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Importance: Long-acting injectable (LAI) antipsychotics have the potential to improve adherence and symptom control in patients with schizophrenia, promoting long-term recovery. Paliperidone palmitate (PP) once every 6 months is the first and currently only LAI antipsychotic with an extended dosing interval of 6 months., Objective: To assess long-term outcomes of PP received once every 6 months in adults with schizophrenia., Design, Setting, and Participants: In a 2-year open-label extension (OLE) study of a 1-year randomized clinical trial (RCT), eligible adults with schizophrenia could choose to continue PP every 6 months if they had not experienced relapse after receiving PP once every 3 or 6 months in the 1-year, international, multicenter, double-blind, randomized noninferiority trial. The present analysis focused on patients receiving PP every 6 months in the double-blind trial through the OLE study (November 20, 2017, to May 3, 2022)., Intervention: Patients received a dorsogluteal injection of PP on day 1 and once every 6 months up to month 30., Main Outcomes and Measures: End points included assessment of relapse and change from the double-blind trial baseline to the OLE end point in Positive and Negative Syndrome Scale (PANSS) total and subscale, Clinical Global Impression-Severity (CGI-S) Scale, and Personal Social Performance (PSP) Scale scores. Treatment-emergent adverse events (TEAEs), injection site evaluations, and laboratory tests were also assessed., Results: Among 121 patients (83 [68.6%] male), mean (SD) age at baseline was 38.6 (11.24) years and mean (SD) duration of illness was 11.0 (9.45) years. At screening of the double-blind study, 101 patients (83.5%) were taking an oral antipsychotic and 20 (16.5%) were taking an LAI antipsychotic. Altogether, 5 of 121 patients (4.1%) experienced relapse during the 3-year follow-up; reasons for relapse were psychiatric hospitalization (2 [1.7%]), suicidal or homicidal ideation (2 [1.7%]), and deliberate self-injury (1 [0.8%]). Patients treated with PP every 6 months were clinically and functionally stable, and outcomes were well maintained, evidenced by stable scores on the PANSS (mean [SD] change, -2.6 [9.96] points), CGI-S (mean [SD] change, -0.2 [0.57] points), and PSP (mean [SD] change, 3.1 [9.14] points) scales over the 3-year period. In total, 101 patients (83.5%) completed the 2-year OLE. At least 1 TEAE was reported in 97 of 121 patients (80.2%) overall; no new safety or tolerability concerns were identified., Conclusions and Relevance: In a 2-year OLE study of a 1-year RCT, results supported favorable long-term outcomes of PP once every 6 months for up to 3 years in adults with schizophrenia.

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: 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.)

Patients with severe mental illness (SMI) who do not adhere to treatment have a lower quality of life, with more hospitalizations, interpersonal relationship conflict, homelessness, substance use problems, and incarceration compared to patients who adhere to treatment. Nonadherence to psychiatric medications has been studied for over a decade in patients diagnosed with bipolar, schizoaffective, and schizophrenia disorders with long-acting injectable antipsychotics (LAI) becoming a mainstay of adherence-focused treatment. Previous studies have shown that LAI treatment can be further optimized with the inclusion of the behavioral intervention, Customized Adherence Enhancement (CAE). It was unclear if outcomes improved similarly across the studies that varied by demographics, diagnoses, and CAE + LAI protocols. We aimed to evaluate CAE + LAI adherence outcomes in SMI by pooling three studies to better understand response to treatment in the setting of varied circumstances. Our findings show that adherence improved similarly across studies despite these differences. Furthermore, it was demonstrated that CAE + LAI improved adherence to a similar degree when primary mood and psychotic disorder cohorts were compared. As the use of LAI expands, our findings show the versatility and effectiveness of including CAE to further optimize adherence and improve other outcomes., (Copyright © 1964–2022 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

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: 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., (© 2022. The Author(s).)

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 Multilevel Facilitation of Long-Acting Antipsychotic Medication Program (MAP) is a novel intervention to increase the appropriate use of long-acting injectable (LAI) antipsychotics in community mental health clinics. The authors investigated the feasibility of MAP, facilitators and barriers to use, and preliminary impact on LAI medication use., Methods: Two clinics in Texas and two in Ohio serving 750 and 617 individuals with schizophrenia receiving oral antipsychotics, respectively, were asked to change clinical procedures for 1 year by using either the not receiving optimum benefit (NOB) checklist or the checklist plus MAP. Providers used the NOB checklist to identify individuals who could benefit from switching to LAI antipsychotics. MAP clinics used the NOB checklist plus nonbranded academic detailing for providers and a shared-decision-making video and tool for consumers. Use of MAP components was tracked, and barriers and facilitators were collected quarterly. Antipsychotic prescription counts were provided by participating clinics., Results: Barriers to use of MAP included loss of local champions and administrators, difficulty with provider buy-in, limited availability of peer specialists, and a lack of infrastructural support to integrate MAP into clinic flow. Higher scores on the NOB checklist were associated with more provider LAI medication offers and greater patient acceptance of LAI antipsychotics. LAI medication use increased in clinics over time, but it is unclear whether this increase was due to MAP., Conclusions: Changing MAP components to fit local procedures and to circumvent unique barriers could aid implementation. Further research should investigate the potential impact of MAP components on LAI medication use.

Purpose: There is limited evidence on the use of antipsychotic medications to treat people with schizophrenia in Sub-Saharan Africa (SSA). This systematic literature review identified original research on use of antipsychotic drugs for primary psychotic disorders in SSA, assessed the methodological quality of studies, summarized intervention strategies, and examined patient-level outcomes., Methods: PubMed, PsychInfo, Cochrane Collaboration, African Journals Online, and CINAHL databases were searched for studies in SSA that focused on antipsychotic treatment for primary psychotic disorders and that investigated at least one patient-level outcome. Articles in English and published before April 2019 were included. Epidemiological studies, drug discontinuation studies, studies with drugs other than antipsychotics, and multicenter studies that did not specify SSA results were excluded. An adapted standardized instrument assessed methodological quality., Results: Twenty-six articles were reviewed. Three levels of evidence were found: single-group reports, quasi-experimental studies, and randomized controlled trials. Study outcomes included change in psychiatric symptoms, adverse effects, remission rates, or change in functional status. Nine studies reported improvements in psychiatric symptoms with antipsychotic medication. Seven studies investigating adverse effects of antipsychotics found that they were associated with an increase in metabolic syndrome. Two studies reported that remission was achieved in most subjects, and one study reported improvements in functional status., Conclusions: Despite adverse effects, treatment with antipsychotic medications may be beneficial for individuals with primary psychotic disorders in SSA. Apart from South Africa, there is a scarcity of research on antipsychotics from countries in SSA, and there are numerous important gaps in the literature.

