BD-II patients more often had a late onset ≥50 years (p = 0.008) and more current severe depression (p = 0.041). BD-I patients were more likely to have a history of psychiatric hospitalization (p < 0.001) and current use of anti-psychotics (p = 0.003). Multivariable analyses showed that BD subtype was not related to GAF, cognitive g-score or somatic burden., Conclusion: BD-I and BD-II patients did not differ in terms of general functioning, cognitive impairment or somatic burden. Some clinical differences were observed between the groups, which could be the consequence of diagnostic definitions. The distinction between BD-I and BD-II is not the best way to subtype OABD patients. Future research should investigate other disease specifiers in this population., (© 2022 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Objectives: There is limited information on the characteristics of older adults with bipolar disorder (OABD) treated with lithium, along with safety concerns about its use by older adults. The aim of the present study is to describe the demographic and clinical characteristics of OABD receiving lithium therapy, using data from the Global Ageing & Geriatric Experiments in Bipolar Disorder (GAGE-BD)., Experimental Procedures: Cross-sectional analysis of the GAGE-BD dataset to determine differences and similarities between lithium users and non-users. We analysed data from 986 participants aged 50 years or older (mean age 63.5 years; 57.5% females) from 12 study sites. Two subgroups ('Lithium'; 'Non-lithium') were defined according to the current prescription of lithium. We compared several outcomes between these groups, controlling for age, gender, and study site., Results: OABD treated with lithium had lower scores on depression rating scales and were less likely to be categorised as with moderate or severe depression. There was a lower proportion of lithium users than non-users among those with evidence of rapid cycling and non-bipolar psychiatric diagnoses. Assessment of global cognitive state and functionality indicated better performance among lithium users. The current use of antipsychotics was less frequent among lithium users, who also reported fewer cardiovascular comorbidities than non-users., Conclusion: We found several potentially relevant differences in the clinical profile of OABD treated with lithium compared with those treated with other mood stabilisers. However, the interpretation of the present results must take into account the methodological limitations inherent to the cross-sectional approach and data harmonisation., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well-characterized samples of individuals with BD., Methods: Thirteen cohorts from 7 countries included n = 5882 individuals with BD across multiple sites. The statistical approach consisted of a systematic uniform application of analyses across sites. Each site performed a logistic regression analysis with empirically derived "higher versus lower function" as the dependent variable and selected clinical and demographic variables as predictors., Results: We found high rates of functional impairment, ranging from 41 to 75%. Lower community functioning was associated with depressive symptoms in 10 of 12 of the cohorts that included this variable in the analysis. Lower levels of education, a greater number of prior mood episodes, the presence of a comorbid substance use disorder, and a greater total number of psychotropic medications were also associated with low functioning., Conclusions: The bipolar clinical research community is poised to work together to characterize the multi-dimensional contributors to impairment and address the barriers that impede patients' complete recovery. We must also identify the core features which enable many to thrive and live successfully with BD. A large-scale, worldwide, prospective longitudinal study focused squarely on BD and its heterogeneous presentations will serve as a platform for discovery and promote major advances toward optimizing outcomes for every individual with this illness., (© 2022 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Objective: Some individuals with bipolar disorder (BD) experience manic and depressive symptoms concurrently, but data are limited on symptom mixity in older age bipolar disorder (OABD). Using the Global Aging & Geriatric Experiments in Bipolar Disorder Database, we characterized mixity in OABD and associations with everyday function., Methods: The sample (n = 805), from 12 international studies, included cases with both mania and depression severity ratings at a single timepoint. Four mixity groups were created: asymptomatic (A), mixed (Mix), depressed only (Dep), and manic only (Man). Generalized linear mixed models used mixity group as the predictor variable; cohort was included as a random intercept. Everyday function was assessed with the Global Assessment of Functioning score., Results: Group proportions were Mix (69.6%; n = 560), followed by Dep (18.4%; n = 148), then A (7.8%; n = 63), then Man (4.2%; n= 34); levels of depression and mania were similar in Mix compared to Dep and Man, respectively. Everyday function was lowest in Mix, highest in A, and intermediate in Man and Dep. Within Mix, severity of depression was the main driver of worse functioning. Groups differed in years of education, with A higher than all others, but did not differ by age, gender, employment status, BD subtype, or age of onset., Conclusions: Mixed features predominate in a cross-sectional, global OABD sample and are associated with worse everyday function. Among those with mixed symptoms, functional status relates strongly to current depression severity. Future studies should include cognitive and other biological variables as well as longitudinal designs to allow for evaluation of causal effects., (Published by Elsevier Inc.)

