Antipsychotic medications and sleep problems in patients with schizophrenia.

BACKGROUND: Sleep problems are common and related to a worse quality of life in patients with schizophrenia. Almost all patients with schizophrenia use antipsychotic medications, which usually increase sleep. Still, the differences in subjective sleep outcomes between different antipsychotic medications are not entirely clear. METHODS: This study assessed 5466 patients with schizophrenia and is part of the nationwide Finnish SUPER study. We examined how the five most common antipsychotic medications (clozapine, olanzapine, quetiapine, aripiprazole, and risperidone) associate with questionnaire-based sleep problems in logistic regression analyses, including head-to-head analyses between different antipsychotic medications. The sleep problems were difficulties initiating sleep, early morning awakenings, fatigue, poor sleep quality, short (≤6 h) and long sleep duration (≥10 h). RESULTS: The average number of antipsychotic medications was 1.59 per patient. Clozapine was associated with long sleep duration (49.0 % of clozapine users vs 30.2 % of other patients, OR = 2.05, 95 % CI 1.83-2.30, p < .001). Olanzapine and risperidone were in head-to-head analyses associated with less sleep problems than patients using aripiprazole, quetiapine, or no antipsychotic medication. Aripiprazole and quetiapine were associated with more insomnia symptoms and poorer sleep quality. Patients without antipsychotic medications (N = 159) had poorer sleep quality than patients with antipsychotic use, and short sleep duration was common (21.5 % of patients using antipsychotics vs 7.8 % of patients using antipsychotics, OR = 2.97, 95 % CI 1.98-4.44, p < .001). CONCLUSIONS: Prevalence of sleep problems is markedly related to the antipsychotic medication the patient uses. These findings underline the importance of considering and assessing sleep problems when treating schizophrenia patients with antipsychotics.

Long-term benzodiazepine use and risk of labor market marginalization in Finland: A cohort study with 5-year follow-up.

BACKGROUND: Benzodiazepines and related drugs (BZDRs) are widely used in the treatment of anxiety and sleep disorders, but cognitive adverse effects have been reported in long-term use, and these may increase the risk of labor market marginalization (LMM). The aim of this study was to investigate whether the risk of LMM is associated with new long-term BZDR use compared to short-term use. METHODS: This register-based nationwide cohort study from Finland included 37,703 incident BZDR users aged 18-60 years who initiated BZDR use in 2006. During the first year of use, BZDR users were categorized as long-term users (≥180 days) versus short-term users based on PRE2DUP method. The main outcome was LMM, defined as receipt of disability pension, long-term sickness absence (>90 days), or long-term unemployment (>180 days). The risk of outcomes was analyzed with Cox regression models, adjusted with sociodemographic background, somatic and psychiatric morbidity, other types of medication and previous sickness absence. RESULTS: During 5 years of follow-up, long-term use (34.4%, N = 12,962) was associated with 27% (adjusted Hazard Ratio, aHR 1.27, 95% CI 1.23-1.31) increased risk of LMM compared with short-term use. Long-term use was associated with 42% (aHR 1.42, 95% CI 1.34-1.50) increased risk of disability pension and 26% increased risk of both long-term unemployment and long-term sickness absence. CONCLUSIONS: These results indicate that long-term use of BZDRs is associated with increased risk of dropping out from labor market. This may be partly explained by cognitive adverse effects of prolonged BZDR use, which should be taken into account when prescribing BZDRs.

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.

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.

Regional differences in mortality risk and in attenuating or aggravating factors in schizophrenia: A systematic review and meta-analysis.

People with schizophrenia die prematurely, yet regional differences are unclear. PRISMA 2020-compliant systematic review/random-effects meta-analysis of cohort studies assessing mortality relative risk (RR) versus any control group, and moderators, in people with ICD/DSM-defined schizophrenia, comparing countries and continents. We conducted subgroup, meta-regression analyses, and quality assessment. The primary outcome was all-cause mortality. Secondary outcomes were suicide-, /natural-cause- and other-cause-related mortality. We included 135 studies from Europe (n = 70), North-America (n = 29), Asia (n = 33), Oceania (n = 2), Africa (n = 1). In incident plus prevalent schizophrenia, differences across continents emerged for all-cause mortality (highest in Africa, RR=5.98, 95 %C.I.=4.09-8.74, k = 1, lowest in North-America, RR=2.14, 95 %C.I.=1.92-2.38, k = 16), suicide (highest in Oceania, RR=13.5, 95 %C.I.=10.08-18.07, k = 1, lowest in North-America, RR=4.4, 95 %C.I.=4.07-4.76, k = 6), but not for natural-cause mortality. Europe had the largest association between antipsychotics and lower all-cause mortality/suicide (Asia had the smallest or no significant association, respectively), without differences for natural-cause mortality. Higher country socio-demographic index significantly moderated larger suicide-related and smaller natural-cause-related mortality risk in incident schizophrenia, with reversed associations in prevalent schizophrenia. Antipsychotics had a larger/smaller protective association in incident/prevalent schizophrenia regarding all-cause mortality, and smaller protective association for suicide-related mortality in prevalent schizophrenia. Additional regional differences emerged in incident schizophrenia, across countries, and secondary outcomes. Significant regional differences emerged for all-cause, cause-specific and suicide-related mortality. Natural-cause death was homogeneously increased globally. Moderators differed across countries. Global initiatives are needed to improve physical health in people with schizophrenia, local studies to identify actionable moderators.

