Trajectories of work disability and unemployment before and after a common mental disorder diagnosis among young private sector employees in Sweden-a register-based longitudinal study.

PURPOSE: To identify trajectory groups of work disability (WD), including sick leave and disability pension, and unemployment three years before and six years (from Y-3 to Y + 6) after a common mental disorder (CMD) diagnosis and to investigate associations of socio-demographic, work-related and clinical factors with trajectory membership. METHODS: A longitudinal nationwide register-based study was conducted including individuals aged 22-29 years, gainfully employed in the private sector, with a CMD diagnosis in specialised healthcare or prescribed antidepressant (N = 12,121) in 2014 (Year 0/Y0), with follow-up from Y-3 to Y + 6. Group-based trajectory analyses identified groups of individuals who followed similar trajectories of months of WD and unemployment, respectively. Multinomial logistic regression determined associations between socio-demographic, work-related and clinical factors and trajectory membership. RESULTS: In the CMD group, we identified three trajectory groups, each for WD and unemployment. Only 7% individuals belonged to a 'Fluctuant high' trajectory group with four months of WD in Y0, which peaked at 7 months in Y + 3 and reduced to 5 months in Y + 6. For unemployment, 15% belonged to an 'Increasing medium' trajectory group that steadily increased from 1.3 months in Y0 to 2.6 months in Y + 6. Sex, educational level and musculoskeletal disorders for WD, and educational level, living area and occupational class for unemployment, influentially determined the variance across the CMD trajectory groups. CONCLUSIONS: Specific vulnerable groups regarding unfavourable WD (women, low education and musculoskeletal disorders) and unemployment (manual work, low education and rural residence) trajectories require special attention regarding their return-to-work process following a CMD diagnosis.

Comparative Effectiveness of Antipsychotics in Patients With Schizophrenia Spectrum Disorder.

Importance: Antipsychotics are the cornerstone of maintenance treatment in schizophrenia spectrum disorders, but it is unclear which agents should be prioritized by prescribers. Objective: To investigate the clinical effectiveness of antipsychotics, including recent market entries, in comparison with oral olanzapine in relapse and treatment failure prevention among individuals with schizophrenia spectrum disorder. Design, Setting, and Participants: This comparative effectiveness research study with a within-individual analysis included data from Swedish health care registers of inpatient and specialized outpatient care, sickness absence, and disability pensions among all individuals aged 16 to 65 years who were diagnosed with schizophrenia spectrum disorder from January 1, 2006, to December 31, 2021, including an incident cohort and a prevalent cohort. Exposures: Specific antipsychotics. Main Outcomes and Measures: The risks for psychosis relapse hospitalization and treatment failure (psychiatric hospitalization, death, or change in an antipsychotic medication) were adjusted for the temporal order of treatments, time since cohort entry, and concomitant drugs. Comparisons of all antipsychotics with oral olanzapine, the most commonly used antipsychotic, were investigated. Results: Among the full cohort of 131 476 individuals, the mean (SD) age of the study cohort was 45.7 (16.2) years (70 054 men [53.3%]). During a median follow-up of 12.0 years [IQR, 5.2-16.0 years], 48.5% of patients (N = 63 730) experienced relapse and 71.1% (N = 93 464) underwent treatment failure at least once. Compared with oral olanzapine, paliperidone 3-month long-acting injectable (LAI) was associated with the lowest adjusted hazard ratio (AHR) in the prevention of relapses (AHR, 0.66; 95% CI, 0.51-0.86), followed by aripiprazole LAI (AHR, 0.77 [95% CI, 0.70-0.84]), olanzapine LAI (AHR, 0.79 [95% CI, 0.73-0.86]), and clozapine (AHR, 0.82 [95% CI, 0.79-0.86]). Quetiapine was associated with the highest risk of relapse (AHR, 1.44 [95% CI, 1.38-1.51]). For prevention of treatment failure, paliperidone 3-month LAI was associated with the lowest AHR (AHR, 0.36 [95% CI, 0.31-0.42]), followed by aripiprazole LAI (AHR, 0.60 [95% CI, 0.57-0.63]), olanzapine LAI (AHR, 0.67 [95% CI, 0.63-0.72]), and paliperidone 1-month LAI (AHR, 0.71 [95% CI, 0.68-0.74]). Conclusions and Relevance: This comparative effectiveness research study demonstrated large differences in the risk of relapse and treatment failure among specific antipsychotic treatments. The findings contradict the widely held conception that all antipsychotics are equally effective in relapse prevention.

