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Antidepressant use and psychosis hospitalization in persons with schizophrenia
- A. Puranen, M. Koponen, M. Lähteenvuo, A. Tanskanen, J. Tiihonen, H. Taipale
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S253-S254
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Introduction
Antidepressants are often used by persons with schizophrenia. These medications are used for a variety of symptoms, such as negative or depressive ones. Effectiveness of antidepressant use in persons with schizophrenia has rarely been studied in the real-world setting.
ObjectivesThe aim of this study was to investigate the risk of hospitalization due to psychosis related to antidepressant use in persons with schizophrenia.
MethodsThis cohort study utilized data combined from Finnish nationwide registers. The study cohort included all 61 889 persons treated in inpatient care due to schizophrenia (defined as International Classification of Diseases, ICD, version 10 codes F20-F25 during 1972–2014 in Finland). National Prescription register data was utilized to obtain drug purchase data, and modelled into drug use periods with PRE2DUP (From Prescriptions to Drug Use Periods) method, developed by our research group. The follow-up covered the years from 1996 to 2017. Antidepressants (Anatomic Therapeutic Chemical classification system, ATC code N06A) were categorized by mechanism of action (non-selective monoamine reuptake inhibitors, TCAs, ATC-codes N06AA, selective serotonin reuptake inhibitors, SSRIs, N06AB and serotonin-norepinephrine reuptake inhibitors, SNRIs, including venlafaxine, milnacipran and duloxetine), and also on drug-substance level. Main outcome was hospitalization due to psychosis (ICD-10 diagnoses F20-F29) as the main diagnosis. We used within-individual design to compare the risk of outcome between the time periods of antidepressant use and non-use within the same person to minimize selection bias. Stratified Cox regression analyses were utilized to calculate adjusted hazard ratios (aHR) with 95% confidence intervals (CIs). These analyses were then adjusted for sequential order of treatments, time since cohort entry, use of antipsychotics, mood stabilizers, benzodiazepines, and Z-drugs.
ResultsThe mean age of the study cohort was 46.2 (SD 16.0) years at cohort entry, and 50.3% of were males. Altogether 49.3% (N=30 508) of the study cohort used antidepressants during the follow-up (median 14.8 years, IQR 7.5-22.0), with citalopram and mirtazapine being the most commonly used antidepressants. The risk of psychosis hospitalization was lower during antidepressant use as compared to non-use (aHR 0.93, 95% CI 0.92-0.95). Use of SSRIs was associated with similar risk (aHR 0.91, 95% CI 0.89-0.93), followed by SNRIs (aHR 0.92, 95% CI 0.88-0.97) and TCAs (aHR 0.93, 95% CI 0.89-0.98). Considering individual drug substances, lowest risk were obserwed with use of sertraline (aHR 0.87, 95% CI 0.83-0.91), fluoxetine (aHR 0.88, 95% CI 0.83-0.91) and citalopram (aHR 0.92, 95% CI 0.90-0.95).
ConclusionsUse of antidepressants was associated with a 7% lowered risk of hospitalization due to psychosis, and AD subgroups did not differ in their real-world effectiveness.
Disclosure of InterestA. Puranen: None Declared, M. Koponen: None Declared, M. Lähteenvuo Shareolder of: Genomi Solutions ltd, Nursie Health ltd, Springflux ltd, Grant / Research support from: Finnish Medical Foundation, Emila Aaltonen Foundation, Speakers bureau of: Sunovion, Lundbeck, Otsuka Pharma, Orion Pharma, Recordati, Janssen, Janssen-Cilag, A. Tanskanen Grant / Research support from: Janssen-Cilag, Eli Lilly, , J. Tiihonen Grant / Research support from: Janssen-Cilag, Eli Lilly, Consultant of: HLS Therapeutics, Orion, and WebMed Global, Speakers bureau of: Eli Lilly, Evidera, Janssen-Cilag, Lundbeck, Mediuutiset, Otsuka, Sidera, and Sunovion, H. Taipale Grant / Research support from: Janssen-Cilag, Eli Lilly, Academy of Finland, Speakers bureau of: Janssen-Cilag, Otsuka
Psychotic depression and the risk of death due to suicide
- T. Paljarvi, J. Tiihonen, M. Lähteenvuo, A. Tanskanen, S. Fazel, H. Taipale
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S442
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Introduction
Depression markedly increases the risk of suicide, and depression is the most common psychiatric disorder diagnosed in persons with a completed suicide, but the interplay between depression and psychotic symptoms in suicides has remained unsettled.
