Schizophrenia In Finland Research Articles

Long-term persistence of the risk of agranulocytosis with clozapine compared with other antipsychotics: a nationwide cohort and case–control study in Finland

Agranulocytosis is a life-threatening side-effect of clozapine, the only approved drug for treatment-resistant schizophrenia. The long-term profile of this complication has not yet been well established. Here we aim to describe the risk of clozapine-induced agranulocytosis over the long term. We used the entire population of Finland to identify people diagnosed with schizophrenia or schizoaffective disorder between 1972 and 2014 and developed a Kaplan-Meier model of time to diagnosis of agranulocytosis during clozapine versus non-clozapine treatment over a 22-year observation period (1996 to 2017). Next, we developed a nested case-control model for agranulocytosis matching by sex, age, time since diagnosis, and being in the incident cohort on a 1 to 5 ratio. Various durations of use for clozapine and non-clozapine antipsychotic treatment were compared to the modal antipsychotic use duration, deriving adjusted odds ratios (aORs) in a multivariable regression model. Recurrence and lethality rates for clozapine-induced agranulocytosis were described. These data reflect on all individuals with lived experience of schizophrenia in Finland during the study time, although individuals with lived experience were not included in the design of the study. We identified 61 769 people with schizophrenia or schizoaffective disorder (14 037 individuals treated with clozapine and 47 732 individuals treated with non-clozapine antipsychotics), with a mean age of 46·67 years (IQR 34·44-57·61), of whom 30 721 (49·7%) were female and 31 048 (50·3%) were male (data on ethnicity not available). Among those, 398 individuals were diagnosed with agranulocytosis (231 individuals treated with clozapine and 167 individuals treated with non-clozapine antipsychotics), representing a cumulative incidence of agranulocytosis for 1·37% (95% CI 0·58-3·16) on clozapine and 0·13% (0·04-0·23) on non-clozapine antipsychotics. In the case (n=398) versus control (n=1987) model, the risk of clozapine-induced agranulocytosis decreased steeply over time from an aOR of 36·01 (95% CI 16·79-77·22) for less than 6 months on clozapine to 4·38 (1·86-10·34) for clozapine use of 54 months or more. Only one of 3559 individuals starting clozapine died because of clozapine-induced agranulocytosis. The risk of clozapine-induced agranulocytosis decreases steeply over time but might be persistently greater than that of non-clozapine antipsychotics. This long-term risk excess seems small in absolute terms compared with the known magnitude of the advantages of clozapine in relevant outcomes, including life expectancy. Given the widespread underuse of clozapine, relaxing the long-term neutrophil monitoring could favour the advantages of long-term clozapine use, including greater life expectancy, without incurring the intolerable risk of clozapine-induced agranulocytosis. Northwell Health and Sigrid Jusèlius Foundation.

Factors and their weight in reducing life expectancy in schizophrenia

BackgroundSchizophrenia is associated with a wide range of socioeconomic and health-related problems, as well as 10–25 potential life-years lost. While lifestyle choices, comorbidities, and choice of medication are associated with schizophrenia disease burden and mortality, real-world evidence on the impact of these factors on expected life-years among patients with schizophrenia is limited. MethodsIn this study, register-based, nationwide data from patients with schizophrenia in Finland during 1972–2015 were analysed to determine influential factors associated with mortality and to demonstrate their impact on expected life-years in patients with schizophrenia. ResultsFactors reducing all-cause mortality were use of antipsychotics: HR 0.46 (95 % CI: 0.45, 0.47), ever use of lipid-modifying agents: HR 0.71 (95 % CI 0.68, 0.73), antidepressants HR 0.87 (95 % CI 0.85, 0.90), and lithium HR 0.90 (95 % CI 0.86, 0.95). Factors increasing all-cause mortality were cardiovascular disease: HR 2.41 (95 % CI: 2.34, 2.49), liver disease: HR 1.98 (95 % CI: 1.78, 2.21), renal disease: HR 1.63 (95 % CI:1.56, 1.70), diabetes: HR 1.40 (95 % C:1.35, 1.45), history of switching antipsychotics: HR 1.39 (95 % CI: 1.35, 1.44), longer duration of previous hospitalisations HR 1.96 (95 % CI: 1.90, 2.02), history of substance abuse HR 1.38 (95 % CI: 1.30, 1.46), and ever use of benzodiazepines HR 1.12 (95 % CI: 1.09, 1.16). ConclusionsThe results from this study could serve to motivate clinicians to support and encourage patients to adhere to antipsychotic treatment and achieve a healthier lifestyle, which could, in turn, increase the expected life-years of patients with schizophrenia.

