Long-Acting Injectable vs Oral Antipsychotics for Relapse Prevention in Schizophrenia: A Meta-Analysis of Randomized Trials

Background: While long-acting injectable antipsychotics (LAIs) are hoped to reduce high relapse rates in schizophrenia, recent randomized controlled trials (RCTs) challenged the benefits of LAIs over oral antipsychotics (OAPs). Methods: Systematic review/meta-analysis of RCTs that lasted ≥6 months comparing LAIs and OAPs. Primary outcome was study-defined relapse at the longest time point; secondary outcomes included relapse at 3, 6, 12, 18, and 24 months, all-cause discontinuation, discontinuation due to adverse events, drug inefficacy (ie, relapse + discontinuation due to inefficacy), hospitalization, and nonadherence. Results: Across 21 RCTs (n = 5176), LAIs were similar to OAPs for relapse prevention at the longest time point (studies = 21, n = 4950, relative risk [RR] = 0.93, 95% confidence interval [CI]: 0.80–1.08, P = .35). The finding was confirmed restricting the analysis to outpatient studies lasting ≥1 year (studies = 12, RR = 0.93, 95% CI:0.71–1.07, P = .31). However, studies using first-generation antipsychotic (FGA)-LAIs (studies = 10, RR = 0.82, 95% CI:0.69–0.97, P = .02) and those published ≤1991 (consisting exclusively of all 8 fluphenazine-LAI studies; RR = 0.79, 95% CI: 0.65–0.96, P = 0.02) were superior to OAPs regarding the primary outcome. Pooled LAIs also did not separate from OAPs regarding any secondary outcomes. Again, studies using FGA-LAIs and those published ≤1991 were associated with LAI superiority over OAPs, eg, hospitalization and drug inefficacy. Conclusions: In RCTs, which are less representative of real-world patients than naturalistic studies, pooled LAIs did not reduce relapse compared with OAPs in schizophrenia patients. The exceptions were FGA-LAIs, mostly consisting of fluphenazine-LAI studies, which were all conducted through 1991. Because this finding is vulnerable to a cohort bias, studies comparing FGA-LAI vs second-generation antipsychotics-LAI and LAI vs OAP RCTs in real-world patients are needed.Key words: antipsychotics, adherence, depot, long-acting injection, meta-analysis, relapse, schizophrenia, treatment discontinuation     

Predictors of Lack of Relapse After Random Discontinuation of Oral and Long-acting Injectable Antipsychotics in Clinically Stabilized Patients with Schizophrenia: A Re-analysis of Individual Participant Data

ObjectiveTo quantify the risk and predictors of relapse among individuals with schizophrenia randomly withdrawn from antipsychotic maintenance treatment.MethodsWe re-analyzed time-to-event and baseline predictors from placebo arms in five placebo-controlled randomized trials of antipsychotics (n = 688 individuals; 173 stabilized on oral antipsychotic [OAP] and 515 on long-acting injectables [LAI]) for relapse-prevention available in the Yale Open Data Access repository. Using a survival and Cox-proportional hazards regression analyses, we estimated survival rates of “relapse-free” individuals by the end of follow-up (median = 118 days, IQR = 52.0–208.0), the rate of study-confirmed relapse, and adjusted hazard ratios (aHR, 95% confidence intervals [CI]) associated with baseline predictors. We also estimated these parameters for individuals followed for >5 half-lives of the stabilizing antipsychotic, and studied predictors of “rebound psychosis” in OAP-stabilized participants, defined as occurring within 30 days of antipsychotic withdrawal.Results29.9% (95%CI = 23.2–38.5) remained relapse-free by the end of follow-up, 11.1% (95%CI = 5.65–21.9) among those OAP-stabilized, 36.4% (95%CI = 28.4–46.7) among those LAI-stabilized. The study-confirmed relapse rate was 45.2%, 62.4% among those OAP-stabilized and 39.4% among those LAI-stabilized. Predictors of relapse included smoking (aHR = 1.54, 95%CI = 1.19–2.00), female sex (aHR = 1.37, 95%CI = 1.08–1.79), and having been stabilized on OAPs vs LAIs (aHR = 3.56, 95%CI = 2.68–4.72). Greater risk of relapse on OAP persisted even after sufficient time had elapsed to clear antipsychotic plasma level among LAI-stabilized (aHR = 5.0, 95%CI = 3.5–7.1). “Rebound psychosis” did not show predictors.Conclusions and relevanceOur results corroborate the high relapse risk following antipsychotic withdrawal after symptom stabilization with limited patient-related predictors of safe treatment discontinuation. Stabilization with LAIs reduces the short-/medium-term relapse risk.     

