There is a lack of large-scale studies exploring labor market marginalization (LMM) among individuals diagnosed with bipolar disorder (BD). We aimed to investigate the association of BD with subsequent LMM in Sweden, and the effect of sex on LMM in BD.

Individuals aged 19–60 years living in Sweden with a first-time BD diagnosis between 2007 and 2016 (n = 25 231) were followed from the date of diagnosis for a maximum of 14 years. Risk of disability pension (DP), long-term sickness absence (SA) (>90 days), and long-term unemployment (>180 days) was compared to a matched comparison group from the general population, matched 1:5 on sex and birth year (n = 126 155), and unaffected full siblings (n = 24 098), using sex-stratified Cox regression analysis, yielding hazard ratios (HRs) with 95% confidence intervals (CIs).

After adjusting for socioeconomic factors, baseline labor market status, and comorbid disorders, individuals with BD had a significantly higher risk of DP compared to the general population (HR = 16.67, 95% CI 15.33–18.13) and their unaffected siblings (HR = 5.54, 95% CI 4.96–6.18). Individuals with BD were also more likely to experience long-term SA compared to the general population (HR = 3.19, 95% CI 3.09–3.30) and their unaffected siblings (HR = 2.83, 95% CI 2.70–2.97). Moreover, individuals diagnosed with BD had an elevated risk of long-term unemployment relative to both comparison groups (HR range: 1.75–1.78). Men with BD had a higher relative risk of SA and unemployment than women. No difference was found in DP.

Individuals with BD face elevated risks of LMM compared to both the general population and unaffected siblings.

A nationwide register-based cohort study from Finland including 48 124 incident benzodiazepines and related drug (BZDR) users aged 18–65 years who initiated use in 2006 and were not dispensed BZDRs during 2004–2005. The follow-up was 5 years or until death, whichever occurred first.

To investigate sociodemographic and clinical factors associated with high-dose use of BZDRs (i.e. Z-drugs) among new BZDR users.

The temporal BZDR dose was calculated as a point estimate every 6 months after initiation as defined daily doses (DDDs) per day, based on the PRE2DUP method (an approach based on mathematical modelling of personal drug purchasing behaviours). Sociodemographic and clinical factors associated with dose categories were studied using multinomial logistic regression.

During the 5-year follow-up, very high-dose BZDR use was observed in 7.4% (n = 3557) and medium high-dose use in 25.5% (n = 12 266) of the users (corresponding to ≥30 mg and 10–29 mg in diazepam equivalents, respectively). Very high-dose use was more common among men compared with women (10.9% versus 4.6%). Very high-dose use patterns were especially observed in younger age groups (18- to 25-year-olds). Compared with oxazepam, initiating BZDR use with clonazepam (adjusted odds ratio 3.86, 95% CI 3.24–4.60), diazepam (2.05, 1.78–2.36) or alprazolam (1.76, 1.52–2.03) was associated with increased odds for very high-dose use. Both medium high-dose and very high-dose BZDR use were associated with a lower level of education. In all, 58% of very high-dose use occurred in BZDR users who received their first prescription from general practitioners.

Clinicians should be aware of the dose escalation risk especially when prescribing diazepam, alprazolam or clonazepam for psychiatric indications. If BZDRs are needed, our findings suggest favouring oxazepam.

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.

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.

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.

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.

Pharmacological treatment patterns for bipolar disorder have changed during recent years, but for better or worse?

To investigate the comparative real-world effectiveness of antipsychotics and mood stabilisers in bipolar disorder.

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.

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.

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.

Evidence on the role of co-occurring psychiatric disorders in mortality associated with psychotic depression is limited.

To estimate the risk of cause-specific mortality in psychotic depression compared with severe non-psychotic depression while controlling for comorbid psychiatric disorders.

This cohort study used routine data from nationwide health registers in Finland. Eligible participants had their first diagnosis for psychotic depression or for severe non-psychotic depression between the years 2000 and 2018, had no pre-existing diagnoses for schizophrenia spectrum disorders or bipolar disorder, and were aged 18–65 years at the index diagnosis. Causes of death were defined by ICD-10 codes. The follow-up time was up to 18 years.

We included 19 064 individuals with incident psychotic depression and 90 877 individuals with incident non-psychotic depression. Half (1199/2188) of the deaths in those with psychotic depression occurred within 5 years from the index diagnosis and the highest relative risk was during the first year after the diagnosis. Compared with individuals with non-psychotic depression, those with psychotic depression had a higher risk of all-cause mortality (adjusted hazard ratio, aHR = 1.59, 95% CI 1.48–1.70), suicides (aHR = 2.36, 95% CI 2.11–2.64) and fatal accidents (aHR 1.63, 95% CI 1.26–2.10) during the subsequent 5-year period after the index diagnosis.

Psychotic symptoms markedly added to the mortality risk associated with severe depression after controlling for psychiatric comorbidity. Prompt treatment and enhanced monitoring for psychotic symptoms is warranted in all patients with severe depression to prevent deaths because of suicides and other external causes.

