Essential data dimensions for prospective international data collection in older age bipolar disorder (OABD): Recommendations from the GAGE-BD group.

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.

An interventional pilot of customized adherence enhancement combined with long-acting injectable antipsychotic medication (CAE-L) for poorly adherent patients with chronic psychotic disorder in Tanzania.

BACKGROUND: Chronic psychotic disorders (CPD) impose a particularly significant burden in resource-limited settings. Combining long-acting antipsychotic medication (LAI) with a customized adherence enhancement intervention (CAE-L) has potential to advance care. METHODS: Nineteen adults ≥ age 18 with CPD who self-reported missing ≥20% of antipsychotic medication within the last month were stabilized on oral haloperidol prior to transitioning to monthly haloperidol decanote for 25 weeks. Outcome evaluations were conducted at baseline and Week 25. Primary outcomes were oral medication adherence assessed via the Tablet Routines Questionnaire (TRQ) and LAI injection frequency. Secondary outcomes included CPD symptoms measured by the Brief Psychiatric Rating Scale and Clinical Global Impressions, functioning evaluated using the Social and Occupational Functioning Scale, and medication attitudes assessed with the Drug Attitudes Inventory. RESULTS: Mean sample age was 38.79 (SD = 9.31) with 18 individuals completing the study. There was one serious adverse event, a relapse into substance use, not deemed study-related. Mean endpoint LAI dosage was 65.79 mg (SD = 22.38). TRQ mean scores were 21.84 (SD =13.83) and 12.94 (SD = 11.93) at screen and baseline respectively. For only two individuals who were on concomitant oral medication at 25 weeks, TRQ change was not calculated. LAI injection frequency was 100%. Medication attitudes scores significantly improved from 7.89 (SD = 2.72) to 9.83 (SD = 0.52) (p = .001.) Changes in CPD symptoms and functioning were non-significant. CONCLUSIONS: CAE-L appears to be preliminarily feasible and acceptable in Tanzanians with CPD. TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov (NCT04327843) on March 31, 2020.

Alcohol use in Tanzanians with chronic psychotic disorders and poor medication adherence.

BACKGROUND: The burden of chronic psychotic disorders (CPDs) in sub-Saharan Africa (SSA) is significant. Poorly medically adherent patients are more likely to have worse outcomes and require more resources. However, factors impacting effective treatment of CPD in this population are unclear. AIM: Examine the relationship between alcohol use and disease management and compare alcohol risk stratification between the Alcohol Use Disorders Identification Test (AUDIT) and Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) in poorly medication adherent Tanzanians with CPD. SETTING: Muhimbili National Hospital and ambulatory clinics in Dar es Salaam, Tanzania. METHODS: 100 Tanzanians with CPDs and suboptimal medication adherence were dichotomized into low and moderate-to-high risk alcohol use based on AUDIT scores and compared regarding medication attitudes, adherence and psychiatric symptoms. Patients completed the ASSIST for comparison to AUDIT risk stratification. RESULTS: Moderate-to-high risk alcohol users had worse medication attitudes (p < 0.01), medication adherence (previous week, p = 0.01; previous month, p < 0.001), and psychiatric symptoms (p = 0.03). They were younger, predominately male and more likely to have a family history of alcohol abuse. A logistic regression analysis found age, gender and family history of abuse as significant predictors of hazardous alcohol use (p = 0.02, 0.02, < 0.01, respectively). Risk stratification between AUDIT and ASSIST aligned in 85% of participants. CONCLUSION: Alcohol use is an important consideration in treating poorly adherent Tanzanians with CPD. The ASSIST was comparable to the AUDIT in stratifying risky alcohol use with the additional benefit of screening for other substances.

The Relationship Between Medication Attitudes and Medication Adherence Behavior in Adults With Bipolar Disorder.

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.

Self-management for adults with epilepsy: Aggregate Managing Epilepsy Well Network findings on depressive symptoms.