Risks of all-cause death and completed suicide in patients with schizophrenia/schizoaffective disorder treated with long-acting injectable or oral antipsychotics: A population-based retrospective cohort study in Taiwan

BackgroundLong-acting injectable (LAI) antipsychotics improve medication adherence in patients with schizophrenia and extend the duration of therapeutic drug levels but with administration of an increased dose. Real-world mortality data in patients prescribed LAIs are lacking. We conducted a population-based cohort study to estimate and compare the incidence rates of all-cause death and completed suicide in patients with schizophrenia/schizoaffective disorder exposed to LAIs and oral antipsychotics.MethodsPatients with a diagnosis of schizophrenia/schizoaffective disorder between January 1, 2015 and November 30, 2019 were enrolled from the Taiwan National Health Insurance Research Database and linked to Death Registry records. Eligible patients were new antipsychotic users. Relative risks of death for each antipsychotic compared with oral paliperidone were evaluated using a Cox proportional hazard model adjusted for age, sex, Charlson Comorbidity Index, index year, bipolar or major depressive or other mood disorders, mental disorders due to drug use, and baseline hospitalization frequency.ResultsThere were 228,791.08 person-years of follow-up (mean 2.48 years). The incidence rates of all-cause death in users of LAI paliperidone administered monthly (PP1M) and every 3 months (PP3M) were 7.40/1,000 person-years (95% confidence interval 5.94–9.11) and 9.93 (5.88–15.79), respectively. The incidences of completed suicide were 2.03/1,000 person-years (1.32–2.99) and 3.10 (1.14–6.88), respectively. No significant associations were observed between PP1M and PP3M compared to oral paliperidone in incidences of all-cause death or for completed suicide.DiscussionNo increased risk of all-cause death or completed suicide was observed in users of antipsychotic LAIs, including PP1M and PP3M.     

Preventing the Second Episode: A Systematic Review and Meta-analysis of Psychosocial and Pharmacological Trials in First-Episode psychosis

Objective: The majority of first-episode psychosis (FEP) patients reach clinical remission; however, rates of relapse are high. This study sought to undertake a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the effectiveness of pharmacological and non-pharmacological interventions to prevent relapse in FEP patients. Methods: Systematic review and meta-analysis of RCTs. Results: Of 66 studies retrieved, 18 were eligible for inclusion. Nine studies investigated psychosocial interventions and 9 pharmacological treatments. The analysis of 3 RCTs of psychosocial interventions comparing specialist FEP programs vs treatment as usual involving 679 patients demonstrated the former to be more effective in preventing relapse (odds ratio [OR] = 1.80, 95% confidence interval [CI] = 1.31–2.48; P < .001; number needed to treat [NNT] = 10). While the analysis of 3 different cognitive-behavioral studies not specifically intended at preventing relapse showed no further benefits compared with specialist FEP programs (OR = 1.95, 95% CI = 0.76–5.00; P = .17), the combination of specific individual and family intervention targeted at relapse prevention may further improve upon these outcomes (OR = 4.88, 95% CI = 0.97–24.60; P = .06). Only 3 small studies compared first-generation antipsychotics (FGAs) with placebo with no significant differences regarding relapse prevention although all individual estimates favored FGAs (OR = 2.82, 95% CI = 0.54–14.75; P = .22). Exploratory analysis involving 1055 FEP patients revealed that relapse rates were significantly lower with second-generation antipsychotics (SGAs) compared with FGAs (OR = 1.47, 95% CI = 1.07–2.01; P < .02; NNT = 10). Conclusions: Specialist FEP programs are effective in preventing relapse. Cognitive-based individual and family interventions may need to specifically target relapse to obtain relapse prevention benefits that extend beyond those provided by specialist FEP programs. Overall, the available data suggest that FGAs and SGAs have the potential to reduce relapse rates. Future trials should examine the effectiveness of placebo vs antipsychotics in combination with intensive psychosocial interventions in preventing relapse in the early course of psychosis. Further studies should identify those patients who may not need antipsychotic medication to be able to recover from psychosis.     

Optimal Doses of Specific Antipsychotics for Relapse Prevention in a Nationwide Cohort of Patients with Schizophrenia