Background: Atherosclerosis accounts for cardiovascular diseases (CVDs). This study aimed to explore the association between carotid intima-media thickness (CIMT), psycho-pharmacotherapy, and inflammatory markers along with other molecules related to atherosclerosis in bipolar disorder (BD)., Methods: The euthymic patients with bipolar I disorder (BD-I) aged over 20 years were recruited to measure CIMT through ultrasound and the blood levels of lipid profiles, soluble tumor necrosis factor receptor-1 (sTNF-R1), soluble interleukin-6 receptor (sIL-6R), monocyte chemoattractant protein-1, chitinase 3-like 1, endothelial adhesive proteins, and thrombin-antithrombin complex., Results: Participants were 103 BD-I patients with mean 44.3 years old. The ratio of lithium exposure in relation to illness chronicity and the current daily dosage of lithium therapy exhibited an inverse relationship with CIMT in the entire sample. After controlling for age and BMI, multivariate regression indicated that a higher lithium level was significantly associated with decreased CIMT in the entire sample, high-risk (those with CVDs or endocrine diseases, N = 48), middle-risk (those without CVDs and endocrine diseases, N = 55), and low-risk (those aged <45 years in the middle-risk subgroup, N = 43) subgroups. Furthermore, higher levels of sTNF-R1 in the entire sample and high-risk subgroup and sIL-6R in the middle- and low-risk subgroups were statistically associated with greater CIMT., Limitation: The age range was too wide to control for the effect of age on CIMT and medication., Conclusions: Lithium exposure may be a protective factor for atherosclerosis progression in BD-I. The chronic inflammation in BD-I with activated macrophages and monocytes may link with the atherosclerosis development over time., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Harmonizing different depression severity scales often requires creation of categorical variables that may decrease the sensitivity of the measure. Our aim was to compare the associations between categorical and continuous and harmonized measures of depression and global functioning in a large dataset of older age patients with bipolar disorder (OABD)., Method: In the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) the 17-item Hamilton Depression scale (HAM-D), Montgomery Asberg Depression Rating Scale (MADRS) or the Center for Epidemiological Studies Depression scales (CES-D) was used to assess current depressive symptoms, while the Global Assessment of Functioning (GAF) assessed functional status. Data were harmonized from 8 OABD studies (n = 582). In each subsample, the relationship of depression severity as a continuous and categorical measure was compared to GAF. In the total sample, harmonized ordinal depression categories were compared to GAF., Results: Effect size and variance explained by the model for the categorical measure in the total sample was higher than both the categorical and continuous measure in the CES-D subsample, higher than the categorical but lower than the continuous measure in the HAM-D subsample, and lower than both the categorical and continuous measures in the MADRS subsample., Limitations: All included studies have different inclusion and exclusion criteria, study designs, and differ in aspects of sociodemographic variables., Conclusions: Associations were only slightly larger for the continuous vs categorical measures of depression scales. Harmonizing different depression scales into ordinal categories for analyses is feasible without losing statistical power., (Copyright © 2022. Published by Elsevier B.V.)

Background: Mood-stabilizing medications are a cornerstone of treatment for people with bipolar disorder, though approximately half of these individuals are poorly adherent with their medication, leading to negative and even severe health consequences. While a variety of approaches can lead to some improvement in medication adherence, there is no single approach that has superior adherence enhancement and limited data on how these approaches can be implemented in clinical settings. Existing data have shown an increasing need for virtual delivery of care and interactive telemedicine interventions may be effective in improving adherence to long-term medication., Methods: Customized adherence enhancement (CAE) is a brief, practical bipolar-specific approach that identifies and targets individual patient adherence barriers for intervention using a flexibly administered modular format that can be delivered via telehealth communications. CAE is comprised of up to four standard treatment modules including Psychoeducation, Communication with Providers, Medication Routines, and Modified Motivational Interviewing. Participants will attend assigned module sessions with an interventionist based on their reasons for non-adherence and will be assessed for adherence, functioning, bipolar symptoms, and health resource use across a 12-month period. Qualitative and quantitative data will also be collected to assess barriers and facilitators to CAE implementation and reach and adoption of CAE among clinicians in the community., Discussion: The proposed study addresses the need for practical adherence interventions that are effective, flexible, and designed to adapt to different settings and patients. By focusing on a high-risk, vulnerable group of people with bipolar disorder, and refining an evidence-based approach that will integrate into workflow of public-sector care and community mental health clinics, there is substantial potential for improving bipolar medication adherence and overall health outcomes on a broad level., Trial Registration: The study was registered on ClinicalTrials.gov NCT04622150 on November 9, 2020., (© 2022. The Author(s).)

Background: Neuroinflammation and brain structural abnormalities are found in bipolar disorder (BD). Elevated levels of cytokines and chemokines have been detected in the serum and cerebrospinal fluid of patients with BD. This study investigated the association between peripheral inflammatory markers and brain subregion volumes in BD patients., Methods: Euthymic patients with bipolar I disorder (BD-I) aged 20-45 years underwent whole-brain magnetic resonance imaging. Plasma levels of monocyte chemoattractant protein-1 (MCP-1), chitinase-3-like protein 1 (also known as YKL-40), fractalkine (FKN), soluble tumour necrosis factor receptor-1 (sTNF-R1), interleukin-1β, and transforming growth factor-β1 were measured on the day of neuroimaging. Clinical data were obtained from medical records and interviewing patients and reliable others., Results: We recruited 31 patients with a mean age of 29.5 years. In multivariate regression analysis, plasma level YKL-40, a chemokine, was the most common inflammatory marker among these measurements displaying significantly negative association with the volume of various brain subareas across the frontal, temporal, and parietal lobes. Higher YKL-40 and sTNF-R1 levels were both significantly associated with lower volumes of the left anterior cingulum, left frontal lobe, right superior temporal gyrus, and supramarginal gyrus. A greater number of total lifetime mood episodes were also associated with smaller volumes of the right caudate nucleus and bilateral frontal lobes., Conclusions: The volume of brain regions known to be relevant to BD-I may be diminished in relation to higher plasma level of YKL-40, sTNF-R1, and more lifetime mood episodes. Macrophage and macrophage-like cells may be involved in brain volume reduction among BD-I patients.

