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.

Cardiovascular mortality in bipolar disorder: Population-based cohort study.

BACKGROUND: Limited evidence base on cause-specific excess cardiovascular disease (CVD) mortality in bipolar disorder (BD) is a barrier to developing preventive interventions aimed at reducing the persistent mortality gap in BD. OBJECTIVE: To investigate cause-specific CVD mortality in BD. METHODS: We identified all individuals aged 15+ years during 2004-2018 with a diagnosis of BD using Finnish nationwide routine data. Standardised mortality ratios (SMR) with 95% confidence intervals (CI) were calculated using the mortality rates in the general population as weights. RESULTS: 53,273 individuals with BD (57% women; median age at BD diagnosis, 40 years), were followed up for 428,426 person-years (median, 8.2 years). There were 5988 deaths due to any cause, of which 26% were due to CVD. The leading cause of absolute excess CVD mortality was coronary artery disease (CAD). The leading causes of relative excess mortality were cardiomegaly (SMR, 4.51; 95% CI, 3.58-5.43), venous thromboembolism (3.03; 2.26-3.81), cardiomyopathy (2.46; 1.95-2.97), and hypertensive heart disease (2.12; 1.71-2.54). The leading causes of absolute CVD mortality showed markedly lower relative excess, including CAD (1.47; 1.34-1.61), ischaemic stroke (1.31; 1.06-1.54), and acute myocardial infarction (1.12; 0.98-1.25). Due to the higher relative excess mortality, structural and functional heart disorders contributed as much as atherosclerotic and ischaemic disorders to the absolute excess mortality. CONCLUSIONS: Cardiomyopathy and hypertensive heart disease as the leading causes of relative excess mortality emphasise the contribution of structural and functional heart disorders to the overall excess mortality alongside coronary artery disease. Interventions targeted at these modifiable causes of death should be priorities in the prevention of premature excess CVD mortality in BD.

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.

Dosing levels of antipsychotics and mood stabilizers in bipolar disorder: A Nationwide cohort study on relapse risk and treatment safety.

BACKGROUND: Finding effective treatment regimens for bipolar disorder is challenging, as many patients suffer from significant symptoms despite treatment. This study investigated the risk of relapse (psychiatric hospitalization) and treatment safety (non-psychiatric hospitalization) associated with different doses of antipsychotics and mood stabilizers in persons with bipolar disorder. METHODS: Individuals aged 15-65 with bipolar disorder were identified from Finnish national health registers in 1996-2018. Studied antipsychotics included olanzapine, risperidone, quetiapine, aripiprazole; mood stabilizers lithium, valproic acid, lamotrigine, and carbamazepine. Medication use was divided into three time-varying dose categories: low, standard, and high. The studied outcomes were risk of psychiatric hospitalization (relapse) and the risk of non-psychiatric hospitalization (treatment safety). Stratified Cox regression in within-individual design was used. RESULTS: The cohort included 60,045 individuals (mean age 41.7 years, SD 15.8; 56.4% female). Mean follow-up was 8.3 years (SD 5.8). Of antipsychotics, olanzapine and aripiprazole were associated with a decreased risk of relapse in low and standard doses, and risperidone in low dose. The lowest adjusted hazard ratio (aHR) was observed for standard dose aripiprazole (aHR 0.68, 95% CI 0.57-0.82). Quetiapine was not associated with a decreased risk of relapse at any dose. Mood stabilizers were associated with a decreased risk of relapse in low and standard doses; lowest aHR was observed for standard dose lithium (aHR 0.61, 95% CI 0.56-0.65). Apart from lithium, high doses of antipsychotics and mood stabilizers were associated with an increased risk of non-psychiatric hospitalization. Lithium was associated with a decreased risk of non-psychiatric hospitalization in low (aHR 0.88, 95% CI 0.84-0.93) and standard doses (aHR 0.81, 95% CI 0.74-0.88). CONCLUSIONS: Standard doses of lithium and aripiprazole were associated with the lowest risk of relapse, and standard dose of lithium with the lowest risk of non-psychiatric hospitalization. Quetiapine was not associated with decreased risk of relapse at any dose.