Background and HypothesisOptimal doses of most antipsychotics in the maintenance treatment of schizophrenia are unknown. We aimed to study the risk of severe relapse indicated by rehospitalization for different dose categories of 15 most frequently used antipsychotics in monotherapy in Finland. Study MethodsWe studied the risk of rehospitalization (Adjusted Hazard Ratio, aHR) associated with six antipsychotic monotherapy dose categories (as time-varying dose, measured in defined daily dose, DDDs/day) in a nationwide cohort of persons diagnosed with schizophrenia (n = 61 889), using within-individual analyses to eliminate selection bias. Study ResultsAmong the 15 most widely used antipsychotics, 13 had a U- or J-shaped dose-response curve, showing the lowest risks of relapse for doses of 0.6–<1.1 DDDs/day vs nonuse of antipsychotics. The exceptions were oral perphenazine (aHR = 0.72, 95% CI = 0.68–0.76, <0.6 DDDs/day), and olanzapine-long-acting injectable (LAI), which had the lowest aHR of any antipsychotic (aHR = 0.17, 95% CI = 0.11–0.25, 1.4–<1.6 DDDs/day). Certain risperidone and perphenazine doses <0.9 DDD/day were associated with 21%–45% lower risk of rehospitalization (P < .001) than the standard dose of 0.9–1.1 DDD/day (ie, 5 mg for risperidone and 30 mg for perphenazine). ConclusionsFor most antipsychotics, the risk of severe relapse was the lowest during use of standard dose. Our results suggest that olanzapine LAI is highly effective in dose ranges >0.9 DDD/day, and especially at 1.4–<1.6 DDDs/day (405 mg/4 weeks) associated with substantially lower risk of rehospitalization than any dose of any other antipsychotic. The current WHO standard dose definitions appear to be clearly too high for perphenazine and somewhat too high for risperidone.     

Antipsychotics Use Is Associated With Greater Adherence to Cardiometabolic Medications in Patients With Schizophrenia: Results From a Nationwide,Within-subject Design Study

BackgroundPeople with schizophrenia/schizoaffective disorder (schizophrenia) die early, largely due to cardiovascular-related mortality. Antipsychotics are associated with lower mortality. We aimed to explore whether antipsychotic use can reduce discontinuation of medications for cardiovascular risk factors and diseases (“cardiometacolic drugs”), using a within-study design controlling for subject-related factors.MethodsPersons diagnosed with schizophrenia between 1972 and 2014, aged <65 years at cohort entry were identified in Finnish national databases. Four subcohorts were formed based on cardiometabolic drug use during the follow-up period, 1996–2017, namely statin (n = 14,047), antidiabetic (n = 13,070), antihypertensive (n = 17,227), and beta-blocker (n = 21,464) users. To control for subject-related factors, including likelihood of adherence as a trait characteristic, we conducted a within-subject study comparing the risk of discontinuation of each cardiometabolic drug during periods on vs off antipsychotics within each subject. We also accounted for number of psychiatric and nonpsychiatric visits in sensitivity analyses.ResultsIn 52,607 subjects with schizophrenia, any antipsychotic use vs nonuse was associated with decreased discontinuation risk of antidiabetics (adjusted hazard ratio [aHR] = 0.56, 95% confidence interval [CI] = 0.47–0.66), statins (aHR = 0.61, 95%CI = 0.53–0.70), antihypertensives (aHR = 0.63, 95%CI = 0.56–0.71), and beta-blockers (aHR = 0.79, 95%CI = 0.73–0.87). Antipsychotics ranking best for discontinuation of all cardiometabolic drug categories were clozapine (aHR range = 0.34–0.55), followed by olanzapine (aHR = 0.43–0.71). For statins, aHRs ranged from aHR = 0.30 (95%CI = 0.09–0.98) (flupentixol-long-acting injectable (LAI) to aHR = 0.71 (95%CI = 0.52–0.97) (risperidone-LAI), for anti-diabetic medications from aHR = 0.37 (95%CI = 0.28–0.50) (clozapine) to aHR = 0.70 (95%CI = 0.53–0.92) (quetiapine), for antihypertensives from aHR = 0.14 (95%CI = 0.04–0.46) (paliperidone-LAI) to aHR = 0.69 (95%CI = 0.54–0.88) (perphenazine), for beta-blockers from aHR = 0.55 (95%CI = 0.48–0.63) (clozapine) to aHR = 0.76 (95%CI = 0.59–0.99) (perphenazine-LAI). The decreased risk of discontinuation associated with antipsychotic use somewhat varied between age strata. Sensitivity analyses confirmed main findings.DiscussionIn this national database within-subject design study, current antipsychotic use was associated with substantially decreased risk of discontinuation of statins, anti-diabetics, antihypertensives, and beta-blockers, which might explain reduced cardiovascular mortality observed with antipsychotics in people with schizophrenia.     

