Antti Tanskanen’s research while affiliated with Niuvanniemi Hospital and other places

Introduction Medication use may significantly affect work ability in bipolar disorder, but this area has been largely overlooked in research. We aimed to investigate how specific mood stabilizer and antipsychotic agents are associated with the risk of sickness absence among employed individuals with bipolar disorder. Methods We identified a nationwide cohort of 22,408 employed individuals with bipolar disorder, including 10,000 first‐episode cases, and followed them from 2005 to 2018 through the nationwide administrative registers. The risk of sickness absence was analyzed using within‐individual Cox regression where each person serves as their own control to eliminate selection bias. Results In the whole cohort, the monotherapies of lithium (HR = 0.75, 95% CI = 0.66–0.84), valproate (HR = 0.77, 0.70–0.85), and lamotrigine (HR = 0.87, 0.80–0.95) were associated with a lower risk of sickness absence than nonuse of mood stabilizers. In contrast, pregabalin monotherapy was associated with an increased risk of sickness absence (HR = 1.63, 1.34–1.99). Of antipsychotics, olanzapine was associated with a lower risk of sickness absence (HR = 0.75, 0.66–0.86) than antipsychotic nonuse. In the first‐episode sample, lithium (HR = 0.51, 0.41–0.64), valproate (HR = 0.63, 0.52–0.75), lamotrigine (HR = 0.79, 0.68–0.91), and olanzapine (HR = 0.69, 0.54–0.87) monotherapies were associated with a lower hazard of sickness absence than nonuse. Conclusions Mood stabilizers including lithium, valproate, and lamotrigine, as well as olanzapine, of antipsychotics may reduce the risk of sickness absence, particularly, in first‐episode patients. These findings encourage the continuous use of these medications to support occupational functioning among people with bipolar disorder.

Background: Deviations in treatment practices toward immigrant groups compared to host populations are common in mental disorders but unknown in bipolar disorder (BD). We aim to close this research gap by analyzing age-stratified use patterns of antidepressants, mood stabilizers, and antipsychotics following an incident diagnosis of BD in Swedish-born, second- and first-generation nonrefugee immigrants, and refugees. Methods: Individuals with incident BD between 2006 and 2018 were identified through Swedish national registers. Medication use was followed up until 5 years after diagnosis. Use rates adjusted for sociodemographic and disease-related covariates were computed with generalized estimation equations for each population group. Marginal means with 95% confidence intervals (CIs) and significance tests for main and interaction effects of population group and time points are presented. Furthermore, significant effects of population group, age group, time point, and their interaction were tested by Type III joint test yielding F and p values. Results: Three months after diagnosis, estimated rates of lack of treatment differed significantly between population groups (p < 0.0001) as Swedish-born (17.3%, CI: 16.8-17.7) lacked disease-specific treatment less often than second-generation immigrants (21.1%, 19.7-22.5), first-generation nonrefugee immigrants (23.1%, 21.3-25.0) and refugees (26.8%, 24.4-29.4). Antidepressant monotherapy was estimated in 17.7% (17.2-18.1) of Swedish-born, 16.8% (15.5-18.3) of second-generation immigrants, 17.7% (16.2-19.4) of first-generation nonrefugee immigrants, and was most prevalent in refugees (20.3%, 18.2-22.7; population group p = 0.0002). Mood stabilizers were most dispensed by Swedish-born (51.3%, 50.6-51.9), followed by second-generation (47.9%, 46.1-49.8) and first-generation nonrefugee immigrants (44.5%, 42.4-46.7) and refugees (35.4%, 32.8-38.2; population group p < 0.0001). Use rates of antipsychotics were similar between population groups (p > 0.05) and estimated at 14.1% (13.7-14.6) in Swedish-born, 14.0% (12.8-15.3) in second-generation, 13.0% in first-generation nonrefugee immigrants (12.0-14.6), and 12.9% (11.1-15.0) in refugees. Following up significant interactions of population and age group, lithium use was estimated to be lower in refugees aged 36-65 years (9.9%, 7.9-12.5; population group p = 0.0008) and olanzapine use to be higher in refugees aged 16-35 (9.2%, 7.1-11.9; population group p = 0.0002), respectively, compared to other population groups of the same age. Conclusions: Immigrants, especially refugees, are at risk of not receiving adequate treatment following BD diagnosis, putatively owing to a lack of transcultural competence in healthcare, economic restraints, and community factors. Antidepressant monotherapy should be reduced, while recommended options such as mood stabilizers and specifically lithium should be considered more often.