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

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

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.

Mortality in psychotic depression: 18-year follow-up study.

BACKGROUND: Evidence on the role of co-occurring psychiatric disorders in mortality associated with psychotic depression is limited. AIMS: To estimate the risk of cause-specific mortality in psychotic depression compared with severe non-psychotic depression while controlling for comorbid psychiatric disorders. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Continuity of antipsychotic medication use among migrant and Finnish-born populations with a psychotic disorder: a register-based study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Labour market marginalisation in young adults diagnosed with attention-deficit hyperactivity disorder (ADHD): a population-based longitudinal cohort study in Sweden.

BACKGROUND: The objective of this population-based register study was (1) to investigate the association between young adults diagnosed with attention-deficit/hyperactivity disorder (ADHD) and subsequent labour market marginalisation (LMM) in two comparison groups, i.e. matched young adults from the general population without ADHD and unaffected siblings to persons with ADHD and (2) to assess the role of comorbid disorders. METHODS: This study included all young adults in Sweden, aged 19-29 years, with an incident diagnosis of ADHD 2006-2011 (n = 9718). Crude and multivariate sex-stratified hazard ratios (HRs) with 95% confidence intervals (CIs) were measured 5 years after the diagnosis of ADHD for the risk of disability pension, long-term sickness absence (SA) (>90 days), long-term unemployment (>180 days) and a combined measure of all three in young adults with ADHD compared to their siblings without ADHD and a matched comparison group. RESULTS: In the adjusted analyses young adults with ADHD had a 10-fold higher risk of disability pension (HR = 10.2; CI 9.3-11.2), a nearly three-fold higher risk of long-term SA (HR = 2.7; CI 2.5-2.8) and a 70% higher risk of long-term unemployment (HR = 1.7; CI 1.6-1.8) compared to the matched comparison group. The risk estimates were lower compared to siblings for disability pension (HR = 9.0; CI 6.6-12.3) and long-term SA (HR = 2.5; CI 2.1-3.1) but higher in the long-term unemployed (HR = 1.9; CI 1.6-2.1). Comorbid disorders explained about one-third of the association between ADHD and disability pension, but less regarding SA and long-term unemployment. CONCLUSIONS: Young adults with ADHD have a high risk for different measures of LMM and comorbidities explain only a small proportion of this relationship.

Differential grandparental investment when maternal grandmothers are living versus deceased.

Grandparents can increase their inclusive fitness by investing time and resources in their grandchildren. However, not all grandparents make such investments equally, and between-grandparent differences in this regard can be predicted based on paternity uncertainty, lineage and grandparents' sex. Using population-based data for English and Welsh adolescents (n = 1430), we examined whether the death of the most important grandparent (in terms of investment), the maternal grandmother (MGM), changes relative support for existing hypotheses predicting differential grandparental-investment patterns. To contrast the predictions of the grandparental investment hypotheses, we used generalized order-restricted information criterion approximation. We consequently found that, when MGMs are alive, the most-supported hypothesis is 'discriminative grandparental solicitude', which ranks grandparental investment as MGMs > maternal grandfathers (MGFs) > paternal grandmothers (PGMs) > paternal grandfathers (PGFs). However, when MGMs are deceased, the paternity uncertainty hypothesis (MGFs = PGMs > PGFs) receives the most support; this is due to increased investment by PGMs. Thus, when the heaviest investors (i.e. MGMs) are deceased, PGM investments are closer to-but do not exceed-MGF investments.

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.

Real-world effectiveness of mood stabilizer use in schizophrenia.