The Effect of Locally Administered Fibrinolytic Drugs Following Aneurysmal Subarachnoid Hemorrhage : A Meta-Analysis with Eight Randomized Controlled Studies

ObjectiveRapid dissolution of blood clots reduces vasospasm and hydrocephalus after subarachnoid hemorrhage (SAH), and locally administered fibrinolytic drugs (LAFDs) could facilitate the dissolution. However, the efficacy of LAFDs remains controversial. The aim of this meta-analysis was to determine the efficacy of LAFDs for vasospasm and hydrocephalus and in clinical outcomes. MethodsFrom PubMed, EMBASE, and Cochrane database, data were extracted by two authors. Meta-analysis was performed using a random effect model. Inclusion criteria were patients who had LAFDs with urokinase-type or recombinant tissue-plasminogen activator after SAH in comparison with medically untreated patients with fibrinolytic drugs. We only included randomized controlled trials (RCTs) in this analysis. The outcomes of interest were vasospasm, hydrocephalus, mortality, and 90-day unfavorable functional outcome. ResultsData from eight RCTs with 550 patients were included. Pooled-analysis revealed that the LAFDs were significantly associated with lower rates of vasospasm (LAFDs group vs. control group, 26.5% vs. 39.2%; odds ratio [OR], 0.48; 95% confidence interval [CI], 0.32–0.73); hydrocephalus (LAFDs group vs. control group, 26.0% vs. 31.6%; OR, 0.54; 95% CI, 0.32–0.91); and mortality (LAFDs group vs. control group, 10.5% vs. 15.7%; OR, 0.58; 95% CI, 0.34–0.99). The proportion of 90-day unfavorable outcomes was lower in the LAFDs group (LAFDs group vs. control group, 32.7% vs. 43.5%; OR, 0.55; 95% CI, 0.37–0.80). ConclusionThis meta-analysis with eight RCTs indicated that LAFDs were significantly associated with lower rates of vasospasm and hydrocephalus after SAH. Thus, LAFDs could consequently reduce mortality and improve clinical outcome after SAH.     

Long-Term Real-World Effectiveness of Pharmacotherapies for Schizoaffective Disorder

ObjectiveTo investigate the long-term real-world effectiveness of antipsychotics and other psychopharmacotherapies in the treatment of schizoaffective disorder (SCHAFF). MethodTwo nationwide cohorts of SCHAFF patients were identified from Finnish and Swedish registers. Within-individual design was used with stratified Cox regression. The main exposure was use of antipsychotics. Adjunctive pharmacotherapies included mood stabilizers, antidepressants, and benzodiazepines and benzodiazepine-related drugs. The main outcome was hospitalization due to psychosis. ResultsThe Finnish cohort included 7655 and the Swedish cohort 7525 patients. Median follow-up time was 11.2 years (IQR 5.6–11.5) in the Finnish and 7.6 years (IQR 3.8–10.3) in the Swedish cohort. Clozapine and long-acting injectable (LAI) antipsychotics were consistently associated with a decreased risk of psychosis hospitalization and treatment failure (psychiatric hospitalization, any change in medication, death) in both cohorts. Quetiapine was not associated with a decreased risk of psychosis hospitalization. Mood stabilizers used in combination with antipsychotics were associated with a decreased risk of psychosis hospitalization (Finnish cohort HR 0.76, 95% CI 0.71–0.81; Swedish cohort HR 0.84, 0.78–0.90) when compared with antipsychotic monotherapy. Combination of antidepressants and antipsychotics was associated with a decreased risk of psychosis hospitalization in the Swedish cohort (HR 0.90, 0.83–0.97) but not in the Finnish cohort (1.00, 0.94–1.07), and benzodiazepine use was associated with an increased risk (Finnish cohort HR 1.07, 1.01–1.14; Swedish cohort 1.21, 1.13–1.30). ConclusionsClozapine, LAIs, and combination therapy with mood stabilizers were associated with the best outcome and use of quetiapine and benzodiazepines with the worst outcome in the treatment of SCHAFF.     

Guideline-Concordant Antipsychotic Use and Mortality in Schizophrenia

Objective: To determine if care concordant with 2009 Schizophrenia Patient Outcomes Research Team (PORT) pharmacological recommendations for schizophrenia is associated with decreased mortality. Methods: We conducted a retrospective cohort study of adult Maryland Medicaid beneficiaries with schizophrenia and any antipsychotic use from 1994 to 2004 (N = 2132). We used Medicaid pharmacy data to measure annual and average antipsychotic continuity, to calculate chlorpromazine (CPZ) dosing equivalents, and to examine anti-Parkinson medication use. Cox proportional hazards regression models were used to examine the relationship between antipsychotic continuity, antipsychotic dosing, and anti-Parkinson medication use and mortality. Results: Annual antipsychotic continuity was associated with decreased mortality. Among patients with annual continuity greater than or equal to 90%, the hazard ratio [HR] for mortality was 0.75 (95% confidence interval [CI] 0.57–0.99) compared with patients with annual medication possession ratios (MPRs) of less than 10%. The HRs for mortality associated with continuous annual and average antipsychotic continuity were 0.75 (95% CI 0.58–0.98) and 0.84 (95% CI 0.58–1.21), respectively. Among users of first-generation antipsychotics, doses greater than or equal to 1500 CPZ dosing equivalents were associated with increased risk of mortality (HR 1.88, 95% CI 1.10–3.21), and use of anti-Parkinson medication was associated with decreased risk of mortality (HR 0.72, 95% CI 0.55–0.95). Mental health visits were also associated with decreased mortality (HR 0.96, 95% CI 0.93–0.98). Conclusions: Adherence to PORT pharmacological guidelines is associated with reduced mortality among patients with schizophrenia. Adoption of outcomes monitoring systems and innovative service delivery programs to improve adherence to the PORT guidelines should be considered.Key words: schizophrenia, antipsychotic continuity, mortality     

