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.

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.

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.

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.

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.

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.

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.

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.

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.

Research Review: Psychological and psychosocial interventions for children and adolescents with depression, anxiety, and post-traumatic stress disorder in low- and middle-income countries - a systematic review and meta-analysis.

BACKGROUND: The incidence of depression, anxiety, and post-traumatic stress disorder (PTSD) among children and adolescents residing in low- and middle-income countries (LMICs) poses a significant public health concern. However, there is variation in the evidence of effective psychological interventions. This meta-analysis aims to provide a complete overview of the current body of evidence in this rapidly evolving field. METHODS: We conducted searches on PubMed, Embase.com, and EBSCO/APA PsycInfo databases up to June 23, 2022, identify randomized controlled trials (RCTs) investigating the effectiveness of psychological interventions in LMICs that targeted children and adolescents with elevated symptoms above a cut-off score for depression, anxiety, and PTSD, comparing a psychological or psychosocial intervention with other control conditions. We conducted random effects meta-analyses for depression, anxiety, and PTSD symptoms. Sensitivity analysis for outliers and high-risk studies, and analyses for the publication bias were carried out. Subgroup analyses investigated how the intervention type, intervention format, the facilitator, study design, and age group of the participant predicted effect sizes. RESULTS: Thirty-one RCTs (6,123 participants) were included. We found a moderate effect of interventions on depression outcomes compared to the control conditions (g = 0.53; 95% CI: 0.06-0.99; NNT = 6.09) with a broad prediction interval (PI) (-1.8 to 2.86). We found a moderate to large effect for interventions on anxiety outcomes (g = 0.88; 95% CI: -0.03 to 1.79; NNT = 3.32) with a broad PI (-3.14 to 4.9). Additionally, a moderate effect was observed on PTSD outcomes (g = 0.54; 95% CI: 0.19-0.9; NNT = 5.86) with a broad PI (-0.64 to 1.72). CONCLUSIONS: Psychological and psychosocial interventions aimed at addressing depression, anxiety, and PTSD among children and adolescents in LMICs have demonstrated promising results. However, future studies should consider the variation in evidence and incorporate long-term outcomes to better understand the effectiveness of these interventions.

Comparison of Hospitalization for Nonaffective Psychotic Disorders Among Refugee, Migrant, and Native-Born Adults in Sweden and Denmark.

