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BackgroundAntipsychotics are increasingly used among women of childbearing age and during pregnancy.ObjectiveTo determine whether children exposed to antipsychotics in utero are at increased risk of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD), accounting for maternal diagnoses of bipolar, psychotic and other psychiatric disorders.DesignPopulation-based cohort study, including a sibling analysis.SettingNationwide data on all pregnant women and their live-born singletons in Denmark (1997-2017), Finland (1996-2016), Iceland (2004-2017), Norway (2004-2017), and Sweden (2006-2016).Participants4 324 086 children were eligible for inclusion to the study cohort.InterventionAntipsychotic exposure in utero, assessed by pregnancy trimester, type of antipsychotic, and varying patterns of use.Main outcome measuresNon-mutually exclusive diagnoses of ADHD and ASD. We used Cox proportional hazard models to calculate hazard ratios (HRs) controlling for maternal psychiatric disorders and other potential confounding factors.FindingsAmong 4 324 086 singleton births, 15 466 (0.4%) were exposed to antipsychotics in utero. During a median follow-up of 10 years, we identified 72 257 children with ADHD and 38 674 children with ASD. Unadjusted HRs were raised for both outcomes but shifted substantially towards the null after adjustment; 1.10 (95%CI 1.00 to 1.27) for ADHD and 1.12 (0.97 to 1.29) for ASD. Adjusted HRs remained consistent by trimester of exposure and type of antipsychotic. Comparing in utero exposure with pre-pregnancy use yielded HRs of 0.74 (0.62 to 0.87) for ADHD and 0.88 (0.70 to 1.10) for ASD. Sibling analyses yielded HRs of 1.14 (0.79 to 1.64) for ADHD and 1.34 (0.75 to 2.39) for ASD.DiscussionOur findings suggest little or no increased risk of child ADHD or ASD after in utero exposure to antipsychotics.Clinical implicationsResults regarding child neurodevelopment are reassuring for women who need antipsychotics during pregnancy.

OBJECTIVE To investigate the health care utilisation (HCU) among patients with treatment-resistant depression (TRD) compared to patients with depression not meeting TRD criteria. METHODS Nationwide Swedish registers were used to identify patients 18-69 years old with incident depression and antidepressant treatment. Patients were followed prospectively and defined as having TRD at start of the third distinct consecutive treatment episode. Each of the 16,329 identified TRD patients were matched with five comparators with depression not meeting criteria for TRD. Main outcome measure was total number of inpatient days and outpatient visits, and secondary outcome was HCU in connection with a main diagnosis of depression or suicide attempt. RESULTS TRD patients had a significantly higher risk of all-cause inpatient care than comparators (first year adjusted risk ratio [aRR] 3.03 [95%CI 3.01-3.05], years 1-3 aRR 2.15 [2.13-2.16]). This was more pronounced when the main diagnosis was depression (first year aRR 4.41 [4.36-4.45]), and after suicide attempt (first year aRR 4.43 [4.26-4.60]). Outpatient visits were also markedly more frequent for patients with TRD (first year aRR 2.05 [2.03-2.07]). Higher HCU among TRD patients persisted throughout follow-up. CONCLUSIONS Patients with TRD may have a twofold to fourfold higher HCU than other patients with depression.KEYPOINTSThis register-based prospective study investigated health care utilisation (HCU) among patients with treatment-resistant depression (TRD) compared to other patients with depression.Patients with TRD had a two to fourfold higher HCU regarding all measured outcomes, including inpatient hospital days and outpatient visits.The elevated HCU persisted for more than three years, although decreasing gradually. This should correspond to increased costs and individual burden for patients with TRD.

Our aim was to explore if different exposure windows for sunshine or temperature are associated with increased suicidal behaviour among people starting antidepressant treatment. 307 completed and 1674 attempted suicides were included as cases in the conditional logistic regression analyses, while controlling for potential confounders, including season, as well as temperature and hours of sunshine when these variables were not the main exposure variable. Ten controls were matched to each case using risk-set sampling. The role of season, age, and sex was examined with likelihood ratio tests (LRTs) with and without the respective interaction terms and with stratified analyses. There was no overall association between temperature or sunshine with suicidal behaviour. Age was a significant effect modifier for suicide and suicide attempt for both sunshine and temperature exposure. In stratified analyses, an increase of one degree Celsius in the average daily temperature during the last 4 weeks was associated, in the unadjusted model, with a 3% increase in the rate of suicide (p = 0.023) amongst older patients (65+). In the same age group, an increase of 1 h in the average daily sunshine during the last 4 weeks was associated with an 8% increase in the rate of suicide attempt (p = 0.002), while the respective increase for the exposure period of 5–8 weeks was 7% (p = 0.007). An increase of one degree Celsius in the average daily temperature during the last 4 weeks was associated with a 3% increase in the rate of suicide attempt (p = 0.007). These associations did not retain statistical significance in the adjusted models. No associations were found in the other age groups. Our results point to a possible effect modification by age, with higher risk of suicidal behavior associated with an increase in sunshine and temperature found in the older age groups.

