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Background and hypothesis Breast cancer is more prevalent in women with severe mental illness than in the general population, and use of prolactin-increasing antipsychotics may be a contributing factor. Study design A nested case–control study was conducted using the Swedish nationwide registers (inpatient/outpatient care, sickness absence, disability pension, prescribed drugs, cancers). All women aged 18–85 years with schizophrenia/schizoaffective/other nonaffective psychotic disorder/bipolar disorder and breast cancer (cases) were matched for age, primary psychiatric diagnosis, and disease duration with five women without cancer (controls). The association between cumulative exposure to prolactin-increasing/prolactin-sparing antipsychotics and breast cancer was analyzed using conditional logistic regression, adjusted for comorbidities and co-medications. Study results Among 132 061 women, 1642 (1.24%) developed breast cancer between 2010 and 2021, at a mean age of 63.3 ± 11.8 years. Compared with 8173 matched controls, the odds of breast cancer increased in women with prior exposure to prolactin-increasing antipsychotics for 1–4 years (adjusted odds ratio [aOR] = 1.20, 95% confidence interval [CI] = 1.03–1.41), and for ≥ 5 years (aOR = 1.47, 95%CI = 1.26–1.71). There were no increased or decreased odds of breast cancer with exposure to prolactin-sparing antipsychotics of either 1–4 years (aOR = 1.17, 95%CI = 0.98–1.40) or ≥5 years (aOR = 0.99, 95%CI = 0.78–1.26). The results were consistent across all sensitivity analyses (ie, according to different age groups, cancer types, and primary psychiatric diagnosis). Conclusions Although causality remains uncertain, exposure to prolactin-elevating antipsychotics for ≥ 1 year was associated with increased odds of breast cancer in women with severe mental illness. When prescribing antipsychotics, a shared decision-making process should consider individual risk factors for breast cancer. [ABSTRACT FROM AUTHOR]

Background and Hypothesis There is a paucity of research on treatment outcomes of patients with psychosis and cannabis use disorder (CUD). We aimed to compare the effectiveness of antipsychotics in reducing the risk of hospitalization in patients with first-episode psychosis (FEP) and co-occurring CUD. Study Design We utilized a nationwide Swedish cohort of patients with longitudinal register data from the year 2006 to 2021. Participants were patients with FEP and co-occurring CUD (n  = 1820, 84.73% men, mean age 26.80 years, SD 8.25 years). The main outcome was hospitalization due to psychotic relapse. Hospitalization due to any psychiatric disorder or substance use disorder (SUD) were examined as secondary outcomes. Within-individual Cox regression models were used to study these associations. Study Results Use of any antipsychotic was associated with a 33% risk reduction of psychotic relapse (aHR = 0.67; 95% CI 0.60–0.75). Clozapine (0.43; 0.29–0.64), long-acting injectable (LAI) formulations of risperidone (0.40; 0.22–0.71), aripiprazole (0.42; 0.27–0.65), and paliperidone (0.46; 0.30–0.69) were associated with the lowest risk of relapse. The association between the LAI formulation of olanzapine and hospitalization due to psychosis was statistically non-significant (0.61; 0.35–1.05). Clozapine was associated with an 86% risk reduction of hospitalization due to SUD (0.14; 0.05–0.44). Of oral non-clozapine antipsychotics, aripiprazole was associated with the lowest risk of hospitalization due to psychotic relapse (0.61; 0.45–0.83). Conclusions These findings support the use of clozapine, LAI formulations of second-generation antipsychotics other than olanzapine, or oral aripiprazole to prevent hospitalization in FEP and co-occurring CUD. [ABSTRACT FROM AUTHOR]