Research on the effectiveness of pharmacotherapies for schizophrenia and comorbid substance use disorder (SUD) is very sparse, and non-existent on the prevention of the development of SUDs in patients with schizophrenia.

To compare the real-world effectiveness of antipsychotics in schizophrenia in decreasing risk of developing an initial SUD, and psychiatric hospital admission and SUD-related hospital admission among patients with an SUD.

Two independent national cohorts including all persons diagnosed with schizophrenia (N = 45 476) were followed up for 22 (Finland: 1996–2017) and 11 (Sweden: 2006–2016) years. Risk of developing an SUD was calculated with between-individual models, and risks of psychiatric and SUD-related hospital admission were calculated with within-individual models, using Cox regression and adjusted hazard ratios (aHRs) for using versus not using certain antipsychotics.

For patients with schizophrenia without an SUD, clozapine use (Finland: aHR 0.20, 95% CI 0.16–0.24, P < 0.001; Sweden: aHR 0.35, 95% CI 0.24–0.50, P < 0.001) was associated with lowest risk of developing an initial SUD in both countries. Antipsychotic polytherapy was associated with second lowest risk (aHR 0.54, 95% CI 0.44–0.66) in Sweden, and third lowest risk (aHR 0.47, 95% CI 0.42–0.53) in Finland. Risk of relapse (psychiatric hospital admission and SUD-related hospital admission) were lowest for clozapine, antipsychotic polytherapy and long-acting injectables in both countries. Results were consistent across both countries.

Clozapine and antipsychotic polytherapy are most strongly associated with reduced risk of developing SUDs among patients with schizophrenia, and with lower relapse rates among patients with both diagnoses.

Higher incidence of psychotic disorders and underuse of mental health services have been reported among many migrant populations. This study examines the initiation and continuity of antipsychotic treatment among migrants and non-migrants with a non-affective psychosis during a new treatment episode.

This study is based on a nationwide sample of migrants and Finnish-born controls. Participants who were diagnosed with a psychotic disorder in 2011–2014 were identified from the Care Register for Health Care (n = 1693). Information on purchases of antipsychotic drugs in 2011–2015 was collected from the National Prescription Register. The duration of antipsychotic treatment since diagnosis was estimated using the PRE2DUP model. Cox regression analysis was used to study factors that are associated with discontinuing the use of medication.

There were fewer initiators of antipsychotic treatment after being diagnosed with psychosis among migrants (68.1%) than among Finnish-born patients (73.6%). After controlling for sociodemographic background and factors related to the type of disorder and treatment, migrants were more likely to discontinue medication (adjusted hazard ratio 1.28, 95% confidence interval 1.08–1.52). The risk of discontinuation was highest among migrants from North Africa and the Middle East and Sub-Saharan Africa and among recent migrants. Non-use of antipsychotic treatment before being diagnosed with psychosis, involuntary hospitalization and diagnosis other than schizophrenia were associated with earlier discontinuation both among migrants and non-migrants.

Migrants with a psychotic disorder are less likely to continue antipsychotic treatment than non-migrants. The needs of migrant patients have to be addressed to improve adherence.

Although clozapine is often discontinued, there is a paucity of guidelines and evidence on treatment options after clozapine discontinuation. Moreover, it is currently unknown whether reinstating clozapine in patients formerly using clozapine should be avoided.

To compare the real-world effectiveness of antipsychotics after clozapine cessation.

From Finnish registry data (1995–2017), we identified 2250 patients with schizophrenia who had been using clozapine for ≥1 year before treatment cessation. The primary analysis consisted of adjusted within-individual analyses of psychiatric ward readmission owing to psychosis and treatment failure. Secondary analyses concerned between-individual mortality differences.

Compared with no use of antipsychotics, risk of psychiatric ward readmission was lowest for reinitiation of clozapine (adjusted hazard ratio (aHR) 0.49; 95% CI 0.40–0.61; P < 0.0001), oral olanzapine (aHR 0.58; 95% CI 0.48–0.71; P < 0.0001) and antipsychotic polypharmacy (aHR 0.62; 95% CI 0.53–0.72; P < 0.0001). Risk of treatment failure was lowest for aripiprazole long acting injectable (aHR 0.42; 95% CI 0.27–0.65; P < 0.0001), reinitiation of clozapine (aHR 0.49; 95% CI 0.43–0.57; P < 0.0001) and oral olanzapine (aHR 0.69; 95% CI 0.61–0.77; P < 0.0001). Mortality risk was lowest for reinitiation of clozapine (aHR 0.18; 95% CI 0.09–0.36; P < 0.0001) and oral olanzapine (aHR 0.26; 95% CI 0.17–0.40; P < 0.0001).

Clozapine and olanzapine are the most effective and safest treatment options in those discontinuing clozapine for undefined reasons. Clozapine should therefore be reconsidered in patients with schizophrenia who previously discontinued this compound.

There is uncertainty about the incidence of breakthrough psychosis in treatment adherent patients, and the role that factors, such as cumulative antipsychotic exposure, play in this phenomenon.