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.

Objective: A nominal group process followed by a modified Delphi method was used to survey expert opinions on best practices for tardive dyskinesia (TD) screening, diagnosis, and treatment and to identify areas lacking in clinical evidence., Participants: A steering committee of 11 TD experts met in nominal group format to prioritize questions to be addressed and identify core bibliographic materials and criteria for survey panelists. Of 60 invited experts, 29 (23 psychiatrists and 6 neurologists) agreed to participate., Evidence: A targeted literature search of PubMed (search term: tardive dyskinesia) and recommendations of the steering committee were used to generate core bibliographic material. Inclusion criteria were as follows: (1) review articles, meta-analyses, guidelines, or clinical trials; (2) publication in English between 2007 and 2017; (3) > 3 pages in length; and (4) publication in key clinical journals with impact factors ≥ 2.0. Of 29 references that met these criteria, 18 achieved a score ≥ 5 (calculated as the number of steering committee votes multiplied by journal impact factor and number of citations divided by years since publication) and were included., Consensus Process: Two survey rounds were conducted anonymously through electronic media from November 2017 to January 2018; responses were collected, collated, and analyzed. Respondent agreement was defined a priori as unanimous (100%), consensus (75%-99%), or majority (50%-74%). For questions using a 5-point Likert scale, agreement was based on percentage of respondents choosing ≥ 4 ("agree completely" or "agree"). Round 1 survey included questions on TD screening, diagnosis, and treatment. Round 2 questions were refined per panelist feedback and excluded Round 1 questions with < 25% agreement and > 75% agreement (unless feedback suggested further investigation)., Conclusions: Consensus was reached that (1) a brief, clinical assessment for TD should be performed at every clinical encounter in patients taking antipsychotics; (2) even mild movements in 1 body area may represent possible TD; (3) management requires an overall evaluation of treatment, including reassessment of antipsychotics and anticholinergics as well as consideration of vesicular monoamine transporter 2 (VMAT2) inhibitors; and (4) informed discussions with patients/caregivers are essential., (© Copyright 2020 Physicians Postgraduate Press, Inc.)

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.)

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.)

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.

Objective: While a number of articles have reviewed the use of long-acting injectable antipsychotics (LAIs) in first-episode psychosis, there has been extremely limited focus on LAIs in children and adolescents. This review of the literature evaluated use of LAIs in children and youth under the age of 18., Methods: We conducted a comprehensive search of the PubMed, PsychINFO, CINAHL, and EMBASE databases using keywords related to LAIs, children, and psychiatric conditions, including schizophrenia, bipolar disorder, and schizoaffective disorder. Reports were included if they were in English, conducted between 1971 and 2015, and reported on use of LAIs in individuals less than the age of 18., Results: The search identified seven reports including one open-label trial, three case reports, and three case series. No controlled trials were found. Sample sizes ranged from 1 to 19 with a total of 36 individuals in all cases combined. Mean sample age was 12.1 ± 2.2 in the open-label trial and calculated to be 14.9 ± 1.5 in the remainder of the reports. Most patients (80.6%) were boys. Primary diagnoses included bipolar I disorder (n = 18; 50%), schizophrenia (n = 7; 19.4%), and bipolar spectrum disorders (n = 6; 16.6%). The LAIs used were risperidone long-acting injection (n = 24; 66.7%), paliperidone palmitate (n = 8; 22.2%), fluphenazine decanoate (n = 1; 2.8%), aripiprazole extended-release injectable (n = 1; 2.8%), zuclopenthixol decanoate (n = 1; 2.8%), and olanzapine extended release (n = 1; 2.8%). Most cases reported clinical improvement and the majority of individuals (n = 14; 82.4%) were reported to tolerate the medication well. The most common side effects were weight gain (mean 5.7 ± 4.1 kg in the open-label trial), tremor (n = 2; 5.6%), and oculogyric crisis (n = 2; 5.6%)., Conclusions: This literature review suggests that LAI use in youth with serious mental illness may improve clinical outcomes and adherence. Side effects of LAIs among youth appear are similar to oral preparations. However, there is a paucity of data despite issues with nonadherence in youth and the fact that they have much to lose and much to gain. Existing reports have substantial methodological limitations, and research is needed to guide the use of LAIs in children and adolescents.

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.)

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., (Copyright © 2014 John Wiley & Sons, Ltd.)

Objective: A three-month prospective trial of a psychosocial intervention--customized adherence enhancement (CAE)--was conducted with 43 medication-nonadherent individuals with bipolar disorder., Methods: CAE modules were administered as indicated by a screen that identifies reasons for nonadherence. The primary outcome was change in adherence to mood-stabilizing medications as measured by the Tablet Routines Questionnaire and pill counts. Secondary outcomes included change in symptoms, measured by the Hamilton Rating Scale for Depression (HAM-D), Young Mania Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS)., Results: Participants completed 76% of sessions. Dropout at three months was 13 (30%). Adherence improved from a baseline mean±SD of 34%±27% of tablets missed in the past month to only 10%±15% (p<.001). BPRS, HAM-D, andYMRS scores all indicated significant improvement at three-month follow-up (p<.05)., Conclusions: Although conclusions must be tempered by the uncontrolled design, CAE appeared to be well accepted and was associated with improvements in adherence, symptoms, and functioning.

