Overview of late-onset psychoses.

BACKGROUND: Several etiologies can underlie the development of late-onset psychosis, defined by first psychotic episode after age 40 years. Late-onset psychosis is distressing to patients and caregivers, often difficult to diagnose and treat effectively, and associated with increased morbidity and mortality. METHODS: The literature was reviewed with searches in Pubmed, MEDLINE, and the Cochrane library. Search terms included "psychosis," "delusions," hallucinations," "late onset," "secondary psychoses," "schizophrenia," bipolar disorder," "psychotic depression," "delirium," "dementia," "Alzheimer's," "Lewy body," "Parkinson's, "vascular dementia," and "frontotemporal dementia." This overview covers the epidemiology, clinical features, neurobiology, and therapeutics of late-onset psychoses. RESULTS: Late-onset schizophrenia, delusional disorder, and psychotic depression have unique clinical characteristics. The presentation of late-onset psychosis requires investigation for underlying etiologies of "secondary" psychosis, which include neurodegenerative, metabolic, infectious, inflammatory, nutritional, endocrine, and medication toxicity. In delirium, psychosis is common but controlled evidence is lacking to support psychotropic medication use. Delusions and hallucinations are common in Alzheimer's disease, and hallucinations are common in Parkinson's disease and Lewy body dementia. Psychosis in dementia is associated with increased agitation and a poor prognosis. Although commonly used, no medications are currently approved for treating psychosis in dementia patients in the USA and nonpharmacological interventions need consideration. CONCLUSION: The plethora of possible causes of late-onset psychosis requires accurate diagnosis, estimation of prognosis, and cautious clinical management because older adults have greater susceptibility to the adverse effects of psychotropic medications, particularly antipsychotics. Research is warranted on developing and testing efficacious and safe treatments for late-onset psychotic disorders.

Generating comparative evidence on new drugs and devices before approval.

Fewer than half of new drugs have data on their comparative benefits and harms against existing treatment options at the time of regulatory approval in Europe and the USA. Even when active-comparator trials exist, they might not produce meaningful data to inform decisions in clinical practice and health policy. The uncertainty associated with the paucity of well designed active-comparator trials has been compounded by legal and regulatory changes in Europe and the USA that have created a complex mix of expedited programmes aimed at facilitating faster access to new drugs. Comparative evidence generation is even sparser for medical devices. Some have argued that the current process for regulatory approval needs to generate more evidence that is useful for patients, clinicians, and payers in health-care systems. We propose a set of five key principles relevant to the European Medicines Agency, European medical device regulatory agencies, US Food and Drug Administration, as well as payers, that we believe will provide the necessary incentives for pharmaceutical and device companies to generate comparative data on drugs and devices and assure timely availability of evidence that is useful for decision making. First, labelling should routinely inform patients and clinicians whether comparative data exist on new products. Second, regulators should be more selective in their use of programmes that facilitate drug and device approvals on the basis of incomplete benefit and harm data. Third, regulators should encourage the conduct of randomised trials with active comparators. Fourth, regulators should use prospectively designed network meta-analyses based on existing and future randomised trials. Last, payers should use their policy levers and negotiating power to incentivise the generation of comparative evidence on new and existing drugs and devices, for example, by explicitly considering proven added benefit in pricing and payment decisions.

Effectiveness of paliperidone palmitate vs haloperidol decanoate for maintenance treatment of schizophrenia: a randomized clinical trial.