Comparative Effectiveness of Risperidone Long-Acting Injectable vs First-Generation Antipsychotic Long-Acting Injectables in Schizophrenia: Results From a Nationwide,Retrospective Inception Cohort Study

Objective: To compare in a generalizable sample/setting objective outcomes in patients receiving first-generation antipsychotic long-acting injectables (FGA-LAIs) or risperidone-LAI (RIS-LAI). Methods: Nationwide, retrospective inception cohort study of adults with International Classification of Diseases-10 schizophrenia using Danish registers from 1995 to 2009 comparing outcomes between clinician’s/patient’s choice treatment with FGA-LAIs or RIS-LAI. Primary outcome was time to psychiatric hospitalization using Cox-regression adjusting for relevant covariates. Secondary outcomes included time to all-cause discontinuation and psychiatric hospitalization in patients without LAI possession gap >28 days, and number of bed-days after psychiatric hospitalization. Results: Among 4532 patients followed for 2700 patient-years, 2078 received RIS-LAI and 2454 received FGA-LAIs (zuclopenthixol decanoate = 52.2%, perphenazine decanoate = 37.2%, haloperidol decanoate = 5.0%, flupenthixol decanoate = 4.4%, fluphenazine decanoate = 1.3%). RIS-LAI was similar to FGA-LAIs regarding time to hospitalization (RIS-LAI = 246.2±323.7 days vs FGA-LAIs = 276.6±383.3 days; HR = 0.95, 95% confidence interval (CI) = 0.87–1.03, P = 0.199) and time to all-cause discontinuation (RIS-LAI = 245.8±324.0 days vs FGA-LAIs = 287.0±390.9 days; HR = 0.93, 95% CI = 0.86–1.02, P = 0.116). Similarly, in patients without LAI discontinuation, RIS-LAI and FGA-LAIs did not differ regarding time to hospitalization (RIS-LAI = 175.0±268.1 days vs FGA-LAIs = 210.7±325.3 days; HR = 0.95, 95% CI = 0.86–1.04, P = 0.254). Finally, duration of hospitalization was also similar (incidence rate ratio = 0.97, 95% CI = 0.78–1.19, P = 0.744). Results were unchanged when analyzing only patients treated after introduction of RIS-LAI. Conclusions: In this nationwide cohort study, RIS-LAI was not superior to FGA-LAIs regarding time to psychiatric hospitalization, all-cause discontinuation, and duration of hospitalization. Given the cost of hospitalization and second-generation antipsychotic (SGA)-LAIs, these findings require consideration when making treatment choices, but also need to be balanced with the individual relevance of adverse effects/patient centered outcomes. In future, head-to-head trials and additional nationwide database studies including other SGA-LAIs is needed.Key words: schizophrenia, long-acting injectable, risperidone, first-generation antipsychotics, hospitalization, all-cause discontinuation, cohort study     

Sex and racial disparity in utilization and outcomes of t-PA and thrombectomy in acute ischemic stroke