Importance: Determining whether migrants with nonaffective psychotic disorders (NAPDs) experience poorer outcomes after illness onset is essential to ensure adequate health care provision to these disadvantaged populations. Objective: To compare cumulative hospital days for NAPDs during the first 5 years of illness among refugee, nonrefugee, and second-generation migrants and their Swedish and Danish peers. Design, Setting, and Participants: This was a prospective cohort study of individuals treated for incident NAPDs in inpatient or outpatient settings between January 1, 2006, and December 31, 2013, and followed up for 5 years. This population-based study used Swedish and Danish national registries. Included participants were individuals in Sweden and Denmark, aged 18 to 35 years, treated for incident NAPDs. Data analyses were conducted from November 2022 to August 2023. Exposures: Population group (determined according to residency in either country, not both countries), categorized as refugee (migrants whose residence in Sweden or Denmark was registered as refugee status or family reunification with a refugee), nonrefugee (all other individuals born outside Sweden and Denmark), second generation (individuals born in Sweden or Denmark with at least 1 parent born abroad), or native born (individuals born in Sweden or Denmark with both parents born in these countries). Main Outcome and Measures: Total hospital days for NAPDs during the first 5 years of illness, analyzed using a hurdle model. Among those ever admitted, total number of admissions and mean admission length were examined. Results: In total, 7733 individuals in Sweden (mean [SD] age, 26.0 [5.1] years; 4919 male [63.6%]) and 8747 in Denmark (mean [SD] age 24.8 [5.0] years; 5324 male [60.9%]) were followed up for 5 years or until death or emigration. After adjusting for a range of sociodemographic and clinical factors, the odds of experiencing any hospital days for NAPD were significantly higher among migrant groups compared with their native-born peers (Sweden: second generation, odds ratio [OR], 1.17; 95% CI, 1.03-1.33; P = .01; nonrefugee migrant, OR, 1.45; 95% CI, 1.21-1.73; P < .001; refugee, OR, 1.25; 95% CI, 1.06-1.47; P = .009; Denmark: second generation, OR, 1.21; 95% CI, 1.05-1.40; P = .01; nonrefugee migrant, OR, 1.33; 95% CI, 1.14-1.55; P < .001). These odds were highest among nonrefugee (Sweden: OR, 2.53; 95% CI, 1.59-4.03; P < .001; Denmark: OR, 2.61; 95% CI, 1.70-4.01; P < .001) and refugee (Sweden: OR, 1.96; 95% CI, 1.43-2.69; P < .001; Denmark: OR, 2.14; 95% CI, 1.42-3.21; P < .001) migrants from Africa and those who had arrived within 3 to 5 years (Sweden: nonrefugee migrants, OR, 1.93; 95% CI, 1.26-2.95; P = .002; refugees, OR, 2.38; 95% CI, 1.46-3.88; P < .001; Denmark: nonrefugee migrants, OR, 1.66; 95% CI, 0.96-2.85; P = .07; refugees, OR, 3.40; 95% CI, 1.13-10.17; P = .03). Among those ever hospitalized, refugees in both countries (Sweden, incidence rate ratio [IRR], 1.30; 95% CI, 1.12-1.51; P < .001; Denmark, IRR, 1.47; 95% CI, 1.24-1.75; P < .001) and second-generation migrants in Denmark (IRR, 1.22; 95% CI, 1.07-1.39; P = .003) experienced more days hospitalized for NAPDs than native-born individuals. Conclusions and Relevance: In this prospective cohort study of individuals with NAPDs, results suggest that refugee, nonrefugee, and second-generation migrants experience more days hospitalized for these disorders than their native-born peers. Patterns were consistent across 2 countries with different models of psychosis care and immigration and integration policies.

Sustainable labour market participation among working young adults with diagnosed attention deficit/hyperactivity disorder (ADHD).

Background: The aims were to study the sustainability of labour-market participation five years after an incident diagnosis of attention-deficit/hyperactivity disorder (ADHD) among young adults with gainful employment, and to examine the impact of sociodemographic-, work- and health-related factors on these findings. Methods: Swedish registers identified 2517 individuals, 19-29 years old, with an incident diagnosis of ADHD and gainful employment during 2006-2011. Labour-market participation was measured by the core-peripheral model, a model that measures the connection to the labour market from a weak connection (peripheral) to a strong connection (core). Sequence analysis analysed clusters of labour-market participation, from one year before and up to five years after diagnosis. Odds ratios (OR) with 95% confidence intervals (CI) between sociodemographic factors, comorbid disorders, and the identified clusters were analysed by multinomial logistic regression. Results: Five clusters of labour-market participation were identified: 60% of individuals belonged to a cluster that maintained labour-market participation throughout the study period (core, close to core); 20% belonged to a cluster with a transition to a weak connection to the labour market (close to peripheral, peripheral); and 20% belonged to a cluster with "middle" labour-market participation, characterised by having long periods of sick leave and unemployment. Individuals with elementary school as highest attained education (OR:4.03;CI:2.35-6.93), comorbid mental disorders (OR:2.77;CI:2.10-3.66), or living in villages/small cities (OR:1.77;CI:1.25-2.51) were most likely to belong to a cluster transitioning towards a "peripheral" labour-market participation. Men were less likely to have peripheral labour-market participation than women (OR:0.55;CI:0.40-0.75). Conclusions: Over half of working individuals with ADHD maintain a strong attachment to the labour market several years after their first diagnosis of ADHD. Therefore, it is important to target those who have problems maintaining a position in the labour market, including women, those with low educational levels, and those living outside large cities.