IMPORTANCE: Long-acting injectable antipsychotics are used to reduce medication nonadherence and relapse in schizophrenia-spectrum disorders. The relative effectiveness of long-acting injectable versions of second-generation and older antipsychotics has not been assessed. OBJECTIVE: To compare the effectiveness of the second-generation long-acting injectable antipsychotic paliperidone palmitate with the older long-acting injectable antipsychotic haloperidol decanoate. DESIGN, SETTING, AND PARTICIPANTS: Multisite, double-blind, randomized clinical trial conducted from March 2011 to July 2013 at 22 US clinical research sites. Randomized patients (n = 311) were adults diagnosed with schizophrenia or schizoaffective disorder who were clinically assessed to be at risk of relapse and likely to benefit from a long-acting injectable antipsychotic. INTERVENTIONS: Intramuscular injections of haloperidol decanoate 25 to 200 mg or paliperidone palmitate 39 to 234 mg every month for as long as 24 months. MAIN OUTCOME MEASURES: Efficacy failure, defined as a psychiatric hospitalization, a need for crisis stabilization, a substantial increase in frequency of outpatient visits, a clinician's decision that oral antipsychotic could not be discontinued within 8 weeks after starting the long-acting injectable antipsychotics, or a clinician's decision to discontinue the assigned long-acting injectable due to inadequate therapeutic benefit. Key secondary outcomes were common adverse effects of antipsychotic medications. RESULTS: There was no statistically significant difference in the rate of efficacy failure for paliperidone palmitate compared with haloperidol decanoate (adjusted hazard ratio, 0.98; 95% CI, 0.65-1.47). The number of participants who experienced efficacy failure was 49 (33.8%) in the paliperidone palmitate group and 47 (32.4%) in the haloperidol decanoate group. On average, participants in the paliperidone palmitate group gained weight and those in the haloperidol decanoate group lost weight; after 6 months, the least-squares mean weight change for those taking paliperidone palmitate was increased by 2.17 kg (95% CI, 1.25-3.09) and was decreased for those taking haloperidol decanoate (-0.96 kg; 95% CI, -1.88 to -0.04). Patients taking paliperidone palmitate had significantly higher maximum mean levels of serum prolactin (men, 34.56 µg/L [95% CI, 29.75-39.37] vs 15.41 µg/L [95% CI, 10.73-20.08]; P <.001, and for women, 75.19 [95% CI, 63.03-87.36] vs 26.84 [95% CI, 13.29-40.40]; P<.001). Patients taking haloperidol decanoate had significantly larger increases in global ratings of akathisia (0.73 [95% CI, 0.59-0.87] vs 0.45 [95% CI, 0.31-0.59]; P=.006). CONCLUSIONS AND RELEVANCE: In adults with schizophrenia or schizoaffective disorder, use of paliperidone palmitate vs haloperidol decanoate did not result in a statistically significant difference in efficacy failure, but was associated with more weight gain and greater increases in serum prolactin, whereas haloperidol decanoate was associated with more akathisia. However, the CIs do not rule out the possibility of a clinically meaningful advantage with paliperidone palmitate. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01136772.

Comparing brief video interventions to reduce public and self-stigma: Randomized control trial.

AIM: Stigma is a major mental healthcare barrier. This study compares the efficacy of two types of brief video interventions, targeting public and self-stigma, in reducing public stigma towards people living with psychosis. We hypothesized both interventions would similarly reduce public stigma and outperform the control group. As a secondary analysis, we explored the effect of familiarity with a person living with serious mental illness (SMI). METHODS: Participants (N = 1215) aged 18-35 recruited through crowdsourcing were assessed pre- and post-intervention and at 30-day follow-up regarding five public stigma domains: social distance, stereotyping, separateness, social restriction and perceived recovery. Both videos present individual narratives using different approaches: the self-stigma video was created through focus groups, while the public stigma video portrays a single person's journey. RESULTS: A 3 × 3 analysis of variance (ANOVA) revealed a significant group-by-time interaction across all five stigma-related domains (p's < .001). Effect sizes (Cohen's d) ranged from 0.29 to 0.52 (baseline to post-intervention), and 0.18 to 0.45 (baseline to 30-day follow-up). The two video interventions did not significantly differ. Linear mixed modelling showed a significant difference between participants familiar and unfamiliar with people living with SMI for the public stigma video, with greater stigma reductions for unfamiliar participants. CONCLUSIONS: This study corroborates previous findings on the positive influence of social contact-based interventions on youth mental health perceptions. Results provide insights into the relationship between public and self-stigma and the impact that familiarity with SMI may have on the efficacy of stigma reduction efforts further validation in diverse groups is needed.

National Cohort Data Suggests an Association Between Serious Mental Illness and Audiometric Hearing Loss.