ObjectivesThe purpose of this study was to establish the risk of suicide associated with incident psychotic depression (PD) compared to incident non-psychotic severe depression (NPD) in a large nationwide cohort.
MethodsThis cohort study used routine data from nationwide health registers in Finland. Eligible participants were aged 18 ̶ 59 years at the index diagnosis. Causes of death were defined by the International Classification of Diseases, 10th revision codes. The follow-up time was up to five years. Adjusted Cox regression models were used to analyse risk of death by method of suicide.
ResultsWe included 17331 individuals with incident PD and 85989 individuals with incident NPD. Most of the deaths due to suicides occurred within the first two years after the index diagnosis. Compared to NPD, PD was associated with an overall two-fold increased risk of suicide (adjusted hazard ratio, (aHR) 2.19, 95% confidence interval (CI) 1.95, 2.46), after adjusting for psychiatric comorbidities. In PD, the highest relative risks were for impact-related suicides (aHR 3.03, 95%CI 2.23, 4.13) and for suffocation-related suicides (aHR 2.72, 95%CI 2.23, 3.30), whereas the lowest relative risk was for intentional poisonings (aHR 1.66, 95%CI 1.37, 2.02).
ConclusionsPsychotic symptoms increased the risk of suicide 2-fold of the risk that was associated with severe depression, after controlling for comorbid psychiatric disorders. The severity of suicidal ideation may be higher in PD than in NPD, which then leads to more lethal methods of self-harm.
Disclosure of InterestT. Paljarvi: None Declared, J. Tiihonen Grant / Research support from: Janssen-Cilag, Eli Lilly, Consultant of: HLS Therapeutics, Orion, and WebMed Global, Speakers bureau of: Eli Lilly, Evidera, Janssen-Cilag, Lundbeck, Mediuutiset, Otsuka, Sidera, and Sunovion, M. Lähteenvuo Shareolder of: Genomi Solutions ltd, Nursie Health ltd, Springflux ltd, Grant / Research support from: Finnish Medical Foundation, Emil Aaltonen Foundation, Speakers bureau of: Sunovion, Lundbeck, Otsuka Pharma, Orion Pharma, Recordati, Janssen, Janssen-Cilag, A. Tanskanen Grant / Research support from: Janssen-Cilag, Eli Lilly, S. Fazel Grant / Research support from: Wellcome Trust, H. Taipale Grant / Research support from: Janssen-Cilag, Eli Lilly, Academy of Finland, Speakers bureau of: Janssen-Cilag, Otsuka
Healthcare costs and productivity losses in treatment-resistant depression in Finland
- S. Rannanpää, H. Taipale, A. Tanskanen, M. Lähteenvuo, S. Huoponen, J. Tiihonen
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- Journal:
- European Psychiatry / Volume 65 / Issue S1 / June 2022
- Published online by Cambridge University Press:
- 01 September 2022, p. S268
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Introduction
Due to its relatively high prevalence and recurrent nature, depression causes a major burden on healthcare systems and societies.
ObjectivesTo investigate healthcare resource utilization and costs associated with treatment-resistant depression (TRD) compared with non-TRD depression in Finland.
MethodsOf 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 but no TRD. TRD was defined as initiation of a third treatment trial after having failed two pharmacological treatment trials. Follow-up period covered five years after TRD or corresponding matching data (until end of 2018). Healthcare resource utilization was studied with negative binomial regression and average excess costs of TRD with generalized estimating equations, by adjusting for baseline costs, comorbidity and baseline severity of depression.