Mental health during the Covid-19 pandemic: An international comparison of gender-related home and work-related responsibilities, and social support.

PURPOSE  : To assess gender differences in COVID-19 related changes in home and work responsibilities longitudinally, and determine whether these differences, together with other potential risk and protective factors, are associated with depression, anxiety, and post-traumatic stress disorder (PTSD) symptomatology. METHOD: Symptoms of depression, anxiety, and PTSD were measured using an online survey instrument, between May 2020 and April 2021, in four waves completed at 3-monthly intervals. Analyses were based on data from the COvid MEntal healTh (COMET) survey which investigated the mental health effects of the COVID-19 outbreak spanning 13 countries on five continents in N = 7,909 participants. RESULTS: From the first to the last wave, women reported a greater increase in home and work responsibilities, and had higher depression, anxiety and PTSD scores compared to men. Women who reported a reduction in income due to the pandemic had higher depression scores. Working harder and experiencing a reduction in income were also associated with higher anxiety scores in women but not in men. Women were more likely to score above the cut-off for depression (32.5% vs 23.6%, p < .001), anxiety (21.2% vs 14.4%, p < .001) and PTSD (21.2% vs 14.4%, p < .001) than men during the first wave. Stronger reliance on socially supported coping mechanisms was a risk factor for depression, anxiety and PTSD in men and women. CONCLUSION: Women were more likely to report mental health problems which may be related to the gender disproportionate increase in home and work responsibilities but not necessarily due to COVID-19 stressors.

Trajectories of work disability among individuals with anxiety-, mood/affective-, or stress-related disorders in a primary healthcare setting.

BACKGROUND: Anxiety-, mood/affective-, or stress-related disorders affect up to one-third of individuals during their lives and often impact their ability to work. This study aimed to delineate trajectories of work disability (WD) among individuals diagnosed with anxiety-, mood/affective-, or stress-related disorder in primary healthcare and to examine associations between trajectory group membership and sociodemographic, clinical, and clinical-related factors. METHODS: The study population included working-age individuals, aged 22-62 years, living in Stockholm County, Sweden, who experienced a new episode of any anxiety-, mood/affective, or stress-related disorder in primary healthcare in 2017 (N = 11,304). Data were obtained from Swedish national and regional registers and were linked using pseudonymised unique personal identification numbers. The primary outcome was days with WD (sum of sickness absence and disability pension days) during the three years before and three years after a diagnosis of anxiety-, mood/affective-, or stress-related disorders in primary healthcare. A zero-inflated Poisson group-based trajectory model was used to identify groups of individuals with similar patterns of WD over the study period, with a multinomial logistic regression used to examine associations of sociodemographic, clinical, and clinical-related factors with trajectory group membership. RESULTS: Four distinct trajectory groups were found, high increasing (5.1%), with high levels, from 16 to 80 days of WD in six-monthly intervals during follow-up, peak (11.1%), with a peak in WD, up to 32 days of WD, around the time of the diagnosis, low increasing (12.8%), with an increase in days of WD from 4 to 22 during the study period, and constant low (71.1%), with almost no WD over the study period. In multinomial regression models, diagnostic category, psychotropic medication use, a diagnosis of a psychiatric disorder within secondary healthcare, age at diagnosis, and occupation were associated with WD trajectory groups. CONCLUSIONS: Around two-thirds of individuals treated for a new episode of any anxiety-, mood/affective-, or stress-related disorder in primary healthcare have an excellent prognosis regarding WD. Several sociodemographic and clinical characteristics were associated with group membership; these factors could identify individuals at risk of long-term welfare dependency and who might benefit from interventions to promote a return to work.

Long-term follow-up on patient attitudes towards renewed ECT: A register-based cohort study.