Background: Cardiovascular disease in individuals with mental health conditions such as bipolar disorder is highly prevalent and often poorly managed. Individuals with bipolar disorder face significant medication adherence barriers, especially when they are prescribed multiple medications for other health conditions including hypertension. Poor adherence puts them at a disproportionate risk for poor health outcomes. As such, there is a need for effective interventions to improve hypertension medication adherence, particularly in patients that struggle with adherence due to mental health comorbidity., Methods: This 5-year project uses a 2-stage randomized controlled trial design to evaluate a brief, practical adherence intervention delivered via interactive text messaging (iTAB-CV) along with self-monitoring of medication taking, mood, and home blood pressure (N = 100) compared to self-monitoring alone (N = 100). Prior to randomization, all participants will view an educational video that emphasizes the importance of medication for the treatment of hypertension and bipolar disorder. Those randomized to the texting intervention will receive daily text messages with predetermined content to address 11 salient domains as well as targeted customized messages for 2 months. This group will then be re-randomized to receive either a high (gradual taper from daily to weekly texts) or low booster (weekly texts) phase for an additional 2 months. All participants will be monitored for 52 weeks. The primary outcomes are systolic blood pressure and adherence to antihypertensive medication as determined by a self-reported questionnaire and validated with an automated pill-monitoring device. Secondary outcomes include adherence to bipolar disorder medications, psychiatric symptoms, health status, self-efficacy for medication-taking behavior, illness beliefs, medication attitudes, and habit strength., Discussion: This study specifically targets blood pressure and mental health symptom control in people with bipolar and includes implementation elements in the study design intended to inform future scale-up. Promising pilot data and a theoretical model, which views sustained medication-taking behavior in the context of habit formation, suggests that this remotely delivered intervention may help advance care for this high-risk population and is amenable to both scale up and easy adaptation for other groups with poor medication adherence., Trial Registration: The study was registered at ClinicalTrials.gov ( NCT04675593 ) on December 19, 2020., (© 2022. The Author(s).)

Objectives: To compare the prevalence of physical morbidities among men and women with older adult bipolar disorder (OABD), and men with and without OABD., Methods: Cross-sectional analysis of the collaborative Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) database and non-OABD data from the Health in Men Study. OABD defined as bipolar disorder among adults aged greater than or equal to 50 years. Outcomes of interest were diseases affecting the cardiovascular, respiratory, gastrointestinal, renal, musculoskeletal and endocrinological systems., Results: We examined 1407 participants with OABD aged 50-95 years, of whom 787 were women. More women than men showed evidence of morbidities affecting the respiratory, gastrointestinal, musculoskeletal and endocrinological systems. More men with than without OABD showed evidence of cardiovascular, renal and endocrinological diseases., Conclusion: GAGE-BD data showed that physical morbidities affect more women than men with OABD, and more men with than without OABD. The underlying reasons for these differences require clarification., (Copyright © 2021 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 1964–2022 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

Background: The onset of bipolar disorder (BD) is common during late adolescence and young adulthood (AYA). Suboptimal medication adherence is a critical yet modifiable risk factor for negative outcomes among AYAs with BD., Methods: This research used an iterative process (e.g., focus groups, advisory board, cognitive interviews) to modify an existing adherence intervention to address suboptimal adherence in AYAs with BD. The modified version of Customized Adherence Enhancement for Adolescents and Young Adults (CAE-AYA) will be compared to an Enhanced Treatment as Usual condition (ETAU) in 40 AYAs intervention using a 6-month prospective, randomized controlled trial (RCT) in a high-risk group of 16-21 year old AYAs with BD with demonstrated non-adherence to their prescribed BD medications., Conclusions: This report describes the methodology and design of the ImprovinG adhereNce In adolescenTs with bipolar disordEr (IGNITE) study. If successful, the CAE-AYA approach has the potential to advance care for vulnerable youth with BD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Literature 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., Methods: This 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)., Results: Mean sample age was 60.8 years (standard deviation [SD] 12.2 years), 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 < 0.0001). The negative relationship between older age and symptom severity was similar across sexes, but was stronger among those with lower education levels. GAF was mildly impaired (mean =62.0, SD = 13.3) and somatic burden was high (mean =2.42, SD = 1.97). Comorbidity burden was not associated with GAF. However, higher depressive (p < 0.0001) and manic (p < 0.0001) symptoms were associated with lower GAF, most strongly among older individuals., Conclusions: Findings suggest an attenuation of BD symptoms in OABD, despite extensive somatic burden. Depressive symptom severity was strongly associated with worse functioning in older individuals, underscoring the need for effective treatments of BD depression in older people. This international collaboration lays a path for the development of a better understanding of aging in BD., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: People with bipolar disorder (BD) often have difficulty with medication adherence. This pilot trial combined a behavioral customized adherence enhancement (CAE) approach with long-acting injectable (LAI) antipsychotic medication and assessed effects on adherence, BD symptoms, and functional status., Methods: This 6-month prospective, uncontrolled trial of the intervention (CAE with LAI) in 30 poorly adherent individuals with BD assessed adherence using the Tablets Routine Questionnaire (TRQ) and symptoms using the Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), and Clinical Global Impressions (CGI). Functioning was assessed via the Social and Occupational Functioning Assessment Scale (SOFAS) and Global Assessment of Functioning (GAF). Assessments were conducted at screening, baseline, week 12, and week 24 (6 months). The LAI was aripiprazole once monthly. The study was conducted between April 2018 and May 2020., Results: The mean age of the sample was 49.5 years (SD = 9.3), and 56.7% were Black. Nine individuals (30%) terminated the study prematurely, 1 due to side effects (tremor). The mean LAI dose was 314.3 mg (SD = 96.4). The proportion of missed medications in the past week (mean TRQ) from screen to 24 weeks significantly improved from 50.1% (SD 24.8) to 16.9% (SD = 27.0) ( P  < .001), and past month TRQ improved from 40.6% (SD = 23.8) to 19.2% (SD = 24.0) (a trend for significance, P  = .0599). TRQ change from baseline to 24 weeks was not significant. There were significant improvements on the BPRS ( P  < .001), MADRS ( P  = .01), YMRS ( P  < .001), CGI ( P  < .001), SOFAS ( P  < .001), and GAF ( P  < .001)., Conclusion: A personalized intervention to address adherence barriers combined with LAI can improve recovery outcomes in high-risk individuals with BD., Trial Registration: ClinicalTrials.gov Identifier: NCT03408873., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