Nordic region suicide trends 2000-2018; sex and age groups.

BACKGROUND AND AIM: Overall, suicide rates in the Nordic region, Denmark, Finland, Iceland, Norway and Sweden, have declined in the past 40 years. The aim of this study was to determine trends in suicide mortality from 2000 to 2018. METHODS: Data were obtained from official suicide statistics for men and women, 15 years and older. Gender and age groups in four calendar periods were analyzed using Joinpoint Estimated Regression Coefficient. RESULTS: The crude regional suicide rate was 17.1, 2000-2004, decreased to 14.1 per 100,000 inhabitants in 2015-2018. Age-standardized rates are 13.6-11.3. The crude rate decreased by 19.5% (16.3% age-standardized), 19.3% for males and 20.5% for females. The largest decrease was found in Finland (34.9%), the smallest in Norway (1.4%). In males, the exception was an increased suicide rate among all Icelandic except 15-24-year olds, and in 45-64 year-old Norwegians. Among females, an increase was seen among 15-24-year olds in all countries except Iceland, in all age groups in Norway, and in 25-44-year olds in Sweden. In males, a decline of the suicide rated lower than 10% was noted in 25-44 olds in Norway and in 15-64 year-olds in Sweden. DISCUSSION: A robust decrease was observed in the overall regional suicide rate in recent years. Exceptions are rising rates in Icelandic males, in Norwegian females, and the youngest female groups in all except Iceland. The small decline among middle-aged males in Norway and Sweden is of concern.

Comparative Effectiveness of Pharmacotherapies for the Risk of Attempted or Completed Suicide Among Persons With Borderline Personality Disorder.

Importance: Suicidal behavior is a significant clinical concern in individuals with borderline personality disorder (BPD), but the effectiveness of pharmacotherapy on reducing suicide risk has remained unknown. Objective: To study the comparative effectiveness of different pharmacotherapies in preventing attempted or completed suicides in patients with BPD in Sweden. Design, Setting and Participants: In this comparative effectiveness research study, nationwide Swedish register databases of inpatient care, specialized outpatient care, sickness absences, and disability pensions were used to identify patients aged 16 to 65 years with registered treatment contact due to BPD during 2006 to 2021. Data were analyzed from September to December 2022. A within-individual design was used, in which each patient was used as their own control to eliminate selection bias. To control protopathic bias, sensitivity analyses were conducted, in which the first 1 or 2 months of medication exposure were omitted from the analyses. Main outcomes and Measures: Hazard ratio (HR) for attempted or completed suicide. Results: A total of 22 601 patients with BPD (3540 [15.7%] men; mean [SD] age, 29.2 [9.9] years) were included. During the 16-year follow-up (mean [SD] follow-up, 6.9 [5.1] years), 8513 hospitalizations due to attempted suicide and 316 completed suicides were observed. Attention-deficit/hyperactive disorder (ADHD) medication treatment, compared with its nonuse, was associated with a decrease in the risk of attempted or completed suicide (HR, 0.83; 95% CI, 0.73-0.95; false discovery rate [FDR]-corrected P = .001). Treatment with mood stabilizers did not have a statistically significant association with the main outcome (HR, 0.97; 95% CI, 0.87-1.08; FDR-corrected P = .99). Antidepressant (HR, 1.38; 95% CI, 1.25-1.53; FDR-corrected P < .001) and antipsychotic (HR, 1.18; 95% CI, 1.07-1.30; FDR-corrected P < .001) treatments were associated with an elevated risk of attempted or completed suicide. Of the investigated pharmacotherapies, treatment with benzodiazepines was associated with the highest risk of attempted or completed suicide (HR, 1.61; 95% CI, 1.45-1.78; FDR-corrected P < .001). These results remained similar when controlling for potential protopathic bias. Conclusions and Relevance: In this comparative effectiveness research study of a Swedish nationwide cohort, ADHD medication was the only pharmacological treatment associated with reduced risk of suicidal behavior among patients with BPD. Conversely, the findings suggest that benzodiazepines should be used with care among patients with BPD due to their association with increased risk of suicide.

