The introduction of second-generation antipsychotic drugs during the 1990s is widely believed to have adversely affected mortality of patients with schizophrenia. Our aim was to establish the long-term contribution of antipsychotic drugs to mortality in such patients.
Nationwide registers in Finland were used to compare the cause-specific mortality in 66 881 patients versus the total population (5.2 million) between 1996, and 2006, and to link these data with the use of antipsychotic drugs. We measured the all-cause mortality of patients with schizophrenia in outpatient care during current and cumulative exposure to any antipsychotic drug versus no use of these drugs, and exposure to the six most frequently used antipsychotic drugs compared with perphenazine use.
Although the proportional use of second-generation antipsychotic drugs rose from 13% to 64% during follow-up, the gap in life expectancy between patients with schizophrenia and the general population did not widen between 1996 (25 years), and 2006 (22.5 years). Compared with current use of perphenazine, the highest risk for overall mortality was recorded for quetiapine (adjusted hazard ratio [HR] 1.41, 95% CI 1.09-1.82), and the lowest risk for clozapine (0.74, 0.60-0.91; p=0.0045 for the difference between clozapine vs perphenazine, and p
Comment In: Lancet. 2009 Nov 7;374(9701):1591; author reply 1592-319897117
Comment In: Lancet. 2009 Nov 7;374(9701):1591; author reply 1592-319897118
Comment In: Lancet. 2009 Aug 22;374(9690):590-219595448
Comment In: Lancet. 2009 Nov 7;374(9701):1592; author reply 1592-319897121
Comment In: Lancet. 2009 Nov 7;374(9701):1592; author reply 1592-319897120
From the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm; the Department of Forensic Psychiatry, University of Eastern Finland, and Niuvanniemi Hospital, Kuopio; the Impact Assessment Unit, National Institute for Health and Welfare, Helsinki; and the School of Pharmacy, University of Eastern Finland, Kuopio.
It is generally believed that after the first episode of schizophrenia, the risk of relapse decreases with time in patients who are stabilized. Many treatment guidelines recommend that after stabilization, antipsychotic treatment should be continued for 1-5 years, and longer exposure should be avoided if possible. However, there is no published evidence to substantiate this view. The authors used nationwide databases to investigate this issue.
Prospectively gathered nationwide register data were used to study the risk of treatment failure (psychiatric rehospitalization or death) after discontinuation of antipsychotic treatment. Multivariate Cox regression was used to assess outcomes among all patients hospitalized for the first time with a schizophrenia diagnosis in Finland during the period of 1996-2014 (N=8,719).
The lowest risk of rehospitalization or death was observed for patients who received antipsychotic treatment continuously (adjusted hazard ratio=1.00), followed by patients who discontinued antipsychotic use immediately after discharge from the first hospital treatment (hazard ratio=1.63, 95% CI=1.52-1.75), within 1 year (hazard ratio=1.88, 95% CI=1.57-2.24), within 1-2 years (hazard ratio=2.12, 95% CI=1.43-3.14), within 2-5 years (hazard ratio=3.26, 95% CI=2.07-5.13), and after 5 years (a median of 7.9 years) (hazard ratio=7.28, 95% CI=2.78-19.05). Risk of death was 174%-214% higher among nonusers and patients with early discontinuation of antipsychotics compared with patients who received antipsychotic treatment continuously for up to 16.4 years.
Whatever the underlying mechanisms, these results provide evidence that, contrary to general belief, the risk of treatment failure or relapse after discontinuation of antipsychotic use does not decrease as a function of time during the first 8 years of illness, and that long-term antipsychotic treatment is associated with increased survival.