Background: It has been demonstrated that 46% to 48% of individuals with bipolar disorder (BD) are at least partially nonadherent with prescribed medication. Reports of whether male gender is a predictor of treatment nonadherence in BD have been inconsistent. The construct of gender may also be a matter of cultural orientation, and psychological gender, as a component of self-perception, may affect the experience of mental illness. Gender identity is the subjective experience of one's individuality as male or female., Objective: This cross-sectional study evaluated gender and gender identity among men and women with BD as they relate to self-reported medication treatment adherence., Methods: This secondary analysis of a larger study on treatment adherence evaluated men and women with BD being treated with mood-stabilizing medications in a community mental health clinic. Gender identity and treatment adherence were evaluated using the Bem Sex Role Inventory (BSRI) and the Tablets Routine Questionnaire, respectively. Other measures included assessing BD symptoms using the Hamilton Depression Rating Scale and mania symptoms using the Young Mania Rating Scale, as well as psychosocial support with the Interpersonal Support Evaluation List and locus of control with the Multidimensional Health Locus of Control Scale., Results: Mean age of the 70 men and 70 women with type I BD was 43.1 years for adherent patients and 40.8 years for nonadherent patients. Women with BD had mean scores on the BSRI consistent with general population norms, whereas men with BD had scores suggesting lower levels of self-perceived masculinity than population norms. There were no differences between men and women on adherence; however, men with high BSRI masculinity scores had less adherence than other men in the sample (P = 0.04). Lower scores on the "powerful others" dimension of locus of control were associated with lower adherence. For women, there was no relationship between BSRI masculinity scores and adherence., Conclusions: Gender identity in men with BD differed from general population norms and appeared to be related to adherence. Treatment approaches that are intended to optimize adherence need to consider the construct of gender identity or gender role. ClinicalTrials.gov ID: NCT00183495., (Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.)

Reflecting an increasing awareness of the importance of treatment adherence on outcomes in psychiatric populations, the National Institute of Mental Health (NIMH) convened a panel of treatment adherence researchers on September 27-28, 2007 to discuss and articulate potential solutions for dealing with methodological adherence research challenges. Panel discussions and presentations were augmented with targeted review of the literature on specific topics, with a focus on adherence to medication treatments in adults with serious mental illness. The group discussed three primary methodological areas: participants, measures, and interventions. When selecting patients for adherence-enhancing interventions (AEIs), a three-tier model was proposed that draws from the universal (targeting all patients receiving medication treatment for a specific condition, regardless of current adherence), selective (targeting patients at risk for nonadherence), and indicated (targeting patients who are currently nonadherent) prevention model and emphasizes careful patient characterization in relevant domains and appropriate matching of interventions to the selected population. Proposals were also made to reduce problematic selection biases in patient recruitment and retention. The panel addressed the pros and cons of various methods that can be used to measure adherence, and concluded that it is appropriate to use multiple measures whenever possible. Finally, the panel identified a broad range of intervention approaches, and conditions under which these interventions are likely to be most effective at reducing barriers to adherence and reinforcing adherence behavior.

Objective: Non-adherence to maintenance medication regimens is a major problem, limiting outcomes for many persons with bipolar disorder. The aim of this paper is to determine the most relevant aspects of adherence attitudes in a sample of bipolar patients selected for problems with adherence behavior., Methods: Among a larger sample of bipolar disorder patients participating in a prospective follow-up study (N = 140), a subsample of patients were selected for non-adherent behavior defined as missing ≥ 30% of medication during the past month (n = 27; 19.3%). Adherence attitudes were assessed with the Rating of Medication Influences scale (ROMI), a self-reported attitudinal measure assessing reasons for and against adherence. Multiple logistic regression models for non-adherence vs. adherence were estimated with each of the 19 ROMI items in the model, while controlling for sex, age, ethnicity, education, duration of illness, and substance abuse., Results: Mean score of ROMI items corresponding to reasons for treatment adherence was greater among adherent participants, whereas the mean score of ROMI items corresponding to reasons for treatment non-adherence was greater among nonadherent participants. The ROMI item identifying that the individual believes that medications are unnecessary had the strongest influence for non-adherence (p < 0.0001). This was followed by ROMI items corresponding to no perceived daily benefit (p = 0.0008), perceived change in appearance (p = 0.0057), and perceived interference with life goals (p = 0.0033). The ROMI item identifying fear of relapse was the strongest predictor for adherence (p = 0.0017)., Conclusions: Non-adherent patients with bipolar disorder differ from adherent patients with bipolar disorder on reasons for adherence and non-adherence. Utilization of tools that evaluate medication treatment attitudes, such as the ROMI or similar measures, may assist clinicians in the selection of interventions that are most likely to modify future treatment adherence.

Background: Subjective experience of illness is a critical component of treatment adherence in populations with bipolar disorder (BPD). This cross-sectional analysis examined clinical and subjective variables in relation to adherence in 140 individuals with BPD receiving treatment with mood-stabilizing medication., Methods: Nonadherence was defined as missing 30% or more of medication on the Tablets Routine Questionnaire, a self-reported measure of medication treatment adherence. Adherent and nonadherent groups were compared on measures of attitudes toward illness and treatment including the Attitudes toward Mood Stabilizers Questionnaire, the Insight and Treatment Attitudes Questionnaire, the Rating of Medication Influences, and the Multidimensional Health Locus of Control Scale., Results: Except for substance abuse comorbidity, adherent individuals (n = 113, 80.7%) did not differ from nonadherent individuals (n = 27, 19.3%) on clinical variables. However, nonadherent individuals had reduced insight into illness, more negative attitudes toward medications, fewer reasons for adherence, and more perceived reasons for nonadherence compared with adherent individuals. The strongest attitudinal predictors for nonadherence were difficulties with medication routines (odds ratio = 2.2) and negative attitudes toward drugs in general (odds ratio = 2.3)., Limitations: Results interpretation is limited by cross-sectional design, self-report methodology, and sample size., Conclusions: Comorbid substance abuse, negative attitudes toward mood-stabilizing medication, and difficulty managing to take medication in the context of one's daily schedule are primary determinants of medication treatment adherence. A patient-centered collaborative model of care that addresses negative attitudes toward medication and difficulty coping with medication routines may be ideally suited to address individual adherence challenges.