OBJECTIVE: Mood stabilizers (MS) are often used as adjunctive medication in patients with schizophrenia. The aim of this study was to investigate the real-world effectiveness of MS use in persons with schizophrenia. METHODS: The study cohort included all persons treated in inpatient care due to schizophrenia during 1972-2014 in Finland (N = 61,889). Drug purchase data were obtained from the national Prescription register and modeled with the PRE2DUP method. The follow-up period covered the years 1996-2017. Mood stabilizers included carbamazepine, valproic acid, lamotrigine, and lithium. The main outcome was psychosis hospitalization. We utilized within-individual design to compare the risk of outcome between time-periods of MS use and non-use within the same person. Stratified Cox regression analyses were conducted with adjusted hazard ratios (aHR) and 95% confidence intervals (CIs). RESULTS: Mean age at cohort entry was 46.2 years (SD 16.0) and 50.3% were male. During the follow-up (maximum of 22 years, median 14.8 years, interquartile range 7.5-22.0), 28.1% (N = 17,370) of the study cohort used MS, valproic acid being the most often used one (60.4%, N = 10,483). Risk of psychosis hospitalization was lower during MS use than non-use (aHR 0.88, 95% CI 0.86-0.90). Use of lithium (0.84, 0.81-0.87), valproic acid (0.87, 0.85-0.90), and lamotrigine (0.90, 0.85-0.95) were associated with lower risk of psychosis hospitalization compared with their non-use, whereas carbamazepine use was not. CONCLUSIONS: Mood stabilizers were relatively often used as adjunctive treatments in schizophrenia and their use was associated with a 12% decreased risk of psychosis rehospitalization, a marker of relapse in schizophrenia.

Use of benzodiazepine and related drugs in migrants and Finnish-born persons: a nationwide register-based study.

AIMS: Benzodiazepines and related drugs (BZDR) are often used longer than generally recommended. The aim is to study patterns of use among migrant and Finnish-born users of BZDR, and to identify factors that are associated with long-term use and BZDR polytherapy. METHODS: This register-based study includes a nationwide sample of migrants (n=8729) and their Finnish-born controls (n=11 388) who had purchased BZDR in 2011-2014, but not in 2009-2010. Information on drug purchases was obtained from the National Prescription Register and the duration of drug use was estimated using PRE2DUP method. The main outcomes were long-term use of BZDR, polytherapy and time until discontinuation of BZDR use. Sociodemographic variables and information on preceding psychiatric diagnoses were included as covariates. Logistic and Cox regression analyses were the statistical methods used. RESULTS: Only migrants from Sub-Saharan Africa were more likely to discontinue the medication once initiated than Finnish-born users. Migrants were significantly less likely to be long-term users (adjusted odds ratio 0.79, 95% CI 0.70-0.89) or polytherapy users (aOR 0.90, 95% CI 0.84-0.97) of BZDR compared with Finnish-born participants. CONCLUSIONS: Migrants had less long-term and concomitant use of several BZDR than Finnish-born participants. The pattern of use is more optimal among migrants, but it may also reflect poorer access to mental health treatment.

Matrilateral bias of grandparental investment in grandchildren persists despite the grandchildren's adverse early life experiences.

Evolutionary theory predicts a downward flow of investment from older to younger generations, representing individual efforts to maximize inclusive fitness. Maternal grandparents and maternal grandmothers (MGMs) in particular consistently show the highest levels of investment (e.g. time, care and resources) in their grandchildren. Grandparental investment overall may depend on social and environmental conditions that affect the development of children and modify the benefits and costs of investment. Currently, the responses of grandparents to adverse early life experiences (AELEs) in their grandchildren are assessed from a perspective of increased investment to meet increased need. Here, we formulate an alternative prediction that AELEs may be associated with reduced grandparental investment, as they can reduce the reproductive value of the grandchildren. Moreover, we predicted that paternal grandparents react more strongly to AELEs compared to maternal grandparents because maternal kin should expend extra effort to invest in their descendants. Using population-based survey data for English and Welsh adolescents, we found evidence that the investment of maternal grandparents (MGMs in particular) in their grandchildren was unrelated to the grandchildren's AELEs, while paternal grandparents invested less in grandchildren who had experienced more AELEs. These findings seemed robust to measurement errors in AELEs and confounding due to omitted shared causes.

Associations between antipsychotic use, substance use and relapse risk in patients with schizophrenia: real-world evidence from two national cohorts.

BACKGROUND: 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. AIMS: 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. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

Twenty-year medication use trends in first-episode bipolar disorder.