OBJECTIVE: To explore whether there is an association between serious mental illness (SMI) and hearing loss (HL) among US Hispanic adults. STUDY DESIGN AND SETTING: Cross-sectional epidemiological study (Hispanic Community Health Study), including multicentered US volunteers. METHODS: Multivariable linear regressions were conducted to study the association between SMI and HL. Adjustments were made for potential confounders including age, sex, education, vascular disease (hypertension or diabetes mellitus), and cognition. SMI was defined by (1) antipsychotic medication classification and (2) the use of at least 1 antipsychotic medication specifically used to treat SMI in clinical psychiatric practice. HL was measured by pure tone audiometry. RESULTS: A total of 7581 subjects had complete data. The mean age was 55.2 years (SD = 7.5 years) and the mean pure tone average in the better ear was 16.8 dB (SD = 10.7 dB). A total of 194 (2.6%) subjects were taking a HCHS-defined antipsychotic and 98 (1.3%) were taking at least 1 antipsychotic specifically used to treat SMI. On multivariable regression, use of HCHS's classified antipsychotics was associated with 3.75 dB worse hearing (95% confidence interval [CI] = 2.36-5.13, P < .001) and use of antipsychotics specific for SMI was associated with 4.49 dB worse hearing (95% CI = 2.56-6.43, P < .001) compared to those not using antipsychotics. CONCLUSION: SMI, as defined by either the use of HCHS-defined antipsychotics or the use of antipsychotic medication specific for SMI, is associated with worse hearing, controlling for potential confounders. Whether SMI contributes to HL, antipsychotic medication (through ototoxicity) contributes to HL, or whether HL contributes to SMI is unknown and warrants further investigation.

Randomized Controlled Trial of a Brief Video Intervention to Reduce Self-Stigma of Mental Illness.

Objective: Self-stigma, a phenomenon wherein individuals internalize self-directed negative stereotypes about mental illness, is associated with negative outcomes related to recovery. This randomized controlled study assessed the efficacy of a brief social contact-based video intervention in reducing self-stigma in a large sample of individuals ages 18-35 endorsing an ongoing mental health condition. We hypothesized that the brief video would reduce self-stigma.Methods: In January and February 2023, we recruited and assigned 1,214 participants to a brief video-based intervention depicting a young individual living with mental illness sharing his personal story or to a non-intervention control. In the 2-minute video, informed by focus groups, a young individual described struggles with mental illness symptoms; this was balanced with descriptions of living a meaningful and productive life. Self-stigma assessments (Stereotype Endorsement, Alienation, Stigma Resistance, Perceived Devaluation Discrimination, Secrecy, and Recovery Assessment Scale) were conducted pre- and post-intervention and at 30-day follow-up.Results: A 2 ✕ 3 group-by-time analysis of variance showed that mean self-stigma scores decreased in the intervention arm relative to control across 5 of 6 self-stigma domains: Stereotype Endorsement (P = .006), Alienation (P < .001), Stigma Resistance (P = .004), Secrecy (P < .001), and Recovery Assessment Scale (P < .001). Cohen d effect sizes ranged from 0.22 to 0.46 for baseline to post-intervention changes. Baseline and 30-day follow-up assessments did not significantly differ.Conclusions: A 2-minute social contact-based video intervention effectively yielded an immediate but not a lasting decrease in self-stigma among young individuals with ongoing mental health conditions. This is the first study to examine the effect of a video intervention on self-stigma. Future trials of self-stigma treatment interventions should explore whether combining existing interventions with brief videos enhances intervention effects.Trial Registration: NCT05878470.

Means of suicide among adults with schizophrenia across the life span.

BACKGROUND AND HYPOTHESES: Adults with schizophrenia have increased risk of suicide with highest risk among younger adults. We investigated whether means of suicide among these adults were different from the general population. STUDY DESIGN: This retrospective longitudinal analysis used the National Death Index to characterize means of suicide among 4 cohorts of Medicare patients with schizophrenia (2007-2016) by age: 18 to 34, 35 to 44, 45 to 54, and aged 55+ years. Means of suicide were categorized by age at death and sex. Adjusted hazard ratios were calculated for common means. Mortality rates per 100,000 person-years were estimated by age group stratified by sex, and standardized to the general population by age, sex, and race-ethnicity using standardized mortality ratios. STUDY RESULTS: 668,836 adults were included with 2218 suicide decedents: 1444 men and 774 women. The most common means of suicide was poisoning (36.8 %), with a significant sex difference by means: 55.9 % of women died by poisoning, 13.8 % by firearms, 11.0 % by hanging and 9.4 % by jumping, while among men suicide by poisoning (26.6 %), firearms (25.5 %), and hanging (24.2 %) were similar, followed by jumping (12.0 %). Suicide by poisoning among the schizophrenia cohort was 10 times that of the general population, while suicide by firearm was twice that of the general population. CONCLUSIONS: Means of suicide differed for patients with schizophrenia compared to the general population: poisoning was the most common means among men and women with schizophrenia, while firearms accounted for over half of all suicides in the general U.S.