Electroconvulsive therapy (ECT) is a safe and effective treatment for major depressive disorder (MDD). After receiving ECT for MDD there is a large risk of relapse within the first year. Patient attitudes towards renewed treatment could impact their decisions regarding future therapy. We conducted a nationwide cohort study, using data from Swedish registers. Patients with MDD who received ECT were followed up to six months after the initial ECT-series. We investigated if certain patient and treatment characteristics during the initial treatment were correlated to their attitude towards renewed ECT at the six-month follow-up. Logistic regression models were used to calculate adjusted odds ratios for predictors. The Bonferroni method was used to adjust significance levels for multiple testing. The study included 1917 patients. 51.1% of patients were positive, 27.6% were undecided and 21.3% were negative towards renewed treatment. Patients with response to treatment were less likely to have a negative attitude towards renewed ECT (odds ratio 0.32, 95% CI 0.25-0.41, P < 0.001). Moreover, patients with experience of ECT prior to the index series were less likely to have a negative attitude towards renewed ECT (odds ratio 0.44, 95% CI 0.34-0.58, P < 0.001). In order to minimize the risk of negative attitudes towards renewed ECT for MDD, treatment should primarily be reserved for patients that are likely to respond to ECT.

Involuntary admissions for non-affective psychotic disorders in young refugees and peers in Denmark: A population cohort study.

INTRODUCTION: People with psychotic disorders are at increased risk of experiencing involuntary hospital admissions relative to other psychiatric patients. Within this group, refugees and other minority groups may be at even greater risk. However, little is known about the role of migration background in the risk of involuntary admissions around the time of first psychosis-related treatment. METHOD: We utilized nationwide administrative data from Denmark covering the period 2006-2018. We included all persons aged 18-35 years in first treatment for psychotic disorders [inpatient and hospital-based outpatient settings (N = 11,871)]. We estimated odds ratios (OR) of any involuntary inpatient admission within three months of first treatment using logistic regression, and rate ratios (RR) of further involuntary admissions, total number of involuntary admissions, and days of involuntary care among patients initially admitted involuntarily using Poisson regression. We compared refugees with majority peers (native-born with native-born parent), other migrants, and descendants of non-refugee migrants. RESULTS: Compared with the majority group, refugees, non-refugee migrants and descendants were at increased risk of involuntarily admissions (ORrange = 2.12-2.69). Differences in sex, age, education, household income and family situation did not explain these disparities. In contrast, the risk of subsequent involuntary care did not differ between groups (RRrange = 0.77-1.31). CONCLUSIONS: The findings highlight the need to review if and why processes of needs detection and voluntary treatment enrolment are less effective for minorities in Denmark. Further studies should investigate the pathways to care across population groups to inform interventions that address disparities.

Does job stress mediate the risk of work disability due to common mental disorders among social workers compared with other health and social care, education, and non-human service professionals? A prospective cohort study of public sector employees in Finland.

OBJECTIVE: This study aimed to investigate (i) the risk of work disability (>10-day sickness absence spell or disability pension) due to common mental disorders (CMD) among social workers compared with other health and social care, education, and non-human service professionals and (ii) whether the risk was mediated by job stress. METHODS: A cohort of 16 306 public sector professionals in Finland was followed using survey data from baseline (2004 or if not available, 2008) on job stress [job strain or effort-reward imbalance (ERI)] and register data on work disability due to CMD from baseline through 2011. A Cox proportional hazards model was used to analyze the risk of work disability due to CMD between three occupation-pairs in a counterfactual setting, controlling for age, sex, job contract, body mass index, alcohol risk use, smoking, and physical inactivity. RESULTS: Social workers' job stress was at higher level only when compared to education professionals. Thus, the mediation hypothesis was analyzed comparing social workers to education professionals. Social workers had a higher risk of work disability due to CMD compared with education professionals [hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.58-2.74]. This HR was partly mediated by job strain (24%) and ERI (12%). Social workers had a higher risk of work disability than non-human service professionals (HR 1.54, 95% CI 1.13-2.09), but not compared with other health and social care professionals. CONCLUSIONS: Job stress partly mediated the excess risk of work disability among social workers only in comparison with education professionals.

Real-world effectiveness of antidepressants, antipsychotics and their combinations in the maintenance treatment of psychotic depression. Evidence from within-subject analyses of two nationwide cohorts.