ResultsPersons with TRD (mean age 38.7, SD 13.1, 60.0% women) had more healthcare 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 higher total costs for persons with TRD, 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 (2002, 95% CI 1853-2151) compared with non-TRD patients. Mean difference was highest during the first year after TRD (total costs difference 11760, 95% CI 11314-12206).
ConclusionsTreatment-resistant depression is associated with a significant cost burden.
DisclosureThis study was funded by Janssen-Cilag Finland and the Finnish Ministry of Social Affairs and Health through the developmental fund for Niuvanniemi Hospital. ML was partly funded by personal grants from the Finnish Medical Foundation and Emil Aaltonen fou
Use of pharmacotherapies for treatment resistant depression in finland: A nationwide cohort study
- H. Taipale, M. Lähteenvuo, A. Tanskanen, S. Rannanpää, J. Tiihonen
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- Journal:
- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, p. S108
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Introduction
There is a lack of knowledge on utilized pharmacotherapies for treatment resistant depression (TRD).
ObjectivesTo investigate the courses of treatment of TRD.
MethodsAll patients aged 16-65 years and diagnosed with depression in Finland during 2004-2016 were included (identified from nationwide registers for inpatient and specialized outpatient care, sick leaves and disability pensions). New antidepressant users were identified with six-month washout period and followed up for two years to observe the possible emergence of TRD, which was defined as initiation of a third treatment after having two failed pharmacological treatments with adequate duration. Pharmacological treatments were analyzed using PRE2DUP-method.
ResultsDuring follow-up, 177,144 persons had their first registered depression (mean age:39.5, 62.5% women). Of them, 10.9% (N=19,322) met TRD criteria. Among the TRD patients, most common first and second lines antidepressants were as follows: SSRIs (44.6%), mirtazapine (19.0%) and SNRIs (16.5%). As the third line of treatment, 44.2% of TRD patients had antidepressant monotherapy, 32.1% a combination of ≥2 antidepressants, 15.8% antipsychotic or mood stabilizer augmentation and an antidepressant, 4.9% both combination of antidepressants and an augmentation with a mood stabilizer or antipsychotic, 2.7% antipsychotic or mood stabilizer monotherapy and 0.3% ECT monotherapy. Of TRD patients, 36.2% (N=6985) progressed to the fourth line of treatment and most common treatments were antidepressant monotherapy (37.5%), antidepressant combinations (30.8%) and augmentation (20.3%).
ConclusionsAlthough antidepressant combination and augmentation strategies became more frequent, antidepressant monotherapies were still the most common third and fourth lines of depression treatment.
DisclosureThe study was funded by Janssen and SR is an employee of Janssen.
Effectiveness of antipsychotics in schizophrenia with comorbid substance use disorder
- M. Lähteenvuo, J. Luykx, H. Taipale, E. Mittendorfer-Rutz, A. Tanskanen, A. Batalla, J. Tiihonen
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- Journal:
- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, p. S161
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Introduction
Schizophrenia is highly comorbid with substance use disorders (SUD), which may negatively impact the course of illness. However, large studies exploring the best lines of treatment for this combination are lacking.
ObjectivesWe investigated what are the most effective antipsychotics for patients with schizophrenia in preventing the development of substance use disorders and preventing hospitalizations in patients already having substance use disorder.
MethodsWe used two independent national cohort registries including all patient with schizophrenia aged under 46 years. Participants were followed during 22 (1996–2017, Finland) and 11 years (2006–2016, Sweden). We studied risk of rehospitalization, and risk of developing an SUD when using vs. not using antipsychotics, using Cox proportional hazards regression analysis models.
Results45,476 patients with schizophrenia were identified (30,860 in Finland; 14,616 in Sweden). For patients without SUD, clozapine and antipsychotic polytherapy were associated with the lowest risks of developing SUD in both countries. For patients with co-existing SUD, the risk of hospitalization was the lowest during clozapine, polytherapy and long-acting injectable use.