Objective: The Veterans Health Administration (VHA) provides a continuum of care over the life course. Among U.S. adults, bipolar disorder and schizophrenia are associated with increased risk of dementia. To inform service planning, this study assessed the incidence of dementia among veteran VHA patients with bipolar disorder or schizophrenia, with adjustment for comorbid medical conditions., Methods: Using data from the VHA Corporate Data Warehouse, the authors identified all veterans who received VHA care in 2004 and 2005 without a dementia diagnosis and who were alive and between ages 18 and 100 as of January 1, 2006. Individuals were categorized as having bipolar disorder, schizophrenia, or neither condition on the basis of diagnoses in 2004-2005. Among ongoing VHA users, incidence of dementia was assessed for up to 10 years (2006-2015)., Results: The cohort included 3,648,852 individuals. After analyses controlled for baseline comorbid general medical conditions and substance use disorders, the incidence rate ratios (IRRs) for dementia were 2.92 for those with schizophrenia and 2.26 for those with bipolar disorder, compared with VHA patients with neither condition., Conclusions: Among veterans receiving VHA care, diagnoses of bipolar disorder and schizophrenia were each associated with increased risk of receiving a new diagnosis of dementia, even when analyses controlled for baseline medical comorbidities. IRRs were elevated for patients with either condition, compared with those with neither condition, and highest for those with schizophrenia. VHA clinicians should evaluate patients for dementia when signs or symptoms of cognitive impairment are present.

Objective: We present a secondary analysis of data reporting differences in medication adherence, psychiatric symptom severity, and internalized stigma levels in older (age ≥ 55 years) versus younger (age < 55 years) adults with bipolar disorder (BD) and poor medication adherence., Methods: Data used for this analysis came from 184 participants in a National Institute of Mental Health-funded randomized controlled trial, comparing a customized adherence enhancement (CAE) intervention intended to promote BD medication adherence with a BD-specific educational program (EDU). At screen, study participants were ≥20% nonadherent with BD medications as measured by the Tablets Routine Questionnaire (TRQ). Psychiatric symptoms, functional status, and internalized stigma were measured using validated scales., Results: Older adults had significantly lower anxiety disorder comorbidity ( P < .01 for 1 or more anxiety disorders), depressive symptom severity scores ( P = .011), and self-stigma scores ( P = .001) compared to their younger counterparts. In the analyses evaluating change over time in TRQ between older and younger participants by treatment arm (ie, CAE and EDU), there was a significant finding of interaction between time, age-group, and treatment arm ( P = .007)., Conclusions: Older adults may be less anxious and depressed, with less self-stigma, compared to younger people with BD and poor adherence. With respect to medication adherence, older individuals in EDU appear to do less well than younger individuals over time.

Background: Oral antipsychotic (AP) medications are frequently prescribed to people with bipolar I disorder (BD-I). A cross-sectional online survey examined the experiences of people living with BD-I with a history of recent AP use., Methods: Adults with self-reported physician-diagnosed BD-I (N = 200) who received oral APs during the prior year completed a survey on AP-related experiences, including side effects and their perceived burden on social functioning, adherence, and work. Items also assessed preferences for trade-offs (balancing symptom management and side effects) when considering a hypothetical new AP. The perceived impact of specific, prevalent side effects on adherence, work, and preferences for a hypothetical AP were also examined. Analyses were descriptive., Results: The survey sample had a mean age of 43.2 (SD = 12.4) years, was 60% female, and 31% nonwhite. Almost all participants (98%) had experienced AP side effects. Common self-reported side effects were feeling drowsy or tired (83%), lack of emotion (79%), anxiety (79%), dry mouth (76%), and weight gain (76%). Weight gain was cited as the most bothersome side effect, rated by most participants (68%) as "very" or "extremely bothersome." Nearly half of participants (49%) reported that AP side effects negatively impacted their job performance; almost all (92%) reported that side effects - most commonly anxiety and lack of emotion - negatively impacted social relationships (e.g., family or romantic partners). The most commonly-reported reason for stopping AP use was dislike of side effects (48%). Side effects most likely to lead to stopping or taking less of AP treatment included "feeling like a 'zombie'" (29%), feeling drowsy or tired (25%), and weight gain (24%). When considering a hypothetical new AP, the most common side effects participants wanted to avoid included AP-induced anxiety (50%), weight gain (48%), and "feeling like a 'zombie'" (47%)., Conclusions: Side effects of APs were both common and bothersome, and impacted social functioning, adherence, and work. Findings highlight the prevailing unmet need for new APs with more favorable benefit-risk profiles.

The relationship between medication attitudes and adherence as well as reliable measures of medication attitudes need further study. This study examined the psychometric properties of the Attitudes Toward Mood Stabilizers Questionnaire (AMSQ) in bipolar participants and the relationship between medication attitudes and adherence, measured by the self-reported Tablets Routine Questionnaire (TRQ). Inclusion criteria included mood stabilizer treatment and 20% or more medication nonadherence. Measures were given pretreatment and posttreatment. Average age was 47 years; majority were female (69%), African American (67%), and unmarried (53%). AMSQ's test-retest reliability was ρ = 0.73 (p < 0.001). AMSQ correlated with TRQ (rs = 0.20, p < 0.01) at baseline. Factor analysis identified three factors: positive/favorable attitudes, negative/critical attitudes, and unintentional nonadherence. Change in AMSQ across time correlated with change in TRQ. The AMSQ is valid psychometrically and is sensitive to change. Medication attitudes are related to adherence behavior. Interventions should include targeting specific domains of medication attitudes, such as illness knowledge.