Psychotic depression (PD) is a severe mental disorder leading to functional disability and high risk of suicide, but very little is known about the comparative effectiveness of medications used in its maintenance treatment. The objective of this study was to investigate the comparative effectiveness of specific antipsychotics and antidepressants, and their combinations, on the risk of psychiatric hospitalization among persons with PD in routine care. Persons aged 16-65 years with a first-time diagnosis of PD were identified from Finnish (years 2000-2018) and Swedish (years 2006-2021) nationwide registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. The main exposures were specific antipsychotics and antidepressants, and the main outcome measure was psychiatric hospitalization as a marker of severe relapse. The risk of hospitalization associated with periods of use vs. non-use of medications (expressed as adjusted hazard ratio, aHR) was assessed by a within-individual design, using each individual as his/her own control, and analyzed with stratified Cox models. The two national cohorts were first analyzed separately, and then combined using a fixed-effect meta-analysis. The Finnish cohort included 19,330 persons (mean age: 39.8±14.7 years; 57.9% women) and the Swedish cohort 13,684 persons (mean age: 41.3±14.0 years; 53.5% women). Individual antidepressants associated with a decreased risk of relapse vs. non-use of antidepressants were bupropion (aHR=0.73, 95% CI: 0.63-0.85), vortioxetine (aHR=0.78, 95% CI: 0.63-0.96) and venlafaxine (aHR=0.92, 95% CI: 0.86-0.98). Any long-acting injectable antipsychotic (LAI) (aHR=0.60, 95% CI: 0.45-0.80) and clozapine (aHR=0.72, 95% CI: 0.57-0.91) were associated with a decreased risk of relapse vs. non-use of antipsychotics. Among monotherapies, only vortioxetine (aHR=0.67, 95% CI: 0.47-0.95) and bupropion (aHR=0.71, 95% CI: 0.56-0.89) were associated with a significantly decreased risk of relapse vs. non-use of both antidepressants and antipsychotics. In an exploratory analysis of antidepressant-antipsychotic combinations, a decreased relapse risk was found for amitriptyline-olanzapine (aHR=0.45, 95% CI: 0.28-0.71), sertraline-quetiapine (aHR=0.79, 95% CI: 0.67-0.93) and venlafaxine-quetiapine (aHR=0.82, 95% CI: 0.73-0.91) vs. non-use of antidepressants and antipsychotics. Benzodiazepines and related drugs (aHR=1.29, 95% CI: 1.24-1.34) and mirtazapine (aHR=1.17, 95% CI: 1.07-1.29) were associated with an increased risk of relapse. These data indicate that, in the maintenance treatment of PD, bupropion, vortioxetine, venlafaxine, any LAI, clozapine, and only few specific antidepressant-antipsychotic combinations are associated with a decreased risk of relapse. These findings challenge the current recommendation by treatment guidelines to combine an antipsychotic with an antidepressant (without further specification) as standard treatment in PD.

Antipsychotic Use and Risk of Breast Cancer in Women With Severe Mental Illness: Replication of a Nationwide Nested Case-Control Database Study.

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 ±â€…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.

Does country of resettlement influence the risk of labor market marginalization among refugees? A cohort study in Sweden and Norway.

OBJECTIVES: This study aimed to compare the risk of labor market marginalization among refugees across different host countries of resettlement and examine the moderating role of birth country and length of stay on these associations. METHODS: Cohorts of refugees and native-born individuals aged 19-60 in Sweden (N=3 605 949, 3.5% refugees) and Norway (N=1 784 861, 1.7% refugees) were followed during 2010-2016. Rates (per 1000 person-years) of long-term unemployment, long-term sickness absence, and disability pension were estimated for refugees and the host populations. Cox regression models estimated crude and adjusted (for sex, age, educational level, and civil status) hazard ratio (HRadj) for refugees compared to their respective host population, with 95% confidence intervals (CI). Analyses were also stratified by birth country and length of stay. RESULTS: Refugees in Norway and Sweden had a higher incidence of labor market marginalization compared to their host population. Refugees in Sweden had a comparatively lower relative risk of long-term unemployment but higher risk of disability pension (HRadj 3.44, 95% CI, 3.38-3.50 and HRadj 2.45, 2.35-2.56, respectively) than refugees in Norway (HRadj 3.70, 3.58-3.82 and HRadj 1.57, 1.49-1.66, respectively). These relative risks varied when stratifying by birth country. A shorter length of stay was associated with a higher risk of long-term unemployment and a lower risk of disability pension, with a stronger gradient in Sweden than in Norway. CONCLUSIONS: The relative risk of labor market marginalization varied by the refugees' birth country but followed similar trends in Sweden and Norway. Although speculative, these findings may hint at non-structural factors related to the refugee experience playing a more important role than host country structural factors for the risk of labor market marginalization among refugees. Future research, including host countries with more variability in structural factors, is required to further investigate these associations. The higher risk of long-term unemployment among refugees with shorter length of stay indicates a need for more efficient labor market integration policies for newly-arrived refugees.