OBJECTIVE: To assess depressive symptom outcomes in a pooled sample of epilepsy self-management randomized controlled trials (RCTs) from the Managing Epilepsy Well (MEW) Network integrated research database (MEW DB). METHODS: Five prospective RCTs involving 453 adults with epilepsy compared self-management intervention (n = 232) versus treatment as usual or wait-list control outcomes (n = 221). Depression was assessed with the nine-item Patient Health Questionnaire. Other variables included age, gender, race, ethnicity, education, income, marital status, seizure frequency, and quality of life. Follow-up assessments were collapsed into a visit 2 and a visit 3; these were conducted postbaseline. RESULTS: Mean age was 43.5 years (SD = 12.6), nearly two-thirds were women, and nearly one-third were African American. Baseline sample characteristics were mostly similar in the self-management intervention group versus controls. At follow-up, the self-management group had a significantly greater reduction in depression compared to controls at visit 2 (P < .0001) and visit 3 (P = .0002). Quality of life also significantly improved in the self-management group at visit 2 (P = .001) and visit 3 (P = .005). SIGNIFICANCE: Aggregate MEW DB analysis of five RCTs found depressive symptom severity and quality of life significantly improved in individuals randomized to self-management intervention versus controls. Evidence-based epilepsy self-management programs should be made more broadly available in neurology practices.

One-year follow-up of a remotely delivered epilepsy self-management program in high-risk people with epilepsy.

OBJECTIVE: "Self-management for people with epilepsy and a history of negative health events" (SMART) is a novel group-format epilepsy self-management intervention demonstrated to reduce negative health events (NHEs) such as accidents, emergency department visits, and seizures in adults with epilepsy in a 6-month prospective randomized controlled trial (RCT); SMART also reduced depressive symptoms and improved health functioning and quality of life. This report describes the longer-term (12-month) post-efficacy RCT outcomes in adults with epilepsy who received SMART. METHODS: After completing a 6-month, prospective RCT that demonstrated efficacy of SMART vs 6-month waitlist control (WL), adults ≥18 years of age with epilepsy were followed for an additional 12 months. Individuals originally randomized to WL received the 8-week SMART intervention immediately following the conclusion of the RCT. For this long-term extension analysis, assessments were conducted at 24 weeks (the 6-month primary outcome time-point of the efficacy RCT), at 32 weeks for individuals originally randomized to WL, and at 48 weeks and 72 weeks for all individuals. Outcomes assessed included past 6-month NHE counts, depressive symptoms assessed with the 9-item Patient Health Questionnaire (PHQ-9) and Montgomery-Asberg Depression Rating Scale (MADRS), and quality of life assessed with the 10-item Quality of Life in Epilepsy (QOLIE-10). RESULTS: At the beginning of this long-term observational period (24-week follow-up time point for the original RCT), there were 50 individuals in the group originally randomized to SMART and 52 originally randomized to WL. Mean age was 41.4 years, 70% women (N = 71), 64% (N = 65) African-American, and 8% Hispanic (N = 8). Study attrition from week 24 to week 72 was 8% in the arm originally randomized to SMART and 17% in the arm originally randomized to WL. During the 12-month observation period (24 weeks to 72 weeks), there were a total of 44 serious adverse events and 4 deaths, none related to study participation. There was no significant change in total past 6-month NHE counts in the group originally randomized to SMART, although the group had significantly reduced 6-month seizure counts. The group originally randomized to WL, who received SMART during this observational period, had a reduction in total NHE counts. The group originally randomized to SMART had relatively stable levels on other outcome variables except for a trend for improved MADRS (p = 0.08). In the group originally randomized to WL, there were significant improvements in PHQ-9 (p = 0.01), MADRS (p ≤ 0.01), and QOLIE-10 (p = 0.004). CONCLUSIONS: This post-RCT extension study suggests that adults with epilepsy who participate in the SMART intervention sustain clinical effects at 1-year follow-up and may have incremental improvements in seizure frequency and mood. Future research needs to identify opportunities for scale-up and outreach to other high-risk groups with epilepsy.