Studies have shown that retired older adults are more likely to volunteer than their working counterparts. However, whether the transition to retirement is associated with increased volunteering frequency and whether this varies according to material and time resources of participants is unclear. We used four waves of data from the longitudinal Survey of Health, Ageing and Retirement in Europe, collected between 2011–2018 across 19 countries (n = 12,400 person-observations from 6200 individuals over 50). Within-person (or panel fixed-effect) regression analyses revealed that transition to retirement was associated with an increased volunteering frequency over time. This association was stronger among individuals with better health, higher education, improved financial situation and in countries with higher gross domestic product per capita. Overall, transition to retirement tends to open new ways of organizing everyday life and is associated with increased frequency of volunteering. [ABSTRACT FROM AUTHOR]

This cohort study examines the risk of pneumonia associated with the use of antipsychotics in patients with schizophrenia. Key Points: Question: What antipsychotics are associated with pneumonia, which is the fourth leading cause of death in patients with schizophrenia? Findings: In this cohort study of 61 889 people with schizophrenia, antipsychotics with high anticholinergic burden were associated with an increased incidence of pneumonia. Significantly higher risks were detected for clozapine (≥180 mg/d), quetiapine (≥440 mg/d), and olanzapine (≥11 mg/d). Meaning: Findings of this study suggest that in patients with schizophrenia, pneumonia is associated with the use of specific antipsychotics, setting the stage for personalized prevention strategies to decrease the incidence of this life-threatening condition in patients with schizophrenia. Importance: Antipsychotic drugs (particularly clozapine) have been associated with pneumonia in observational studies. Despite studies of the associations between antipsychotic use and incident pneumonia, it remains unclear to what degree antipsychotic use is associated with increased risk of pneumonia, whether dose-response associations exist, and what agents are specifically associated with incident pneumonia. Objective: To estimate pneumonia risk associated with specific antipsychotics and examine whether polytherapy, dosing, and receptor binding properties are associated with pneumonia in patients with schizophrenia. Design, Setting, and Participants: This cohort study identified patients with schizophrenia or schizoaffective disorder (hereafter, schizophrenia) aged 16 years or older from nationwide Finnish registers from 1972 to 2014. Data on diagnoses, inpatient care, and specialized outpatient care were obtained from the Hospital Discharge Register. Information on outpatient medication dispensing was obtained from the Prescription Register. Study follow-up was from 1996 to 2017. Data were analyzed from November 4, 2022, to December 5, 2023. Exposures: Use of specific antipsychotic monotherapies; antipsychotics modeled by dosage as low (<0.6 of the World Health Organization defined daily dose [DDD] per day), medium (0.6 to <1.1 DDDs per day), or high dose (≥1.1 DDDs per day); antipsychotic polypharmacy; and antipsychotics categorized according to their anticholinergic burden as low, medium, and high. Main Outcomes and Measures: The primary outcome was hospitalization for incident pneumonia. Pneumonia risk was analyzed using adjusted, within-individual Cox proportional hazards regression models, with no antipsychotic use as the reference. Results: The study included 61 889 persons with schizophrenia (mean [SD] age, 46.2 [16.0] years; 31 104 men [50.3%]). During 22 years of follow-up, 8917 patients (14.4%) had 1 or more hospitalizations for pneumonia and 1137 (12.8%) died within 30 days of admission. Compared with no antipsychotic use, any antipsychotic use overall was not associated with pneumonia (adjusted hazard ratio [AHR], 1.12; 95% CI, 0.99-1.26). Monotherapy use was associated with increased pneumonia risk compared with no antipsychotic use (AHR, 1.15 [95% CI, 1.02-1.30]; P =.03) in a dose-dependent manner, but polytherapy use was not. When categorized by anticholinergic burden, only the use of antipsychotics with a high anticholinergic burden was associated with pneumonia (AHR, 1.26 [95% CI, 1.10-1.45]; P <.001). Of specific drugs, high-dose quetiapine (AHR, 1.78 [95% CI, 1.22-2.60]; P =.003), high- and medium-dose clozapine (AHR, 1.44 [95% CI, 1.22-1.71]; P <.001 and AHR, 1.43 [95% CI, 1.18-1.74]; P <.001, respectively), and high-dose olanzapine (AHR, 1.29 [95% CI, 1.05-1.58]; P =.02) were associated with increased pneumonia risk. Conclusions and Relevance: Results of this cohort study suggest that in patients with schizophrenia, antipsychotic agents associated with pneumonia include not only clozapine (at dosages ≥180 mg/d) but also quetiapine (≥440 mg/d) and olanzapine (≥11 mg/d). Moreover, monotherapy antipsychotics and antipsychotics with high anticholinergic burden are associated with increased pneumonia risk in a dose-dependent manner. These findings call for prevention strategies aimed at patients with schizophrenia requiring high-risk antipsychotics. [ABSTRACT FROM AUTHOR]