Background/purpose: Racial/ethnic and sex disparity may occur in stroke throughout the continuum of care. Endovascular therapy (EVT) became standard of care in 2015 for eligible patients with acute ischemic stroke (AIS). We evaluated for racial and sex differences in t-PA and EVT utilization and outcomes in 2016 in the National Inpatient Sample.Methods: Treatment rates for t-PA, EVT, and t-PA+EVT and outcomes including home discharge, in-hospital mortality and prolonged length of stay (pLOS) were evaluated by sex and race. Multivariate survey-logistic regression was performed to evaluate outcomes.ResultsThe study had 468,630 patients – 49.3% men, 50.7% women; 69.3% whites, and 30.7% non-whites. There was no difference in treatment utilization by sex, women vs men for t-PA (7.65% vs 7.76%; aOR:1.02; 95% CI:0.97–1.07), EVT (1.74% vs 1.67%; aOR:1.09; 95% CI:0.99–1.20) and t-PA+EVT (0.57% vs 0.57%; aOR:1.01; 95% CI:0.85–1.21); and by race, non-white vs white for t-PA (7.62% vs 7.74%; aOR:0.98; 95% CI:0.93–1.05), EVT (1.62% vs 1.74%; aOR:0.91; 95% CI:0.78–1.07), and t-PA+EVT(0.59% vs 0.56%; aOR:1.05; 95% CI:0.84–1.30). Compared to men, women treated with t-PA had less home discharge (37.2% vs 46.3%; aOR:0.81; 95% CI:0.72–0.90), more in-hospital mortality (5.7% vs 3.9%; aOR:1.37; 95% CI:1.06–1.77) and less pLOS (8.3% vs 9.6%; aOR:0.82; 95% CI:0.69–0.98); women treated with EVT had less home discharge (15.8% vs 23.7%; aOR:0.69; 95% CI:0.52-0.91). Compared to whites, non-whites treated with t-PA had lower odds of home discharge (42.1% vs 41.6%; aOR:0.79; 95% CI:0.69–0.90), less in-hospital mortality (3.7% vs 5.3%; aOR:0.65; 95% CI:0.49–0.87), and higher pLOS (11.4% vs 7.9%; aOR:1.3; 95% CI:1.07–1.56); non-whites treated with EVT had less home discharge (18%vs 20.2%; aOR:0.70; 95% CI:0.51–0.97) and higher pLOS (35.1% vs 24%; aOR:1.52; 95% CI:1.16–1.99).Conclusion: Sex and racial disparity exists for outcomes of t-PA and EVT despite no difference in utilization rates.     

Decreased Health-Seeking Behaviors in People With Depressive Symptoms: The Korea National Health and Nutrition Examination Survey 2014, 2016, and 2018

ObjectiveThe purpose of this study was to investigate the effects of depressive symptoms on health-seeking behaviors using the large epidemiological study data of the Korea National Health and Nutrition Examination (KNHANES). MethodsData from the Korea National Health and Nutrition Examination Survey (KNHANES), which is a large-scale national survey, were used in this study. The Patient Health Questionnaire-9 (PHQ-9) was used to assess the depressive state of the participants. Specialized self-reported questionnaires that included questions about health-seeking behaviors were also performed. To examine the relationships between depression and health-seeking behaviors, complex sample logistic regression models with control for covariates were used. ResultsThere was a significant association between decreased health-seeking behaviors and depressive symptoms in adults (odds ratio [OR]: 3.11, 95% confidence interval [CI]: 2.44–3.96). The association was found to be especially strong in males (OR: 2.63, 95% CI: 1.69–4.10) versus in females (OR: 2.49, 95% CI: 1.90–3.27). With regard to age group, younger adults (19–44 years of age) showed the highest OR (OR: 3.07, 95% CI: 2.12–4.45). ConclusionOur findings support the idea that there is a significant association between health-seeking behaviors and depressive symptoms in the Korean population. These results suggest that individuals with decreased health-seeking behaviors could be evaluated for depressive symptoms.     

Dysphagia screening and pneumonia after subarachnoid hemorrhage: Findings from the Chinese stroke center alliance

Background and PurposeDysphagia is common and is associated with aspiration pneumonia. However, little is known about the prevalence of and factors influencing dysphagia screening (DS) and pneumonia after subarachnoid hemorrhage (SAH).MethodsWe used data on SAH patients admitted to 1476 hospitals from the China Stroke Center Alliance (CSCA) from August 2015 to July 2019 to analyze the rates of DS and pneumonia. We then conducted univariate and multivariable analyses to examine the relationship between DS and pneumonia.ResultsAmong 4877 SAH patients who were eligible for DS and had complete data on pneumonia status, 3527 (72.3%) underwent DS, and 1006 (20.6%) developed pneumonia. Compared with patients without pneumonia, patients with pneumonia were older (mean: 63.4 vs. 57.8 years of age), had lower Glasgow Coma Scale (GCS) scores at admission (mean: 13.5 vs. 14.3), were more likely to have dysphagia (15.2% vs. 3.3%), and were more likely to have undergone aneurysm isolation (19.1% vs. 10.0%). In multivariable analyses, factors independently associated with a higher risk of pneumonia were dysphagia [odds ratio (OR), 3.77; 95% confidence interval (CI), 2.85–4.98], age (OR, 1.50 per 10‐year increase; 95% CI, 1.40–1.60), male sex (OR, 1.23; 95% CI, 1.02–1.49), arrival at the hospital by emergency medical services (OR, 1.36; 95% CI, 1.16–1.58), nimodipine treatment (OR, 1.42; 95% CI, 1.11–1.81), endovascular embolization of aneurysms (OR, 1.23; 95% CI, 1.03–1.47), cerebral ventricular shunt placement (OR, 2.24; 95% CI, 1.41–3.54), and treatment at a higher grade hospital (OR, 1.44; 95% CI, 1.21–1.71).ConclusionMore than a quarter of patients with SAH did not have documented DS, while one‐fifth developed pneumonia. DS performance was associated with a lower risk of pneumonia. Randomized controlled trials may be needed to determine the effectiveness of DS.     