Background: Response rates after and tolerability of electroconvulsive therapy (ECT) in depressive disorders with psychiatric comorbidity are uncertain. Methods: Data on patients with a depressive episode and a first course of ECT were collected from the Swedish National Quality Register for ECT. Logistic regression analyses, adjusted for gender, age, and depressive episode severity, were used to compare patients with and without comorbidity. The clinical response assessment Clinical Global Impression - Improvement Scale was used in 4413 patients and the memory item from the Comprehensive Psychiatric Rating Scale was used for subjective memory impairment rating after ECT in 3497 patients. Results: In patients with depressive disorder and comorbid personality disorder or anxiety disorder, 62.7% and 73.5%, respectively, responded after ECT compared with 84.9% in patients without comorbidity [adjusted odds ratio (aOR) 0.43, 95% confidence interval (CI) 0.34-0.55, and aOR 0.61, 95% CI 0.51-0.73, respectively]. The proportion of responding patients with comorbid alcohol use disorder was 77.1%, which was not significantly different from that in patients without comorbidity (aOR 0.75, 95% CI 0.57-1.01). The impact of comorbidity decreased with higher age and depressive episode severity. Subjective ratings of memory impairment did not differ between patients with and without comorbidity. Limitations: Observational non-validated clinical data. Conclusions: The response rate after ECT in depression may be lower with concurrent personality disorder and anxiety disorder; however, the majority still respond to ECT. This implies that psychiatric comorbidity should not exclude patients from ECT. Funding Agencies|Uppsala Universityhospitals research fund; Swedish Research CouncilSwedish Research CouncilEuropean Commission [201602362]

Background and aims: Treatment-resistant depression (TRD), defined as inadequate treatment response after at least two adequate treatment trials, is common among patients initiating antidepressant treatment. Current or previous substance use disorders (SUD) are common among patients with depression and often lead to worse treatment outcomes. However, in clinical studies, SUD have not been found to increase the risk for TRD. The aim of this study was to investigate the association between SUD and TRD. Design: Nested case-control study. Setting: Nation-wide governmental health-care registers in Sweden. Cases and controls: Data on prescribed drugs and diagnoses from specialized health care were used to establish a prospectively followed cohort of antidepressant initiators with depression (n = 121 669) from 2006 to 2014. Of these, 15 631 patients (13%) were defined as TRD cases, with at least three treatment trials within a single depressive episode. Each case with TRD was matched on socio-demographic data with five controls with depression. Measurements: Crude and adjusted odds ratios (aOR) with 95% confidence intervals (CI) estimated the association between TRD and SUD diagnosis and/or treatment in five different time intervals until the time for fulfillment of TRD definition for the case. The analysis was adjusted for clinical and socio-demographic covariates. Findings: Having any SUD during, or

Objective To investigate suicide ideation and behavior as risk factors for suicide in schizophrenia during varying time periods. Method Cases were 84 patients who died by suicide within 5 years from diagnosis in a source population of patients discharged for the first time from psychiatric hospitals in Stockholm County, Sweden, with a schizophrenia spectrum diagnosis. One control was individually matched with each suicide case. Data were retrieved from clinical records in a blind fashion. Thoughts of death, thoughts of suicide, suicide plan, and suicide attempt during varying time periods were investigated as risk factors for subsequent completed suicide. Results In adjusted analyses, thoughts of suicide, suicide plan, and suicide attempt were significantly associated with subsequent completed suicide in the following year. The highest suicide risk was found within a year following suicide attempt (adjusted OR 9.9, 95% confidence interval 2.5-39.0). The association between suicide ideation and behavior and subsequent suicide declined over time. Conclusions Several types of suicide ideation and behavior were associated with suicide, and the association was stronger for suicidal behavior. The clinical significance of suicidal communication appears highest during the following month or/and year. Many suicides occurred without recorded short-term suicidal communication.