Background Accurate mortality risk prediction could enhance treatment planning in bipolar disorder, where mortality rates rival those of many cancers. Such prognostic tools are lacking in psychiatry, where assessments typically emphasize immediate suicidality while neglecting long-term mortality risks, and their clinical use is debated. We evaluated the recently developed machine learning model MIRACLE-FEP, initially developed for first-episode psychosis, in predicting all-cause mortality in patients with first-episode bipolar disorder (FEBD), hypothesizing that it would provide accurate risk prediction and guide pharmacotherapy decisions. Methods We utilized national register-based cohorts of FEBD patients from Sweden (N = 31,013, followed 2006–2021) and Finland (N = 13,956, followed 1996–2018). We assessed the MIRACLE-FEP model’s performance in predicting all-cause mortality using the area under the receiver operating characteristic curve (AUROC), calibration, and decision curve analysis. Additionally, we conducted a pharmacoepidemiologic analysis to examine the relationship between predicted mortality risk and pharmacotherapy effectiveness. Findings MIRACLE-FEP achieved an AUROC = 0.77 (95%CI = 0.73–0.80) for 2-year mortality prediction in Sweden and 0.71 (95%CI = 0.67–0.75) in Finland. For 10-year all-cause mortality prediction, the model demonstrated an AUROC of 0.71 in both cohorts. The model demonstrated relatively good calibration and indicated potential clinical utility in decision curve analysis. Among patients with predicted risk exceeding the observed two-year mortality rate in FEBD, the lowest mortality risk was observed with polytherapy regimens (compared to non-use of antipsychotics or mood stabilizers), including quetiapine and lamotrigine (HR = 0.42, 95%CI = 0.23–0.80) or mood stabilizer polytherapy (HR = 0.47, 95%CI = 0.27–0.82). Conversely, in patients with predicted risk below this threshold, complex pharmacotherapy was not associated with a significant reduction in mortality risk. Interpretation MIRACLE-FEP offers a promising approach to predicting long-term mortality risk and could guide proactive treatment decisions, such as targeting combination pharmacotherapy, in FEBD. Funding The Swedish Research Council for Health, Working Life and Welfare, FORTE (2021-01079).

Background Pneumonia is a common cause for hospitalization and excess mortality among persons with Alzheimer’s disease (AD), but little research exists evaluating drug use as its risk factor. Objective We investigated the association between opioid use and hospital-treated pneumonia among community dwellers with AD. Methods This study was part of the Medication use and Alzheimer’s Disease (MEDALZ) cohort. We included all community dwellers newly diagnosed with AD during 2010–2011 in Finland with incident prescription opioid use (n = 5,623) and age-, sex-, and time since AD diagnosis-matched nonusers (n = 5,623). Opioid use data, modelled from pharmacy dispensing data, and hospital-treated pneumonia were retrieved from nationwide registers. Patients with active cancer treatment were excluded. Hazard models compared opioid users to nonusers, adjusting for comorbidities, socioeconomic position. and other drug use. Results Incident opioid use was associated with an increased risk of hospital-treated pneumonia compared to nonuse (adjusted HR, aHR 1.34, 95% CI 1.14–1.57). Highest risk was observed during the first two months of use (aHR 2.58, 95% CI 1.87–3.55). Compared to weak opioids, buprenorphine was not associated with a higher risk of pneumonia (aHR 1.20, 95% CI 0.83–1.76), but strong opioids were (aHR 1.84, 95% CI 1.15–2.97). The risk was higher for those using ≥50 morphine milligram equivalents (MME)/day (aHR 2.03, 95% CI 1.24–3.31), compared to using <50 MME/day. Conclusions Opioid use was associated with a risk of hospital-treated pneumonia in a dose-dependent manner among persons with AD. Risk-minimization strategies should be considered if opioid therapy is needed.

Background The best pharmacological treatment practices for relapse prevention in patients with first-episode schizophrenia are unclear. We aimed to assess different treatment strategies used before and after the first relapse, and their associations with subsequent relapse risk. Methods In this population-based cohort study, we enrolled individuals (aged ≤45 years) with first-episode schizophrenia who were hospitalised and subsequently relapsed between 1996 and 2014 from the nationwide Finnish Hospital Discharge Register. Individuals who had not been taking antipsychotics within the year preceeding initial hospitalisation and who had a relapse within 5 years of discharge were included in the analyses. Treatment strategies were assessed during the 30 days before hospitalisation for the first relapse and 30 days after discharge and were categorised as either long-acting injectable, clozapine, non-clozapine oral antipsychotic monotherapy, non-clozapine oral antipsychotic polypharmacy, and antipsychotic non-use. Adjusted hazard ratios (aHRs) of the risk of second relapse based on treatment type were analysed with Cox regression models for 2 years after the first relapse, or until death or end of data linkage (Dec 31, 2017). People with lived experience of schizophrenia were not involved in the research and writing process. Findings Between Jan 31, 1996 and Dec 31, 2017, 3000 individuals had their first psychosis relapse and were eligible for analysis. Mean age was 30·0 years (SD 7·6), 1069 (35·6%) of patients were women and 1931 (64·4%) men. No ethnicity data were available. 2148 (71·7%) had a second relapse within 2 years. Before first relapse, most individuals were either not using antipsychotics (n=1366 [45·5%]), or were using non-clozapine oral antipsychotic monotherapy (n=973 [32·4%]). Compared with continuing the same treatment strategy used before the first relapse, switching to clozapine was associated with the lowest risk of second relapse compared with continuing any non-clozapine oral antipsychotic monotherapy (aHR 0·66, 95% CI 0·49–0·89; relapse rate 73·2% with oral non-clozapine antipsychotic monotherapy continuation vs 57·1% with switch to clozapine). Switching to another non-clozapine oral antipsychotic monotherapy (0·99, 0·76–1·28) was approximately as unhelpful in preventing the next relapse as switching to antipsychotic non-use (1·07, 0·80–1·42). Interpretation In patients with first-episode schizophrenia having their first psychosis relapse despite use of non-clozapine oral antipsychotics, continuation with the same antipsychotic modality or switch to another non-clozapine oral antipsychotic did not show evidence of being beneficial in relapse prevention, suggesting that clozapine should be started instead. This finding, together with existing knowledge of decreased risk of mortality associated with clozapine, challenges current treatment guidelines that recommend clozapine as a third-line treatment, resulting in treatment practices characterised by long delays to clozapine initiation. Funding Sigrid Jusélius Foundation.