Objective: There is a dearth of research about the aging process among individuals with bipolar disorder (BD). One potential strategy to overcome the challenge of interpreting findings from existing limited older-age bipolar disorder (OABD) research studies is to pool or integrate data, taking advantage of potential overlap or similarities in assessment methods and harmonizing or cross-walking measurements where different measurement tools are used to evaluate overlapping construct domains. This report describes the methods and initial start-up activities of a first-ever initiative to create an integrated OABD-focused database, the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD) project., Methods: Building on preliminary work conducted by members of the International Society for Bipolar Disorders OABD taskforce, the GAGE-BD project will be operationalized in four stages intended to ready the dataset for hypothesis-driven analyses, establish a consortium of investigators to guide exploration, and set the stage for prospective investigation using a common dataset that will facilitate a high degree of generalizability., Results: Initial efforts in GAGE-BD have brought together 14 international investigators representing a broad geographic distribution and data on over 1,000 OABD. Start-up efforts include communication and guidance on meeting regulatory requirements, establishing a Steering Committee to guide an incremental analysis strategy, and learning from existing multisite data collaborations and other support resources., Discussion: The GAGE-BD project aims to advance understanding of associations between age, BD symptoms, medical burden, cognition and functioning across the life span and set the stage for future prospective research that can advance the understanding of OABD., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Although 25% of people with bipolar disorder (BD) are over age 60, there is a dearth of research on older age bipolar disorder (OABD). This report describes an initial effort to create an integrated OABD database using the U.S. National Institute of Mental Health Data Archive (NDA). Goals were to: 1) combine data from three BD studies in the United States that included overlapping data elements; 2) investigate research questions related to aims of the original studies; and 3) take an important first step toward combining existing datasets relevant to aging and BD., Methods: Data were prepared and uploaded to the NDA, with a focus on data elements common to all studies. As appropriate, data were harmonized to select or collapse categories suitable for cross-walk analysis. Associations between age, BD symptoms, functioning, medication load, medication adherence, and medical comorbidities were assessed. The total sample comprised 451 individuals, mean age 57.7 (standard deviation: 13.1) years., Results: Medical comorbidity was not significantly associated with either age or functioning and there did not appear to be an association between medication load, comorbidity, age, and adherence. Men and African-Americans were significantly more likely to have poor adherence. Both BD mania and depression symptoms were associated with functioning, but this differed across studies., Conclusion: Despite limitations including heterogeneity in study design and samples and cross-sectional methodology, integrated datasets represent an opportunity to better understand how aging may impact the presentation and evolution of chronic mental health disorders across the lifespan., (Copyright © 2019 American Association for Geriatric Psychiatry. All rights reserved.)

Objective: This study evaluated the feasibility, acceptability, and preliminary efficacy of psychoeducation plus an automated text messaging intervention (Individualized Texting for Adherence Building-Cardiovascular [iTAB-CV]) to improve adherence to antihypertensives and bipolar disorder medication., Methods: After a psychoeducation program, iTAB-CV was administered for 2 months. In month 1, participants received one educational-motivational and one mood rating text daily. In month 2, medication reminders were added., Results: The sample (N=38) was 74% African American and 53% women, with a mean±SD age of 51.53±9.06. Antihypertensive nonadherence decreased from a mean of 43%±23% to 21%±18% at 12 weeks (χ 2 =34.6, df=3, p<0.001). Systolic blood pressure decreased from a mean of 144.8±15.5 mmHg to 136.0±17.8 mmHg (χ 2 =17.6, df=3, p<.001). Retention was 100%., Conclusions: In this uncontrolled trial, participants were highly engaged and medication adherence and reduced systolic blood pressure were sustained after psychoeducation plus iTAB-CV. Because iTAB-CV is automated and delivered remotely, it has the potential to reach a large and challenging population.

Objectives: Despite the growing numbers and proportion of older adults with bipolar disorder (OABD), there are very limited guidelines for the use of lithium with its double-edged potential for effectiveness and toxicity in this population. The primary aims of this Delphi survey were: (a) To determine the place of lithium among the preferred choices for maintenance treatment of OABD. (b) To provide detailed clinical guidelines for the safe and effective use of lithium in OABD., Methods: In the face of limited evidence, the Delphi survey method was used to achieve consensus by a group of 25 experts in OABD from nine countries. An oversight committee monitored and analyzed the results of each survey and formulated more focused questions with each subsequent iteration., Results: A 100% response rate was achieved for all three iterations of the survey. Lithium was the preferred choice for maintenance monotherapy in OABD. Serum levels of 0.4-0.8 mmol/L were recommended for ages 60-79 and serum levels of 0.4-0.7 mmol/L were recommended for ages 80 and over. Specific recommendations achieved consensus for second line monotherapy as well as for other drugs to be used in combination with lithium if necessary. Guidelines for routine monitoring of lithium in OABD were provided for laboratory investigations and clinical assessments., Conclusions: Lithium remains the preferred choice for maintenance monotherapy in OABD. Laboratories should report the therapeutic range for serum levels of lithium separately for older adults., (© 2018 The Authors. Bipolar Disorders Published by John Wiley & Sons Ltd.)

Objective: To derive new criteria sets for defining manic and hypomanic episodes (and thus for defining the bipolar I and II disorders), an international Task Force was assembled and termed AREDOC reflecting its role of Assessment, Revision and Evaluation of DSM and other Operational Criteria. This paper reports on the first phase of its deliberations and interim criteria recommendations., Method: The first stage of the process consisted of reviewing Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition , and recent International Classification of Diseases criteria, identifying their limitations and generating modified criteria sets for further in-depth consideration. Task Force members responded to recommendations for modifying criteria and from these the most problematic issues were identified., Results: Principal issues focussed on by Task Force members were how best to differentiate mania and hypomania, how to judge 'impairment' (both in and of itself and allowing that functioning may sometimes improve during hypomanic episodes) and concern that rejecting some criteria (e.g. an imposed duration period) might risk false-positive diagnoses of the bipolar disorders., Conclusion: This first-stage report summarises the clinical opinions of international experts in the diagnosis and management of the bipolar disorders, allowing readers to contemplate diagnostic parameters that may influence their clinical decisions. The findings meaningfully inform subsequent Task Force stages (involving a further commentary stage followed by an empirical study) that are expected to generate improved symptom criteria for diagnosing the bipolar I and II disorders with greater precision and to clarify whether they differ dimensionally or categorically.