Functional health status of adults with serious mental illness and diabetes mellitus: A latent profile analysis.

OBJECTIVE: Adults with serious mental illness are at increased risk for diabetes mellitus and diabetes-related complications. This article classifies subgroups among people with serious mental illness and comorbid diabetes with respect to functional status and examines differences among those groups. METHODS: This analysis used a baseline sample of 157 adults with serious mental illness and diabetes mellitus enrolled in a National Institute of Health-funded research study. Latent profile analysis was used to distinguish health status profiles and investigate how these subgroups differed across assessment domains. RESULTS: Participants with depression, schizophrenia, and bipolar disorder (n = 157) were included in the study. Mean age was 52.9 years (standard deviation = 9.8), and 62 (40%) were African American. From the latent profile analysis, a three-class model appeared to provide the best fit. Class 1 (34.9%) had a very low functional health status approximately two standard deviations below the general population mean. Class 2 (43.7%) had a low functional status approximately one standard deviation below the general mean. Class 3 (21.4%) had moderate functional status with scores near population mean. Groups differed on measures of personal characteristics, clinical status and symptom severity, self-care behaviors, and environmental characteristics. CONCLUSIONS: Although individuals with schizophrenia generally have poor prognosis once they develop diabetes, latent profile analysis identified distinct health status subgroups. Although all three groups demonstrated illness burden, the pattern of differences between these groups across measures may suggest the need for different interventions for highly diverse adults who received care within safety-net primary care.

A 6-month prospective randomized controlled trial of remotely delivered group format epilepsy self-management versus waitlist control for high-risk people with epilepsy.

OBJECTIVE: Despite advances in care, many people with epilepsy have negative health events (NHEs) such as accidents, emergency department visits, and poor quality of life. "Self-management for people with epilepsy and a history of negative health events" (SMART) is a novel group format epilepsy self-management intervention. A community participatory approach informed the refinement of SMART, which was then tested in a 6-month randomized controlled trial of SMART (n = 60) versus waitlist control (WL, n = 60). METHODS: Participants were adults aged ≥18 years with epilepsy and an NHE within the past 6 months (seizure, accident, self-harm attempt, emergency department visit, or hospitalization). Assessments were conducted at screening, baseline, 10 weeks, and 24 weeks (6 months). Primary outcome was 6-month change in total NHE count. Additional outcomes included depression on the nine-item Patient Health Questionnaire and Montgomery-Asberg Depression Rating Scale, quality of life on the 10-item Quality of Life in Epilepsy, functioning on the 36-item Short-Form Health Survey, and seizure severity on the Liverpool Seizure Severity Scale. RESULTS: Mean age was 41.3 years (SD = 11.82), 69.9% were African American, 74.2% were unemployed, and 87.4% had an annual income < US$25 000; 57.5% had a seizure within 30 days of enrollment. Most NHEs were seizures. Six-month study attrition was 14.2% overall and similar between arms. Individuals randomized to SMART had greater reduction in total median NHEs from baseline to 6 months compared to WL (P = 0.04). SMART was also associated with improved nine-item Patient Health Questionnaire (P = 0.032), Montgomery-Asberg Depression Rating Scale (P = 0.002), 10-item Quality of Life in Epilepsy (P < 0.001), and 36-item Short-Form Health Survey (P = 0.015 physical health, P = 0.003 mental health) versus WL. There was no difference in seizure severity. SIGNIFICANCE: SMART is associated with reduced health complications and improved mood, quality of life, and health functioning in high-risk people with epilepsy. Additional efforts are needed to investigate potential for scale-up.

Clinical correlates of negative health events in a research sample with epilepsy.