The objective of this study was to assess international trends in antipsychotic use, using a standardised methodology. A repeated cross-sectional design was applied to data extracts from the years 2005 to 2014 from 16 countries worldwide. During the study period, the overall prevalence of antipsychotic use increased in 10 of the 16 studied countries. In 2014, the overall prevalence of antipsychotic use was highest in Taiwan (78.2/1000 persons), and lowest in Colombia (3.2/1000). In children and adolescents (0-19 years), antipsychotic use ranged from 0.5/1000 (Lithuania) to 30.8/1000 (Taiwan). In adults (20-64 years), the range was 2.8/1000 (Colombia) to 78.9/1000 (publicly insured US population), and in older adults (65+ years), antipsychotic use ranged from 19.0/1000 (Colombia) to 149.0/1000 (Taiwan). Atypical antipsychotic use increased in all populations (range of atypical/typical ratio: 0.7 (Taiwan) to 6.1 (New Zealand, Australia)). Quetiapine, risperidone, and olanzapine were most frequently prescribed. Prevalence and patterns of antipsychotic use varied markedly between countries. In the majority of populations, antipsychotic utilisation and especially the use of atypical antipsychotics increased over time. The high rates of antipsychotic prescriptions in older adults and in youths in some countries merit further investigation and systematic pharmacoepidemiologic monitoring.

Background Data on real-world rehospitalization risks in patients using different drugs and combination therapies for relapse prevention after a manic episode is limited. Methods We conducted a nationwide population based cohort study using data from Swedish national registers. Swedish residents aged 18–75 years who were hospitalized for a manic episode between July 1, 2006 and December 2, 2014 were included. Prescription fills of lithium, valproate, olanzapine, quetiapine and aripiprazole were recorded throughout the first four weeks after hospital discharge, after which the patients were followed for up to one year. General and treatment specific rehospitalization risks were determined and results were adjusted for clinical and sociodemographic factors. Results The study included follow-up data from 6 502 hospitalizations for mania. Pharmacologic relapse prevention was used after 78% of these hospitalizations. Monotherapies and combination therapies were equally common. The average one-year rehospitalization risk for patients who did versus did not initiate prophylactic treatment was 39% and 46%, respectively. The lowest rehospitalization risks were seen in patients on combination therapy with olanzapine and valproate or olanzapine and lithium, experiencing one year rehospitalization risks of 32% and 34% (adjusted hazard ratios 0.76 (95% confidence interval [CI] 0.62–0.93) and 0.83 (95% CI 0.70–0.98), compared to lithium monotherapy). Limitations Register data does not provide information on all clinical parameters affecting treatment choices. Conclusions One-year rehospitalization rates after a manic episode are considerable also for patients who initiate prophylactic treatment. Combination therapies including olanzapine and a classic mood-stabilizer may be beneficial for reducing rehospitalization risks after a manic episode., final draft, peerReviewed

The risk of suicide is elevated among patients with treatment-resistant depression (TRD). Risk factors for suicide and suicide attempts among cases and controls with TRD were investigated using data from nationwide Swedish registers. Among 119,407 antidepressant initiators with a diagnosis of depression, 15,631 patients who started a third sequential treatment trial during the same depressive episode were classified with TRD. A nested case-control study compared cases with suicide and suicide attempts with up to three closely matched controls. Sociodemographic and clinical risk factors were assessed using conditional logistic regression analyses. In all, 178 patients died by suicide and 1,242 experienced a suicide attempt during follow-up. History of suicide attempts, especially if1 year after the attempt, was a significant independent risk factor for suicide (adjusted odds ratio [aOR], 8.9; 95% confidence interval [CI], 5.1-15.7) as were 10 to 12 years of education compared to lower education (aOR, 1.69; 95% CI, 1.02-2.81). For attempted suicide, the strongest independent risk factors were history of suicide attempts (1 year aOR, 5.1; 95% CI, 4.0-6.5), substance abuse (aOR, 2.6; 95% CI, 2.2-3.1), personality disorders (aOR, 1.9; 95% CI, 1.5-2.3), and somatic comorbidity (aOR, 2.0; 95% CI, 1.04-3.9). Suicide attempts, especially if recent, are strong risk factors for completed suicide among patients with TRD. Established risk factors for suicide attempts were confirmed for patients with TRD.