Real-world effectiveness of antipsychotic doses for relapse prevention in patients with first-episode schizophrenia in Finland: a nationwide, register-based cohort study

Antipsychotic doses for relapse prevention in patients with first-episode schizophrenia that have the highest likelihood of success are unknown. We aimed to study the evolution of antipsychotic dose and risk of severe relapse indicated by psychiatric rehospitalisation associated with antipsychotic use and specific dose categories. We did a nationwide, register-based cohort study in Finland. Patients were identified from the nationwide Hospital Discharge register, which records all inpatient hospital stays. Patients with first-episode schizophrenia diagnosed as inpatients and who were 45 years or younger were followed-up for 5 years of illness or until a fifth relapse episode. The primary measure was rehospitalisation due to psychosis, which was used as a marker of relapse and defined as inpatient hospital care with an ICD-10 code of F20-F29 diagnosis recorded as the main discharge diagnosis. Time between relapses was required to be at least 30 days to be considered a next relapse. Antipsychotic use was derived from the prescription register. Dose was summed from all concomitant antipsychotics. Antipsychotic effectiveness for preventing rehospitalisation was studied using within-individual analyses to eliminate selection bias, stratifying time to before and after the second relapse. In total, the study population comprised 5367 patients, of whom 3444 (64·2%) were men and 1923 (35·8%) were women, with a mean age of 29·5 years (SD 7·8) at the start of follow-up. Ethnicity data were not available. 3058 (57·0%) of 5367 patients required hospitalisations. In these patients, the mean dose increased gradually after each new relapse from 1·22 defined daily doses per day (95% CI 1·18-1·26) before the first relapse to 1·56 defined daily doses per day (1·48-1·64) before the fifth relapse. Adjusted hazard ratio (aHR) for rehospitalisation with antipsychotic use versus non-use increased from 0·42 (95% CI 0·35-0·51) before the second relapse to 0·78 (0·62-0·99) after the second relapse (p<0·0001), indicating markedly decreased effectiveness. Analysing specific dose categories revealed a U-shaped curve, showing the lowest rehospitalisation risk during use of the standard dose (0·9 to <1·1 defined daily doses per day) before but not after the second relapse. Low dose (<0·6 defined daily doses per day) was associated with substantially higher rehospitalisation risk (aHR 1·54 [95% CI 1·06-2·24]) versus standard dose before the second relapse, but not after the second relapse (1·11 [0·76-1·62]), owing to reduced effectiveness of all doses after the second relapse. The effectiveness of antipsychotics for relapse prevention decreased substantially after the second relapse. Therefore, prevention of the second relapse is essential, and all patients should receive sufficient antipsychotic doses and enhanced relapse prevention efforts after their first relapse. Academy of Finland and Finnish Ministry of Social Affairs and Health.