CommentIn: Am J Psychiatry. 2018 Aug 1;175(8):712-713 PMID 30064241
CommentIn: Am J Psychiatry. 2018 Sep 1;175(9):908-909 PMID 30173547
CommentIn: Am J Psychiatry. 2018 Sep 1;175(9):909 PMID 30173555
CommentIn: Am J Psychiatry. 2018 Dec 1;175(12):1266-1267 PMID 30501413
CommentIn: Am J Psychiatry. 2018 Dec 1;175(12):1267 PMID 30501421
Recent evidence suggests that schizophrenia may result from a disruption of normal brain development during a critical, prenatal risk period in the 6th month of gestation. The phenotypic diagnostic manifestation of a basic genetic-neurodevelopmental disorder may consist of characteristics approximated by the DSM-IV diagnosis of "schizotypal personality disorder" (SPD). We identified male conscripts in Finland who, as fetuses, were exposed to the 1969 Hong Kong Influenza epidemic, along with a group of controls born during a relatively low year (1971) for infectious epidemics. It was hypothesized that among fetuses exposed to the influenza epidemic in their 6th month of gestation, we would observe an increased frequency of elevated (upper quartile) scores on a schizotypal personality characteristics (SPC) scale as compared to controls. A significantly higher proportion of the 6th month index exposed subjects (39%) had "elevated" SPC scale scores as compared to their controls (26%) (p
Advanced paternal age (APA) is a risk factor for nonaffective psychosis (NAP) in the offspring, although the mechanism(s) of this association are not clear. The aim of this study was to examine whether later childbearing can be explained by parental schizophrenia, and in doing so, further evaluate the "de novo mutation" hypothesis for the association between APA and NAP.
Using binary logistic regression, the association between APA and parental history of schizophrenia in the offspring, considering maternal and paternal history separately, was examined in 1) all persons with NAP born in Finland between 1950 and 1969 (Finnish NAP Cohort, n = 13,712), and 2) members of the Northern Finland 1966 Birth Cohort (NFBC 1966, n = 10,224), a general population birth cohort.
In the Finnish NAP Cohort, having a mother with schizophrenia was associated with APA (Odds Ratio [OR] for linear trend = 1.20, 95% confidence interval 1.12-1.29, p
Alexithymic features are often associated with depression, which is the most important risk factor for suicidal behaviors. Nevertheless, little is known about the associations between alexithymia and suicidality. In this 12-month follow-up study we investigated the relationship between alexithymia and suicidal ideation in a sample of the general population (N = 1,563) using the 20-item Toronto Alexithymia Scale (TAS-20) and the 21-item Beck Depression Inventory (BDI). Suicidal ideation was more common among subjects with alexithymia than among nonalexithymic subjects (32% v 9% at baseline and 36% v 9% after 12 months). In cross-sectional analyses, alexithymia associated with the presence of suicidal ideation even after adjustment for sex, age, and several psychosocial and socioeconomic factors and the presence of depression. Moreover, after adjustment for depression at baseline, the decrease and increase in alexithymic features during the study period associated independently with recovery from and the occurrence of suicidal ideation, respectively. Nevertheless, these associations were no longer independent when adjusted for concomitant changes in the level of depressive symptoms. In conclusion, if depression presents alexithymic features the subject has an additive impact on the risk of suicidal ideation.
The objective of this study was to investigate the prevalence of acetylcholinesterase inhibitor (AChEI) and memantine use, duration of treatment, concomitant use of these drugs, and factors associated with the discontinuation of AChEI therapy during 2006-2009. We utilized data from a nationwide sample of community-dwelling individuals with a clinically verified Alzheimer's disease diagnosed during the year 2005 (n=6858) as a part of the MEDALZ-2005 study. During the 4-year follow-up, 84% used AChEI and 47% used memantine. Altogether, 22% of the sample used both drugs concomitantly. The median duration of the first AChEI use period was 860 (interquartile range 295-1458) days and 1103 (interquartile range 489-1487) days for the total duration of AChEI use. Although 20% of the AChEI users discontinued the use during the first year, over half of them restarted later. The risk of discontinuation was higher for rivastigmine [hazard ratio 1.34 (confidence interval 1.22-1.48)] and galantamine users [hazard ratio 1.23 (confidence interval 1.15-1.37)] compared with donepezil users in the adjusted model. In conclusion, median time for AChEI use was over 3 years and every fifth Alzheimer's disease patient used AChEI and memantine concomitantly during the follow-up. The low rate of discontinuation is consistent with the Finnish Care Guideline but in contrast to the results reported from many other countries.
It is unknown if antidepressant treatment is associated with either increased or decreased risk of suicide.
To estimate the risk of suicide, attempted suicide, and overall mortality during antidepressant treatments in a real-life setting with high statistical power.