AIMS: In spite of advances in care, people with epilepsy experience negative health events (NHEs), such as seizures, emergency department (ED) visits, and hospitalizations. Being able to identify characteristics that are associated with NHE risk can help inform care approaches that reduce complications and burden. This analysis using baseline data from a larger randomized epilepsy self-management clinical trial assessed the relationship between demographic and clinical variables vs. seizure-related complications among people with epilepsy. METHODS: Data were derived from a baseline sample of a larger prospective study of 120 individuals with epilepsy who experienced an NHE within the last 6months. Demographic characteristics, depression assessed with the 9-item Patient Health Questionnaire (PHQ-9) and the Montgomery-Asberg Depression rating scale (MADRS), quality of life assessed with the 10-item Quality of Life in Epilepsy Inventory (QOLIE-10), self-efficacy assessed the Epilepsy Self-Efficacy Scale (ESES), social support assessed with the Multidimensional Scale of Perceived Social Support (MSPSS), self-management assessed with the Epilepsy Self-Management Scale (ESMS), and stigma assessed with the Epilepsy Stigma Scale (ESS) were all examined in association with past 6-month NHE frequency and 30-day seizure frequency. RESULTS: Except for lower levels of education and lower levels of income being associated with higher 30-day and 6-month seizure frequency, demographic variables were generally not significantly associated with NHEs. Higher 30-day seizure frequency was associated with greater depression severity on PHQ-9 (p<0.01) and MADRS (p<0.01). Higher 6-month seizure frequency was also associated with greater depression severity on PHQ-9 (p<.001) and MADRS (p=0.03). Both 30-day and 6-month seizure frequency were significantly negatively associated with QOLIE-10 (p<0.001). Both 30day (p=0.01) and 6-month (p=0.03) seizure frequency were associated with worse stigma on ESS. Total NHE count was associated with more severe depression on PHQ-9 (p=0.02), and MADRS (p=0.04), worse quality of life on QOLIE-10 (p<0.01), and more stigma on ESS (p=0.03). CONCLUSIONS: Consistent with previous literature, more frequent seizures were associated with worse depression severity and quality of life. A finding that is less established is that higher seizure frequency is also associated with worse epilepsy-related stigma. Epilepsy self-management approaches need to address depression and stigma as well as seizure control.

Assessing depression severity with a self-rated vs. rater-administered instrument in patients with epilepsy.

RATIONALE: Up to 30-50% of individuals with epilepsy have depressive symptoms, which often complicate seizure management and reduce overall quality of life. To identify and manage depressive symptoms appropriately, clinicians need standardized instruments that can accurately identify and monitor those with clinically significant depression. The self-reported 9-item Patient Health Questionnaire (PHQ-9) has been used relatively widely to screen and monitor depression in epilepsy. The rater-administered Montgomery-Asberg Depression Rating Scale (MADRS) is a rater-administered instrument widely used in depression treatment trials but less widely applied in epilepsy. This secondary analysis from 2 epilepsy self-management clinical trials compared depression severity ratings using the PHQ-9 and the MADRS instruments. METHODS: Data for this analysis were derived from pooled baseline and longitudinal data from 2 prospective epilepsy self-management randomized controlled trials (RCTs). Both RCTs assessed depression with the PHQ-9 and the MADRS. For this analysis, total depression severity scores and case classification of individuals with no/minimal, mild, moderate/moderately severe, and severe depression were assessed using both PHQ-9 and MADRS. RESULTS: The sample contained 164 individuals with epilepsy. Demographic and clinical variables between the 2 studies were generally similar. There were 107 women (64.8%), 106 African-Americans (64.2%), and 51 Whites (30.9%). Individuals had epilepsy for an average of 22.1 (SD: 15.5). Mean past 30-day seizure frequency at baseline was 3.1 (SD: 11.6). Baseline mean PHQ-9 was 10.7 (SD: 6.80) with depression severity of 32 (19.6%) not or minimally depressed, 47 (28.8%) mildly depressed, 37 (22.7%) moderately depressed, 27 (16.6%) moderately severely depressed, and 20 (12.3%) severely depressed. Baseline mean MADRS severity was 18.5 (SD: 11.3) with 30 (18.8%) not or minimally depressed, 27 (16.9%) mildly depressed, 92 (56.1%) moderately depressed, and 11 (6.9%) severely depressed. The correlation between total PHQ-9 and total MADRS was 0.843 (p < .01) although case classification by depression severity varied somewhat between the two instruments. CONCLUSIONS: Standardized measures to evaluate depression severity in people with epilepsy can help identify cases and monitor treatment. The PHQ-9 and MADRS both perform well in assessing depression in people with epilepsy although administration burden is less with PHQ-9 thus making it likely preferable for settings where time and epilepsy specialty resources are limited.