Morbidity and mortality in schizophrenia with comorbid substance use disorders in Finland and Sweden

IntroductionSchizophrenia is highly comorbid with substance use disorders (SUD) but large epidemiological cohorts exploring the prevalence and prognostic significance of SUD are lacking.ObjectivesTo investigate the prevalence of SUD in patients with schizophrenia in Finland and Sweden, and the effect of these co-occurring disorders on risks of psychiatric hospitalization and mortality.Methods45,476 individuals with schizophrenia from two independent national cohort studies, aged &lt;46 years at cohort entry, were followed during 22 (1996-2017, Finland) and 11 years (2006-2016, Sweden). We first assessed SUD prevalence (excluding smoking). Then we performed Cox regression on risk of psychiatric hospitalization and mortality in patients with schizohrenia and SUD compared with those without SUD.ResultsThe prevalence of SUD in specialized healthcare ranged from 26% (Finland) to 31% (Sweden). Multiple drug use and alcohol use disorders were the most prevalent SUD, followed by cannabis use disorders. Any SUD comorbidity, and particularly multiple drug use and alcohol use, were associated with 50% to 100% increases in hospitalization and mortality compared to individuals without SUD. Elevated mortality risks were observed especially for deaths due to suicide and other external causes. All results were similar across countries.ConclusionsCo-occurring SUD, and particularly alcohol and multiple drug use, are associated with high rates of hospitalization and mortality in patients with schizophrenia. Preventive interventions should prioritize detection and tailored treatments for these co-morbidities, which often remain underdiagnosed and untreated.Conflict of interestML: Genomi Solutions Ltd, Nursie Health Ltd, Sunovion, Orion Pharma, Janssen-Cilag, Finnish Medical Foundation, Emil Aaltonen Foundation. HT, EMR, AT: Eli Lilly, Janssen–Cilag. JT: Eli Lilly, Janssen-Cilag, Lundbeck, Otsuka.

Incidence of schizophrenia and influence of prenatal and infant exposure to viral infectious diseases

There is conflicting evidence in recent literature about whether the incidence of schizophrenia is increasing or decreasing. A role for prenatal and early childhood viral infections in the aetiology of schizophrenia has also been debated. We examined the incidence of schizophrenia and the catatonic subtype of schizophrenia over a 30-year period in Finland. We also investigated whether the incidence rate of the catatonic subtype of schizophrenia was linked to changes in exposure to viral infection (polio and measles) during the prenatal or infant period. Persons with schizophrenia were identified from the Hospital Discharge Register. Cumulative incidence of schizophrenia from 1956 to 1989 in 4 age groups was calculated with follow-up from 1972 to 2014. Annual rates of polio and measles were derived from nationwide registers. The association between log-transformed polio and measles incidence and incidence of schizophrenia, and specifically catatonic schizophrenia, were analysed using linear models. Cumulative incidence of schizophrenia among individuals born 1956-1989 decreased by 23% (from 13 to 10 cases per 1000 live births). The decline was the most prominent in those with onset of schizophrenia diagnosed 16-25years of age (-41%). The incidence of catatonic schizophrenia declined by 90% over three decades, and there was a significant association between annual polio incidence during the birth year and incidence of catatonic schizophrenia. The results indicate that the incidence of schizophrenia in Finland has declined for individuals born between 1956 and 1989, and that the decline of catatonic schizophrenia may be partially attributable to eradication of polio.

Morbidity and mortality in schizophrenia with comorbid substance use disorders.

ObjectiveSchizophrenia is highly comorbid with substance use disorders (SUD) but large epidemiological cohorts exploring the prevalence and prognostic significance of SUD are lacking. Here, we investigated the prevalence of SUD in patients with schizophrenia in Finland and Sweden, and the effect of these co‐occurring disorders on risks of psychiatric hospitalization and mortality.Methods45,476 individuals with schizophrenia from two independent national cohort studies, aged <46 years at cohort entry, were followed during 22 (1996–2017, Finland) and 11 years (2006–2016, Sweden). We first assessed SUD prevalence (excluding smoking). Then, we performed Cox regression on risk of psychiatric hospitalization and all‐cause and cause‐specific mortality in SUD compared with those without SUD.ResultsThe prevalence of SUD ranged from 26% (Finland) to 31% (Sweden). Multiple drug use (n = 4164, 48%, Finland; n = 3268, 67%, Sweden) and alcohol use disorders (n = 3846, 45%, Finland; n = 1002, 21%, Sweden) were the most prevalent SUD, followed by cannabis. Any SUD comorbidity, and particularly multiple drug use and alcohol use, were associated with 50% to 100% increase in hospitalization (aHR any SUD: 1.53, 95% CI = 1.46–1.61, Finland; 1.83, 1.72–1.96, Sweden) and mortality (aHR all‐cause mortality: 1.65, 95% CI = 1.50–1.81, Finland; 2.17, 1.74–2.70, Sweden) compared to individuals without SUD. Elevated mortality risks were observed especially for suicides and other external causes. All results were similar across countries.ConclusionCo‐occurring SUD, and particularly alcohol and multiple drug use, are associated with high rates of hospitalization and mortality in schizophrenia. Preventive interventions should prioritize detection and tailored treatments for these comorbidities, which often remain underdiagnosed and untreated.