Background: This study investigated the effect on antipsychotic treatment adherence of combining quetiapine or risperidone with lithium, anticonvulsants, and/or antidepressants among bipolar individuals with predominantly manic/mixed or depressive symptoms., Methods: Treatment episodes with quetiapine or risperidone were identified from individuals with medical claims for bipolar/manic disorder. Multiple regression analysis was used to evaluate the impact of antipsychotic combinations on treatment adherence, as measured by intensity (medication possession ratio [MPR]) and treatment duration., Results: Among mixed/manic individuals, combination therapies were associated with lower antipsychotic MPRs than monotherapy (P< .05), with MPR decreasing with number of medications. Quetiapine showed a similar pattern among depressed individuals, whereas risperidone showed a weaker association. For both subgroups, antipsychotic combinations with anticonvulsants were associated with lower MPRs than combinations with lithium. For manic/mixed individuals, combining quetiapine with an anticonvulsant and lithium was associated with shorter treatment durations than quetiapine alone (P

Claims data were examined to evaluate the association between antipsychotic dose and treatment adherence among individuals with predominantly manic/mixed or depressed symptoms of bipolar disorder. Two measures of treatment adherence were used, intensity (medication possession ratio) and treatment duration (uncensored treatment episodes). Effects of higher antipsychotic doses on adherence were evaluated using multiple regression analysis. Dose effects on adherence intensity in subsequent (3-month) treatment stages were examined over 15 months. Antipsychotic treatment episodes (13 921) were analyzed. For manic/mixed individuals, risperidone, olanzapine, and typical antipsychotics showed reduced adherence intensity with higher doses in all treatment stages (P<0.05). Among depressed individuals, higher doses of olanzapine and typical antipsychotics were associated with reduced adherence intensity in all stages, with most associations reaching significance (P<0.05). Higher doses of quetiapine and risperidone were associated with increased adherence intensity in months 4-6 (P<0.05), but risperidone showed reduced intensity in months 7-9 (P<0.001). For all risperidone-treated or quetiapine-treated individuals, higher doses were associated with longer treatment durations (P<0.05). Higher doses of olanzapine and typical antipsychotics (and in manic/mixed individuals, risperidone as well) seem to adversely impact adherence intensity. Among depressed individuals, higher doses of quetiapine and risperidone are initially associated with increased adherence intensity.

Objectives: A post hoc analysis of pooled data from two quetiapine monotherapy clinical trials was conducted to evaluate the efficacy and tolerability of quetiapine therapy (twice daily, 400-800 mg/day) among bipolar manic adults aged 55 years and older. The primary efficacy endpoint was the change from baseline in Young Mania Rating Scale (YMRS) total score at Day 21. A secondary endpoint was change from baseline in YMRS score at Day 84., Methods: A total of 407 patients made up the safety population, consisting of 59 older adults (aged >or=55 years) and 348 younger adults. A total of 403 patients made up the efficacy population, consisting of 59 older adults and 344 younger adults. Efficacy outcomes were analyzed using covariance models (ANCOVA); descriptive statistics are presented for safety outcomes., Results: Both older and younger individuals treated with quetiapine had significant improvement from baseline on YMRS scores compared with placebo-treated patients. The older adult group demonstrated a sustained reduction in YMRS score compared with placebo that was apparent by Day 4 of treatment. For the quetiapine treatment groups, the most common adverse effects (at a frequency >or=10%) were dry mouth, somnolence, postural hypotension, insomnia, weight gain, and dizziness in older adults, and dry mouth, somnolence, and insomnia in younger adults. For the placebo treatment groups, insomnia was the most common adverse event in both older and younger adults., Conclusions: This secondary analysis suggests that quetiapine represents a potentially useful treatment option among older adults with bipolar I mania. Studies with a primary focus of geriatric bipolar mania, and including larger patient numbers, are needed to confirm these findings.

Objective: Clinical characteristics, adverse effects of medication, and treatment attitudes have been associated with adherence in bipolar populations in cross-sectional studies. The aim of this secondary analysis from a larger study was to identify the association between baseline variables and average treatment adherence over a subsequent three-year period., Methods: Veterans with bipolar disorder were evaluated on self-reported adherence status at baseline and every six months over a three-year period. The sample was dichotomized into two clinically relevant categories: those who were primarily adherent and those who were primarily nonadherent. Demographic and clinical variables were examined for the two groups of patients in relation to their average adherence over the three-year period., Results: The study recruited a sample of 306 persons with severe bipolar disorder. The sample was predominantly male (278 men, or 91%), with a mean+/-SD age of 46.6+/-10.1 years. A total of 240 individuals (78%) were largely adherent to treatment, and 37 individuals (12%) were largely nonadherent to treatment. Nonadherent individuals were less likely to be on intensive somatotherapy regimens (p=.001); experienced more barriers to care, including lack of telephone access (p<.05) and life obligations and commitments (p<.05); and had more prior suicide attempts (p=.003)., Conclusions: Nonadherent individuals with bipolar disorder received less intensive pharmacologic treatments, had more suicide attempts, and experienced more barriers to care than adherent individuals. Nonadherence may have system as well as patient components. Consideration of nonadherence as a function of both patient factors and system factors will enhance our ability to understand nonadherence and intervene more effectively.

Background: Up to 48% of patients with bipolar disorder are either nonadherent or partially adherent to antipsychotic drug treatment. Medication adherence may differ by bipolar disorder subtype., Objective: This study evaluated the association between antipsychotic treatment adherence and mental health care use among individuals with bipolar disorder with predominantly manic/mixed symptoms or predominantly depressive symptoms., Methods: Individuals with bipolar or manic disorder who had at least 1 medical claim with International Classification of Diseases, Ninth Revision, Clinical Modification codes 296.4-296.8 (bipolar disorder) or 296.0 or 296.1 (manic disorder) were identified from medical and pharmacy claims in the PharMetrics database for the period from January 1999 through December 2004. Adherence was measured by intensity (medication possession ratio [MPR]) and treatment duration. The association between adherence and health care use during and after antipsychotic treatment was evaluated using multiple regression analysis. The traditional P < 0.05 threshold was used for statistical significance; however, results that approached significance at P < 0.10 were also noted., Results: Claims data were examined for 13,941 antipsychotic treatment episodes occurring in 12,952 individuals with bipolar or manic disorder. Of these, 6153 treatment episodes occurred in 5711 individuals with predominantly manic/mixed symptoms, and 2617 occurred in 2381 individuals with predominantly depressive symptoms. The remaining 5171 treatment episodes occurred in 4860 individuals with unspecified bipolar disorder and were not included in the analysis. In individuals with manic/mixed symptoms, a higher MPR was associated with reduced total and outpatient mental health expenditures over subsequent stages of treatment (reduction in total expenditure per 1-point increment in MPR: $123-$439; P < 0.001). In individuals with predominantly depressive symptoms, the association between MPR and subsequent mental health expenditure reached statistical significance only in months 10-12, the 3rd of the 4 treatment segments examined (total mental health expenditure: -$714 [P < 0.001]; outpatient mental health expenditure: -$468 [P < 0.001]). A higher MPR was also associated with a lower likelihood of acute mental health care (inpatient hospitalization or an emergency department visit) in subsequent months in individuals with manic/mixed symptoms or depressive symptoms (odds ratio = 0.545 [95% CI, 0.30- 1.00] and 0.395 [95% CI, 0.14-1.12], respectively; both NS at the P < 0.05 threshold), and was not associated with mental health inpatient days. In both subgroups, a longer duration of treatment was associated with lower total and outpatient mental health expenditures during the 4 months after the termination of treatment (both, P < 0.01)., Conclusions: In these individuals with bipolar or manic disorder, improved adherence to antipsychotic treatment was associated with lower subsequent total and outpatient mental health care expenditures. This association was less pronounced in individuals with predominantly depressive symptoms than in those with predominantly manic/mixed symptoms.