Importance Preliminary studies suggest that glucagon-like peptide-1 receptor (GLP-1) agonists, used to treat type 2 diabetes and obesity, may decrease alcohol consumption. Objective To test whether the risk of hospitalization due to alcohol use disorder (AUD) is decreased during the use of GLP-1 agonists compared with periods of nonuse for the same individual. Design, Setting, and Participants This cohort study was an observational study conducted nationwide in Sweden using data from January 2006 to December 2023. The population-based cohort was identified from registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. Participants were all residents aged 16 to 64 years who had a diagnosis of AUD. Exposures The primary exposure was use of individual GLP-1 agonists (compared with nonuse of GLP-1 agonists), and the secondary exposure was medications with indication for AUD. Main Outcomes and Measures The primary outcome was AUD hospitalization analyzed in a Cox regression within-individual model. Secondary outcomes were any substance use disorder (SUD)–related hospitalization, somatic hospitalization, and suicide attempt. Results The cohort included 227 866 individuals with AUD; 144 714 (63.5%) were male and 83 154 (36.5%) were female, with a mean (SD) age of 40.0 (15.7) years. Median (IQR) follow-up time was 8.8 (4.0-13.3) years. A total of 133 210 individuals (58.5%) experienced AUD hospitalization. Semaglutide (4321 users) was associated with the lowest risk (AUD: adjusted hazard ratio [aHR], 0.64; 95% CI, 0.50-0.83; any SUD: aHR, 0.68; 95% CI, 0.54-0.85) and use of liraglutide (2509 users) with the second lowest risk (AUD: aHR, 0.72; 95% CI, 0.57-0.92; any SUD: aHR, 0.78; 95% CI, 0.64-0.97) of both AUD and SUD hospitalization. Use of any AUD medication was associated with a modestly decreased risk (aHR, 0.98; 95% CI, 0.96-1.00). Semaglutide (aHR, 0.78; 95% CI, 0.68-0.90) and liraglutide (aHR, 0.79; 95% CI, 0.69-0.91) use were also associated with decreased risk of somatic hospitalizations but not associated with suicide attempts (semaglutide: aHR, 0.55; 95% CI, 0.23-1.30; liraglutide: aHR, 1.08; 95% CI, 0.55-2.15). Conclusions and Relevance Among patients with AUD and comorbid obesity/type 2 diabetes, the use of semaglutide and liraglutide were associated with a substantially decreased risk of hospitalization due to AUD. This risk was lower than that of officially approved AUD medications. Semaglutide and liraglutide may be effective in the treatment of AUD, and clinical trials are urgently needed to confirm these findings.

We studied the incidence and duration of cumulative bisphosphonate use among older Finnish women and men with or without Alzheimer’s disease (AD). The MEDALZ-2005 cohort is a nationwide sample of all persons with clinically diagnosed AD on 31 December 2005 and their age-, gender-, and region of residence-matched control persons without AD. Information on bisphosphonate use by persons with an AD diagnosis and their controls without AD during 2002–2009 was obtained from the prescription register database containing reimbursed medications. A total of 6,041 (11.8%) persons used bisphosphonates during the 8-year follow-up. Bisphosphonates were more commonly used among persons without AD (n = 3121, 12.3%) than among persons with AD (n = 2,920, 11.2%) (p = 0.001). The median duration of bisphosphonate use was 743 days (IQR). Among persons with AD, the median duration of use was 777 days (IQR) and among persons without AD, 701 days (IQR) (p = 0.011). People without AD more often used bisphosphonate combination preparations including vitamin D than did people with AD (p < 0.0001). Bisphosphonate use was more common among people without AD who had comorbidities, asthma/COPD, or rheumatoid arthritis compared with users with AD. Short-term users were more likely to be male, at least 80 years old, and not having AD. Although the incidence of bisphosphonate use was slightly higher among persons without AD, the cumulative duration of bisphosphonate use was longer in persons with AD. Short-term use was associated with male gender, older age, and not having AD.

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.