Objective: Nonadherence in bipolar disorder (BD) ranges from 20% to 60%. Customized adherence enhancement (CAE) is a brief, BD-specific approach that targets individual adherence barriers. This prospective, 6-month, randomized controlled trial conducted from October 2012 to July 2017 compared CAE versus a rigorous BD-specific educational program (EDU) on adherence, symptoms, and functional outcomes in poorly adherent individuals., Methods: One hundred eighty-four participants with DSM-IV BD were randomized to CAE (n = 92) or EDU (n = 92). Primary outcome was adherence change measured by the Tablets Routine Questionnaire (TRQ) and BD symptoms measured by the Brief Psychiatric Rating Scale. Other outcomes were scores on the Global Assessment of Functioning, Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale, and Clinical Global Impressions Scale. Assessments were conducted at screening, baseline, 10 weeks, 14 weeks, and 6 months., Results: The sample mean (SD) age was 47.40 (10.46) years; 68.5% were female, and 63.0% were African American. At screening, individuals missed a mean (SD) of 55.15% (28.22%) of prescribed BD drugs within the past week and 48.01% (28.46%) in the past month. Study attrition was < 20%. At 6 months, individuals in CAE had significantly improved past-week (P = .001) and past-month (P = .048) TRQ scores versus those in EDU. Past-week TRQ score improvement remained significant after adjustment for multiple comparisons. There were no treatment arm differences in BPRS scores or other symptoms, possibly related to low symptom baseline values. Baseline-to-6-month comparison showed significantly higher GAF scores (P = .036) for CAE versus EDU. Although both groups used more mental health services at 6 months compared to baseline, increase for CAE was significantly less than that for EDU (P = .046)., Conclusions: Whereas both CAE and EDU were associated with improved outcomes, CAE had additional positive effects on adherence, functioning, and mental health resource use compared to EDU., Trial Registration: ClinicalTrials.gov identifier: NCT00183495., (© Copyright 2018 Physicians Postgraduate Press, Inc.)

Objectives: More than 50% of people with bipolar disorder will be age 60 years or older by 2030. There is a need for more data to guide assessment and treatment in older age bipolar disorder (OABD); however, interpretation of findings from small, single-site studies may not be generalizable and there are few large trials. As a step in the direction of coordinated large-scale OABD data collection, it is critical to identify which measurements are currently used and identify potential gaps in domains typically assessed., Methods: An international group of OABD experts performed a systematic literature review to identify studies examining OABD in the past 6 years. Relevant articles were assessed to categorize the types of clinical, cognitive, biomarker, and neuroimaging OABD tools routinely used in OABD studies., Results: A total of 53 papers were identified, with a broad range of assessments. Most studies evaluated demographic and clinical domains, with fewer studies assessing cognition. There are relatively few biomarker and neuroimaging data, and data collection methods were less comprehensively covered., Conclusion: Assessment tools used in the recent OABD literature may help to identify both a minimum and a comprehensive dataset that should be evaluated in OABD. Our review also highlights gaps where key clinical outcomes have not been routinely assessed. Biomarker and neuroimaging assessment could be further developed and standardized. Clinical data could be combined with neuroimaging, genetic, and other biomarkers in large-scale coordinated data collection to further improve our understanding of OABD phenomenology and biology, thereby contributing to research that advances care., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This analysis was conducted on baseline data from 178 nonadherent bipolar disorder subjects in a randomized controlled trial. Medication adherence was measured with Tablets Routine Questionnaire as percentage of days with missed doses. Inclusion criteria required at least 20% nonadherence. Medication adherence, symptomatology, and functioning in individuals with and without a comorbid anxiety disorder were compared. There were 78.9% of subjects who had at least one or more current anxiety disorder, with the most common being posttraumatic stress disorder, panic disorder, and generalized anxiety disorder. The percentage of days with missed doses over the past month was significantly lower in those with anxiety disorders compared with those without (40.1% vs 50.5%, p = 0.03). Those with comorbid anxiety disorders and those with greater number of anxiety disorder diagnoses had significantly worse mean scores on the Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale, Clinical Global Impression-Bipolar Version, and Global Assessment of Functioning.