Self-stigma among people with serious mental illnesses: The use of focus groups to inform the development of a brief video intervention.

OBJECTIVE: People with mental illnesses may avoid or delay treatment due to a fear of labeling and discrimination, a phenomenon known as self-stigma. Self-stigma is a major barrier to care and creates obstacles to pursuing employment, independent living, and a fulfilling social life. We aimed to gather input from people with lived experience of mental illness to develop a social-contact-based, brief video-based intervention to reduce self-stigma. METHOD: Two (n = 12) focus groups were conducted to inform video content and led to the creation of a script and brief video using a professional actor, who described a story of living with schizophrenia while focusing on symptoms, personal struggles, and recovery. Two (n = 9) additional focus groups were held after video development to gather feedback and suggested edits. Focus group transcripts were analyzed using thematic content analysis. RESULTS: Themes emerging in prevideo development included the negative effects of being diagnosed with severe mental illnesses, being stereotyped, the value of relatable recovery stories and seeing the person as a whole, and the utility of focusing on symptoms and experiences rather than diagnosis-specific language. Feedback in the postvideo focus groups was mainly favorable and resulted in edits related to language about "responsibility" and a disclaimer about using a professional actor. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: While participants' experiences of stigma are consistent with extant literature, this is the first study to elicit the perspectives of people living with mental illnesses in developing a video intervention to reduce self-stigma. Studies are needed to examine the efficacy of these videos in reducing self/public stigma. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Variation in Psychotropic Medication Prescription for Adults With Schizophrenia in the United States.

OBJECTIVE: Variation in prescription of psychotropic medications to patients with schizophrenia spectrum disorders may underlie health inequities. Using a national U.S. Medicaid sample, the authors examined prescription patterns of psychotropic medications commonly used for managing schizophrenia. METHODS: Data from the 2011-2012 Medicaid Analytic eXtract were examined for demographic predictors of and variation across states in psychotropic medication prescription among adult patients diagnosed as having schizophrenia spectrum disorders (N=357,914). Percentages of patients in each state who filled prescriptions of at least 15 days of any antipsychotic, clozapine, antidepressant, benzodiazepine, mood stabilizer, or long-acting injectable (LAI) antipsychotic medication were determined after adjustment for demographic and clinical covariates. Multivariate regressions of clinical and demographic factors predicting prescription patterns were conducted. RESULTS: Prescribing patterns for all types of psychotropic medications varied across states. Clozapine and LAI prescriptions showed the most dramatic differences across states and among patients with different demographic characteristics. Across states, adjusted proportions of prescriptions ranged from 4% to 22% for LAIs and from 1% to 11% for clozapine. Non-Hispanic Blacks and people of other race-ethnicities were more likely than non-Hispanic Whites to fill prescriptions for LAIs, and non-Hispanic Whites were more likely than individuals from other racial-ethnic groups to fill prescriptions for clozapine and all other medications. CONCLUSIONS: Considerable variation in prescribing patterns of LAIs and clozapine by race-ethnicity and across states suggests uneven quality of care for individuals with schizophrenia spectrum disorders in the United States. A better understanding of what causes this variation could inform policy makers to improve treatment for this vulnerable population.

Development of the First Episode Digital Monitoring mHealth Intervention for People With Early Psychosis: Qualitative Interview Study With Clinicians.