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.

Polygenic liability for antipsychotic dosage and polypharmacy - a real-world registry and biobank study.

Genomic prediction of antipsychotic dose and polypharmacy has been difficult, mainly due to limited access to large cohorts with genetic and drug prescription data. In this proof of principle study, we investigated if genetic liability for schizophrenia is associated with high dose requirements of antipsychotics and antipsychotic polypharmacy, using real-world registry and biobank data from five independent Nordic cohorts of a total of N = 21,572 individuals with psychotic disorders (schizophrenia, bipolar disorder, and other psychosis). Within regression models, a polygenic risk score (PRS) for schizophrenia was studied in relation to standardized antipsychotic dose as well as antipsychotic polypharmacy, defined based on longitudinal prescription registry data as well as health records and self-reported data. Meta-analyses across the five cohorts showed that PRS for schizophrenia was significantly positively associated with prescribed (standardized) antipsychotic dose (beta(SE) = 0.0435(0.009), p = 0.0006) and antipsychotic polypharmacy defined as taking ≥2 antipsychotics (OR = 1.10, CI = 1.05-1.21, p = 0.0073). The direction of effect was similar in all five independent cohorts. These findings indicate that genotypes may aid clinically relevant decisions on individual patients´ antipsychotic treatment. Further, the findings illustrate how real-world data have the potential to generate results needed for future precision medicine approaches in psychiatry.

Physical activity, suicidal ideation, suicide attempt and death among individuals with mental or other medical disorders: A systematic review of observational studies.

A growing body of research has demonstrated the potential role for physical activity as an intervention across mental and other medical disorders. However, the association between physical activity and suicidal ideation, attempts, and deaths has not been systematically appraised in clinical samples. We conducted a PRISMA 2020-compliant systematic review searching MEDLINE, EMBASE, and PsycINFO for observational studies investigating the influence of physical activity on suicidal behavior up to December 6, 2023. Of 116 eligible full-text studies, seven (n = 141691) were included. Depression was the most frequently studied mental condition (43%, k = 3), followed by chronic pain as the most common other medical condition (29%, k = 2). Two case-control studies examined suicide attempts and found an association between physical activity and a reduced frequency of such attempts. However, in studies examining suicidal ideation (k = 3) or suicide deaths (k = 2), no consistent associations with physical activity were observed. Overall, our systematic review found that physical activity may be linked to a lower frequency of suicide attempts in non-prospective studies involving individuals with mental disorders.

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.

Effect of severity of depression on augmentation of antidepressant medication in young adults with depression.

BACKGROUND: Antipsychotics (AP) have been used to augment antidepressant (AD) medication in treatment-resistant depression. In this study we examined factors (including severity of depression and initial antidepressant) affecting AP augmentation, as well as which APs were initiated as augmentation in young adults. METHODS: Data were extracted from Finnish nationwide registers. Of persons aged 18-29 years diagnosed with a depression during 2004-2017 we focused on incident AD users (who initiated AD 6 months before and after the diagnosis) whose severity level of depression was recorded (N = 21,966). AP augmentation was studied during 1 year after diagnosis of depression. Persons diagnosed with severe depression with psychotic features (n = 1486) were excluded from main analyses and analyzed separately. RESULTS: Overall, 8.4% of new antidepressant users initiated AP augmentation. Risk of augmentation increased with severity of depression as 3.9%, 5.8%, and 14.0% of persons with mild, moderate, and severe depression, respectively, initiated augmentation. Male sex, comorbid anxiety and personality disorders, substance abuse and selfharm/suicide attempt were positively associated with augmentation. Compared to citalopram, use of tricyclic antidepressant, paroxetine and venlafaxine were associated with increased risk of augmentation, while use of bupropion was associated with a decreased risk. Quetiapine and risperidone were the most common APs used in augmentation. Among persons with severe depression with psychotic features, use of sertraline was associated with AP augmentation, whereas use of fluoxetine decreased risk of augmentation. CONCLUSIONS: Use of APs as augmentation of AD therapy was common in severe depression. Comorbidities had only a small effect to augmentation, but selection of initial AD was more closely associated to risk of augmentation. Interestingly, use of bupropion decreased risk of augmentation, which warrants further studies, as well as the decrease in risk of augmentation when fluoxetine in case of psychotic depression was used.

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.

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.

Real-world use of pharmacological treatments for incident bipolar disorder: A Finnish nationwide cohort study.

