Exposure to risperidone versus other antipsychotics and risk of osteoporosis-related fractures: a population-based study.

OBJECTIVE: Antipsychotics may increase serum prolactin, which has particularly been observed with risperidone. Further, hyperprolactinemia has been linked to osteoporosis-related fractures. Therefore, we investigated fracture risk in a nationwide cohort exposed to antipsychotics. METHODS: Swedish registers were used to identify adults with two consecutive dispensations of risperidone (n = 38 211), other atypical antipsychotics not including paliperidone (n = 60 691), or typical antipsychotics (n = 17 445) within three months between 2006 and 2013. An osteoporosis-related fracture was defined as a non-open hip/femur fracture in primary analyses. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Risperidone users were on average older (mean age of 68, 44, and 63 years for risperidone, other atypical antipsychotics, and typical antipsychotics respectively). Compared with other atypical antipsychotics, there was no association between risperidone and osteoporosis-related fractures in the overall (HR = 1.04, CI: 0.91-1.19) or age-stratified analyses. A significantly increased risk of typical antipsychotics (HR = 1.24, CI: 1.07-1.45) compared with other atypical antipsychotics remained for ages >45 years. CONCLUSION: Risperidone does not appear to be associated with an increased risk of osteoporosis-related fracture compared with other atypical antipsychotic agents as a group. For typical antipsychotics, a moderately elevated risk of hip fractures was noted compared with other atypical antipsychotics, possibly because of residual confounding.

Trends in antidepressant use among children and adolescents: a Scandinavian drug utilization study.

OBJECTIVE: To compare antidepressant utilization in individuals aged 5-19 years from the Scandinavian countries. METHODS: A population-based drug utilization study using publicly available data of antidepressant use from Denmark, Norway, and Sweden. RESULTS: In the study period from 2007 to 2017, the proportion of antidepressant users increased markedly in Sweden (9.3-18.0/1000) compared to Norway (5.1-7.6/1000) and Denmark (9.3-7.5/1000). In 2017, the cumulated defined daily doses (DDD) of selective serotonin reuptake inhibitors were 5611/1000 inhabitants in Sweden, 2709/1000 in Denmark, and 1848/1000 in Norway. The use of 'other antidepressants' (ATC code N06AX) also increased in Sweden with a higher DDD in 2017 (497/1000) compared to Denmark (225/1000) and Norway (170/1000). The use of tricyclic antidepressants was generally low in 2017 with DDDs ranging between 30-42 per 1000. The proportion of antidepressant users was highest among 15- to 19-year-old individuals. Girls were more likely to receive treatment than boys, and the treated female/male ratios per 1000 were similar in Sweden (2.39), Denmark (2.44), and Norway (2.63). CONCLUSION: Even in highly comparable healthcare systems like the Scandinavian countries', variation in antidepressant use is considerable. Swedish children and adolescents have a markedly higher and still increasing use of antidepressants compared to Danish and Norwegian peers.

International trends in clozapine use: a study in 17 countries.

OBJECTIVE: There is some evidence that clozapine is significantly underutilised. Also, clozapine use is thought to vary by country, but so far no international study has assessed trends in clozapine prescribing. Therefore, this study aimed to assess clozapine use trends on an international scale, using standardised criteria for data analysis. METHOD: A repeated cross-sectional design was applied to data extracts (2005-2014) from 17 countries worldwide. RESULTS: In 2014, overall clozapine use prevalence was greatest in Finland (189.2/100 000 persons) and in New Zealand (116.3/100 000), and lowest in the Japanese cohort (0.6/100 000), and in the privately insured US cohort (14.0/100 000). From 2005 to 2014, clozapine use increased in almost all studied countries (relative increase: 7.8-197.2%). In most countries, clozapine use was highest in 40-59-year-olds (range: 0.6/100 000 (Japan) to 344.8/100 000 (Finland)). In youths (10-19 years), clozapine use was highest in Finland (24.7/100 000) and in the publicly insured US cohort (15.5/100 000). CONCLUSION: While clozapine use has increased in most studied countries over recent years, clozapine is still underutilised in many countries, with clozapine utilisation patterns differing significantly between countries. Future research should address the implementation of interventions designed to facilitate increased clozapine utilisation.

Suicide in first episode psychosis: a nationwide cohort study.