ConclusionsIn patients with schizophrenia and comorbid SUD, antipsychotic medications were effective in preventing relapses. In those without an SUD, antipsychotic use was associated with a markedly reduced risk of developing an initial SUD. Clozapine and long-acting injectables should be considered treatments of choice in patients with schizophrenia and SUD, or at risk of developing co-morbid SUD.
DisclosureML: Genomi Solutions Ltd, DNE 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.
Morbidity and mortality in schizophrenia with comorbid substance use disorders in Finland and Sweden
- M. Lähteenvuo, A. Batalla, J. Luykx, E. Mittendorfer-Rutz, A. Tanskanen, J. Tiihonen, H. Taipale
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- European Psychiatry / Volume 64 / Issue S1 / April 2021
- Published online by Cambridge University Press:
- 13 August 2021, pp. S237-S238
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Introduction
Schizophrenia 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 <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.
Real-world effectiveness of antipsychotic treatments among patients with schizophrenia and affective symptoms
- J. Tiihonen, M. Lähteenvuo, F. Hoti, P. Vattulainen, H. Taipale, A. Tanskanen
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- European Psychiatry / Volume 41 / Issue S1 / April 2017
- Published online by Cambridge University Press:
- 23 March 2020, p. S386
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Introduction
The clinical distinction between schizophrenia and affective psychoses is often not clear-cut, and very little is known about the effectiveness of treatments among patients having both schizophrenia and affective symptoms.
ObjectivesTo study the comparative real-world effectiveness of antipsychotic treatments among patients having schizophrenia and affective symptoms.
MethodsWe studied the risk of all-cause rehospitalization during use of specific antipsychotics during 1996–2012 among all patients who had been previously hospitalized with both schizophrenia and mood disorder diagnoses in Finland since 1987 (n = 28,015). We linked nation-wide databases on hospitalization, mortality, and filled prescriptions. The primary analysis was within-individual analysis, in which each individual was used as his/her own control to eliminate selection bias. The effect of concomitant psychotropic medications, and the temporal orders of exposure and non-exposure periods were adjusted.
ResultsWhen 22 specific antipsychotic treatments were compared with the most frequently used antipsychotic quetiapine, the lowest rehospitalization risks were observed during the treatment periods of olanzapine long-acting injection (LAI) (HR: 0.52; 95% CI: 0.34–0.80), risperidone LAI (0.67; 0.56–0.81), and clozapine (0.68; 0.63–0.74). The worst outcome was observed for periciazine (1.19; 0.96–1.48) and no antipsychotic use (1.09; 1.04–1.13).
ConclusionsOlanzapine LAI, risperidone LAI, and clozapine use are associated with the lowest risk of rehospitalization among patients with schizophrenia and affective symptoms.
Disclosure of interestJari Tiihonen has served as a consultant to The Finnish Medicines Agency Fimea, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, F. Hoffman-La Roche, Janssen-Cilag, Lundbeck, Organon, and Finnish Medicines Agency he has received fees for giving expert testimony to AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Otsuka and Pfizer lecture fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Novartis, Otsuka, Pfizer and grants from Stanley Foundation and Sigrid Jusélius Foundation. Tiihonen is a member of advisory boards for AstraZeneca, Eli Lilly, Janssen-Cilag, and Otsuka, and has research collaboration with Lilly and Janssen. Markku Lähteenvuo is a major shareholder and board member at Genomi Solutions ltd, a Finnish based bioinformatics company. He has also received research grants or awards from Boehringer-Ingelheim, and is working as a coordinator for a research project funded by the Stanley Foundation. Fabian Hoti and Pia Vattulainen are employed by EPID Research, which is a contract research organization that performs commissioned pharmacoepidemiological studies and thus its employees have been and currently are working in collaboration with several pharmaceutical companies. Antti Tanskanen and Heidi Taipale have participated in research projects funded by Janssen with grants paid to the Karolinska Institutet.