Associations among comorbid anxiety, psychiatric symptomatology, and diabetic control in a population with serious mental illness and diabetes: Findings from an interventional randomized controlled trial.

Objective Serious mental illness and type II diabetes mellitus have a high comorbidity, and both have a higher prevalence of anxiety disorders compared to the general population. Targeted Training in Illness Management is a group-based self-management training approach which targets serious mental illness and type II diabetes mellitus concurrently. This analysis examines data from a randomized controlled trial of Targeted Training in Illness Management intervention to examine the impact of comorbid anxiety on baseline psychiatric symptomatology and diabetic control, and on longitudinal treatment outcomes. Methods We conducted secondary analyses on data from a prospective, 60-week, randomized controlled trial testing Targeted Training in Illness Management versus treatment as usual in 200 individuals with serious mental illness and diabetes. Primary outcomes included measures related to serious mental illness symptoms, functional status, general health status, and diabetes control. Measures were compared between those participants with anxiety disorders versus those without anxiety at baseline as well as over time using linear mixed effects analyses. Results Forty seven percent of the participants had one or more anxiety disorders. At baseline, those with an anxiety diagnosis had higher illness severity, depressive, and other psychiatric symptomatology and disability. Diabetic control (HbA1c) was not significantly different at baseline. In the longitudinal analyses, no significant mean slope differences over time (group-by-time interaction effect) between those with anxiety diagnoses and those without in treatment as usual group were found for primary outcomes. Within the Targeted Training in Illness Management arm, those with anxiety disorders had significantly greater improvement in mental health functioning. Those with anxiety comorbidity in the Targeted Training in Illness Management group demonstrated significantly lower HbA1c levels compared to no anxiety comorbidity and also demonstrated a greater improvement in HbA1c over the first 30 weeks compared to those without anxiety comorbidity. Conclusion Comorbid anxiety in serious mental illness and type II diabetes mellitus population is associated with increased psychiatric symptomatology and greater disability. Individuals from this population appear to experience greater improvement in functioning from baseline with the Targeted Training in Illness Management intervention. Anxiety comorbidity in the serious mental illness and type II diabetes mellitus population does not appear to have a negative impact on diabetic control. These complex relationships need further study. Clinical Trials Registration ClinicalTrials.gov: Improving outcomes for individuals with serious mental illness and diabetes (NCT01410357).

A 6-Month Prospective Trial of a Personalized Behavioral Intervention + Long-Acting Injectable Antipsychotic in Individuals With Schizophrenia at Risk of Treatment Nonadherence and Homelessness.