Background and aims Treatment-resistant depression (TRD) is common among patients with major depressive disorder (MDD). MDD may increase the risk for developing substance use disorders (SUD). The aim of this study was to investigate the risk for developing SUD among patients with TRD compared with other depressed patients. Design Observational cohort study. Setting Nation-wide governmental health registers in Sweden. Participants All patients aged 18-69 years with an MDD diagnosis in specialized health care who had received at least one antidepressant prescription during 2006-14 were identified. Patients with at least three treatment trials within a single depressive episode were classified with TRD. Measurements Patients with TRD were compared with the whole MDD cohort regarding risk for obtaining a SUD diagnosis or medication using survival analyses adjusted for socio-demographics and comorbidities. Findings Of 121 669 MDD patients, 13% were classified with TRD. Among the patients without any history of SUD, patients with TRD had a risk increase for any SUD both ≤ 1 and > 1 year after antidepressant initiation [> 1 year hazard ratio (HR) = 1.4; 95% confidence interval (CI) = 1.3-1.5]. Risks were elevated for the subcategories of opioid (HR = 1.9, 95% CI = 1.4-2.5) and sedative SUD (HR = 2.7, 95% CI = 2.2-3.2). Patients with a history of SUD had a risk increase for any SUD ≤ 1 year after start of treatment (HR = 1.2, 95% CI = 1.1-1.4), and both ≤ 1 year and > 1 year for sedative (> 1 year HR = 2.0, 95% CI = 1.3-3.0) and multiple substance SUD (HR = 1.9, 95% CI = 1.4-2.5). Conclusions Patients with treatment-resistant depression may be at greater risk for substance use disorders compared with other patients with major depressive disorder. Patterns may differ for patients with and without a history of substance use disorders, and for different categories of substance use disorder.

BackgroundTreatment-resistant depression (TRD) may represent a substantial proportion of major depressive disorder (MDD); however, the risk of mortality in TRD is still incompletely assessed.MethodsData were obtained from Optum Clinformatics™ Extended, a US claims database. Date of the first antidepressant (AD) dispensing was designated as the index date for study entry and 6 months prior to that was considered the baseline period. Patients with MDD aged ≥ 18 years, index date between January 1, 2008 and September 30, 2015, no AD claims during baseline, and continuous enrollment in the database during baseline were included. Patients who started a third AD regimen after two regimens of appropriate duration were included in the TRD cohort. All-cause mortality was compared between patients with TRD and non-TRD MDD using a proportional hazards model and Kaplan–Meier estimate with TRD status being treated as a time-varying covariate. The model was adjusted for study year, age, gender, depression diagnosis, substance use disorder, psychiatric comorbidities, and Charlson comorbidity index.ResultsOut of 355,942 patients with MDD, 34,176 (9.6%) met the criterion for TRD. TRD was associated with a significantly higher mortality compared with non-TRD MDD (adjusted HR: 1.29; 95% CI 1.22–1.38;p p ConclusionsPatients with TRD had a higher all-cause mortality compared with non-TRD MDD patients.

OBJECTIVE: This study explores suicide risk in schizophrenia in relation to side effects from antipsychotic medication. METHODS: Among patients with a first clinical discharge diagnosis of schizophrenia or schizoaffective disorder in Stockholm County between 1984 and 2000 (n = 4000), those who died by suicide within 5 years from diagnosis were defined as cases (n = 84; 54% male). For each case, one individually matched control was identified from the same population. Information on antipsychotic side effects, including extrapyramidal symptoms (EPS) and akathisia, as well as prescriptions of anticholinergic medication, was retrieved from clinical records in a blinded fashion. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of the association between suicide and side effects as well as anticholinergic medication were estimated using conditional logistic regression. RESULTS: A lower suicide risk was found in patients with a history of EPS (aOR 0.33, 95% CI 0.12-0.94). There was no statistically significant association between akathisia or anticholinergic medication use and the suicide risk. CONCLUSIONS: A lower suicide risk identified among patients with EPS could potentially reflect higher antipsychotic adherence, exposure to higher dosage, or polypharmacy among these patients. Copyright © 2016 John Wiley & Sons, Ltd.Copyright © 2016 John Wiley & Sons, Ltd. Language: en