Medication Use and Health Care Utilization After a Cost-sharing Increase in Schizophrenia: A Nationwide Analysis.

Increases in prescription drug cost-sharing may decrease adherence to treatment among persons with schizophrenia and lead to discontinuation of use and an increased risk of hospitalization. The objective of this study was to investigate the impact of new deductible and increased drug copayments implemented on antipsychotic and other drug purchases and on rates of hospitalizations and primary care contacts among persons with schizophrenia in Finland. Interrupted time series analysis. All persons with schizophrenia in Finland who were alive at the beginning of 2015 (N=41,017). We measured the rates of antipsychotic, other psychotropic and cardiometabolic drug purchasers, hospitalizations, and primary care contacts during 2015 and 2016 with data collected from several nationwide health care registers. During 2016, the proportion of antipsychotic purchasers decreased by -0.26 percentage points per month [95% confidence interval (CI): -0.47 to -0.05] compared with 2015. The trend of other psychotropic purchasers decreased to -0.13 percentage points per month in 2016 (95% CI: -0.22 to -0.04) compared with 2015 and cardiometabolic drug purchases to -0.17 percentage points per month (95% CI: -0.29 to -0.05) compared with 2015. The decreasing trend of psychiatric hospitalizations in 2015 halted in 2016. There were no other significant differences in health care utilization. In our nationwide time-series analysis, we observed decreases in the slopes of antipsychotic and other drug purchases of persons with schizophrenia after prescription drug cost-sharing increase implementation on January 1, 2016. Policymakers need to be aware of the unintended consequences of increasing cost-sharing among people with severe mental disorders.

S210. COMPARATIVE EFFECTIVENESS OF ANTIPSYCHOTICS FOR RISK OF ATTEMPTED OR COMPLETED SUICIDE AMONG PERSONS WITH SCHIZOPHRENIA

BackgroundSuicidal attempts and suicide are rather common phenomena in persons with schizophrenia whom are 6–14 times more likely to die due to suicide than the general population. Very little is known on effectiveness of antipsychotics in preventing suicide attempts and completed suicides among patients with schizophrenia. Whether all antipsychotics are effective in preventing attempted or completed suicides also remains unclear. The objective of our study was to investigate comparative effectiveness of antipsychotics for risk of attempted or completed suicide among all patients with schizophrenia in Finland and Sweden.MethodsTwo nationwide register-based cohort studies were conducted including all individuals with schizophrenia in Finland (N=61889) and Sweden (N=29823). The Finnish cohort included all persons treated for schizophrenia in inpatient care (1972–2014), with follow-up for drug use and outcomes during 1996–2017. The Swedish cohort included all persons with treatment contact due to schizophrenia in inpatient or specialized outpatient care, sickness absence, or disability pension (2006–2013), with follow-up for drug use and outcomes during 2006–2016. The main exposure included the ten most commonly used antipsychotic monotherapies, and also adjunctive pharmacotherapies (antidepressants, mood stabilizers, lithium, benzodiazepines and related drugs were investigated). The main outcome measure was attempted or completed suicide which was analyzed with within-individual models by comparing use and non-use periods in the same individual. Sensitivity analyses were conducted by between-individual models, with attempted suicide (hospitalization only) as an outcome, and by censoring first 30 days from each exposure. Results are reported as hazard ratios (HRs) with 95 % confidence intervals (95% CI).ResultsCompared with no use of antipsychotics, clozapine was the only antipsychotic therapy consistently associated with a decreased risk of suicidal outcomes. Hazard ratios (HRs) and 95% CI for attempted or completed suicide were 0.64 (95% CI 0.49–0.84) in the Finnish cohort, and 0.66 (0.43–0.99) in the Swedish cohort, and for attempted suicide 0.60 (0.46–0.79) in the Finnish cohort and 0.62 (0.40–0.95) in the Swedish cohort. No other antipsychotic was associated with a reduced risk of attempted and/or completed suicide than clozapine. Regarding adjunctive pharmacotherapies, benzodiazepines and Z-drugs were associated with an increased risk of suicide attempts or deaths (HRs for benzodiazepines 1.29–1.30 and 1.33–1.62 for Z-drugs, not reaching statistical significance in the Swedish cohort).DiscussionThe results from two large nationwide cohorts provide the first evidence on comparative real-world effectiveness of specific antipsychotics in the prevention of severe suicidal behavior. Clozapine was the only pharmacological treatment associated with a substantially decreased risk of attempted or completed suicide and should be considered as a first-line treatment for patients with suicidal ideation or behavior.