PURPOSE: Long-acting injectable antipsychotics (LAI) can optimize adherence for high-risk serious mental illness (SMI). This customized adherence-enhancement approach delivered by social worker interventionists was combined with LAI (CAE-L) of paliperidone palmitate for homeless, poorly adherent individuals with SMI. METHODS: This 6-month prospective, uncontrolled trial of CAE-L in 30 recently homeless individuals with SMI assessed adherence using the Tablets Routine Questionnaire, injection frequency, and SMI symptoms measured by the Positive and Negative Syndrome Scale, Brief Psychiatric Rating Scale, and Clinical Global Impressions. The Social and Occupational Functioning Assessment Scale measured social function. Standardized scales assessed extrapyramidal effects. FINDINGS: Patients' mean age was 43.6 (SD, 9.53) years, and they were mainly minorities (86.7% African American) and single/never married (72.4%). Rate of substance abuse within the past year was 40.0%, and rate of incarceration within the past 6 months was 32.1%. Four participants (13.3%) terminated the study prematurely. Customized adherence enhancement + LAI was associated with good adherence to LAI (92.9%) and improved adherence with oral drug as measured by Tablets Routine Questionnaire (P = 0.02). There were significant improvements in Positive and Negative Syndrome Scale (P < 0.01), Brief Psychiatric Rating Scale (P < 0.001), Clinical Global Impressions (P = 0.003), and Social and Occupational Functioning Assessment Scale (P = 0.005). There were no significant extrapyramidal effects. IMPLICATIONS: While findings must be tempered by the methodological limitations, CAE-L seems associated with multiple domains of improvement in homeless/recently homeless individuals with SMI. Adverse effects limit tolerability in some individuals, and not all will remain engaged. However, LAI combined with a patient-centered behavioral approach can improve outcomes for some high-risk individuals with SMI.

A Reexamination of Nonpsychiatric Medication Adherence in Individuals With Bipolar Disorder and Medical Comorbidities.

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.

A Preliminary Analysis of Individuals With Serious Mental Illness and Comorbid Diabetes.

OBJECTIVE: To understand factors related to managing illness in older individuals with serious mental illness (SMI). METHODS: Baseline data from 200 individuals with SMI and diabetes enrolled in a study were used to compare characteristics between older (age >55) vs. younger (age ≤55) individuals. RESULTS: Older individuals had better diabetes control compared to younger individuals, those with major depressive disorder had diabetes for a longer duration, worse diabetic control, and more emergency department encounters. CONCLUSIONS: Helping younger individuals with SMI learn to manage their mental and physical health early-on might minimize the negative and cumulative effect of diabetes.

Symptom severity, self-reported adherence, and electronic pill monitoring in poorly adherent patients with bipolar disorder.

OBJECTIVES: This analysis of screening and baseline data from an ongoing trial examined self-report versus automated adherence monitoring and assessed the relationship between bipolar disorder (BD) symptoms and adherence in 104 poorly adherent individuals. METHODS: Adherence was measured with the Tablets Routine Questionnaire (TRQ) and the Medication Event Monitoring System (MEMS). Symptoms were measured with the Montgomery-Åsberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), and the Brief Psychiatric Rating Scale (BPRS). RESULTS: The mean age of the sample was 46.3 years [standard deviation (SD) = 9.41 years], with 72% (n = 75) women and 71% (n = 74) African American subjects. Adherence improved from screening to baseline, with a mean missed drug proportion measured by TRQ of 61.43% (SD = 26.48%) versus a baseline mean of 46.61% (SD = 30.55%). The mean proportion of missed medication using MEMS at baseline was 66.43% (SD = 30.40%). The correlation between TRQ and MEMS was 0.47. The correlation between a single index drug and all BD medications was 0.95. Symptoms were generally positively correlated with TRQ (worse adherence = more severe symptoms), but in most instances was only at a trend level (p > 0.05), with the exception of the correlations between baseline TRQ and MADRS and BPRS, which were positive (r = 0.20 and r = 0.21, respectively) and significant (p ≤ 0.05). CONCLUSIONS: In patients with BD, monitoring increased adherence by 15%. MEMS identified 20% more non-adherence than self-report. Using a standard procedure to identify a single index drug for adherence monitoring may be one way to assess global adherence in patients with BD receiving polypharmacy treatment. Greater BD symptom severity may be a clinical indicator to assess for adherence problems.

Asenapine in the treatment of older adults with bipolar disorder.

