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.

Antipsychotic use among persons with schizophrenia in Sweden and Finland, trends and differences.

OBJECTIVES: To compare the differences in prevalence of antipsychotic and adjunctive pharmacotherapy use among individuals with schizophrenia between Sweden and Finland during 2006-2016. METHODS: Nationwide register-based data were utilized for constructing two separate cohorts: all persons in Finland with a diagnosis of schizophrenia treated in inpatient care during 1972-2014, and persons in Sweden aged 16-64 with recorded diagnoses of schizophrenia in inpatient or specialized outpatient care, sickness absence or disability pension during 2005-2013. The prevalence of use was assessed as a point prevalence on 31 October each year 2006-2016, based on drug use periods modelled with the PRE2DUP method. In 2016, the Finnish cohort included 37,780 persons and Swedish cohort 25,433 persons. RESULTS: The most commonly used antipsychotic in 2016 was oral olanzapine in both countries (22.7% [95% CI 21.6-22.4] in Finland, 20.9% [20.4-21.4] in Sweden), followed by clozapine which was more frequently used in Finland (22.0%, 21.6-22.4) than in Sweden (14.8%, 14.4-15.3). Long-acting injectable (LAI) use was almost two times more likely in Sweden (21.6%, 95% CI 21.1-22.1) than in Finland (12.8%, 12.5-13.1), a difference which was due to more common use of FG-LAIs in Sweden. A four-fold difference was observed in Z-drugs use (19.9% in Sweden versus 5.0% in Finland). CONCLUSION: Potential explanations for the observed discrepancies include differences in national treatment guidelines, methods of data collection, patient characteristics and/or attitudes towards treatment among both patients and physicians.

Use of antidepressants and mood stabilizers in persons with first-episode schizophrenia.

PURPOSE: Antipsychotics are first-line treatment of schizophrenia. They are often accompanied by adjunctive treatments, such as antidepressant (AD) or mood stabilizer (MS), although there is only limited information of their use in first-episode schizophrenia. This study aimed to investigate AD and MS initiation and factors associated with initiation in persons with first-episode schizophrenia. METHODS: Register-based data was utilized to identify persons who received inpatient care due to schizophrenia during 1996-2014 in Finland and who did not use AD or MS at the time of first inpatient care diagnosis of schizophrenia (N = 7667, mean age 40.2, SD 18.2). Drug purchase data (1995-2017) was obtained from the National Prescription register and modelled with PRE2DUP method. Initiations of AD and MS use were followed up 3 years from first schizophrenia diagnoses. Cox proportional hazard models were used to investigate factors associated with AD or MS initiation. RESULTS: Among persons with first-episode schizophrenia, 35.4% initiated AD and 14.1% initiated MS use within three years from diagnoses. Female gender, younger age, and benzodiazepine use were associated with higher risk of AD and MS initiation. The number of previous psychoses was associated with decreased risk of AD and increased risk of MS initiation. CONCLUSION: Clinical guidelines rarely recommend the use of AD or MS as adjunctive treatment in persons with schizophrenia. However, this population is often treated with AD or MS. More studies are needed to evaluate benefits and risks of these medications as adjunctive treatment of schizophrenia.

Incidence of antidepressant use in community-dwelling persons with and without Alzheimer's disease: 13-year follow-up.

OBJECTIVES: The study aimed to investigate the incidence of antidepressant use in persons with and without Alzheimer's disease (AD) from 9 years before to 4 years after AD diagnosis and to examine the incidence of different antidepressant groups. METHODS: We used register-based data from the Medication use and Alzheimer's disease cohort including all Finnish persons diagnosed with AD in 2005-2011 with their age-matched and gender-matched comparison persons without AD. In this study, 62,104 persons with AD and 62,104 comparison persons were included. Data on dispensed antidepressants during 1995-2012 were collected from the Prescription Register. A 1-year washout period was utilized to measure the rate of new antidepressant users every 6-month period starting from 9 years before and until 4 years after the AD diagnoses. The incidence rate between persons with and without AD was compared with Poisson regression. RESULTS: The incidence of antidepressant use in persons with AD was higher during the whole study period compared with that in persons without AD. The incidence rate was highest at 6 months after AD diagnosis (incidence rate ratio = 5.22, 95% confidence interval 4.77-5.72). Selective serotonin reuptake inhibitors were the most frequently initiated group (61.3% of initiations in persons with AD). CONCLUSIONS: The incidence of antidepressant use was higher in persons with AD than in comparison persons, and it was not explained by history of hospital-treated psychiatric disorders. Widespread use of antidepressants in persons with AD is concerning as their efficacy is controversial and their use is associated with adverse events. Copyright © 2016 John Wiley & Sons, Ltd.

Real-world effectiveness of antidepressant use in persons with schizophrenia: within-individual study of 61,889 subjects.

The aim of this study was to investigate the real-world effectiveness of antidepressant use in persons with schizophrenia. The register-based study cohort included all 61,889 persons treated in inpatient care due to schizophrenia during 1972-2014 in Finland. The main outcome was hospitalization due to psychosis and secondary outcomes included non-psychiatric hospitalization and all-cause mortality. We used within-individual design to compare the risk of hospitalization-based outcomes during the time periods of antidepressant use to antidepressant non-use periods within the same person, and traditional between-individual Cox models for mortality. The risk of psychosis hospitalization was lower during antidepressant use as compared to non-use (adjusted Hazard Ratio, aHR, 0.93, 95% CI 0.92-0.95). Antidepressants were associated with a decreased risk of mortality (aHR 0.80, 95% CI 0.76-0.85) and a slightly increased risk of non-psychiatric hospitalization (aHR 1.03, 95% CI 1.01-1.06). In conclusion, these results indicate that antidepressants might be useful and relatively safe to use in this population.