Johan Reutfors

Risks of adverse pregnancy and birth outcomes in women treated or not treated with mood stabilisers for bipolar disorder: population based cohort study

Objective To investigate the risks of adverse pregnancy and birth outcomes for treated and untreated bipolar disorder during pregnancy. Design Population based cohort study using data from national health registers. Setting Sweden. Participants 332 137 women with a last menstrual period anytime after 1 July 2005 and giving birth anytime before the end of 31 December 2009. Women with a record of at least two bipolar diagnoses were identified and grouped as treated (n=320)—those who had filled a prescription for mood stabilisers (lithium, antipsychotics, or anticonvulsants) during pregnancy—or untreated (n=554). Both groups were compared with all other women giving birth (n=331 263). Main outcome measures Preterm birth, mode of labour initiation, gestational diabetes, infants born small or large for gestational age, neonatal morbidity, and congenital malformations. Results Of the untreated women, 30.9% (n=171) were induced or had a planned caesarean delivery compared with 20.7% (n=68 533) without bipolar disorder (odds ratio 1.57, 95% confidence interval 1.30 to 1.90). The corresponding values for the treated women were 37.5% (n=120) (2.12, 1.68 to 2.67). The risks of preterm birth in both treated and untreated women were increased by 50%. Of the untreated women, 3.9% (n=542) had a microcephalic infant compared with 2.3% (324 844) of the women without bipolar disorder (1.68, 1.07 to 2.62). The corresponding values for the treated women were 3.3% (n=311) (1.26, 0.67 to 2.37). Similar trends were observed for risks of infants being small for gestational age infants for weight and length. Among infants of untreated women, 4.3% (n=24) had neonatal hypoglycaemia compared with 2.5% (n=8302) among infants of women without bipolar disorder (1.51, 1.04 to 2.43), and 3.4% (n=11) of the treated women (1.18, 0.64 to 2.16). The analyses of variation in outcomes did not support any significant differences between treated and untreated women. Conclusions Bipolar disorder in women during pregnancy, whether treated or not, was associated with increased risks of adverse pregnancy outcomes.

Antipsychotics During Pregnancy Relation to Fetal and Maternal Metabolic Effects

CONTEXT Knowledge about the effects of exposure to the newer antipsychotics during pregnancy is limited. OBJECTIVE To investigate the effects of maternal use of antipsychotics during pregnancy on gestational diabetes and fetal growth. DESIGN Population-based cohort study comparing women exposed and not exposed to antipsychotics during pregnancy. Exposure was defined as prescriptions filled. SETTING Swedish national health registers. PARTICIPANTS All women giving birth in Sweden from July 1, 2005, through December 31, 2009, grouped by filled prescriptions for (1) olanzapine and/or clozapine, the most obesogenic and diabetogenic antipsychotics (n = 169), (2) other antipsychotics (n = 338), or (3) no antipsychotics (n = 357,696). MAIN OUTCOME MEASURES Odds ratios (ORs) with 95% CIs for gestational diabetes and being small for gestational age (SGA) and large for gestational age for birth weight, birth length, and head circumference. RESULTS Exposure to other antipsychotics was associated with an increased risk of gestational diabetes (adjusted OR, 1.77 [95% CI, 1.04-3.03]). The risk increase with olanzapine and/or clozapine was of similar magnitude but not statistical significance (adjusted OR, 1.94 [95% CI, 0.97-3.91]). Infants exposed to either group of antipsychotics had increased risks of being SGA on birth weight, whereas only exposure to other antipsychotics yielded increased risks of being SGA for birth length and head circumference. None of the risks for SGA measurements remained significant after adjusting for maternal factors. There were no increased risks of being large for gestational age for birth weight or birth length after exposure to olanzapine and/or clozapine, but the risk increased for head circumference (OR, 3.02 [95% CI, 1.60-5.71]). CONCLUSIONS Women who used antipsychotics during pregnancy had increased risks of gestational diabetes. The increased risks of giving birth to an SGA infant seemed to be an effect of confounders, such as smoking. Except for macrocephaly, olanzapine and/or clozapine exposure was not associated with anabolic fetal growth.

Risk factors for suicide in schizophrenia: Findings from a Swedish population-based case-control study

Previous reports regarding risk factors for suicide in schizophrenia have been inconclusive. We performed a matched case-control study of in-patient-treated schizophrenia patients in order to assess the suicide risk associated with socioeconomic, demographic, and psychiatric factors. The cases were 84 patients who died by suicide within five years after diagnosis in a cohort of all patients discharged for the first time from psychiatric hospitals in Stockholm County, Sweden, with a diagnosis of schizophrenia, schizophreniform disorder or schizoaffective disorder between the years 1984 and 2000. One control was individually and randomly matched with each case from the same cohort by date (+/-1 year) and age (+/-5 years) at index diagnosis. Data were retrieved from clinical records of the case-control pairs in a blind fashion. Of the suicides, 54% were men and 46% were women. In multivariate analyses, higher educational attainment (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.03-8.0), age >or=30 years at onset of symptoms (OR 4.8, CI 1.1-21.2), and a history of a suicide attempt requiring non-psychiatric medical treatment (OR 5.0, CI 1.6-15.4) were found to be significantly associated with an increased suicide risk. Gender did not significantly affect the suicide risk, nor did a history of self-discharge, compulsory in-patient treatment, substance-use disorder or a family history of mental disorders or suicide. In schizophrenia, certain suicide risk factors may differ from those in the general population. Clinical suicide risk assessment for schizophrenia patients should be performed taking this into account.