Long-term Continuity of Antipsychotic Treatment for Schizophrenia: A Nationwide Study

Schizophrenia often requires long-term treatment with antipsychotic medication. This study aims to measure the continuity of antipsychotic treatment over the course of illness in schizophrenia, as well as factors involved in the interruption of treatment. For this, we followed up a national cohort of first-episode psychosis patients in Finland for up to 18 years. Stratified Cox proportional hazards regressions were conducted for “within-participant” risk of discontinuation of subsequent treatments compared to the first, and by specific antipsychotic compared to oral olanzapine, the most prescribed antipsychotic in this cohort. Adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) were calculated. Among 3343 participants followed up for a mean of 8 years (SD = 4.93), the median number of continuous treatment episodes was 6 (interquartile range [IQR] = 3–11) with a median duration of 11.4 months (IQR = 5.3–25.6). In the first year after diagnosis, the incidence rate of treatment discontinuation was 30.12 (95% CI = 29.89–30.35) events per 100 participant-years, decreasing to 8.90 (95% CI = 8.75–9.05) in the 10th year. The risk of discontinuation progressively decreased over successive treatment episodes (aHR = 0.30; 95% CI = 0.20–0.46 for episodes after the 15th compared to the first). Individuals were 67% less likely to interrupt treatment with long-acting injectable than oral antipsychotics (aHR = 0.33; 95% CI = 0.27–0.41). Treatment for schizophrenia over the long term is often characterized by recurrent cycles of interruptions and reintroductions of antipsychotic medication, which is typically not recommended by management guidelines. Greater utilization of long-acting injectable formulations earlier in the course of illness may facilitate the continuity of antipsychotic treatment in schizophrenia.     

Hyperintense Vessel Sign in Large-Vessel Occlusion Stroke of Mild-to-Moderate Severity Ineligible for Recanalization

Background and PurposeThe impact of fluid-attenuated inversion recovery hyperintense vessels (FHVs) on outcomes in patients ineligible for recanalization therapy with large-vessel occlusion (LVO) is unclear. We investigated the impact of FHVs determined using the FHV–Alberta Stroke Program Early CT Score (ASPECTS) on clinical outcomes in patients with LVO stroke of mild-to-moderate severity ineligible for recanalization therapy.MethodsSixty-eight consecutive patients with M1-middle cerebral artery occlusion who underwent magnetic resonance imaging within 24 hours of symptom onset and were ineligible for recanalization were included. Patients were dichotomized into a severe-FHV group (FHV-ASPECTS ≤4; n=33) and a mild-FHV group (FHV-ASPECTS >4; n=35), and multiple logistic regression analysis was used to examine the relationships of FHV scores with early neurological deterioration (END) and an unfavorable 3-month outcome (modified Rankin Scale score ≥3).ResultsMean age was 66.2±13.5 years (mean±SD), and 30 (44%) were female. The severe-FHV group had a larger infarct volume (median, 5.5 mL vs. 3 mL) and more frequently exhibited the susceptibility vessel sign (30% vs. 3%) than the mild-FHV group. Ipsilateral old nonlacunar infarct was more frequent in the mild-FHV group than in the severe-FHV group (37% vs. 15%). The severe-FHV group had a fivefold higher risk of END (odds ratio [OR] 5.02, 95% confidence interval [CI] 1.36–18.45) and unfavorable outcome (OR 5.97, 95% CI 1.18–33.31, p=0.03) compared with the mild-FHV group.ConclusionsGreater FHV extent was associated with higher risk of END and unfavorable outcome in patients with LVO stroke of mild-to-moderate severity.     

Suicide Risk in Patients With Diabetes Varies by the Duration of Diabetes: The Korea National Health and Nutrition Examination Survey (2019)