OBJECTIVES: To study the medication use patterns in patients newly diagnosed with bipolar disorder (BD) in Finland during the past 20 years. METHODS: All persons diagnosed with BD between 1996 and 2018, aged 16-65 years, with no previous BD diagnosis were identified from nationwide Finnish registers (N = 26,395). The point prevalences of medication use were observed up until 5 years after the first diagnosis. Five sub-cohorts according to calendar year of first diagnosis were also formed and the prevalence of medication use was compared between sub-cohorts 3 months after diagnosis. Medication data were modeled with the PRE2DUP-method using dispensing data. RESULTS: The prevalence of overall medication use declined during the 5-year follow-up period in the total cohort. The highest prevalence of use was seen 3 months after diagnosis for the three main medication classes-antidepressants (40.8%), antipsychotics (30.8%) and mood stabilizers (29.2%). The prevalence of lithium use varied between 5.9% and 6.5% during the 5 years in the total cohort, and the lowest prevalence of use at 3 months was seen in sub-cohort diagnosed in 2016-2018 (4.1%) versus 12.1% in 1996-2000 sub-cohort. The prevalence of benzodiazepine use was between 12.4% and 13.5% and the prevalence of Z-drugs was between 7.3% and 7.9% during the 5 years. The prevalence of long-acting injectable antipsychotic (LAI) use was the highest in patients diagnosed in 2016-2018, although still only 0.8%. CONCLUSIONS: (i) The use of antidepressants is too prevalent, (ii) the use of lithium is declining and needs to be increased, and (iii) LAIs are markedly underutilized as compared to their oral counterparts.

Automated multi-dose dispensing in persons with and without Alzheimer's disease-impacts on pharmacotherapy.

PURPOSE: We investigated the drug use before and after transition to automated multi-dose dispensing (MDD) service among persons with Alzheimer's disease (AD) and compared whether the changes were similar in persons without AD. METHODS: The register-based Finnish nationwide MEDALZ cohort includes 70,718 community-dwelling persons diagnosed with AD during 2005-2011. Each person who initiated MDD was matched in both groups with a comparison person without MDD by age, gender and for persons with AD, also time since AD diagnosis at the start of MDD. The study cohort included 15,604 persons with AD in MDD and 15,604 no-MDD, and 5224 persons without AD in MDD and 5224 no-MDD. Point prevalence of drug use was assessed every 3 months, from 1 year before to 2 years after the start of MDD and compared between persons in MDD to those who did not have MDD. RESULTS: MDD was started on average 2.9 (SD 2.1) years after AD diagnosis. At the start of MDD, the prevalence of drug use increased especially for antipsychotics, antidepressants, opioids, paracetamol and use of ≥ 10 drugs among persons with and without AD. Prevalence of benzodiazepine use (from 12% 12 months before to 17% at start of MDD), memantine (from 29 to 46%) and ≥ 3 psychotropics (from 3.2 to 6.0%) increased among persons with AD. Decreasing trend was observed for benzodiazepine-related drugs, urinary antispasmodics and non-steroidal anti-inflammatory drugs. CONCLUSION: MDD seems to be initiated when use of psychotropics is initiated and the number of drugs increases.

Healthcare utilization, costs, and productivity losses in treatment-resistant depression in Finland - a matched cohort study.