Objective: Antipsychotic effectiveness in preventing relapse declines around menopausal age in women with schizophrenia or schizoaffective disorder (SSD). It is not known whether systemic menopausal hormone therapy (MHT) can help to prevent psychosis relapse. Methods: A within-subject study design was used to study the effectiveness of MHT in preventing relapse in a Finnish nationwide cohort of women with SSD between 40 and 62 years of age who used MHT during follow-up (1994–2017). Hazard ratios adjusted for age and psychotropic drug use were calculated for psychosis relapse as main outcome and any psychiatric hospitalization as secondary outcome. Results: The study population comprised 3,488 women using MHT. Use of MHT was associated with a 16% lower relapse risk (adjusted hazard ratio [aHR]=0.84, 95% CI=0.78–0.90) when compared to non-use. Stratified by age, MHT was associated with decreased relapse risks when used between ages 40–49 (aHR=0.86, 95% CI=0.78–0.95) and ages 50–55 (aHR=0.74, 95% CI=0.66–0.83), but not between ages 56–62 (aHR=1.11, 95% CI=0.91–1.37). Similar effectiveness was found for estrogen alone or combined with fixed or sequential progestogens (aHRs between 0.79 and 0.86), transdermal and oral formulations (aHRs 0.75–0.87), and for most specific formulations (aHRs 0.75–0.85), except tibolone (aHR=1.04, 95% CI=0.75–1.44) and formulations with dydrogesterone (aHR=1.05, 95% CI=0.85–1.30). Similar results were observed with any psychiatric hospitalization as outcome measure. Conclusions: The findings underscore the potential value of MHT in preventing psychosis relapse among women with SSD of menopausal age. These findings translate clinical evidence on the neuroprotective effects of estrogens to real-world settings, encompassing a group of women for whom current antipsychotic treatment options may be insufficient. [ABSTRACT FROM AUTHOR]

Objective: The authors used longitudinal biobank data with up to 25 years of follow-up on over 2,600 clozapine users to derive reliable estimates of the real-world burden of clozapine adverse drug events (ADEs). Methods: A total of 2,659 participants in the FinnGen biobank project had a schizophrenia diagnosis and clozapine purchases with longitudinal electronic health record follow-up for up to 25 years after clozapine initiation. Diseases and health-related events enriched during clozapine use were identified, adjusting for disease severity. The incidence and recurrence of ADEs over years of clozapine use, their effect on clozapine discontinuation and deaths, and their pharmacogenetics were studied. Results: Median follow-up time after clozapine initiation was 12.7 years. Across 2,157 diseases and health-related events, 27 were enriched during clozapine use, falling into five disease categories: gastrointestinal hypomotility, seizures, pneumonia, other acute respiratory tract infections, and tachycardia, along with a heterogeneous group including neutropenia and type 2 diabetes, among others. Cumulative incidence estimates for ileus (severe gastrointestinal hypomotility) and pneumonia were 5.3% and 29.5%, respectively, 20 years after clozapine initiation. Both events were significantly associated with increased mortality among clozapine users (ileus: odds ratio=4.5; pneumonia: odds ratio=2.8). Decreased genotype-predicted CYP2C19 and CYP1A2 activities were associated with higher pneumonia risk. Conclusions: Clozapine-induced ileus and pneumonia were notably more frequent than has previously been reported and were associated with increased mortality. Two CYP genes influenced pneumonia risk. Pneumonia and ileus call for improved utilization of available preventive measures. [ABSTRACT FROM AUTHOR]