BACKGROUND: Relatively little is known about suicide in diagnostic subtypes of first episode psychosis (FEP). Our aim was to assess suicide rates and potential risk factors for suicide in FEP. METHODS: This is a national register-based cohort study of patients born in 1973-1978 in Sweden and who were hospitalized with a FEP between ages 15 and 30years (n=2819). The patients were followed from date of discharge until death, emigration, or 31st of December 2008. The suicide rates for six diagnostic subtypes of FEP were calculated. Suicide incidence rate ratios (IRRs) were calculated to evaluate the association between suicide and psychiatric, familial, social, and demographic factors. RESULTS: In total 121 patients died by suicide. The overall suicide rate was 4.3 (95% confidence interval [CI] 3.5-5.0) per 1000person-years. The highest suicide rates were found in depressive disorder with psychotic symptoms and in delusional disorder. In an adjusted model, the strongest risk factors for suicide were self-harm (IRR 2.7, CI 1.7-4.4) or a conviction for violent crime (IRR 2.0, CI 1.3-3.2). Also having a first-degree relative with a schizophrenia/bipolar diagnosis (IRR 2.1, CI 1.2-3.6) or substance use disorder (IRR 2.0, CI 1.2-3.2) were significant risk factors for suicide. CONCLUSIONS: Impulsive behavior such as self-harm as well as having a family history of severe mental disorder or substance use are important risk factors for suicide in FEP.

A five year diagnostic follow-up of 1,840 patients after a first episode non-schizophrenia and non-affective psychosis.

OBJECTIVE: It is not clear which patients with a first psychotic episode will develop schizophrenia. We performed a diagnostic follow-up of patients treated for a first time non-affective, non-schizophrenia psychosis and explored potential predictors of a subsequent schizophrenia or schizoaffective diagnosis. METHODS: This register-based cohort study comprises individuals born between 1973 and 1978 in Sweden, with a first hospital-treated psychosis excluding schizophrenia, schizoaffective disorder, bipolar disorder and depressive disorder with psychotic symptoms (n=1840). The patients were followed for five years regarding subsequent diagnoses. Psychiatric, social, family history of psychiatric illness, premorbid intellectual level, head injuries and obstetrical complications were investigated by logistic regression as predictors of schizophrenia or schizoaffective diagnosis. RESULTS: During the follow-up, 18% were diagnosed with schizophrenia or schizoaffective disorder, 5% were diagnosed with bipolar disorder, whereas 29% were not re-admitted to a psychiatric clinic. Patients with a first-degree relative hospitalized for schizophrenia and/or bipolar disorder had an increased risk of subsequent diagnosis for schizophrenia or schizoaffective disorder (odds ratio 1.9 and 95% confidence interval 1.1 to 3.0)), whereas previous severe criminality was associated with a decreased risk (odds ratio 0.5, 95% confidence interval 0.3-0.8). CONCLUSION: Diagnostic outcome was diverse after a first non-schizophrenia and non-affective psychosis. Family history of severe mental illness and no previous conviction for severe criminality were the strongest risk factors for a future schizophrenia or schizoaffective diagnosis.

Suicide seasonality and antidepressants: a register-based study in Sweden.

OBJECTIVE: Seasonality of completed suicides with a peak in spring and early summer is a well-documented finding. The circannual serotonergic functioning is hypothesized to be central in this phenomenon. Antidepressant medications exert their pharmacological action mainly by regulating serotonin. Our aim is to study the amplitude of the seasonal effect among suicide victims positive for different classes of antidepressants or without any antidepressants at the time of death. METHOD: By using Swedish Registers, 12 448 suicides with forensic data for antidepressive medication and information on in-patient-treated mental disorder were identified during 1992-2003. Seasonality was estimated with a Poisson regression variant of the circular normal distribution of completed suicides. RESULTS: Higher suicide seasonality was found for individuals treated with selective serotonin reuptake inhibitor (SSRIs) compared to those with other antidepressant treatment or without any antidepressant treatment. The finding is more evident for men and violent suicide methods and those without history of in-patient treatment. CONCLUSION: Our results provide preliminary support for the serotonergic hypothesis of suicide seasonality and raise the question of a possible accentuation of the natural suicide seasonality in patients treated with SSRIs, a hypothesis that warrants further investigation.

Antidepressant medication prevents suicide in depression.

OBJECTIVE: Ecological studies have demonstrated a substantial decrease in suicide in parallel with an increasing use of antidepressants. To investigate on the individual level the hypothesis that antidepressant medication was a causal factor. METHOD: Data on the toxicological detection of antidepressants in 18 922 suicides in Sweden 1992-2003 were linked to registers of psychiatric hospitalization as well as registers with sociodemographic data. RESULTS: The probability for the toxicological detection of an antidepressant was lowest in the non-suicide controls, higher in suicides, and even higher in suicides that had been psychiatric in-patients but excluding those who had been in-patients for the treatment of depression. CONCLUSION: The finding that in-patient care for depression did not increase the probability of the detection of antidepressants in suicides is difficult to explain other than by the assumption that a substantial number of depressed individuals were saved from suicide by postdischarge treatment with antidepressant medication.