SU50 - THE NDE1 GENOMIC LOCUS CAN AFFECT TREATMENT OF PSYCHIATRIC ILLNESS THROUGH GENE EXPRESSION CHANGES RELATED TO MICRORNA-484

Background Genetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes, DISC1, NDE1, NDEL1, PDE4B and PDE4D, the DISC1 network. Here, we utilize gene expression and psychoactive medication use data to study their biological consequences and potential treatment implications. Methods Gene expression levels were determined in 64 individuals from 18 families, whilst prescription medication information has been collected over a ten-year period for 931 affected individuals. Results We demonstrate that the NDE1 SNP rs2242549 associates with significant changes in a large number of probes (n=2,908), of which 944 genes were replicable. A significant number of the total genes altered (347 out of 2,510, p=3.0×10-8) were predicted targets of microRNA-484, located on a non-coding exon of NDE1. Variants within the NDE1 locus also displayed significant genotype by gender interaction to early cessation of psychoactive medications metabolized by CYP2C19. Furthermore, we demonstrate that miR-484 can affect the expression of CYP2C19 in a cell culture system. Discussion Thus, mutations at the NDE1 locus may alter risk to mental illness, in part through modification of miR-484, and such modification alters treatment response to specific psychoactive medications, leading to the potential use of this locus in targeting treatment.

Mortality in schizophrenia: 30-year nationwide follow-up study.

Recent reports suggest that the mortality gap between persons with schizophrenia and the general population is increasing. We investigated the mortality, age at death, and causes of death among persons diagnosed with schizophrenia and the general population in Finland during 1984-2014. All persons with schizophrenia in Finland were identified from hospital discharge register, and compared with the Finnish population aged 16 years and older during 1984-2014, based on data from Statistics Finland. Age at death and standardized mortality ratio (SMR) were calculated for each follow-up year. Mean age at death increased from 57.6 years in 1984 to 70.1 years in 2014 in persons with schizophrenia, and from 70.9 to 77.5 years in the general population. All-cause SMR remained stable during the follow-up (2.6 in 1984 and 2.7 in 2014). A major change was observed in SMR for suicides which decreased from 11.0 in 1984 to 6.6 in 2014 (-40%). The SMRs for cardiovascular and cancer deaths showed increasing trends. The longevity of persons with schizophrenia is improving at approximately the same rate as the general population but suicide rates have declined substantially. However, there is still a major disparity in mortality compared with general population.

The NDE1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microRNA-484.

Genetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes, DISC1, NDE1, NDEL1, PDE4B and PDE4D, the ‘DISC1 network’. Here, we use gene expression and psychoactive medication use data to study their biological consequences and potential treatment implications. Gene expression levels were determined in 64 individuals from 18 families, while prescription medication information has been collected over a 10-year period for 931 affected individuals. We demonstrate that the NDE1 SNP rs2242549 associates with significant changes in gene expression for 2908 probes (2542 genes), of which 794 probes (719 genes) were replicable. A significant number of the genes altered were predicted targets of microRNA-484 (p = 3.0 × 10−8), located on a non-coding exon of NDE1. Variants within the NDE1 locus also displayed significant genotype by gender interaction to early cessation of psychoactive medications metabolized by CYP2C19. Furthermore, we demonstrate that miR-484 can affect the expression of CYP2C19 in a cell culture system. Thus, variation at the NDE1 locus may alter risk of mental illness, in part through modification of miR-484, and such modification alters treatment response to specific psychoactive medications, leading to the potential for use of this locus in targeting treatment.

Pharmacoeconomics of long-acting atypical antipsychotics for acutely relapsed chronic schizophrenia in Finland

Background:Atypical long-acting injectable (LAI) antipsychotics are increasingly available for treating chronic schizophrenia in patients chronically non-adherent to prescribed regimens. Few economic studies have compared these products.Purpose:To determine the cost-effectiveness of aripiprazole (ARI-LAI), paliperidone (PP-LAI), olanzapine (OLZ-LAI), and risperidone (RIS-LAI) in patients with chronic schizophrenia in Finland.Methods:A 1-year decision tree model was adapted with guidance from an expert panel. Patients started hospitalized in relapse; those who responded continued treatment, others were switched to secondary drugs, then clozapine in the event of 2nd line failure. Rates of adherence, stable disease, relapse, and hospitalization were taken from pivotal trials, and utilities from published research. Included were direct costs paid by the Finnish Ministry of Health, in 2015 euros. Outcomes included quality-adjusted life-years (QALYs), hospitalization rates, and rates of relapse not requiring hospitalization. Model robustness was assessed using a series of 1-way and multivariate sensitivity analyses.Results:Expected costs were lowest for PP-LAI at 41,148€, followed by 41,543€ for ARI-LAI, 42,067€ for RIS-LAI and 45,406€ for OLZ-LAI. Respective QALYs were 0.683, 0.671, 0.666, and 0.672. Re-hospitalization rates and non-admitted relapses were 23.6% and 3.9% for PP-LAI, 28.5% and 4.1% for ARI-LAI, 28.8% and 5.0% for RIS-LAI, 28.3% and 5.2% for OLZ-LAI. PP-LAI treatment was associated with the most days with stable disease (132.0), followed by OLZ-LAI (125.5), ARI-LAI (122.6), and RIS-LAI (114.4). Sensitive inputs between PP-LAI and ARI-LAI included rates of adherence, dropouts, and relapses plus drug prices; dropout and relapse rates for RIS-LAI; OLZ-LAI results were insensitive. In probability sensitivity analyses, PP-LAI dominated ARI-LAI in 75.8% of the 10,000 iterations, RIS-LAI in 83.1% and OLZ-LAI in 95.7%.Conclusions:PP-LAI dominated the other atypicals. It appears to be the preferred option for treating chronic relapsing schizophrenia.

PMH20 - Real-World Budget impact analysis of atypical long-acting Anti-Psychotics in Finland