In a nationwide cohort of individuals treated for schizophrenia-spectrum disorders in Finland between 1 January 1996 and 31 December 2015, ‘Breakthrough Psychosis on Antipsychotic Maintenance Medication’ (BAMM) was defined as hospitalization for psychosis despite ongoing continuous treatment with long-acting injectable antipsychotics (LAIs) or oral antipsychotics (OAPs) for ⩾8 weeks. Incidence rates, survival curves, and risk factors were presented.

In a cohort of 16 031 continuous LAI treatment episodes with virtually assured adherence [median duration = 441 days, interquartile range (IQR) = 155–1277], BAMM incidence was 31.5%. For 42 867 OAPs treatment episodes (median duration = 483 days, IQR = 167–1491), for whom adherence was modeled by the PRE2DUP method, BAMM incidence was 31.1%. Factors related to illness instability at treatment onset were associated with BAMM, although median time to BAMM was 291 days (IQR = 121–876) for LAIs and 344 days (IQR = 142–989) for OAPs, and 27.4% (N = 1386) of the BAMM events in the LAI, and 32.9% (N = 4378) in the OAP group occurred despite >1 year since last hospitalization at treatment onset. Cumulative antipsychotic exposure was not a consistent risk factor.

BAMM was relatively common even when adherence was confirmed with LAIs. Illness instability at treatment onset accounted for most cases, but relapse after years of continuous treatment was still prevalent. There was insufficient evidence to support causality between cumulative antipsychotic exposure and BAMM. Future research needs to address the role of symptom severity and neurobiology in BAMM.

We analyzed the impact of opioid initiation on the prevalence of antipsychotic and benzodiazepine and related drug (BZDR) use among community-dwelling persons with Alzheimer's disease (AD).

We utilized the register-based Medication use and Alzheimer's disease (MEDALZ) cohort for this study. We included all community-dwelling persons diagnosed with AD during 2010–2011 in Finland initiating opioid use (n = 3,327) and a matched cohort of persons not initiating opioids (n = 3,325). Interrupted time series analyses were conducted to compare the prevalence of antipsychotic and BZDR use in 30-day periods within six months before opioid initiation to 30-day periods six months later.

Before opioid initiation, prevalence of antipsychotic use among opioid initiators was 13.3%, 18.3% at opioid initiation, and 17.3% six months later. Prevalences of BZDR use were 27.1% six months prior, 28.9% at opioid initiation, and 26.9% six months later. After opioid initiation, antipsychotic and BZDR use declined by 0.3 percentage points (pps, 95% confidence interval 0.1–0.5) and 0.4 pps (0.2–0.7) per month, respectively, until the end of the follow-up. Compared to persons not initiating opioid use, opioid initiation immediately resulted in an increase in prevalence of 1.9 pps (0.9–2.8) for antipsychotics and of 1.6 pps (0.9–2.2) for BZDR use. However, in total there was a comparative decrease of 0.5 pps (0.3–0.8) per month for antipsychotics and of 0.4 pps (0.2–0.6) for BZDR use until the end of the follow-up.

Our results suggest that opioid initiation may reduce antipsychotic and BZDR use among persons with AD.

Behavioural and psychological symptoms of dementia are frequently treated with antipsychotics.

To determine the incidence of antipsychotic use in relation to diagnosis of Alzheimer's disease.

Cohort of all community-dwellers in Finland diagnosed with Alzheimer's disease in 2005 and matched controls. All antipsychotics dispensed between 1995 and 2009 were extracted from the Finnish National Prescription Register.

Altogether 1996/6087 (32.8%) persons with Alzheimer's disease initiated antipsychotic use. The incidence of antipsychotic use was fivefold among persons with Alzheimer's disease compared with controls, started to increase 2–3 years before diagnosis and was highest during the first 6 months after diagnosis.

A distinct increase in antipsychotic initiations occurs in the same time window as Alzheimer's disease diagnosis.

Objective: To date no studies have investigated the personality functioning underlying patients diagnosed with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) using the performance-based Rorschach test.

Methods: We scored and interpreted the Rorschach protocols of eight carefully diagnosed PLOSL patients according to Exner's Comprehensive System. The structural variables in the Rorschach are organised around the seven dimensions of personality functioning that they assess: coping style and resources, organising information, perceiving events, forming concepts and ideas, handling of emotions, self-perception and interpersonal perception.

Results: As a group PLOSL patients had many personality liabilities when contrasted with typical avoidant non-patient adults. A majority of patients showed an avoidant coping style (Lambda > 0.99), low productivity and poor verbal output in the low number of responses and few Blends. Also, they showed limited available resources to cope with problem-solving test. Problems in organising information efficiently, and perceiving events realistically as well as signs of disturbed thinking and concept formation were observed in many patients. Handling of emotions was characterised by avoidance of emotional stimuli but at the same time poor affect modulation. Capacities to view themselves and others were thoroughly limited.

Conclusions: PLOSL tends to have repercussions throughout the personality functioning. In line with clinical findings and later neuroradiological and neuropathological examinations the Rorschach revealed personality features typical for frontal type of dementia.