OBJECTIVE: In spite of growing numbers of older people, there are few treatment studies on late-life bipolar disorder (BD). This was a 12-week prospective, open-label trial to assess efficacy and tolerability of adjunct asenapine in non-demented older adults (≥ 60 years) with sub-optimal previous response to BD treatments. METHODS: Asenapine was initiated at 5 mg/day and titrated as tolerated. Effects on global psychopathology were measured with Clinical Global Impression, bipolar version (CGI-BP), and the Brief Psychiatric Rating Scale (BPRS). Mood polarity severity was measured with the Hamilton Depression Rating Scale, Montgomery Asberg Depression Rating Scale, and Young Mania Rating Scale. Other outcomes included the World Health Organization Disability Assessment Schedule II. RESULTS: Fifteen individuals were enrolled (mean age 68.6, SD 6.12; 53% female; 73% Caucasian, 13% African American, and 7% Asian). There were 4/15 (27%) individuals who prematurely terminated the study, whereas 11/15 (73%) completed the study. There were significant improvements from baseline on the BPRS (p < 0.05), on CGI-BP overall (p < 0.01), and on CGI-BP mania (p < 0.05) and depression (p < 0.01) subscales. The mean dose of asenapine was 11.2 (SD 6.2) mg/day. The most common reported side effects were gastrointestinal discomfort (n = 5, 33%), restlessness (n = 2, 13%), tremors (n = 2, 13%), cognitive difficulties (n = 2, 13%), and sluggishness (n = 2, 13%). CONCLUSIONS: Older people with BD had global improvements on asenapine. Most reported adverse effects were mild and transient, but adverse effects prompted drug discontinuation in just over one quarter of patients. Although risks versus benefits in older people must always be carefully considered, asenapine may be a treatment consideration for some non-demented geriatric BD patients.

Trajectories of medication attitudes and adherence behavior change in non-adherent bipolar patients.

OBJECTIVES: While medication treatment is necessary for the successful management of bipolar disorder (BD), non-adherence rates are up to 60%. Although medication attitudes are believed to be relevant to adherence behavior, few studies have investigated the trajectories of adherence change. This study evaluated attitudinal correlates of adherence conversion in 86 poorly adherent individuals with BD. METHODS: This secondary analysis pooled data from two uncontrolled prospective trials of customized adherence enhancement (CAE), a psychosocial intervention delivered over 4-6 weeks. Poor adherence was defined as missing at least 20% of prescribed BD medication based on the self-reported Tablets Routine Questionnaire (TRQ). The sample was dichotomized into converters who achieved good adherence (N=44) and non-converters who remained poorly adherent (N=21). Converters vs. non-converters were compared on adherence, attitudes, and symptoms at baseline, 6 weeks and 3 months. RESULTS: At baseline, converters and non-converters were similar demographically and clinically, but converters were less non-adherent (32% doses missed) than non-converters (59% missed). At 6 weeks, converters had better attitudes than non-converters. At 3 months, converters maintained improvements, but group differences were less pronounced due to some improvement in non-converters. Converters had better adherence at 3 months and trajectories differed for the groups on attitudes. Symptoms gradually improved for both converters and non-converters. CONCLUSIONS: Over two-thirds of poorly adherent BD patients who received CAE converted to good adherence. Improved medication attitudes may be a driver of improved adherence behavior and ultimately reduce BD symptoms.

Comparing medication attitudes and reasons for medication nonadherence among three disparate groups of individuals with serious mental illness.

This analysis compared medication attitudes and reasons for nonadherence in three distinct groups of patients with serious mental illness (SMI). Cohort 1 had 43 patients with bipolar disorder (BD) treated in a community mental health setting, cohort 2 had 43 patients with BD taking an atypical antipsychotic and treated in an academic medical center, and cohort 3 had 30 patients with schizophrenia or schizoaffective disorder who had been homeless in the last year. Standardized attitudinal scales found generally negative attitudes toward medication and limited illness insight. Although the three cohorts differed with regard to severity of symptoms, age of onset, education, baseline adherence, and race, the groups had similar medication attitudes before and after treatment. Despite group differences in demographic and clinical variables, our analyses found more similarities than differences in medication attitudes among these three discrete groups of poorly adherent, symptomatic patients with SMI. The common attitudinal characteristics have implications for delivery of health care services that can enhance treatment adherence in high-risk SMI patients.