Background In the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, a third of patients did not achieve remission or adequate response after two treatment trials, fulfilling requirements for treatment resistant depression (TRD). The present study is a secondary analysis of the STAR*D data conducted to compare the humanistic outcomes in patients with TRD and non-TRD MDD. Methods Patients with major depressive disorder who entered level 3 of the STAR*D were included in the TRD group, while patients who responded to treatment and entered follow-up from level 1 or 2 were included in the non-TRD group. The first visit in level 1 was used for baseline assessments. The time-point of assessments for comparison was the first visit in level 3 for TRD patients (median day: 141), and the visit closest to 141 ± 60 days from baseline for non-TRD patients. Outcomes were assessed by the 12-item Short Form Health Survey (SF12), 16-item Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Work and Social Adjustment Scale (WSAS), and Work Productivity and Activity Impairment scale (WPAI). Scores were compared in a linear model with adjustment for covariates including age, gender, and depression severity measured by the 17-item Hamilton Rating Scale for Depression (HDRS17) and Quick Inventory of Depressive Symptomatology (QIDS). Results A total of 2467 (TRD: 377; non-TRD: 2090) patients were studied. TRD patients were slightly older (mean age 44 vs 42 years), had a higher proportion of men (49% vs 37%, p

Treatment guidelines state that all patients with bipolar disorder should use pharmacological prophylaxis; however the actual use of prophylactic drugs after bipolar disorder diagnosis is unknown. Our aim was to assess the use of, and predictors for, pharmacoprophylaxis in newly diagnosed bipolar disorder patients.Data from three Swedish nationwide registers were obtained. We identified patients aged 18-75 with a first time diagnosis of bipolar disorder between 2006 and 2012 (n=31,770) and reviewed subsequent mood-stabilizer and antipsychotic prescription fills. In multivariable Cox regression models, we studied demographic and illness related factors as predictors of prescription fills after diagnosis.In total, 72.2% (95% confidence interval [CI] 71.7-72.7%) of the patients filled a prescription of a prophylactic drug within 3 months after diagnosis. Pharmacological prophylaxis was mainly associated with a longer duration of hospitalization at bipolar disorder diagnosis (adjusted hazard ratio [AHR] 2.18; CI 2.02-2.35 for a hospitalization of ≥28 days compared to7 days) and previous use of any mood-stabilizer or antipsychotic (inpatients: AHR 1.24; CI 1.17-1.31 and outpatients: AHR 1.78; CI 1.73-1.84).We had no information on drug prescriptions that were never filled.The proportion of newly diagnosed bipolar disorder patients without pharmacological prophylaxis is substantial. Patients who are naïve to mood-stabilizers and antipsychotics and are hospitalized for a brief period at diagnosis are the ones least likely to initiate pharmacoprophylaxis, suggesting that this group deserves attention in order to improve the long term prognosis.

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 (1019 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.

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 30 years (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 1000 person-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.

Background Hematological malignancies can cause high levels of distress, but few studies have assessed risk of suicidal behavior among these patients. Methods We evaluated risk of attempted and completed suicide in a cohort of 46,309 patients diagnosed with malignant lymphoma, myeloma and leukemia in Sweden 1992 to 2009 and 107,736 cancer-free subjects, using Poisson regression. Results In all, 146 suicide attempts and 63 completed suicides occurred during a median follow up of 3.1 years (maximum 19 years). The risk of completed suicide was 3.5-fold increased among patients with myeloma [incidence rate ratio (IRR) = 3.52, 95% confidence interval (CI) = 2.05−6.03] and 1.9-fold increased among patients with lymphoma (IRR = 1.87, 95% CI = 1.31−2.67) but not significantly increased among patients with leukemia. Risk of attempted suicide was increased among patients with myeloma (IRR = 2.13, CI = 1.39−3.26) and lymphoma (IRR = 1.34, 95% CI = 1.07−1.69). Both male and female patients were at increased risk of attempted as well as completed suicide. A pre-malignant history of mental disorders conferred 15-fold to 30-fold increased risks, but elevated risks were also observed among patients without such history. Conclusions Suicidal actions in patients with hematological malignancies have high suicidal intent, and that subgroups of patients should be monitored for suicidal ideation. Copyright © 2014 John Wiley & Sons, Ltd.