BACKGROUND: Mobile health (mHealth) technologies have been used extensively in psychosis research. In contrast, their integration into real-world clinical care has been limited despite the broad availability of smartphone-based apps targeting mental health care. Most apps developed for treatment of individuals with psychosis have focused primarily on encouraging self-management skills of patients via practicing cognitive behavioral techniques learned during face-to-face clinical sessions (eg, challenging dysfunctional thoughts and relaxation exercises), reminders to engage in health-promoting activities (eg, exercising, sleeping, and socializing), or symptom monitoring. In contrast, few apps have sought to enhance the clinical encounter itself to improve shared decision-making (SDM) and therapeutic relationships with clinicians, which have been linked to positive clinical outcomes. OBJECTIVE: This qualitative study sought clinicians' input to develop First Episode Digital Monitoring (FREEDoM), an app-based mHealth intervention. FREEDoM was designed to improve the quality, quantity, and timeliness of clinical and functional data available to clinicians treating patients experiencing first-episode psychosis (FEP) to enhance their therapeutic relationship and increase SDM. METHODS: Following the app's initial development, semistructured qualitative interviews were conducted with 11 FEP treatment providers at 3 coordinated specialty care clinics to elicit input on the app's design, the data report for clinicians, and planned usage procedures. We then generated a summary template and conducted matrix analysis to systematically categorize suggested adaptations to the evidence-based intervention using dimensions of the Framework for Reporting Adaptations and Modifications-Enhanced (FRAME) and documented the rationale for adopting or rejecting suggestions. RESULTS: The clinicians provided 31 suggestions (18 adopted and 13 rejected). Suggestions to add or refine the content were most common (eg, adding questions in the app). Adaptations to context were most often related to plans for implementing the intervention, how the reported data were displayed to clinicians, and with whom the reports were shared. Reasons for suggestions primarily included factors related to health narratives and priorities of the patients (eg, focus on the functional impact of symptoms vs their severity), providers' clinical judgment (eg, need for clinically relevant information), and organizations' mission and culture. Reasons for rejecting suggestions included requests for data and procedures beyond the intervention's scope, concerns regarding dilution of the intervention's core components, and concerns about increasing patient burden while using the app. CONCLUSIONS: FREEDoM focuses on a novel target for the deployment of mHealth technologies in the treatment of FEP patients-the enhancement of SDM and improvement of therapeutic relationships. This study illustrates the use of the FRAME, along with methods and tools for rapid qualitative analysis, to systematically track adaptations to the app as part of its development process. Such adaptations may contribute to enhanced acceptance of the intervention by clinicians and a higher likelihood of integration into clinical care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04248517; https://tinyurl.com/tjuyxvv6.

Criminal justice system involvement among people with schizophrenia.

There is growing concern that people with schizophrenia and other severe mental illnesses are increasingly at risk for unnecessary criminal justice system (CJS) involvement. There has been limited examination, however, of which individual characteristics predict future CJS involvement. This study uses data from the Clinical Antipsychotic Trials of Intervention Effectiveness on sociodemograhic characteristics, baseline clinical status, and service use among patients diagnosed with schizophrenia to prospectively identify predictors of CJS involvement during the following year. A series of bivariate chi-square and F tests were conducted to examine whether significant relationships existed between CJS involvement during the first 12 months of the trial and baseline measures of sociodemographic characteristics, psychiatric status, substance abuse, and other patient characteristics. Multivariate logistic regression analysis was then used to identify the independent strength of the relationship between 12-month CJS involvement and potential risk factors that were found to be significant in bivariate analyses. Multivariate logistic regression analyses indicated that past adolescent conduct disorder, being younger and male, symptoms of Akathisia (movement disorder, most often develops as a side effect of antipsychotic medications), and particularly drug abuse increase the risk for CJS involvement. Since CJS involvement among people with schizophrenia was most strongly associated with drug abuse, treatment of co-morbid drug abuse could reduce the risk of stigma, pain, and other adverse consequences of CJS involvement as well as save CJS expenditures.

Suicide Risk in Medicare Patients With Schizophrenia Across the Life Span.