The role of sociodemographic and clinical factors in the initiation and discontinuation of attention deficit hyperactivity disorder medication among young adults in Sweden.

Introduction: Long-term medication use is a recommended treatment for attention-deficit/hyperactivity disorder (ADHD), however, discontinuation is common. Non-medical factors which might influence initiation and discontinuation are understudied. Therefore, we investigated how different sociodemographic factors and comorbidities were associated with the initiation and discontinuation of ADHD medication use among young adults. Methods and results: We conducted a population-based prospective cohort study using individually linked administrative register data, in which we included all individuals residing in Sweden, between the age of 19 and 29 who were first diagnosed with ADHD between January 2006 and December 2016 (n = 59224). ADHD medication initiation was defined as the first prescription of ADHD medication in the period from 3 months before to 6 months after the cohort entry date. Those who initiated ADHD medication were followed up for medication use until discontinuation, death/emigration, or until 2019. Logistic and Cox regression models were used to investigate the associations between sociodemographics, health-related predictors and initiation, as well as discontinuation. Overall, 48.7% of the 41399 individuals initiated ADHD medication, most often methylphenidate (87%). Among the initiators, 15462 (77%) discontinued medication use during the follow-up (median time: 150 days). After mutually adjusting all other predictors, initiation was positively associated with older age, male sex, higher level of education, and negatively associated with living at home with parents, immigrant status, being unemployed during the year before inclusion, being on disability pension, having autism, substance use, schizophrenia-spectrum disorders, other mental disability/developmental disorders, cardiovascular diseases or previous accidents. Discontinuation was positively associated with being born abroad, living in big cities, being unemployed during the year before inclusion, having cancer, and negatively associated with a higher educational level, having depression, anxiety or stress-related disorder, autism spectrum disorder or diabetes. Conclusion: Besides medical factors, sociodemographics, such as educational attainment and immigrant status might also play a role in the initiation and discontinuation of ADHD medication use among young adults newly diagnosed with ADHD.

Are we equally at risk of changing smoking behavior during a public health crisis? Impact of educational level on smoking from the TEMPO cohort.

BACKGROUND: The COVID-19 pandemic as a public health crisis has led to a significant increase in mental health difficulties. Smoking is strongly associated with mental health conditions, which is why the pandemic might have influenced the otherwise decline in smoking rates. Persons belonging to socioeconomically disadvantaged groups may be particularly affected, both because the pandemic has exacerbated existing social inequalities and because this group was more likely to smoke before the pandemic. We examined smoking prevalence in a French cohort study, focusing on differences between educational attainment. In addition, we examined the association between interpersonal changes in tobacco consumption and educational level from 2018 to 2021. METHODS: Using four assessments of smoking status available from 2009 to 2021, we estimated smoking prevalence over time, stratified by highest educational level in the TEMPO cohort and the difference was tested using chi2 test. We studied the association between interpersonal change in smoking status between 2018 and 2021 and educational attainment among 148 smokers, using multinomial logistic regression. RESULTS: Smoking prevalence was higher among those with low education. The difference between the two groups increased from 2020 to 2021 (4.8-9.4%, p < 0.001). Smokers with high educational level were more likely to decrease their tobacco consumption from 2018 to 2021 compared to low educated smokers (aOR = 2.72 [1.26;5.89]). CONCLUSION: Current findings showed a widening of the social inequality gap in relation to smoking rates, underscoring the increased vulnerability of persons with low educational level to smoking and the likely inadequate focus on social inequalities in relation to tobacco control policies during the pandemic.

Association of pharmacological treatments and real-world outcomes in borderline personality disorder.