Antipsychotic Use and Psychiatric Hospitalization in First-Episode Non-affective Psychosis and Cannabis Use Disorder: A Swedish Nationwide Cohort Study.

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.

Attention-Deficit/Hyperactivity Disorder Medications and Work Disability and Mental Health Outcomes.

Importance: Individuals with attention-deficit/hyperactivity disorder (ADHD) often have comorbid psychiatric conditions. Relatively little is known about how specific ADHD medications are associated with overall treatment outcomes among these patients. Objective: To investigate the association of the use of specific ADHD medications with hospitalization outcomes and work disability among adolescents and adults with ADHD. Design, Setting, and Participants: This nationwide register-based cohort study identified individuals (aged 16-65 years) with ADHD from Swedish nationwide registers of inpatient health care, specialized outpatient health care, sickness absence, and disability pension during the years 2006 to 2021. Data analysis was performed from November 2022 to August 2023. Exposure: Use of specific ADHD medications. Main Outcomes and Measures: The main outcome measure was psychiatric hospitalization, and secondary outcomes were suicide attempt and/or death by suicide, nonpsychiatric hospitalization, and work disability (ie, sickness absence or disability pension). The risk of outcomes between use vs nonuse periods of ADHD medications was compared in a within-individual design, where a person acts as their own control, and was analyzed with stratified Cox models. Results: A total of 221 714 persons with ADHD were included in the study cohort (mean [SD] age, 25.0 [11.2] years; 120 968 male individuals [54.6%]). Methylphenidate was the most commonly used ADHD medication (151 837 individuals [68.5%]), followed by lisdexamphetamine (78 106 individuals [35.2%]) during the follow-up (mean [SD], 7.0 [4.7] years). The following medications were associated with a decreased risk of psychiatric hospitalization: amphetamine (adjusted hazard ratio [aHR], 0.74; 95% CI, 0.61-0.90), lisdexamphetamine (aHR, 0.80; 95% CI, 0.78-0.82), ADHD drug polytherapy (aHR, 0.85; 95% CI, 0.82-0.88), dexamphetamine (aHR, 0.88; 95% CI, 0.83-0.94), and methylphenidate (aHR, 0.93; 95% CI, 0.92-0.95). No associations were found for modafinil, atomoxetine, clonidine, and guanfacine. Decreased risk of suicidal behavior was associated with the use of dexamphetamine (aHR, 0.69; 95% CI, 0.53-0.89), lisdexamphetamine (aHR, 0.76; 95% CI, 0.68-0.84), and methylphenidate (aHR, 0.92; 95% CI, 0.86-0.98). None of the medications was associated with increased risk of nonpsychiatric hospitalization; instead, use of amphetamine, lisdexamphetamine, polytherapy, dexamphetamine, methylphenidate, and atomoxetine were associated with decreased risk of nonpsychiatric hospitalization. The results regarding work disability were significant only for the use of atomoxetine (aHR, 0.89; 95% CI, 0.82-0.97), especially among adolescents and young adults aged 16 to 29 years, (aHR, 0.82; 95% CI, 0.73-0.92). Conclusions and Relevance: In this nationwide cohort study of adolescents and adults with ADHD, the use of ADHD medication was associated with fewer hospitalizations for both psychiatric and nonpsychiatric morbidity and lower suicidal behavior.

Development and Validation of a Machine Learning-Based Model of Mortality Risk in First-Episode Psychosis.