Objective: To evaluate the safety and effectiveness of 6 months of treatment with lurasidone in older adults with a diagnosis of bipolar I depression., Design: Post-hoc analysis of a multicenter, 6-month, open-label extension study., Setting: Outpatient., Participants: Patients aged 55 to 75 years with a DSM-IV-TR diagnosis of bipolar I depression who had completed 6 weeks of double-blind, placebo-controlled treatment with either lurasidone monotherapy (1 study) or adjunctive therapy with lithium or valproate (2 studies)., Intervention: Flexible doses of lurasidone, 20 to 120 mg/day, either as monotherapy, or adjunctive with lithium or valproate., Measurements: Effectiveness was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS; change from open-label-baseline to month-6, observed case analysis)., Results: A total of 141 older adults entered the extension study (monotherapy, N = 55; 39%; adjunctive therapy, N = 86; 61%). At the end of 6 months of open-label treatment with lurasidone, as monotherapy or adjunctive therapy, minimal changes were observed in the older adult sample in mean weight (-1.0 kg and -0.4 kg, respectively); and median total cholesterol (-2.0 mg/dL and +6.0 md/dL, respectively), triglycerides (+2.5 mg/dL and +6.0 mg/dL, respectively), and HbA1c (0.0% and -0.1%, respectively). Patients treated with 6 months of lurasidone showed a mean improvement on the MADRS in both the monotherapy (-6.2) and adjunctive therapy (-6.7) groups., Conclusions: Results of these post-hoc analyses found that up to 7.5 months of lurasidone treatment for bipolar depression in older adults was associated with minimal effects on weight and metabolic parameters, with low rates of switching to hypomania or mania, and was well tolerated. The antidepressant effectiveness of lurasidone in this age group was maintained over the 6-month treatment period., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: 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., Methods: 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., Results: 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., Conclusions: 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 Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Objective: Clinicians treating older patients with bipolar disorder with mood stabilizers need evidence from age-specific randomized controlled trials. The authors describe findings from a first such study of late-life mania., Method: The authors compared the tolerability and efficacy of lithium carbonate and divalproex in 224 inpatients and outpatients age 60 or older with bipolar I disorder who presented with a manic, hypomanic, or mixed episode. Participants were randomly assigned, under double-blind conditions, to treatment with lithium (target serum concentration, 0.80-0.99 mEq/L) or divalproex (target serum valproate concentration, 80-99 μg/mL) for 9 weeks. Participants with an inadequate response after 3 weeks received open adjunctive risperidone. The authors hypothesized that divalproex would be better tolerated and more efficacious than lithium. Tolerability was assessed based on a measure of sedation and on the proportions of participants achieving target concentrations. Efficacy was assessed with the Young Mania Rating Scale (YMRS)., Results: Attrition rates were similar for lithium and divalproex (14% and 18% at week 3 and 51% and 44% at week 9, respectively). The groups did not differ significantly in sedation. Participants in the lithium group tended to experience more tremor. Similar proportions of participants in the lithium and divalproex groups achieved target concentrations (57% and 56%, respectively). A longitudinal mixed model of improvement (change from baseline in YMRS score) favored lithium (change in score, 3.90; 97.5% CI=1.71, 6.09). Nine-week response rates did not differ significantly between the lithium and divalproex groups (79% and 73%, respectively). The need for adjunctive risperidone was low and similar between groups (17% and 14%, respectively)., Conclusions: Both lithium and divalproex were adequately tolerated and efficacious; lithium was associated with a greater reduction in mania scores over 9 weeks.

Objectives: A 60-week randomized controlled trial assessed the effects of targeted training in illness management (TTIM) versus treatment as usual among 200 individuals with serious mental illness and diabetes mellitus., Methods: The study used the Clinical Global Impression (CGI), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Brief Psychiatric Rating Scale (BPRS) to assess psychiatric symptoms; the Global Assessment of Functioning (GAF) and the Sheehan Disability Scale (SDS) to assess functioning; the 36-Item Short-Form Health Survey (SF-36) to assess general health, and serum glycosylated hemoglobin (HbA1c) to assess diabetes control., Results: Participants' mean±SD age was 52.7±9.5 years, and 54% were African American. They were diagnosed as having depression (48%), schizophrenia (25%), and bipolar disorder (28%). At baseline, depression severity was substantial but psychosis severity was modest. At 60 weeks, there was greater improvement among TTIM participants versus treatment-as-usual recipients on the CGI (p<.001), the MADRS (p=.016), and the GAF (p=.003). Diabetes knowledge was significantly improved among TTIM participants but not in the treatment-as-usual group. In post hoc analyses among participants whose HbA1c levels at baseline met recommendations set by the American Diabetes Association for persons with high comorbidity (53%), TTIM participants had minimal change in HbA1c over the 60-week follow-up, whereas HbA1c levels worsened in the treatment-as-usual group., Conclusions: TTIM was associated with improved psychiatric symptoms, functioning, and diabetes knowledge compared with treatment as usual. Among participants with better diabetes control at baseline, TTIM participants had better diabetes control at 60 weeks compared with recipients of treatment as usual.

Purpose of Review: The population over age 60 is growing more rapidly than the general population. Given the projected increase and need for data that can inform treatment, this review provides a brief description of newer publications focused on mania in older-age bipolar disorder (OABD), including epidemiology, diagnosis, and treatments., Recent Findings: Age cutoffs to define OABD range from 50 to 65 years. OABD clinical presentation and course of illness is highly variable, often characterized by mood episode recurrence, medical comorbidity, cognitive deficits, and impaired functioning. There is little pharmacotherapy data on mania in OABD. Lithium and valproate have been tested in a single randomized controlled trial and there is data of more limited quality with other compounds. Treating OABD is challenging due to medical complexity, comorbidity, diminished tolerance to treatment, and a limited evidence base. More data is needed to keep pace with clinical demand.

Individuals with bipolar disorder (BD) have high rates of nonadherence, medical illness, and premature mortality. This analysis reexamined correlates of poor adherence to nonpsychiatric medication in 73 patients with BD and medical comorbidities. The majority was female (74%) and African American (77%) with mean age of 48.08 (SD, 8.04) years, mean BD duration of 28.67 (SD, 10.24) years, mean years of education of 12.01 (SD, 1.87), and mean proportion of days with missed doses in past week of 43.25 (SD, 31.14). Sex, age, education, race, and living alone did not correlate with adherence. More BD medications and more severe psychiatric symptoms correlated with worse adherence. Specifically, poor adherence correlated with the retardation and vegetative factors of Montgomery-Åsberg Depression Rating Scale and affect factor of the Brief Psychiatric Rating Scale. Among poorly adherent patients with BD and medical comorbidities, the number of BD medications, tension/anxiety, and somatic symptoms of depression related to worse nonpsychiatric medication adherence.