Objective The objectives of this study were to investigate the suicide risk in diabetes patients and evaluate the variations in suicide risk by the duration of diabetes using a large population sample in South Korea. Methods Data from 6,296 adults in the 2019 Korea National Health and Nutrition Examination Survey were included. The suicidal ideation, suicide plans, and suicidal behavior of diabetes patients were compared to the general population. After classifying the patients into ≤1 year, 2 to 9 years, and ≥10 years of diabetes duration, we evaluated the relationship between the duration of diabetes and the suicide risk. Results Diabetes patients had higher prevalences of suicidal ideation (9.1%, p<0.001) and suicide plans (3.6%, p<0.001) than the general population. After adjusting for potential confounding factors, suicide plans (adjusted odds ratio [aOR]=2.926, 95% confidence interval [CI]=1.325–6.463) were significantly associated with diabetes. In the 2 to 9 years group of diabetes patients, we found an increase in the risk of suicidal ideation (aOR=2.035, 95% CI=1.129–3.670), suicide plans (aOR=3.507, 95% CI=1.538–7.996), and suicidal behavior (aOR=7.130, 95% CI=2.035–24.978) after adjusting for the covariates. However, no increases in suicide risk were observed ≤1 year and ≥10 years after diabetes diagnosis. Conclusion In adults, diabetes is associated with an increase in suicide risk. Suicide risk in diabetes patients showed an inverted U-shaped depending upon the duration of diabetes.     

The use of atypical antipsychotics in nursing homes

BACKGROUND: Use of atypical antipsychotics for "off-label" indications, such as behavioral and psychological symptoms of dementia, depression, and bipolar disorder, have been frequently reported, although not systematically studied. We describe the pattern of atypical antipsychotic use among nursing home residents and identify demographic and clinical correlates. METHOD: We conducted a cross-sectional study on 139,714 nursing home residents living in 1732 nursing homes in 5 U.S. states from Jan. 1, 1999, to Jan. 31, 2000. Data were obtained from the computerized Minimum Data Set (MDS) assessment records. RESULTS: Behavior problems associated with cognitive impairment were manifest in 86,514 residents, and, of these, 18.2% received an antipsychotic. Approximately 11% received an atypical antipsychotic, while 6.8% received a conventional agent. Clinical correlates of atypical antipsychotic use were Parkinson's disease (adjusted odds ratio [OR] = 1.57, 95% confidence interval [CI] = 1.34 to 1.84), depression (OR = 1.35, 95% CI = 1.24 to 1.46), antidepressant use (OR = 1.38, 95% CI = 1.27 to 1.49), Alzheimer's disease (OR = 1.21, 95% CI = 1.12 to 1.32), non-Alzheimer dementia (OR = 1.15, 95% CI = 1.07 to 1.24), and cholinesterase inhibitor use (OR = 1.74, 95% CI = 1.52 to 1.98). Severe functional impairment was inversely related to atypical antipsychotic use (OR = 0.76, 95% CI = 0.65 to 0.89). CONCLUSION: Atypical antipsychotics are now used more than conventional antipsychotic agents in U.S. nursing homes. Indications and dosages seem appropriate relative to labeling. Clinical and demographic differences between atypical and conventional antipsychotic users tend to be relatively small, suggesting that other factors may explain the choice of prescribing physicians. The impact of facility factors, economic forces, and physician characteristics needs to be investigated.     

Metabolic syndrome in outpatients receiving antipsychotic therapy in routine clinical practice: a cross-sectional assessment of a primary health care database.

OBJECTIVE: To determine the prevalence of metabolic syndrome (MS) in outpatients treated with antipsychotics included in a primary-health-care database. METHODS: A cross-sectional study was carried out assessing an administrative outpatients claim-database from 5 primary-health-centers. Subjects on antipsychotics for more than 3 months were included. The control group was formed by the outpatients included in the database without exposition to any antipsychotic drugs. MS was defined according to the modified NCEP-ATP III criteria, and required confirmation of at least 3 of the 5 following components: body mass index >28.8 kg/m(2), triglycerides >150 mg/ml, HDL-cholesterol <40 mg/ml (men)/<50mg/ml (women), blood pressure >130/85 mmHg, and fasting serum glucose >110 mg/dl. RESULTS: We identified 742 patients [51.5% women, aged 55.1 (20.7) years] treated with first- or second-generation antipsychotics during 27.6 (20.3) months. Controls were 85.286 outpatients [50.5% women, aged 45.5 (17.7) years]. MS prevalence was significantly higher in subjects on antipsychotics: 27.0% (95% CI, 23.8-30.1%) vs. 14.4% (14.1-14.6%); age- and sex-adjusted OR=1.38 (1.16-1.65, P<0.001). All MS components, except high blood pressure, were significantly more prevalent in the antipsychotic group, particularly body mass index >28.8 kg/m(2): 33.0% (29.6-36.4%) vs. 17.8% (17.6-18.1%), adjusted OR=1.63 (1.39-1.92, P<0.001), and low HDL-cholesterol levels: 48.4% (44.8-52.0%) vs. 29.3% (29.0-29.6%); adjusted OR=1.65 (1.42-1.93, P<0.001). Compared with the reference population, subjects with schizophrenia or bipolar disorder (BD), but not dementia, showed a higher prevalence of MS. CONCLUSIONS: Compared with the general outpatient population, the prevalence of MS was significantly higher in patients with schizophrenia or BD treated with antipsychotics.