OBJECTIVE: Most patients with borderline personality disorder (BPD) receive psychopharmacological treatment, but clinical guidelines on BPD lack consensus on the role of pharmacotherapy. We investigated the comparative effectiveness of pharmacological treatments for BPD. METHODS: We identified patients with BPD with treatment contact during 2006-2018 using Swedish nationwide register databases. By leveraging within-individual design, in which each individual was used as their own control to eliminate selection bias, we assessed the comparative effectiveness of pharmacotherapies. For each medication, we calculated the hazard ratios (HRs) for the following outcomes: (1) psychiatric hospitalization and (2) hospitalization owing to any cause or death. RESULTS: We identified 17,532 patients with BPD (2649 men; mean [SD] age = 29.8 [9.9]). Treatment with benzodiazepines (HR = 1.38, 95% CI = 1.32-1.43), antipsychotics (HR = 1.19, 95% CI = 1.14-124), and antidepressants (HR = 1.18, 95% CI = 1.13-1.23) associated with increased risk of psychiatric rehospitalization. Similarly, treatment with benzodiazepines (HR = 1.37, 95% CI = 1.33-1.42), antipsychotics (HR = 1.21, 95% CI = 1.17-1.26), and antidepressants (HR = 1.17, 95% CI = 1.14-1.21) was associated with a higher risk of all-cause hospitalization or death. Treatment with mood stabilizers did not have statistically significant associations with the outcomes. Treatment with ADHD medication was associated with decreased risk of psychiatric hospitalization (HR = 0.88, 95% CI = 0.83-0.94) and decreased risk of all-cause hospitalization or death (HR = 0.86, 95% CI = 0.82-0.91). Of the specific pharmacotherapies, clozapine (HR = 0.54, 95% CI = 0.32-0.91), lisdexamphetamine (HR = 0.79, 95% CI = 0.69-0.91), bupropion (HR = 0.84, 95% CI = 0.74-0.96), and methylphenidate (HR = 0.90, 95% CI = 0.84-0.96) associated with decreased risk of psychiatric rehospitalization. CONCLUSIONS: ADHD medications were associated with a reduced risk of psychiatric rehospitalization or hospitalization owing to any cause or death among individuals with BPD. No such associations were found for benzodiazepines, antidepressants, antipsychotics, or mood stabilizers.

Antipsychotic treatment patterns in refugees and their Swedish-born peers with first-episode non-affective psychosis: findings from the REMAIN study.

BACKGROUND: Previous studies suggest that migrants tend to utilise antipsychotics less often than their native-born peers. However, studies examining antipsychotic use among refugees with psychosis are lacking. AIMS: To compare the prevalence of antipsychotic drug use during the first 5 years of illness among refugees and Swedish-born individuals with a newly diagnosed non-affective psychotic disorder, and to identify sociodemographic and clinical factors associated with antipsychotic use. METHOD: The study population included refugees (n = 1656) and Swedish-born persons (n = 8908) aged 18-35 years during 2007-2018, with incident diagnosis of non-affective psychotic disorder recorded in the Swedish in-patient or specialised out-patient care register. Two-week point prevalence of antipsychotics use was assessed every 6 months in the 5 years following first diagnosis. Factors associated with antipsychotic use (versus non-use) at 1 year after diagnosis were examined with modified Poisson regression. RESULTS: Refugees were somewhat less likely to use antipsychotics at 1 year after first diagnosis compared with Swedish-born persons (37.1% v. 42.2%, age- and gender-adjusted risk ratio 0.88, 95% CI 0.82-0.95). However, at the 5-year follow-up, refugees and Swedish-born individuals showed similar patterns of antipsychotic use (41.1% v. 40.4%). Among refugees, higher educational level (>12 years), previous antidepressant use and being diagnosed with schizophrenia/schizoaffective disorder at baseline were associated with an increased risk of antipsychotics use, whereas being born in Afghanistan or Iraq (compared with former Yugoslavia) was associated with decreased risk. CONCLUSIONS: Our findings suggest that refugees with non-affective psychotic disorders may need targeted interventions to ensure antipsychotic use during the early phase of illness.