Objective: Bipolar disorder in older adult populations has gained increasing attention due to the growing proportion of elderly in the United States and worldwide. A continuing unmet need is the identification of agents that are generally well-tolerated and effective in later life bipolar disorder. Aripiprazole is an atypical antipsychotic compound that is approved by the U.S. Food and Drug Administration for the treatment of bipolar mania and for the long-term treatment of bipolar disorder. This study is an open-label, prospective trial of aripiprazole therapy in 20 older adult patients with bipolar disorder., Method: Older adults with bipolar I disorder (confirmed by the Mini-International Neuropsychiatric Interview) who were currently suboptimally responsive to their prescribed medication treatments received 12 weeks of open-label aripiprazole added on to existing mood stabilizer medication treatment. Aripiprazole was initiated at 5 mg daily and increased as tolerated. Efficacy outcomes included psychopathology measures (the Young Mania Rating Scale [YMRS] and the Hamilton Rating Scale for Depression [HAM-D]), extrapyramidal symptoms, and a level of functioning measure (the Global Assessment Scale [GAS]). The study was conducted from April 2004 to June 2005., Results: Twenty older adults (mean age = 59.6 years, range 50-83 years) received aripiprazole therapy. Compared to baseline, individuals had significant reductions in mean depression scores (HAM-D baseline = 13.8, HAM-D end point = 6.1, p < .001), as well as mania scores (YMRS baseline = 8.6, YMRS end point = 3.9, p < .03). There were also significant improvements in functional status as measured by the GAS (p < .001). The mean +/- SD daily dose of aripiprazole was 10.26 +/- 4.9 mg/day. Overall, aripiprazole was adequately tolerated in this older adult population., Conclusion: Aripiprazole therapy may reduce symptoms in bipolar older adults, and it appears to be reasonably tolerated. However, larger, controlled trials are needed to confirm these preliminary findings.

Background: Few studies have evaluated medication adherence among older vs younger individuals with bipolar disorder (BPD). We compared adherence with antipsychotic medication among older (age 60 and older) and younger individuals using a large case registry (n = 73,964)., Methods: Adherence was evaluated using the medication possession ratio (MPR) for patients receiving antipsychotic medication., Results: Twenty six thousand five hundred and thirty younger individuals (mean age 46.9) and 6,461 older individuals (mean age 69.2) were prescribed antipsychotic medication. Among older individuals, 61.0% (n = 3,350) were fully adherent, while 19.0% (n = 1,043) were partially adherent and 20.0% (n = 1,098) were non-adherent. Among younger individuals, 49.5% (n = 10,644) were fully adherent, while 21.8% (n = 4,680) were partially adherent, and 28.7% (n = 6,170) were non-adherent. As with younger patients, comorbid substance abuse and homelessness predicted non-adherence among older patients with BPD., Conclusion: Older individuals with BPD were more adherent with antipsychotic medications compared to younger individuals. However, a substantial proportion (approximately 39%) of older patients with BPD still have difficulties with adherence., (Copyright (c) 2007 John Wiley & Sons, Ltd.)

Antipsychotic medications are clearly identified as important in the treatment of individuals with schizophrenia and with bipolar disorder. However, negative societal reaction related to having a serious mental illness and the socially undesirable side effects associated with antipsychotic medication treatment may combine to worsen stigma associated with treatment for mental illness. Specific stigmatizing effects of antipsychotic therapy may be difficult to evaluate independently from factors such as symptoms, insight into illness and side effects. Attitudes towards antipsychotic medication may be positive in individuals who recognize therapeutic drug effects, however other individuals may view medications negatively due to a sense of stigma. Stigma among individuals with bipolar disorder in relation to treatment with antipsychotic medication has not been well addressed in the literature. An additional concern among individuals with bipolar disorder who receive antipsychotic medications may be the notion that antipsychotics are 'schizophrenia drugs', and thus an inappropriate treatment for their condition. Antipsychotic medications can be stigmatizing for patients with serious mental illness, however the roots of stigma are extensive, and efforts to minimize stigma can only be successful when addressed by the individual with illness, their families and loved ones, treatment providers and society at large.

This study evaluated treatment adherence among patients with schizophrenia receiving atypical and typical antipsychotics. Claims data for 7017 treatment episodes of commercially insured patients with schizophrenia (ICD-9-CM) receiving antipsychotics, covering the period from January 1999 through August 2003, were assessed. Overall adherence was evaluated by adherence intensity (medication possession ratio) and treatment duration (length of treatment episode). Pair-wise comparisons of the individual atypicals and a combined group of leading typical antipsychotics were undertaken using multiple regression, adjusting for differing patient characteristics. Each atypical antipsychotic demonstrated a significantly higher adherence intensity than the combined typicals, while quetiapine demonstrated a significantly greater adherence intensity than risperidone and olanzapine. None of the atypicals showed treatment durations significantly different from the typicals. While the small improvements in adherence intensity among atypical agents do not appear to be clinically important, they may reflect an underlying, stronger tendency to use filled prescriptions.