Objective: Care for people with serious mental illness and diabetes is complicated by clinical heterogeneity. This cross-sectional analysis of 200 individuals with comorbid serious mental illness and diabetes explored differentiation between patient subgroups that were characterized on the basis of selected dimensions within a biopsychosocial framework., Methods: Relationships between self-efficacy, treatment expectation, social support, and depression were first assessed via bivariate Spearman correlations among 200 individuals participating in a randomized controlled trial who had diabetes along with major depression, bipolar disorder, or schizophrenia. Next, latent profile analyses were conducted to determine underlying subgroups on the basis of these variables. The resultant groups were compared on diabetes control, function, and symptoms., Results: Two subgroups emerged. One had more severe psychiatric symptoms, low scores on other psychosocial variables, and worse diabetes control. The other had low levels of psychiatric symptoms, better scores on other variables, and better diabetes control., Conclusions: Symptom presentation and internal and external resources appeared to be related to diabetes control for people with comorbid diabetes and serious mental illness. Care approaches need to go beyond standard education and consider biopsychosocial variables.

Objective: Older adults with bipolar disorder (OABD) are a growing segment of patients with bipolar disorder (BD) for which specific guidelines are warranted. Although, OABD are frequently excluded from randomized controlled trials due to their age or somatic comorbidity, more treatment data from a variety of sources have become available in recent years. It is expected that at least some of this emerging information on OABD would be incorporated into treatment guidelines available to clinicians around the world., Methods: The International Society of Bipolar Disorders OABD task force compiled and compared recommendations from current national and international guidelines that specifically address geriatric or older individuals with BD (from year 2005 onwards)., Results: There were 34 guidelines, representing six continents and 19 countries. The majority of guidelines had no separate section on OABD. General principles for treating OABD with medication are recommended to be similar to those for younger adults, with special caution for side effects due to somatic comorbidity and concomitant medications. Therapeutic lithium serum levels are suggested to be lower but recommendations are very general and mostly not informed by specific research evidence., Conclusions: There is a lack of emphasis of OABD-specific issues in existing guidelines. Given the substantial clinical heterogeneity in BD across the life span, along with the rapidly expanding population of older individuals worldwide, and limited mental health workforce with geriatric expertise, it is critical that additional effort and resources be devoted to studying treatment interventions specific to OABD and that treatment guidelines reflect research findings. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: Internalized stigma, which occurs when stigmatized individuals accept society's assessment and incorporate this assessment into their sense of self, is prevalent in individuals with bipolar disorder (BD). This study explored the correlates of internalized stigma in a research sample of patients with BD who were poorly adherent to their medications., Methods: Both quantitative and qualitative analyses were performed. Scores of 115 individuals with BD on the Internalized Stigma of Mental Illness (ISMI) scale were correlated with scores on the General Self-Efficacy (GSE) Scale, Brief Psychiatric Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS). Regression was run for GSE (dependent variable) and ISMI (independent variable). In-depth qualitative interviews were conducted on a representative subsample (N=21)., Results: Internalized stigma levels were moderately high. Internalized stigma and self-efficacy correlated, and internalized stigma related to self-efficacy after adjusting for demographic variables (age, gender, years of education), comorbidities, and symptom severity (BPRS and MADRS). Internalized stigma was also associated with the BD symptoms of depression, anxiety, guilt feelings, suspiciousness, and hallucinogenic behaviors. No association was found with mania., Conclusions: Because internalized stigma has strong psychosocial and psychiatric symptom associations, it is recommended that clinicians address both societal stigma and internalized stigma. Strategies such as cognitive-behavioral therapy may help modify BD patients' internalized stigma., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: The aim of this post hoc analysis was to evaluate the efficacy of lurasidone in patients aged 55 years and older with bipolar depression., Methods: A post hoc analysis was performed on the older adult subgroup (n = 142) of outpatients meeting DSM-IV-TR criteria for bipolar I depression in 2 placebo-controlled, 6-week, randomized, double-blind studies conducted from 2009-2012: a monotherapy study comparing fixed flexible-dose ranges of lurasidone 20-60 mg/d or 80-120 mg/d with placebo and an adjunctive therapy study comparing flexible doses of lurasidone 20-120 mg/d with placebo adjunctive to either lithium or valproate. The primary endpoint was mean change at week 6 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score., Results: In the randomized sample, the proportion of older adults was 88/505 (17.4%) in the monotherapy study and 54/348 (15.5%) in the adjunctive therapy study. In the older adult subgroup in the monotherapy study, mean change at week 6 in the MADRS was significantly greater for lurasidone versus placebo (-14.8 vs -7.1; P = .003; effect size, 0.83; pooled doses), and in the adjunctive therapy study, mean change for lurasidone was not significantly different from placebo (-13.9 vs -11.1; P = .398; effect size, 0.26). Discontinuation rates due to adverse events for lurasidone versus placebo were similar for the monotherapy (6.8% vs 6.9%) and adjunctive therapy (3.8% vs 7.1%) studies. Lurasidone had minimal effects on metabolic laboratory values., Conclusions: The results of these post hoc analyses, which assessed the efficacy of lurasidone in older adults with bipolar disorder, found that monotherapy was significantly effective while adjunctive therapy was not associated with significant improvement. Both monotherapy and adjunctive therapy with lurasidone were safe and well-tolerated in this older adult population., Trial Registration: ClinicalTrials.gov identifiers: NCT00868699, NCT00868452., (© Copyright 2016 Physicians Postgraduate Press, Inc.)

Poor medication adherence is a pervasive problem that causes disability and suffering as well as extensive financial costs among individuals with bipolar disorder (BD). Barriers to adherence are numerous and cross multiple levels, including factors related to bipolar pathology and those unique to an individual's circumstances. External factors, including treatment setting, healthcare system, and broader health policies, can also affect medication adherence in people with BD. Fortunately, advances in research have suggested avenues for improving adherence. A comprehensive review of adherence-enhancement interventions for the years 2005-2015 is included. Specific bipolar adherence-enhancement approaches that target knowledge gaps, cognitive patterns, specific barriers, and motivation may be helpful, as may approaches that capitalize on technology or novel drug-delivery systems. However, much work remains to optimally facilitate long-term medication adherence in people with BD. For adherence-enhancement approaches to be widely adapted, they need to be easily accessible, affordable, and practical.