BACKGROUND: Due to its relatively high prevalence and recurrent nature, depression causes a major burden on healthcare systems, societies and individuals. Our objective was to investigate healthcare resource utilization and costs associated with treatment-resistant depression (TRD) compared with non-treatment-resistant depression in Finland. METHODS: Of all patients aged 16-65 years and diagnosed with depression in Finland during 2004-2016, persons with TRD (N = 15,405) were identified from nationwide registers and matched 1:1 with comparison persons with depression who initiated antidepressant use but did not have TRD at the time of matching. TRD was defined as initiation of a third treatment trial after having failed two pharmacological treatment trials. Follow-up period covered 5 years after TRD or corresponding matching date (until end of 2018). Health care resource utilization was studied with negative binomial regression and costs of TRD (per patient per year) with generalized estimating equations, by adjusting for baseline costs, comorbidity and baseline severity of depression. RESULTS: Persons with TRD (mean age 38.7, SD 13.1, 60.0% women) had more health care utilization and work disability (sick leaves and disability pensions), adjusted incidence rate ratio for work disability days was 1.72 (95% CI 1.64-1.80). This resulted in 1.9-fold higher total costs for persons with TRD (15,907 versus 8335 EUR), adjusted mean difference 7572 (95% CI 7215-7929) EUR per patient per year, higher productivity losses (due to sick leaves and disability pensions, mean difference 5296, 95% CI 5042-5550), and direct healthcare costs (2003, 95% CI 1853-2151) compared with non-TRD patients. Mean difference was the highest during the first year after TRD (total costs difference 11,760, 95% CI 11,314-12,206) and the difference decreased gradually after that. CONCLUSION: Treatment-resistant depression is associated with about two-fold cost burden compared with non-treatment-resistant depression.

Prevalence of oral anticoagulant use among people with and without Alzheimer's disease.

BACKGROUND: Although cardio- and cerebrovascular diseases are common among people with Alzheimer's disease (AD), it is unknown how the prevalence of oral anticoagulant (OAC) use changes in relation to AD diagnosis. We investigated the prevalence of OAC use in relation to AD diagnosis in comparison to a matched cohort without AD. METHODS: Register-based Medication use and Alzheimer's disease (MEDALZ) cohort includes 70 718 Finnish people with AD diagnosed between 2005-2011. Point prevalence of OAC use (prescription register) was calculated every three months with three-month evaluation periods, from five years before to five years after clinically verified diagnosis and compared to matched cohort without AD. Longitudinal association between AD and OAC use was evaluated by generalized estimating equations (GEE). RESULTS: OAC use was more common among people with AD until AD diagnosis, (OR 1.17; 95% CI 1.13-1.22), and less common after AD diagnosis (OR 0.87; 95% CI 0.85-0.89), compared to people without AD. At the time of AD diagnosis, prevalence was 23% and 20% among people with and without AD, respectively. OAC use among people with AD began to decline gradually two years after AD diagnosis while continuous increase was observed in the comparison cohort. Warfarin was the most common OAC, and atrial fibrillation was the most common comorbidity in OAC users. CONCLUSION: Decline in OAC use among people with AD after diagnosis may be attributed to high risk of falling and problems in monitoring. However, direct oral anticoagulants (DOACs) that are nowadays more commonly used require less monitoring and may also be safer for vulnerable people with AD.

Maternal smoking during pregnancy and offspring psychiatric disorder: a longitudinal birth cohort study.

BACKGROUND: There is evidence that prenatal stress and smoking during pregnancy both independently increase the risk of offspring psychopathology. Here we examine whether increased levels of self-reported stress is associated with increased smoking in a population of pregnant women, and whether prenatal smoking is associated with offspring psychiatric diagnoses independent of prenatal stress exposure. METHOD: Using a longitudinal birth cohort, we used ordered logistic regressions to examine associations between maternal stress and smoking during pregnancy. We then used logistic regression analyses to examine associations between prenatal smoking and later offspring psychiatric disorders. RESULTS: A dose-response relationship was found between maternally reported stress and smoking during pregnancy. Pregnant women reporting severe stress were more likely to smoke compared to both the moderate stress and no stress groups, and those reporting moderate stress were significantly more likely to smoke compared to the no stress group. Smoking more than 5 cigarettes daily during pregnancy increased the risk of offspring personality disorder (OR 3.08, 95% CI 1.60-5.94) as well as developing any Axis 1 psychiatric disorder, inclusive of mood, anxiety and psychotic disorders (OR 1.45, 95% CI 1.04-2.04). After adjusting for parental psychiatric history and maternal self-reported stress during pregnancy, associations between smoking more than 5 cigarettes daily when pregnancy and offspring personality (OR 2.58 95% CI 1.32-5.06) disorder remained. CONCLUSION: Exposure to cigarette smoking during gestation could impact a child's mental health. Smoking during pregnancy is a prime target for preventative interventions as unlike most other environmental risk factors, it is very amenable to change.