The long-acting injectable aripiprazole once-monthly 400 mg (AOM 400) has been approved for treatment of schizophrenia in Finland since November 2013. Other atypical anti-psychotics, risperidone, paliperidone and olanzapine are also available as long-acting injectable formulations. A mixed treatment comparison has demonstrated that AOM 400 is at least as efficacious as other atypical long-acting anti-psychotics (ALAIs). However, cost of administration and drug (treatment cost) vary among the ALAIs. This analysis aims to investigate the total treatment costs of ALAIs using real-world data in Finland. A one-year time horizon budget impact analysis was conducted to compare the treatment costs of ALAIs in Finland. The real-world doses were calculated using sales data. One of the ALAIs (olanzapine) can be given in intervals of 2 or 4 weeks using the 300 mg strength. Half of the patients were assumed treated with the 300 mg dose every 2 weeks, the other half every 4 weeks. Prices for ALAIs were obtained from the official national price list. The cost of administration for AOM 400, paliperidone-LAI and risperidone-LAI was based on the cost of a short nurse visit (30 minutes) to a psychiatry outpatient clinic. The cost of administration of olanzapine-LAI was based on the cost of a longer visit (120-180 minutes), as the product information recommends monitoring for three hours after injection. The expected cost for drug and administration per patient, per year, for AOM 400 is 5158 EUR. The expected yearly costs per patient for drug and administration for paliperidone-LAI, risperidone-LAI and olanzapine-LAI are 6021 EUR, 6706 EUR and 11646 EUR respectively. In a budget impact analysis, using the method, data and assumptions described, AOM 400 is expected to be cost saving, in the real-world setting, in terms of cost of drug and administration, compared to other ALAIs available in Finland.

PMH44 - Pharmacoeconomic analysis of paliperidone palmitate for chronic relapsing schizophrenia in Finland

PMH44 - Pharmacoeconomic analysis of paliperidone palmitate for chronic relapsing schizophrenia in Finland

Cost-effectiveness analysis of atypical long-acting antipsychotics for treating chronic schizophrenia in Finland

Objective:In Finland, regional rates of schizophrenia exceed those in most countries, impacting the healthcare burden. This study determined the cost-effectiveness of long-acting antipsychotic (LAI) drugs paliperidone palmitate (PP-LAI), olanzapine pamoate (OLZ-LAI), and risperidone (RIS-LAI) for chronic schizophrenia.Method:This study adapted a decision tree analysis from Norway for the Finnish National Health Service. Country-specific data were sought from the literature and public documents, guided by clinical experts. Costs of health services and products were retrieved from literature sources and current price lists. This simulation study estimated average 1-year costs for treating patients with each LAI, average remission days, rates of hospitalization and emergency room visits and quality-adjusted life-years (QALY).Results:PP-LAI was dominant. Its estimated annual average cost was €10,380/patient and was associated with 0.817 QALY; OLZ-LAI cost €12,145 with 0.810 QALY; RIS-LAI cost €12,074 with 0.809 QALY. PP-LAI had the lowest rates of hospitalization, emergency room visits, and relapse days. This analysis was robust against most variations in input values except adherence rates. PP-LAI was dominant over OLZ-LAI and RIS-LAI in 77.8% and 85.9% of simulations, respectively. Limitations include the 1-year time horizon (as opposed to lifetime costs), omission of the costs of adverse events, and the assumption of universal accessibility.Conclusion:In Finland, PP-LAI dominated the other LAIs as it was associated with a lower cost and better clinical outcomes.

PMH23 A Cost-Effectiveness Analysis of the Long-Acting Antispychotic Drugs Paliperidone Palmitate, Olanzapine Pamoate and Risperidone in the Treatment of Schizophrenia in Finland

PMH23 A Cost-Effectiveness Analysis of the Long-Acting Antispychotic Drugs Paliperidone Palmitate, Olanzapine Pamoate and Risperidone in the Treatment of Schizophrenia in Finland

Incidence of hospitalised schizophrenia in Finland since 1980: decreasing and increasing again

It is suggested that the incidence of schizophrenia is decreasing. However, changes in the number of psychiatric beds available and diagnostic practice have not always been taken into account. We studied the annual first-admission rate (per 100,000) for schizophrenia (FARsch) during a rapid deinstitutionalisation period in Finland. From the National Finnish Hospital discharge register, we identified all 30,041, 15- to 64-year-old patients admitted for the first time with schizophrenia to hospitals in Finland between 1980 and 2003. FARsch decreased from 56.39 in 1980 to 29.51 in 1991 and slightly increased thereafter. Changes in FARsch corresponded with changes in all admissions. FARsch was higher when using ICD-8, but lower when DSM-IIIR and ICD-10 were used. Changes in the number of psychiatric beds available, admission policy and diagnostic practice may explain the majority of variations in FARsch. Possibly, increased use of illegal drugs and improved treatment of depression are reflected in the increase in FARsch.