Six-month outcomes of customized adherence enhancement (CAE) therapy in bipolar disorder.

BACKGROUND: There are few psychosocial interventions specifically focused on improved treatment adherence in people with bipolar disorder (BD). Customized adherence enhancement (CAE) is a needs-based, manualized approach intended to improve medication adherence in individuals with BD. This was a six-month prospective trial of a CAE among 43 medication non-adherent individuals with BD who were receiving treatment in a community mental health clinic (CMHC). METHODS: CAE was flexibly administered in modules applied as indicated by an initial adherence vulnerabilities screening. Screening identified reasons for non-adherence and modules were then administered using pre-set criteria. CAE effects were evaluated at six-week, three-month, and six-month follow-up. The six-month follow-up was our primary time point of interest. The primary outcome was change from baseline in adherence using the Tablets Routine Questionnaire (TRQ) and pill counts. Secondary outcomes included change from baseline in BD symptoms [Hamilton Depression Rating Scale (HAM-D), Young Mania Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS)]. RESULTS: Subjects completed 86% of scheduled sessions, with only two individuals (5%) not participating in any sessions. The number of dropouts at six months was 12 (28%). Mean baseline non-adherence by TRQ was 48% [standard error (SE) 4.8%] missed tablets within the previous week and 51% (4.1%) missed tablets within the previous month. At six-month follow-up, mean TRQ non-adherence improved to 25% (6.8%) missed tablets for the previous week (p = 0.002) and 21% (5.5%) for the previous month (p < 0.001). Symptoms improved, with a change in the baseline mean (SE) BPRS of 43.6 (1.8) versus an endpoint of 36.1 (2.3) (p = 0.001), and baseline mean (SE) HAM-D of 17.8 (1.1) versus an endpoint of 15.3 (1.6) (p = 0.044). CONCLUSION: CAE was associated with improvements in adherence, symptoms, and functional status. Controlled trials are needed to confirm these preliminary findings.

Correlates of treatment response in depressed older adults with bipolar disorder.

AIMS: To identify baseline clinical factors associated with acute treatment response in depressed older adults with bipolar disorder (BD) receiving lamotrigine. METHODS: Secondary analysis of a multisite, 12-week, open-label, uncontrolled study of add-on lamotrigine in 57 adults 60 years and older with BD I or II depression. Measures included the Montgomery Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS). Cardiometabolic risk was measured with total serum cholesterol and the Cumulative Illness Rating Scale-Geriatric (CIRS-G) item #13 (endocrine/metabolic burden). Neurocognitive (executive) function was evaluated using the Trail Making Test. RESULTS: Greater reduction in MADRS from baseline was associated with higher baseline cardiometabolic burden at 6 and 9 weeks and lower YMRS scores at 9 weeks. At 12 weeks, improvement in the MADRS from baseline was no longer significantly related to baseline cardiometabolic burden or YMRS scores. A longitudinal mixed model of MADRS scores corroborated these findings with a significant finding of time-by-baseline cholesterol level interaction. In a subset of participants, better baseline executive function was related to greater improvement in the MADRS at 9 weeks but not at 6 or 12 weeks. Among all participants, higher baseline YMRS scores were related to greater likelihood of dropout. CONCLUSIONS: Lamotrigine appears to work best in depressed elderly patients with BD who have high cardiometabolic risk and low level of mania. Agents like lamotrigine that act primarily on neuroprogressive pathways involving oxidative stress, neurotrophins, and inflammation may be particularly effective in individuals with BD who have significant cardiometabolic burden because of their effects on shared vulnerability factors in BD and medical illness.