Early non-adherence to medication and other risk factors for rehospitalization in schizophrenia and schizoaffective disorder

Non-adherence to antipsychotic medication and hospitalization in psychotic disorders are common and costly problems. Our aim was to identify risk factors for rehospitalization of patients with recent onset schizophrenia or schizoaffective disorder in a population-based cohort study. All patients with a first hospitalization for schizophrenia or schizoaffective disorder between 2006 and 2007 were included (n = 861). Patients were identified through and data retrieved from national Swedish health and population registers. We investigated how socio-demographic variables, duration of first hospitalization and prescription fills of antipsychotics were associated with rehospitalization in Cox regression models. A higher risk for rehospitalization within 28 days was observed in patients with a first hospitalization that was shorter than two weeks compared with patients who were hospitalized for more than four weeks: hazard ratio (HR) 2.30, 95% confidence interval (CI) 1.42 to 3.74. Further, patients who did not fill a prescription of antipsychotics within the first week after discharge had a higher risk of early rehospitalization than patients who were given antipsychotics (HR 1.75, 95% CI 1.13 to 2.72). More than 12 years of education was associated with a lower risk of early rehospitalization (HR 0.44, 95% CI 0.26 to 0.77). Sex, age, being born in Sweden, urban area residence and prescription fills of antipsychotics prior to first admission did not significantly affect the risk of early rehospitalization. In conclusion, we identified two potentially modifiable risk factors for rehospitalization: short duration of initial hospitalization and early non-adherence to medication.

Seasonality of suicide in Sweden: Relationship with psychiatric disorder

BACKGROUND Little is known as to whether suicide seasonality is related to psychiatric disorders affecting suicide risk/incidence. The present study aims to assess suicide seasonality patterns with regard to the history of psychiatric morbidity among suicide victims. METHODS The history of psychiatric inpatient diagnoses in the five years prior to suicide was identified among all suicides in Sweden from 1992 to 2003. Suicide seasonality was estimated as the relative risk of suicide during the month of highest to that in the month of lowest suicide incidence. Analyses were performed with respect to sex, suicide method and history of inpatient treatment of psychiatric disorder. RESULTS Among both male (n=9,902) and female (n=4,128) suicide victims, there were peaks in suicide incidence in the spring/early summer. This seasonal variation was more evident in suicide victims with a psychiatric inpatient diagnosis than in those without such a diagnosis. A seasonal variation was found in most diagnostic groups, with significant peaks in males with a history of depression and in females with a history of a neurotic, stress-related, or somatoform disorder. Overall, suicide seasonality was more evident in violent than in non-violent suicide methods. LIMITATION Only psychiatric disorders severe enough to require hospital admission were studied. CONCLUSION A history of inpatient-treated psychiatric disorder appears to be associated with an increase in suicide seasonality, especially in violent suicide methods. This increase is found in several psychiatric disorders.

Suicide and hospitalization for mental disorders in Sweden: A population-based case-control study

The aim of this study was to estimate suicide risk during hospitalization and in the year following discharge for patients with mental disorders. All suicide cases in Sweden 18 years and older, between 1991 and 2003 (N=20,675; 70% male), were individually matched to 10 controls from the general Swedish population. Discharge diagnoses in the year before suicide of any mental disorder, mood disorder, schizophrenia spectrum disorder, and alcohol use disorder were identified from the Swedish Patient Register. Highest suicide risk during hospitalization and in the year following discharge was found for mood disorder [odds ratio (OR) 55 (95% CI, 47-65) for men and 86 (95% CI, 70-107) for women], with the risk peaking in the first week following discharge [OR 177 (95% CI, 78-401) for men and OR 268 (95% CI, 85-846) for women]. Compared to that for mood disorder, the suicide risk for schizophrenia spectrum disorder and alcohol use disorder was about half and more constant over time. The majority of suicide victims with a psychiatric diagnosis had been discharged from psychiatric treatment more than a month before the suicide. Over time, a constant proportion of 25% of the suicide victims had been hospitalized with a mental disorder in the year before suicide (23% of males and 31% of females), despite a significant decrease in psychiatric hospitalizations in the population. In conclusion, suicide risk was found to vary by type of mental disorder, time since discharge, and sex. This should be taken into account when planning suicide preventive efforts.

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.

Medication and suicide risk in schizophrenia: a nested case-control study.

INTRODUCTION Patients with schizophrenia are at increased risk of suicide, but data from controlled studies of pharmacotherapy in relation to suicide risk is limited. AIM To explore suicide risk in schizophrenia in relation to medication with antipsychotics, antidepressants, and lithium. METHODS Of all patients with a first clinical discharge diagnosis of schizophrenia or schizoaffective disorder in Stockholm County between 1984 and 2000 (n=4000), patients who died by suicide within five years from diagnosis were defined as cases (n=84; 54% male). Individually matched controls were identified from the same population. Information on prescribed medication was retrieved from psychiatric records in a blinded way. Adjusted odds ratios [OR] of the association between medication and suicide were calculated by conditional logistic regression. RESULTS Lower suicide risk was found in patients who had been prescribed a second generation antipsychotic (clozapine, olanzapine, risperidone, or ziprasidone; 12 cases and 20 controls): OR 0.29 (95% confidence interval [CI], 0.09-0.97). When the 6 cases and 8 controls who had been prescribed clozapine were excluded, the OR was 0.23 (95% CI 0.06-0.89). No significant association was observed between suicide and prescription of any antipsychotic, depot injection antipsychotics, antidepressants, SSRI, or lithium. CONCLUSIONS Lower suicide risk for patients who had been prescribed second generation antipsychotics may be related to a pharmacological effect of these drugs, to differences in adherence, or to differences in other patient characteristics associated with lower suicide risk.

International trends in clozapine use: a study in 17 countries

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.

Antidepressant medication prevents suicide in depression

Isacsson G, Reutfors J, Papadopoulos FC, Ösby U, Ahlner J. Antidepressant medication prevents suicide in depression.