Schizophrenia and schizoaffective disorder are prevalent in 1% of the adult population. The condition was thought to predominantly affect the young however recent studies have shown that the condition occurs in individuals throughout the life-span. The aim of this review is to discuss the role of atypical antipsychotics in treating schizoaffective disorder and schizophrenia in the elderly. The advent of atypical antipsychotics has made significant strides in the pharmacotherapy of schizophrenia in the elderly. They are as efficacious as conventional agents in reducing the positive symptoms, possibly some what more efficacious in reducing negative symptoms and appear to have a relatively safer adverse effect profile. However metabolic side affects particularly glucose abnormalities and weight gain, cerebrovascular effects, and mortality risk noted in dementia patients are gaining increasing attention. Appropriate monitoring for the metabolic side effects has been recommended by agencies such as the FDA (United States Food and Drug Administration), ADA (American Diabetic Association) and APA (American Psychiatric Association). Treatment of elderly patients is complicated by age related biological factors affecting drug response and presence of comorbid medical conditions and concomitant medication. Current research supports the role of atypical antipsychotics in the treatment of schizophrenia and schizoaffective disorder in the elderly. Despite advantages compared with conventional agents, challenges to successful therapy remain, even with these better tolerated agents.

Objectives: Atypical antipsychotic medications are a relatively new, increasingly prominent component of the treatment armamentarium for bipolar disorder. Information on adherence with antipsychotics among individuals with bipolar disorder in general, and atypical antipsychotics in particular, is currently quite limited. Using data from the VA National Psychosis Registry, we examined adherence with antipsychotic medications among patients with bipolar disorder (n = 73,964)., Methods: Antipsychotic medication adherence among veterans with bipolar disorder was evaluated using the medication possession ratio and categorizing patients into three groups: fully adherent, partially adherent and non-adherent. We compared characteristics of bipolar patients who received versus those who did not receive antipsychotic medication, and also identified predictors of poor adherence with antipsychotic medications., Results: Approximately 45% (n = 32,993) of all individuals with bipolar disorder were prescribed antipsychotic medication. Individuals who were prescribed antipsychotic medications were younger and more often had comorbid substance abuse or post-traumatic stress disorder compared to individuals with bipolar disorder who were not prescribed antipsychotic medication. Just over half (51.9%) of individuals appear to be fully adherent with antipsychotic medications, while 48.1% of individuals are either partially adherent or non-adherent with antipsychotic medications. Factors associated with treatment non-adherence were younger age, minority ethnicity, comorbid substance abuse and homelessness., Conclusions: Treatment non-adherence is a major issue for close to half of individuals with bipolar disorder prescribed antipsychotic medication. Additional studies are needed to better understand treatment adherence within the full range of pharmacologic therapies among individuals with bipolar disorder.

Objective: This retrospective claims-based study evaluated treatment adherence among patients with bipolar or manic disorder treated with atypical and typical antipsychotics., Method: Claims data for 18,158 antipsychotic treatment episodes in 15,224 commercially insured patients with bipolar or manic disorder (ICD-9-CM criteria), from January 1999 through August 2003, were evaluated. Overall adherence was measured by adherence intensity (medication possession ratio) and treatment duration (length of treatment episodes). Treatment-related factors that may affect medication adherence were also investigated. Pairwise comparisons of the individual atypicals and a combined group of leading typical antipsychotics were undertaken using multiple regression analysis adjusting for differing patient characteristics., Results: Adherence intensity with quetiapine was 3% greater than with the typicals combined (p=.002) and was greater than with risperidone or olanzapine by 4% (p<.001) and 2% (p=.001), respectively. Olanzapine (2%, p<.001) and ziprasidone (3%, p=.001) showed significantly greater adherence intensity than risperidone. Risperidone (p=.002), olanzapine (p=.055), and the typicals (p=.021) demonstrated negative associations between dose and adherence intensity, while quetiapine showed a nonsignificant trend for a positive association (p=.074). Quetiapine and risperidone had significantly longer treatment durations than the typicals combined (1.05 and 1.00 months, respectively, p<.001) and longer treatment durations than olanzapine (0.75 and 0.79 months, respectively, p<.001) or ziprasidone (0.78 months, p=.002 and 0.69 months, p=.003, respectively). Shorter treatment durations were associated with switching to other antipsychotics or remaining on or switching to other psychotropics (e.g., traditional mood stabilizers) only. All of the atypicals except ziprasidone were associated with a significantly lower likelihood of switching compared with the typicals (p<.05)., Conclusions: The claims-based findings of this study suggest that, for bipolar or manic disorder, quetiapine therapy may be associated with better treatment adherence than typical or some atypical antipsychotics. Estimated differences, however, were relatively small, particularly for adherence intensity.

Objective: Treatment nonadherence has been identified as an understudied, yet frequent, cause of relapse among patients with bipolar disorder. This study evaluated factors related to treatment adherence., Methods: This study was a cross-sectional analysis of patient characteristics, features of the patient-provider relationship, and barriers to care as they related to self-reported treatment adherence among veterans with bipolar disorder. Data were collected before patients were randomly assigned to treatment in a multicenter trial. Participants were enrolled in the study from 1997 to 2000., Results: This analysis found that individuals with bipolar disorder who were adherent to medication (N=113) differed from those who were not (N=71) on patient characteristics and variables related to the patient-provider relationship. Individuals with bipolar disorder who were not adherent to medication were more likely than those who were adherent to have a current substance use disorder. A past substance use disorder was not associated with treatment nonadherence. Adherence to medication was not predicted by symptoms, overall health status, functional level, or gender. Individuals who were adherent to medication took a greater number of different medications than those who were nonadherent., Conclusions: Treatment adherence is a multidimensional entity and includes not only patient characteristics but also factors related to patient-provider interactions. Therapeutic approaches that address or incorporate an individual's comorbid conditions and are able to optimize intensity of treatment may have the greatest effect on treatment adherence attitudes and behaviors.

Aims: This article investigates the subjective experience of the process of improvement and recovery from the point of view of persons diagnosed (according to research diagnostic criteria) with schizophrenia and schizo-affective disorders., Methods: A community study of persons using psychiatric services was conducted for a sample of ninety subjects taking atypical antipsychotic medications. Sociodemographic data and clinical ratings were collected to complement the qualitatively developed Subjective Experience of Medication Interview (SEMI), which elicits narrative data on everyday activities, medication and treatment, management of symptoms, expectations concerning recovery, stigma, and quality of life., Results: Recovery was observed through: (1) relatively low ratings of psychiatrically observed symptomatology through BPRS scores; (2) the subjective sense among the majority (77.4%) of participants that taking medication plays a critical role in managing symptoms and avoiding hospitalization; and (3) the subjective sense articulated by the vast majority (80%) that they would recover from their illness and that the quality of their lives would improve (70.6%)., Conclusion: The overall quality of improvement and recovery is best characterized as an incremental, yet definitively discernable, subjective process.