Importance: There is an absence of mortality risk assessment tools in first-episode psychosis (FEP) that could enable personalized interventions. Objective: To examine the feasibility of machine learning (ML) in discerning mortality risk in FEP and to assess whether such risk predictions can inform pharmacotherapy choices. Design, Setting, and Participants: In this prognostic study, Swedish nationwide cohort data (from July 1, 2006, to December 31, 2021) were harnessed for model development and validation. Finnish cohort data (from January 1, 1998, to December 31, 2017) were used for external validation. Data analyses were completed between December 2022 and December 2023. Main Outcomes and Measures: Fifty-one nationwide register variables, encompassing demographics and clinical and work-related histories, were subjected to ML to predict future mortality risk. The ML model's performance was evaluated by calculating the area under the receiver operating characteristic curve (AUROC). The comparative effectiveness of pharmacotherapies in patients was assessed and was stratified by the ML model to those with predicted high mortality risk (vs low risk), using the between-individual hazard ratio (HR). The 5 most important variables were then identified and a model was retrained using these variables in the discovery sample. Results: This study included 24 052 Swedish participants (20 000 in the discovery sample and 4052 in the validation sample) and 1490 Finnish participants (in the validation sample). Swedish participants had a mean (SD) age of 29.1 (8.1) years, 62.1% were men, and 418 died with 2 years. Finnish participants had a mean (SD) age of 29.7 (8.0) years, 61.7% were men, and 31 died within 2 years. The discovery sample achieved an AUROC of 0.71 (95% CI, 0.68-0.74) for 2-year mortality prediction. Using the 5 most important variables (ie, the top 10% [substance use comorbidities, first hospitalization duration due to FEP, male sex, prior somatic hospitalizations, and age]), the final model resulted in an AUROC of 0.70 (95% CI, 0.63-0.76) in the Swedish sample and 0.67 (95% CI, 0.56-0.78) in the Finnish sample. Individuals with predicted high mortality risk had an elevated 15-year risk in the Swedish sample (HR, 3.77 [95% CI, 2.92-4.88]) and an elevated 20-year risk in the Finnish sample (HR, 3.72 [95% CI, 2.67-5.18]). For those with predicted high mortality risk, long-acting injectable antipsychotics (HR, 0.45 [95% CI, 0.23-0.88]) and mood stabilizers (HR, 0.64 [95% CI, 0.46-0.90]) were associated with decreased mortality risk. Conversely, for those predicted to survive, only oral aripiprazole (HR, 0.38 [95% CI, 0.20-0.69]) and risperidone (HR, 0.38 [95% CI, 0.18-0.82]) were associated with decreased mortality risk. Conclusions and Relevance: In this prognostic study, an ML-based model was developed and validated to predict mortality risk in FEP. These findings may help to develop personalized interventions to mitigate mortality risk in FEP.

Efficacy and effectiveness of antipsychotics in schizophrenia: network meta-analyses combining evidence from randomised controlled trials and real-world data.

BACKGROUND: There is debate about the generalisability of results from randomised clinical trials (RCTs) to real-world settings. Studying outcomes of treatments for schizophrenia can shed light on this issue and inform treatment guidelines. We therefore compared the efficacy and effectiveness of antipsychotics for relapse prevention in schizophrenia and estimated overall treatment effects using all available RCT and real-world evidence. METHODS: We conducted network meta-analyses using individual participant data from Swedish and Finnish national registries and aggregate data from RCTs. The target population was adults (age >18 and <65 years) with schizophrenia and schizoaffective disorder with stabilised symptoms. We analysed each registry separately to obtain hazard ratios (HRs) and 95% CIs for relapse within 6 months post-antipsychotic initiation as our main outcome. Interventions studied were antipsychotics, no antipsychotic use, and placebo. We compared HRs versus a reference drug (oral haloperidol) between registries, and between registry individuals who would be eligible and ineligible for RCTs, using the ratio of HRs. We synthesised evidence using network meta-analysis and compared results from our network meta-analysis of real-world data with our network meta-analysis of RCT data, including oral versus long-acting injectable (LAI) formulations. Finally, we conducted a joint real-world and RCT network meta-analysis. FINDINGS: We included 90 469 individuals from the Swedish and Finnish registries (mean age 45·9 [SD 14·6] years; 43 025 [47·5%] women and 47 467 [52·5%] men, ethnicity data unavailable) and 10 091 individuals from 30 RCTs (mean age 39·6 years [SD 11·7]; 3724 [36·9%] women and 6367 [63·1%] men, 6022 White [59·7%]). We found good agreement in effectiveness of antipsychotics between Swedish and Finnish registries (HR ratio 0·97, 95% CI 0·88-1·08). Drug effectiveness versus no antipsychotic was larger in RCT-eligible than RCT-ineligible individuals (HR ratio 1·40 [1·24-1·59]). Efficacy versus placebo in RCTs was larger than effectiveness versus no antipsychotic in real-world (HR ratio 2·58 [2·02-3·30]). We found no evidence of differences between effectiveness and efficacy for between-drug comparisons (HR ratio vs oral haloperidol 1·17 [0·83-1·65], where HR ratio >1 means superior effectiveness in real-world to RCTs), except for LAI versus oral comparisons (HR ratio 0·73 [0·53-0·99], indicating superior effectiveness in real-world data relative to RCTs). The real-world network meta-analysis showed clozapine was most effective, followed by olanzapine LAI. The RCT network meta-analysis exhibited heterogeneity and inconsistency. The joint real-world and RCT network meta-analysis identified olanzapine as the most efficacious antipsychotic amongst those present in both RCTs and the real world registries. INTERPRETATION: LAI antipsychotics perform slightly better in the real world than according to RCTs. Otherwise, RCT evidence was in line with real-world evidence for most between-drug comparisons, but RCTs might overestimate effectiveness of antipsychotics observed in routine care settings. Our results further the understanding of the generalisability of RCT findings to clinical practice and can inform preferential prescribing guidelines. FUNDING: None.