BACKGROUND: Pharmacotherapy remains crucial for treating bipolar disorder (BD), but knowledge on the treatments actually used by newly diagnosed patients in real-world settings is sparse. METHODS: Individuals newly diagnosed with BD during 1996-2018, aged 15-65 years, were identified from national Finnish registers. The patients' use of different drug classes (mood stabilizers, antipsychotics and antidepressants) or combinations of these drug classes were followed from initial pharmacotherapy (first line) after BD diagnosis until the fifth line of treatment or until the two-year follow-up time ended. Clinical and sociodemographic factors associated with antidepressants-only as the first treatment line were assessed with logistic regression. RESULTS: 82.6 % of all patients used BD medication during the follow-up. 33.9 % had antidepressants-only as the first, 22.9 % as the second and 19.7 % as the third treatment line. Use of combinations of mood stabilizers, antipsychotics and antidepressants increased by successive treatment lines. Factors associated with antidepressants-only as the first treatment line included older age (>45 years aOR 2.20, 95% CI: 2.01-2.40, 25-45 years: 1.55, 1.42-1.68, compared with those aged <25), diabetes (1.35, 1.17-1.55) and female sex (1.29, 1.21-1.37). BD diagnosis registered in 2016-2018 (0.48, 0.42-0.55) and substance abuse (0.77, 0.71-0.83) were associated with decreased odds. LIMITATIONS: Due to the register-based nature of this study, not all potentially important clinical factors influencing medication use could be controlled for. CONCLUSIONS: A large proportion of patients with bipolar disorder are not treated according to treatment guidelines, as use of antidepressants alone is common. Reasons for not following evidence-based recommendations need to be further researched.

Real-world effectiveness of pharmacological treatments for bipolar disorder: register-based national cohort study.

BACKGROUND: Pharmacological treatment patterns for bipolar disorder have changed during recent years, but for better or worse? AIMS: To investigate the comparative real-world effectiveness of antipsychotics and mood stabilisers in bipolar disorder. METHOD: Register-based cohort study including all Finnish residents aged 16-65 with a diagnosis of bipolar disorder from in-patient care, specialised out-patient care, sickness absence and disability pensions registers between 1996 and 2018, with a mean follow-up of 9.3 years (s.d. = 6.4). Antipsychotic and mood stabiliser use was modelled using the PRE2DUP method and risk for hospital admission for psychiatric and non-psychiatric reasons when using versus not using medications was estimated using within-individual Cox models. RESULTS: Among 60 045 individuals (56.4% female; mean age 41.7 years, s.d. = 15.8), the five medications associated with lowest risk of psychiatric admissions were olanzapine long-acting injection (LAI) (aHR = 0.54, 95% CI 0.37-0.80), haloperidol LAI (aHR = 0.62, 0.47-0.81), zuclopenthixol LAI (aHR = 0.66, 95% CI 0.52-0.85), lithium (aHR = 0.74, 95% CI 0.71-0.76) and clozapine (aHR = 0.75, 95% CI 0.64-0.87). Only ziprasidone (aHR = 1.26, 95% CI 1.07-1.49) was associated with a statistically higher risk. For non-psychiatric (somatic) admissions, only lithium (aHR = 0.77, 95% CI 0.74-0.81) and carbamazepine (aHR = 0.91, 95% CI 0.85-0.97) were associated with significantly reduced risk, whereas pregabalin, gabapentin and several oral antipsychotics, including quetiapine, were associated with an increased risk. Results for a subcohort of first-episode patients (26 395 individuals, 54.9% female; mean age 38.2 years, s.d. = 13.0) were in line with those of the total cohort. CONCLUSIONS: Lithium and certain LAI antipsychotics were associated with lowest risks of psychiatric admission. Lithium was the only treatment associated with decreased risk of both psychiatric and somatic admissions.

Cause-specific excess mortality after first diagnosis of bipolar disorder: population-based cohort study.

BACKGROUND: Bipolar disorder (BD) is associated with increased mortality, but evidence on cause-specific mortality is limited. OBJECTIVE: To investigate cause-specific premature excess mortality in BD. METHODS: Finnish nationwide cohort study of individuals with and without a diagnosis of BD who were aged 15-64 years during 2004-2018. Standardised mortality ratios (SMRs) with 95% CIs were calculated for BD using the mortality rates in the Finnish general population without BD as weights. Causes of death were defined by the International Classification of Diseases, 10th revision codes. FINDINGS: Of the included 47 018 individuals with BD, 3300 (7%) died during follow-up. Individuals with BD had sixfold higher mortality due to external causes (SMR: 6.01, 95% CI: 5.68, 6.34) and twofold higher mortality due to somatic causes (SMR: 2.06, 95% CI: 1.97, 2.15). Of the deaths due to external causes, 83% (1061/1273) were excess deaths, whereas 51% (1043/2027) of the deaths due to somatic causes were excess. About twice the number of potential years of life were lost in excess due to external causes than due to somatic causes. Alcohol-related causes contributed more to excess mortality than deaths due to cardiovascular disease. CONCLUSION: External causes of death contributed more to the mortality gap than somatic causes after controlling for age-specific background general population mortality. CLINICAL IMPLICATION: A balanced consideration between therapeutic response, different treatment options and risk of cause-specific mortality is needed to prevent premature mortality in BD and to reduce the mortality gap.