The authors review the literature on persistent sequelae of neuroleptic malignant syndrome (NMS). They highlight the clinical presentations, assessment, and management of persistent sequelae and stress the need to take preventive steps to minimize their occurrence. The authors conducted a Medline and PubMed search for papers on residual sequelae of NMS. They cross-referenced the available papers and "operationalized" the diagnostic criteria for persistent neuropsychiatric sequelae. A total of 31 cases of neuropsychiatric sequelae of NMS were identified. With reduction in mortality from NMS, persistent sequelae of NMS have assumed clinical importance. Long-term sequelae persist for weeks to months after amelioration of an acute episode. Individuals with a preexisting CNS insult are more predisposed to develop persistent sequelae. A high index of awareness for persistent sequelae is warranted because antipsychotics are widely used for psychiatric disorders besides schizophrenia. Awareness of such outcomes and the use of evidence-based strategies to minimize risk factors will help clinicians in reducing the persistent sequelae of NMS.

An emerging literature suggests that a collaborative care model, in which patients are active managers of their illness within a supportive social environment, is a beneficial approach for individuals with bipolar disorder. One aspect of treatment that is often suboptimal among individuals with bipolar disorder is treatment adherence. Establishing an ideal collaborative model may offer an opportunity to enhance treatment adherence among individuals with bipolar disorder. This paper presents results from a qualitative exploration of patients' attitudes towards the collaborative care model and how individuals with bipolar disorder perceive treatment adherence within the context of the collaborative care model. All participants were actively enrolled in outpatient treatment at a Community Mental Health Center and part of a larger study that evaluated the Life Goals Program, a manual-driven structured group psychotherapy for bipolar disorder that is based on the collaborative practice model. The Life Goals Program is designed to assist individuals to participate more effectively in the management of their bipolar illness and to improve their social and work-related problems. Individuals were queried regarding their opinions on the ingredients for an effective client-provider relationship. Quantitative data were collected on baseline treatment adherence as well. Individuals treated for bipolar disorder in a community mental health clinic identified 12 key elements that they felt were critical ingredients to a positive collaborative experience with their mental health care provider. The authors conceptualized these elements around 3 emerging themes: patient-centered qualities, provider-centered qualities, and interactional qualities. Individuals with bipolar disorder perceived the ideal collaborative model as one in which the individual has specific responsibilities such as coming to appointments and sharing information, whereas the provider likewise has specific responsibilities such as keeping abreast of current "state-of-the-arf" prescribing practices and being a good listener. Treatment adherence was identified as a self-managed responsibility within the larger context of the collaborative model. Individuals with bipolar disorder in this study placed substantial emphasis on the interactional component within the patient-provider relationship, particularly with respect to times when the individual may be more symptomatic and more impaired. It is important that clinicians and care providers gather information related to patients' perceptions of the patient-provider relationship when designing or evaluating services aimed at enhancing treatment adherence.

Objective: The efficacy and tolerability of mood stabilizers in older adults with bipolar disorder remains understudied. Authors retrospectively examined response to lamotrigine, lithium, and placebo in older (>or=age 55) adults with Bipolar I disorder (DSM-IV) who participated in two mixed-age, maintenance studies examining time to intervention for an emerging mood episode (manic/hypomanic/mixed or depressed) and drug tolerability., Methods: In all, 588 patients received double-blind lamotrigine (LTG, 100 mg-400 mg/day), lithium (Li, 0.8 mEq/L-1.1 mEq/L), or placebo (PBO); data from 98 older adults (LTG: 33, Li: 34, PBO: 31) were examined. Mean modal total daily doses were LTG 240 mg and Li 750 mg., Results: LTG significantly delayed time to intervention for any mood episode and for a depressive episode, compared with placebo. Li significantly delayed time to intervention for mania/hypomania/mixed compared with placebo. Back pain and headache were the most common adverse events during LTG treatment; rash: LTG, 3%; Li, 6%; and PBO, 0; no serious rash was reported. The most common adverse events (>10%) during lithium treatment were dyspraxia, tremor, xerostomia, headache, infection, amnesia, dizziness, diarrhea, nausea, and fatigue., Conclusion: Lamotrigine and lithium may be effective and well-tolerated maintenance therapies for older adults with Bipolar I depression.

Atypical antipsychotic medications are a relatively new, increasingly prominent component of the treatment armamentarium for bipolar disorder -- a development that provides more options for potentially improved outcomes for patients and families affected by bipolar disorder. The US Food and Drug Administration-approved bipolar indications for risperidone include monotherapy for the short-term treatment of acute manic or mixed episodes associated with bipolar I disorder and combination therapy with lithium or valproate for the short-term treatment of acute manic or mixed episodes associated with bipolar I disorder. Risperidone is also approved in over 30 countries worldwide for bipolar mania either as monotherapy, adjunct therapy, or both monotherapy and adjunct therapy. A number of controlled and open-label treatment trials have shown risperidone's efficacy and tolerability in the manic phase of bipolar disorder. Risperidone has also been reported to be useful in the longer-term treatment of bipolar disorder. This drug profile of risperidone for bipolar disorder will address the chemistry, pharmacodynamics, pharmacokinetics and metabolism of risperidone, clinical trials in bipolar disorder, postmarketing surveillance, safety, tolerability and regulatory issues. Finally, a discussion of potential future directions, a summary of key issues and information resources are provided.

Clinical research in geriatric psychopharmacology has been a relatively neglected focus compared with the wealth of information on younger populations, and there is a dearth of published, controlled trials. Similarly, these are limited data in the area of geriatric bipolar disorder. Although there is an absence of rigorous, evidence-based information, preliminary data on older adults with bipolar disorder suggest some promising treatment options and important differences in older versus younger patients with bipolar illness. Lithium, while widely utilised in younger populations, is often poorly tolerated in the elderly. Clinical evidence regarding use of antiepileptic compounds in late-life bipolar disorder is generally compiled from bipolar disorder studies in mixed populations, studies in older adults with seizure disorders, and studies on dementia and psychotic conditions other than bipolar disorder. Valproate semisodium and carbamazepine are widely prescribed compounds in older adults with bipolar disorder. However, the popularity of these compounds has occurred in context of an absence of evidence-based data. The atypical antipsychotics have expanded the treatment armamentarium for bipolar disorder in mixed populations and may offer particular promise in management of bipolar illness in older populations as well. Olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole are atypical antipsychotics that have been approved by the US FDA for the treatment of bipolar disorder; however, there are no published, controlled trials with atypical antipsychotics specific to mania in geriatric patients. Preliminary reports on the use of clozapine, risperidone, olanzapine and quetiapine suggest a role for the use of these agents in late-life bipolar disorder. Information with ziprasidone and aripiprazole specific to geriatric bipolar disorder is still lacking.