The risk and development of work disability among individuals with gambling disorder: a longitudinal case-cohort study in Sweden.

BACKGROUND: This longitudinal register study aimed to investigate the association between gambling disorder (GD) and work disability and to map work disability in subgroups of individuals with GD, three years before and three years after diagnosis. METHODS: We included individuals aged 19-62 with GD between 2005 and 2018 (n = 2830; 71.1% men, mean age: 35.1) and a matched comparison cohort (n = 28 300). Work disability was operationalized as the aggregated net days of sickness absence and disability pension. Generalized estimating equation models were used to calculate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for the risk of long-term work disability (>90 days of work disability/year). Secondly, we conducted Group-based Trajectory Models on days of work disability. RESULTS: Individuals with GD showed a four-year increased risk of long-term work disability compared to the matched cohort, peaking at the time of diagnosis (AOR = 1.89; CI 1.67-2.13). Four trajectory groups of work disability days were identified: constant low (60.3%, 5.6-11.2 days), low and increasing (11.4%, 11.8-152.5 days), medium-high and decreasing (11.1%, 65.1-110 days), and constant high (17.1%, 264-331 days). Individuals who were females, older, with prior psychiatric diagnosis, and had been dispensed a psychotropic medication, particularly antidepressants, were more likely to be assigned to groups other than the constant low. CONCLUSION: Individuals with GD have an increased risk of work disability which may add financial and social pressure and is an additional incentive for earlier detection and prevention of GD.

Labour market integration among young adults diagnosed with attention-deficit/hyperactivity disorder (ADHD) at working age.

METHODS: Multiple Swedish nationwide registers were used to identify 8045 individuals, aged 20-29, with an incident diagnosis of ADHD 2006-2011. Labour market integration was conceptualized according to the core-peripheral model as a continuum from a strong (core) to a weak (peripheral) connection to the labour market. Sequence analyses categorized clusters of labour market integration, from 1 year before to 5 years after their ADHD diagnosis for individuals diagnosed with ADHD and a matched control group without ADHD. Multinomial logistic regression computed odds ratios (ORs) with 95% confidence intervals (CIs) between sociodemographic factors and comorbid disorders and the identified clusters. RESULTS: About one-fourth of the young adults diagnosed with ADHD belonged to clusters characterized by a transition to a mainly peripheral labour market position, which was approximately four-times higher compared to controls without ADHD. Foremost, those living in small cities/villages (OR 1.9; CI 1.5-2.2), those having comorbid autism-spectrum disorder (OR 13.7; CI 6.8-27.5) or schizophrenia/psychoses (OR 7.8; CI 3.8-15.9) were associated with a transition towards a peripheral labour market position throughout the study period. Those with a high educational level (OR 0.1; CI 0.1-0.1), and men (OR 0.7; CI 0.6-0.8) were less likely to have a peripheral labour market position. CONCLUSIONS: Young adults diagnosed with ADHD are four-times more likely to be in the peripheral labour market position compared to those without ADHD. To increase labour market participation, special attention is warranted to those with low educational level, those living outside big cities and those with comorbid mental disorders.

Risk of unemployment and work disability among refugee and non-refugee migrants with incident psychotic disorders in Sweden and Denmark.