Importance: Although adults with schizophrenia have an increased risk of suicide, sample size limitations of previous research have hindered characterizations of suicide risk across the life span. Objective: To describe suicide mortality rates and correlates among adults with schizophrenia across the life span and standardized mortality ratios (SMRs) for suicide compared with the general US population. Design, Setting, and Participants: Five national retrospective longitudinal cohorts of patients with schizophrenia in the Medicare program from January 1, 2007, to December 31, 2016, were identified by age: 18 to 34, 35 to 44, 45 to 54, 55 to 64, and 65 years or older. Death record information was obtained from the National Death Index. The total cohort included 668 836 Medicare patients with schizophrenia, 2 997 308 years of follow-up, and 2218 suicide deaths. Data were analyzed from September 30, 2020, to March 10, 2021. Main Outcomes and Measures: For each age group, suicide mortality rates per 100 000 person-years and adjusted hazard ratios (aHRs) with 95% CIs of suicide were determined. Suicide SMRs were estimated for the total cohort and by sex and age cohorts standardized to the general US population by age, sex, and race/ethnicity. Results: The study population of adults 18 years and older included 668 836 Medicare recipients with schizophrenia (52.5% men, 47.5% women). The total suicide rate per 100 000 person-years was 74.00, which is 4.5 times higher than that for the general US population (SMR, 4.54; 95% CI, 4.35-4.73) and included a rate of 88.96 for men and 56.33 for women, which are 3.4 (SMR, 3.39; 95% CI, 3.22-3.57) and 8.2 (SMR, 8.16; 95% CI, 7.60-8.75) times higher, respectively, than the rates for the general US population. Suicide rates were significantly higher for men (aHR, 1.44; 95% CI, 1.29-1.61) and those with depressive (aHR, 1.32; 95% CI, 1.17-1.50), anxiety (aHR, 1.15; 95% CI, 1.02-1.30), drug use (aHR, 1.55; 95% CI, 1.36-1.76), and sleep disorders (aHR, 1.22; 95% CI, 1.07-1.39), suicidal ideation (aHR, 1.41; 95% CI, 1.22-1.63), and suicide attempts or self-injury (aHR, 2.48; 95% CI, 2.06-2.98). The adjusted hazards of suicide were lower for Hispanic patients (aHR, 0.66; 95% CI, 0.54-0.80) or Black patients (aHR, 0.29; 95% CI, 0.24-0.35) than White patients. The suicide rate declined with age, from 141.95 (SMR, 10.19; 95% CI, 9.29-11.18) for patients aged 18 to 34 years to 24.01 (SMR, 1.53; 95% CI, 1.32-1.77) for patients 65 years or older. The corresponding declines per 100 000 person-years were from 153.80 (18-34 years of age) to 34.17 (65 years or older) for men and from 115.70 (18-34 years of age) to 18.66 (65 years or older) for women. In the group aged 18 to 34 years, the adjusted hazards of suicide risk were significantly increased for patients with suicide attempt or self-injury (aHR, 2.57; 95% CI, 18.20-2.04) and with comorbid drug use disorders (aHR, 1.48; 95% CI, 1.17-1.88), but not with comorbid depressive disorders (aHR, 0.99; 95% CI, 0.38-1.26) during the year before the start of follow-up. Conclusions and Relevance: In this cohort study of adult Medicare patients with schizophrenia, suicide risk was elevated, with the highest absolute and relative risk among young adults. These patterns support suicide prevention efforts with a focus on young adults with schizophrenia, especially those with suicidal symptoms and substance use.

Mortality Risk of Antipsychotic Augmentation for Adult Depression.

(Reprinted with permission from PLOS ONE 2020).

Age-Specific Prevalence and Incidence of Dementia Diagnoses Among Older US Adults With Schizophrenia.

Importance: People with schizophrenia are at high risk of receiving a diagnosis of dementia. Understanding the magnitude and timing of this increased risk has important implications for practice and policy. Objective: To estimate the age-specific incidence and prevalence of dementia diagnoses among older US adults with schizophrenia and in a comparison group without serious mental illness (SMI). Design, Setting, and Participants: This retrospective cohort study used a 50% random national sample of Medicare beneficiaries 66 years or older with fee-for-service plans and Part D prescription drug coverage from January 1, 2007, to December 31, 2017. The cohort with schizophrenia included adults with at least 12 months of continuous enrollment in fee-for-service Medicare and Part D and at least 2 outpatient claims or at least 1 inpatient claim for schizophrenia during the qualifying years. The comparison group included adults with at least 12 months of continuous enrollment in fee-for-service Medicare and Part D and without a diagnosis of schizophrenia, bipolar disorder, or recurrent major depressive disorder during the qualifying year. Data were analyzed from January 1 to July 31, 2020. Main Outcomes and Measures: Dementia was defined using the Centers for Medicare & Medicaid Services Chronic Conditions Warehouse diagnosis codes for Alzheimer disease and related disorders or senile dementia. Incident diagnoses were defined by at least 12 consecutive eligible months without a qualifying code before meeting dementia criteria. Results: The study population of 8 011 773 adults 66 years or older (63.4% women; mean [SD] age, 74.0 [8.2] years) included 74 170 individuals with a diagnosis of schizophrenia (56.6% women) and 7 937 603 without an SMI diagnosis (63.5% women) who contributed 336 814 and 55 499 543 person-years of follow-up, respectively. At 66 years of age, the prevalence of diagnosed dementia was 27.9% (17 640 of 63 287) among individuals with schizophrenia compared with 1.3% (31 295 of 2 389 512) in the group without SMI. By 80 years of age, the prevalence of dementia diagnoses was 70.2% (2011 of 2866) in the group with schizophrenia and 11.3% (242 094 of 2 134 602) in the group without SMI. The annual incidence of dementia diagnoses per 1000 person-years at 66 years of age was 52.5 (95% CI, 50.1-54.9) among individuals with schizophrenia and 4.5 (95% CI, 4.4-4.6) among individuals without SMI and increased to 216.2 (95% CI, 179.9-252.6) and 32.3 (95% CI, 32.0-32.6), respectively, by 80 years of age. Conclusions and Relevance: In this cohort study, compared with older adults without SMI, those with schizophrenia had increased risk of receiving a diagnosis of dementia across a wide age range, possibly because of cognitive and functional deterioration related to schizophrenia or factors contributing to other types of dementia. High rates of dementia among adults with schizophrenia have implications for the course of illness, treatment, and service use.