Objective: This retrospective analysis of a large Department of Veterans Affairs (VA) database evaluated differences in clinical presentation, health service use, and use of psychotropic medications between older and younger adults with bipolar disorder., Methods: The results presented in this article focus on veterans with bipolar disorder who were active in the VA's National Psychosis Registry in federal fiscal year 2001 (FY01)., Results: The registry listed 65,556 individuals as having bipolar disorder in FY01. In FY01, nearly 25 percent of veterans with bipolar disorder (more than 16,000 individuals) were aged 60 years or older, and more than 10 percent were aged 70 years or older. Elderly persons were hospitalized at similar or slightly lower rates than middle-aged persons but tended to have longer hospital stays. Use of outpatient services was also higher in older populations. Patterns of use of psychotropic medications indicated that valproate is the most commonly used mood-stabilizing agent in the VA, in use by 72.9 percent of patients who receive a mood stabilizer. Use of lithium is substantial as well, with more than 40 percent of patients taking this agent. In addition, just over 40 percent of all veterans with bipolar disorder receive antipsychotic medication., Conclusions: Bipolar disorder affects large numbers of veterans across the entire life span, and use of VA resources by this population becomes greater with advancing age. Data from this study provide new information about the unique treatment requirements and clinical presentations of older patients with bipolar disorder.

Atypical antipsychotic agents have a broad range of therapeutic efficacy, a relatively low incidence of causing extrapyramidal adverse effects, and a low tardive dyskinesia profile. This has led to very rapid growth in the use of these compounds as broad-spectrum psychotropic agents, and it has been reported that more than 70% of prescriptions for atypical antipsychotic medications are being used for conditions other than schizophrenia. In the area of bipolar disorder, in particular, atypical antipsychotic agents appear to positively affect illness outcome, and are considered potential first-line treatment agents. Quetiapine was approved by the US Food and Drug Administration in 1997, and is currently marketed in the US to treat schizophrenia. Aripiprazole was recently approved for the treatment of schizophrenia by the US Food and Drug Administration in late 2002, and is being used increasingly in clinical settings. Recent reports suggest that quetiapine and aripiprazole are valuable additions to the psychotropic armamentarium for the treatment of mood and anxiety disorders. Data from clinical trials and clinical reports are discussed herewith.

Background: The treatment of psychotic symptoms in patients with mood disorders is a complex challenge. Antipsychotic medications in these individuals may be associated with extrapyramidal symptoms (EPS), worsening of depression, and functional impairment. Atypical antipsychotics such as quetiapine and risperidone are associated with a decreased incidence of adverse events such as EPS. The objective of this study was to compare the efficacy and tolerability of quetiapine and risperidone for the treatment of depressive symptoms in outpatients with psychosis., Method: In this 4-month, multicenter, open-label trial, patients were randomly assigned in a 3:1 ratio of quetiapine to risperidone, and both drugs were flexibly dosed. Eligible patients had psychoses and demonstrated 1 of several DSM-IV diagnoses, including schizoaffective disorder, bipolar I disorder, major depressive disorder, delusional disorder, Alzheimer's dementia, schizophreniform disorder, vascular dementia, and substance abuse dementia. Patients were classified as mood disordered if they had bipolar disorder, major depressive disorder, or schizoaffective disorder. Efficacy was assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impressions scale. The Hamilton Rating Scale for Depression (HAM-D) was used to assess the level of depressive symptoms. The primary tolerability assessment was presence or absence of substantial EPS, defined as EPS severe enough to require an alteration in treatment., Results: A total of 554 patients were randomly assigned to quetiapine and 175 to risperidone. Mean doses at 16 weeks were 318 mg for quetiapine and 4.4 mg for risperidone. Although both agents produced improvements in mean HAM-D scores, quetiapine produced a greater improvement than risperidone in all patients (p =.0015). Within the mood-diagnosed population, incidences of both substantial EPS (p =.001) and at least moderate EPS (p =.0373) occurred significantly less frequently among patients taking quetiapine. For patients with non-mood diagnoses, incidences of substantial EPS were fewer for patients taking quetiapine than for those taking risperidone (p =.062); however, this was not statistically significant., Conclusion: These results suggest that quetiapine may be a useful agent in the management of depressive symptoms in patients with psychosis.

This study assessed symptoms, severity of illness functional level, insight into illness, and attitudes toward medication in a sample of psychiatric patients who were newly admitted to a state hospital. The patients were evaluated before and after treatment with atypical, conventional, or mixed (atypical plus conventional) antipsychotic medication regimens with the Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impression, the Global Assessment of Functioning, the Scale to Assess Unawareness of Mental Disorder, and the Drug Attitude Inventory. Overall, the patients showed significant improvement in symptoms, severity of illness, functional level, and insight into their illness during the course of hospitalization. Their attitudes toward medications changed minimally during treatment. Only the patients who were treated with conventional antipsychotics showed significant improvement in their attitudes toward medication. However, the change was not large enough to differentiate the conventional antipsychotic treatment group from the other treatment groups.

Background: It has been reported that 10% of all patients with bipolar disorder develop their illness after the age of 50, with bipolar disorder accounting for 5-19% of mood disorder presentations in the elderly. There has been a growing awareness regarding the manifestation of bipolar disorder among older adults due to both changes in national demographics, and developing sophistication in the treatment of bipolar illness. A persistent problem in our understanding of management of late life bipolar disorder is the paucity of research and rigorous published studies on the psychopharmacology of this condition., Objective: This paper reviews medication treatments, non-medication biological therapies, and psychosocial interventions for bipolar disorder in late life with a particular emphasis on age related modifiers of treatment., Methods: Findings are based upon review of the current literature., Results: There are multiple, significant gaps in our knowledge of bipolar disorder in late life which have important implications in the optimum treatment of elderly individuals with bipolar illness., Conclusion: There are a number of areas of needed future research in late life bipolar disorder., (Copyright 2002 John Wiley & Sons, Ltd.)