Regional Differences in Five-Year Mortality After a First Episode of Schizophrenia in Finland

Objective: This study analyzed gender-specific mortality of patients with a first episode of schizophrenic illness, particularly deaths from circulatory system diseases and suicide. Methods: This was a nationwide register-based five-year follow-up study of all patients with onset of schizophrenia between 1995 and 2001. Standardized mortality ratios (SMRs) were calculated by matching patients’ data with the general Finnish population on age, gender, and place of residence. Results: During the five-year follow-up of 7,591 schizophrenia patients, 403 (5%) patients died. They had 4.45-fold higher mortality than the general population, and patients’ mortality was significantly elevated in all age groups. The SMRs for all-cause mortality, circulatory system diseases, and suicides were higher for females than males in almost all age groups. The largest single unnatural cause of death was suicide. In natural causes of death, the SMR for ill-defined and unknown causes of death was almost 25. Total mortality, circulatory deaths, and suicides differed among the 20 hospital districts examined. Regional variations in SMRs were not associated with population characteristics or psychiatric health care resources of a hospital district. Conclusions: In this nationwide registerbased study, excess mortality among persons with schizophrenia was clearly observed. Regional differences in mortality were evident, indicating a need for further research to understand the mortality gap and why it might vary regionally. (Psychiatric Services 61:272–279, 2010)

Regional Differences in Five-Year Mortality After a First Episode of Schizophrenia in Finland

This study analyzed gender-specific mortality of patients with a first episode of schizophrenic illness, particularly deaths from circulatory system diseases and suicide. This was a nationwide register-based five-year follow-up study of all patients with onset of schizophrenia between 1995 and 2001. Standardized mortality ratios (SMRs) were calculated by matching patients' data with the general Finnish population on age, gender, and place of residence. During the five-year follow-up of 7,591 schizophrenia patients, 403 (5%) patients died. They had 4.45-fold higher mortality than the general population, and patients' mortality was significantly elevated in all age groups. The SMRs for all-cause mortality, circulatory system diseases, and suicides were higher for females than males in almost all age groups. The largest single unnatural cause of death was suicide. In natural causes of death, the SMR for ill-defined and unknown causes of death was almost 25. Total mortality, circulatory deaths, and suicides differed among the 20 hospital districts examined. Regional variations in SMRs were not associated with population characteristics or psychiatric health care resources of a hospital district. In this nationwide register-based study, excess mortality among persons with schizophrenia was clearly observed. Regional differences in mortality were evident, indicating a need for further research to understand the mortality gap and why it might vary regionally.

The role of DTNBP1, NRG1, and AKT1 in the genetics of schizophrenia in Finland

Several putative schizophrenia susceptibility genes have recently been identified. Significant associations between schizophrenia and neuregulin 1 ( NRG1) and dysbindin ( DTNBP1) were first reported in 2002 and studies in several populations have since independently reported positive associations to these gene regions. Further, both tentative functional and genetic data have implicated the role of AKT1 in the genetic background of this disorder. However, findings have not been consistent in all populations. We investigated the allelic diversity of these three genes NRG1, DTNBP1 and AKT1 in a representative nation-wide study sample of 441 Finnish schizophrenia families consisting of 865 affected individuals, in order to assess their role in one of the largest population-based study samples. DTNBP1 and AKT1 failed to show evidence of association, whereas two SNPs in the 3′ region of the NRG1 gene yielded suggestive evidence of association ( p = 0.012 and p = 0.048) in family-based association analyses. Thus, our study does not indicate that AKT1 or DTNBP1 play a role in the etiology of schizophrenia in the Finnish population. Furthermore, results do not support a major role for NRG1, but we cannot completely exclude a minor role of this gene in the Finnish population.