Violence risk assessment for young adults receiving treatment for early psychosis.

AIM: Although the absolute risk of violence is small for individuals with mental illnesses, a specific subgroup of individuals who appear to be at increased risk for violence includes young people experiencing emerging or early psychosis. Prior research has identified risk factors for violence in this population, though no prior studies using a formal risk assessment tool have been identified. This study used the Historical Clinical Risk Management-20, version 3 (HCR-20) to identify risk of future violence among a sample of young adults with early psychosis and relevant predictors of risk unique to this population. METHODS: The HCR-20 was administered to a sample of young adults with early psychosis (N = 53) enrolled at one OnTrackNY site, part of a statewide program providing early intervention services to young adults presenting with a first episode of non-affective psychosis. A Confirmatory Factor Analysis (CFA) was conducted to explore the relative importance of the HCR-20 items for this population. RESULTS: The average age of participants was 21.9 years (SD 3.6 years) and most were male (69.8%, n = 37). Most patients were assessed to be at low risk for future violence based on the Case Prioritization summary risk rating (67.9%, n = 36). The CFA identified 4 items that were not of relative predictive value in identifying the risk of violence in this sample: history of substance use (item H5), history of major mental disorder (item H6), living situation (item R2), and personal support (item R3). CONCLUSION: This study presents a formal approach to assessing violence risk in a population at elevated risk of violence, demonstrates the feasibility of using a standardized risk assessment tool in early intervention services, and identifies factors of particular importance associated with predicting violence in this population. Future research should implement violence risk assessment with a structured tool such as the HCR-20 and assess its accuracy in predicting future violent behavior in this setting.

A candidate gene study of Tardive dyskinesia in the CATIE schizophrenia trial.

Tardive dyskinesia (TD) is a movement disorder characterized by involuntary oro-facial, limb, and truncal movements. As a genetic basis for inter-individual variation is assumed, there have been a sizeable number of candidate gene studies. All subjects met diagnostic criteria for schizophrenia and were randomized to receive antipsychotic medications as participants in the Clinical Antipsychotic Trials of Intervention Effectiveness project (CATIE). TD was assessed via the Abnormal Involuntary Movement Scale at regular intervals. Probable TD was defined as meeting Schooler-Kane criteria at any scheduled CATIE visit (207/710 subjects, 29.2%). A total of 128 candidate genes were studied in 710 subjects-2,580 SNPs in 118 candidate genes selected from the literature (e.g., dopamine, serotonin, glutamate, and GABA pathways) and composite genotypes for 10 drug-metabolizing enzymes. No single marker or haplotype association reached statistical significance after adjustment for multiple comparisons. Thus, we found no support for either novel or prior associations from the literature.

No association of the serotonin transporter polymorphisms 5-HTTLPR and RS25531 with schizophrenia or neurocognition.

A promoter polymorphism in the serotonin transporter gene has been widely studied in neuropsychiatry. We genotyped the 5-HTTLPR/rs25531 triallelic polymorphism in 728 schizophrenia cases from the CATIE study and 724 control subjects. In a logistic regression with case/control status as dependent variable and 7 ancestry-informative principal components as covariates, the effect of 5-HTTLPR/rs25531 composite genotype was not significant (odds ratio = 1.008, 95% CI 0.868-1.172, P = 0.91). In cases only, 5-HTTLPR/rs25531 was not associated with neurocognition (summary neurocognitive index P = 0.21, working memory P = 0.32) or symptomatology (PANSS positive P = 0.67 and negative symptoms P = 0.46). We were unable to identify association of the triallelic 5-HTTLPR with schizophrenia, neurocognition, or core psychotic symptoms even at levels of significance unadjusted for multiple comparisons.