A cohort study in which all subjects without psychosis, hospitalized because of a suicide attempt from January 1, 1997, to December 31, 2003, in Finland, were followed up through a nationwide computerized database.
A total of 15 390 patients with a mean follow-up of 3.4 years.
The propensity score-adjusted relative risks (RRs) during monotherapy with the most frequently used antidepressants compared with no antidepressant treatment.
In the entire cohort, fluoxetine use was associated with the lowest risk (RR, 0.52; 95% confidence interval [CI], 0.30-0.93), and venlafaxine hydrochloride use with the highest risk (RR, 1.61; 95% CI, 1.01-2.57), of suicide. A substantially lower mortality was observed during selective serotonin reuptake inhibitor use (RR, 0.59; 95% CI, 0.49-0.71; P
Comment In: Evid Based Ment Health. 2007 Aug;10(3):9017652572
To study whether antidepressant use is associated with an increased risk of hip fracture among community-dwelling persons with and without Alzheimer's disease (AD), and to compare the risk according to duration of use and between antidepressant groups.
Retrospective cohort study, including 50,491 persons with AD (mean age 80) and 100,982 comparison persons without AD from Finnish register-based MEDALZ cohort. Antidepressant use was compared with nonuse with Cox proportional hazard models. Incident users were identified with a one year washout period from Prescription register data. Main outcome was hospitalization due to hip fracture.
During antidepressant use, the age-adjusted rate of hip fractures per 100 person-years was 3.01 (95% CI 2.75-3.34) among persons with and 2.28 (1.94-2.61) among persons without AD. Antidepressant use was associated with an increased risk of hip fracture among persons with and without AD (adjusted HR 1.61, 95% CI 1.45-1.80 and 2.71, 2.35-3.14, respectively) compared with nonuse. The risk was most prominent in the beginning of use and was elevated even up to 4 years. The risk was increased with all of the most frequently used antidepressants.
Use of antipsychotics for treatment of behavioral and psychological symptoms of dementia is frequent among persons with Alzheimer disease (AD). Doses used in long-term therapy have not been previously reported. We describe antipsychotic doses used among community-dwelling persons with AD and investigate factors associated with high-dose use. The MEDALZ-2005 (Medication use and Alzheimer disease) cohort is a nationwide sample including all persons with clinically diagnosed AD at the end of year 2005 in Finland (n = 28,093). Data including prescriptions, comorbidities, and hospital discharge diagnoses were collected from nationwide registers. Antipsychotic doses in monotherapy were investigated during 2006 to 2009. Among 8920 antipsychotic users, 4% (n = 336) used antipsychotics with high dose. Typical antipsychotics were more often used with high dose than atypical antipsychotics. High-dose use was associated with younger age (
Antipsychotic polypharmacy (APP) is not recommended in treatment of behavioral and psychological symptoms of dementia (BPSD). There is lack of studies concerning prevalence of APP among persons with dementia.
The objective of our study was to describe prevalence and risk factors associated with antipsychotic polypharmacy among antipsychotic users with Alzheimer's disease (AD).
Data from nationwide MEDALZ-2005 cohort including all community-dwelling persons diagnosed with AD in Finland was utilized. Register-based data included prescriptions, comorbidities, and hospital discharge diagnoses. Users of antipsychotics during 2006-2009 were included (n = 9,803). The risk of starting antipsychotic polypharmacy was evaluated with Cox proportional hazards model.
Prevalence of antipsychotic polypharmacy was 8% (n = 750) among antipsychotic users (n = 9,803). Quetiapine and risperidone was the most common combination of two antipsychotics followed by combination of quetiapine and haloperidol. Antipsychotic polypharmacy was associated with younger age (HR 1.35 [Confidence Interval, CI, 1.16-1.56]), male gender (HR 1.18 [CI 1.02-1.38]), and history of psychiatric disorder (HR 1.50 [CI 1.26-1.78]) in the adjusted model.
In conclusion, we found higher prevalence of APP than previously reported among older populations. This is concerning since effectiveness of APP has not been demonstrated and APP is not recommended in the treatment of BPSD. Clinicians should pay more attention to avoid APP and use of antipsychotics to other indications than BPSD among persons with AD.