BACKGROUND: Unemployment and work disability are common among individuals with non-affective psychotic disorders (NAPDs) but it is unknown whether rates differ among migrants and native-born individuals. The present study aimed to compare the risk of these outcomes during the first 5 years of illness in non-refugee migrants, refugees and native-born individuals with NAPDs in Sweden and Denmark-two countries with different immigration policies and models of early psychosis care. METHODS: Using national registers, we identified all individuals aged 18-35 years in Sweden and Denmark who received an incident NAPD diagnosis between 2006 and 2013 (N = 6750 and 8320, respectively). Cohorts were followed for 5 years to determine the days of unemployment and sickness absence (analyzed using zero-inflated negative binomial models) and the time to receipt of disability pension (analyzed using complementary log-log models). RESULTS: Relative to their native-born peers, refugees and non-refugee migrants in Sweden and non-refugee migrants in Denmark were significantly less likely to have zero unemployment days (OR range: 0.54-0.72) and all migrant groups experienced more unemployment days (IRR range: 1.26-1.37). Results were largely unchanged after adjustment for sociodemographic and clinical factors. In the adjusted model, both Swedish migrant groups and refugees in Denmark were more likely to experience zero sickness absence days than native-born individuals (OR range: 1.48-1.56). Only refugees in Denmark were at greater risk of disability pension. CONCLUSIONS: Non-refugee migrants and refugees with NAPDs in both Sweden and Denmark are particularly vulnerable to experiencing unemployment. Targeted interventions may help to reduce these disparities and promote long-term work ability among migrant groups.

Understanding the protective effect of social support on depression symptomatology from a longitudinal network perspective.

BACKGROUND: Higher social support protects people from developing mental disorders. Limited evidence is available on the mechanism through which social support plays this protective role. OBJECTIVE: To investigate the stress-buffering process of social support on depressive symptoms using a novel longitudinal dynamic symptom network approach. METHODS: A total of 4242 adult participants who completed the first two waves (from May to October 2020) of the International Covid Mental Health Survey were included in the study. Cross-lagged panel network modelling was used to estimate a longitudinal network of self-reported social support, loneliness and depressive symptoms. Standardised regression coefficients from regularised cross-lagged regressions were estimated as edge weights of the network. FINDINGS: The results support a unidirectional protective effect of social support on key depressive symptoms, partly mediated through loneliness: A higher number of close confidants and accessible practical help was associated with decreased anhedonia (weight=-0.033) and negative self-appraisal symptoms (weight=-0.038). Support from others was also negatively associated with loneliness, which in turn associated with decreased depressed mood (weight=0.086) and negative self-appraisal (weight=0.077). We identified a greater number of direct relationships from social support to depressive symptoms among men compared with women. Also, the edge weights from social support to depression were generally stronger in the men's network. CONCLUSIONS: Reductions in negative self-appraisal might function as a bridge between social support and other depressive symptoms, and, thus, it may have amplified the protective effect of social support. Men appear to benefit more from social support than women. CLINICAL IMPLICATIONS: Building community-based support networks to deliver practical support, and loneliness reduction components are critical for depression prevention interventions after stressful experiences.

Incidence of non-affective psychotic disorders in refugees and peers growing up in Denmark and Sweden: a registry linkage study.

PURPOSE: Higher rates of non-affective psychotic disorders (NAPD) in minority groups have been reported in many countries. However, few studies have explored how rates differ between refugees and other minority groups and none with an international comparative angle. A comparative perspective makes it possible to relate group differences to aspects national context that underpin the social determinants of disease. METHODS: We compared the incidence of treated NAPD among youth born in or who immigrated to Denmark/Sweden before turning 18. Youth aged 18-35 during 2006-2018 were included (NDenmark/NSweden = 1,606,423/2,614,721) and were followed until first NAPD treatment (cases [Denmark/Sweden] = 12,193/9,641), 36th birthday, emigration or death. Incidence rates (IR) and ratios (IRR) comparing refugees, non-refugee migrants, descendants of non-refugee migrants and majority youth were obtained through Poisson regression on data aggregated by country, sex and age, contrasted by sex and country. Complementary analyses on individual-level data adjusting for further socio-demographic factors were conducted in each country separately. RESULTS: Incidence rates were higher in all groups compared with the majority group (IRRrange = 1.4-2.9, 95% CI[min, max] = 1.2-3.1). Relative differences between the three minority groups were smaller (IRRrange = 0.7-1.0, 95% CI[min, max] = 0.5-1.2). Although incidence rates were higher in Denmark than Sweden, relative group differences were similar. CONCLUSION: Exposures shared between young refugees and other minority groups growing up in Denmark and Sweden may be especially important for their excess risk of NAPD. Further studies should investigate the mechanisms behind the elevated rates in minority groups with special paid attention to factors such as discrimination, social exclusion and acculturation stress.