A single assessment with the Brief Adherence Rating Scale (BARS) discriminates responders to long-acting injectable antipsychotic treatment in patients with schizophrenia.

OBJECTIVE: To determine if a single baseline adherence assessment (Brief Adherence Rating Scale [BARS]) could identify patients who are likely to respond to long-acting injectable (LAI) antipsychotic treatment. METHOD: The current secondary analysis included a sub-sample of adult outpatients (N = 176) with schizophrenia or schizoaffective disorder who participated in the "A Comparison of Long-Acting Injectable Medications for Schizophrenia (ACLAIMS)" trial and had a baseline BARS assessment and a baseline and month 3 Positive and Negative Syndrome Scale (PANSS) rating. The main outcome was LAI treatment response, defined as a ≥ 20% decrease (baseline to month 3) on the PANSS total score. Receiver Operating Characteristic (ROC) and Area Under the Curve (AUC) analysis was conducted to determine the optimal cutpoint of baseline BARS adherence in discriminating LAI treatment response at month 3. A logistic mixed model estimated the odds of response to LAI treatment at month 3 from the optimal baseline BARS cutpoint. RESULTS: The ROC analysis determined that the single baseline BARS rating (cutoff ≤66%), indicating low adherence, best discriminated patients likely to respond to LAI treatment (AUC = 0.603, SE = 0.046, 95% binomial exact CI = 0.527 to 0.676, p = 0.025), with 38% sensitivity and 85% specificity. The logistic mixed model analysis revealed that patients with ≤66% BARS adherence had 3.464 times the predicted odds (95% CI = 1.604 to 7.480, p = 0.001) of responding to LAI treatment than those who were >66% BARS adherent. CONCLUSION: A single baseline BARS assessment discriminated response to LAI treatment suggesting it is a reasonable tool to identify candidates for LAI antipsychotic treatment.

Mortality risk of antipsychotic augmentation for adult depression.

IMPORTANCE: Randomized controlled trials have demonstrated increased all-cause mortality in elderly patients with dementia treated with newer antipsychotics. It is unknown whether this risk generalizes to non-elderly adults using newer antipsychotics as augmentation treatment for depression. OBJECTIVE: This study examined all-cause mortality risk of newer antipsychotic augmentation for adult depression. DESIGN: Population-based new-user/active comparator cohort study. SETTING: National healthcare claims data from the US Medicaid program from 2001-2010 linked to the National Death Index. PARTICIPANTS: Non-elderly adults (25-64 years) diagnosed with depression who after ≥3 months of antidepressant monotherapy initiated either augmentation with a newer antipsychotic or with a second antidepressant. Patients with alternative indications for antipsychotic medications, such as schizophrenia, psychotic depression, or bipolar disorder, were excluded. EXPOSURE: Augmentation treatment for depression with a newer antipsychotic or with a second antidepressant. MAIN OUTCOME: All-cause mortality during study follow-up ascertained from the National Death Index. RESULTS: The analytic cohort included 39,582 patients (female = 78.5%, mean age = 44.5 years) who initiated augmentation with a newer antipsychotic (n = 22,410; 40% = quetiapine, 21% = risperidone, 17% = aripiprazole, 16% = olanzapine) or with a second antidepressant (n = 17,172). The median chlorpromazine equivalent starting dose for all newer antipsychotics was 68mg/d, increasing to 100 mg/d during follow-up. Altogether, 153 patients died during 13,328 person-years of follow-up (newer antipsychotic augmentation: n = 105, follow-up = 7,601 person-years, mortality rate = 138.1/10,000 person-years; antidepressant augmentation: n = 48, follow-up = 5,727 person-years, mortality rate = 83.8/10,000 person-years). An adjusted hazard ratio of 1.45 (95% confidence interval, 1.02 to 2.06) indicated increased all-cause mortality risk for newer antipsychotic augmentation compared to antidepressant augmentation (risk difference = 37.7 (95%CI, 1.7 to 88.8) per 10,000 person-years). Results were robust across several sensitivity analyses. CONCLUSION: Augmentation with newer antipsychotics in non-elderly patients with depression was associated with increased mortality risk compared with adding a second antidepressant. Though these findings require replication and cannot prove causality, physicians managing adults with depression should be aware of this potential for increased mortality associated with newer antipsychotic augmentation.