Objective Assessment of factors influencing antipsychotic prescription fills in the early phase of schizophrenia or schizoaffective disorder. Methods We used the Swedish Patient Register to identify patients younger than 45 years with a first hospitalization for schizophrenia or schizoaffective disorder between 2006 and 2007 (904 patients). Data on medication were obtained from the Prescribed Drug Register. Filling a prescription of an antipsychotic drug after discharge was used to estimate medication adherence. In Cox regression models, we studied sex, country of birth, metropolitan residence, educational level, age, duration of hospitalization, history of substance use disorder, and previous use of antipsychotic drugs as predictors for antipsychotic fills. Results Among all patients, 53.1% (95% confidence interval [CI] 49.9%–56.4%) had filled an antipsychotic prescription within 1 week from discharge. After 6 months, the proportion had increased to 80.2% (95% CI, 77.4%–82.8%) with no further increase thereafter. Prescription filling of an antipsychotic drug was primarily associated with antipsychotic use before the hospitalization (hazard ratio, 1.64; 95% CI, 1.33–2.03; for patients with access to antipsychotic drugs at admission compared with no previous use) and with longer hospitalization (hazard ratio, 1.60; 95% CI, 1.27–2.02 for 15–28 days compared with shorter hospitalization). Conclusions Among patients who filled a prescription of an antipsychotic drug after discharge, the majority did so within 1 week. Previous adherent use of antipsychotic drugs and longer hospitalization may be predictors of primary adherence to antipsychotic drug treatment in schizophrenia or schizoaffective disorder.

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.

Decreased binding capacity of SERT in the prefrontal cortex has been observed in both suicide victims and suicide attempters. Moreover, some studies have shown that SERT has a seasonal variation with lower binding capacity in the spring and summer, which coincides with a seasonal peak of suicides. Our aim was to explore whether the season of treatment initiation with antidepressants is associated with suicide or suicide attempt and compare it with the underlying suicide seasonality in the general population.Using Swedish registers, patients who initiated treatment with an antidepressant were followed up to three months for suicidal behavior. Cox regression analyses were used. Results were compared with the underlying seasonal pattern by calculating standardized mortality ratios (SMRs) for suicides and standardized incidence ratios (SIRs) for suicide attempts.Patients aged ≥65 years had higher risk for suicide when initiating antidepressant treatment in the summer, and also a higher risk for suicide attempt when initiating treatment in the spring and summer. Young patients (0-24 years) presented a higher risk for suicide attempt when initiating treatment in the autumn. Patients with previous suicide attempt had a seasonal pattern, with a higher risk to carry out a suicide attempt in the summer and autumn. Results from the SMR and SIR calculations numerically support these findings.We used information of filling an antidepressant prescription as a proxy of actual antidepressant treatment. Patients with combination, augmentation therapy or those switching antidepressant during follow-up were excluded. Thus, our results refer to less complicated psychopathology.Our results indicate an interaction between biological and health care-related factors for the observed seasonal pattern of suicidal behavior in the elderly, whereas psychological and societal factors may be more important for the seasonality observed in the younger patients.

Background Several antipsychotics, especially risperidone, are known to increase serum prolactin. Hyperprolactinemia has been linked to the development of mammary gland tumors in animal studies. We therefore investigated the risk of breast cancer in a nationwide cohort of women using risperidone or other antipsychotics. Methods All women, 18 years or older, who initiated treatment with risperidone or any other antipsychotic between 2006 and 2012 were identified in Swedish nationwide registers. Patients with two consecutive dispensations of the same antipsychotic within 3 months, no previous cancer diagnosis, and no previous dispensations of paliperidone were included. The final cohort consisted of 55976 women of whom 22908, 24524, and 8544 were exposed to risperidone, other atypical antipsychotics, and typical antipsychotics, respectively. A Cox regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between antipsychotics and breast cancer. Results Patients were followed prospectively, the mean follow-up time ranging from 2.4 to 2.8 years between treatment groups. After adjusting for age, there was no increased risk for breast cancer among risperidone users compared to patients exposed to another atypical antipsychotic (HR 0.94, 95% CI 0.72–1.22) or a typical antipsychotic (HR 1.25, 95% CI 0.94–1.66). Analyses stratified by tumor stage, using active treatment follow-up time, or including only treatment naive patients did not reveal any noteworthy change in the results. Conclusion Risperidone use does not confer an increased short-term risk of breast cancer compared to other antipsychotic agents.

ObjectiveSeasonality 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 phenome ...

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.

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. Language: en

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.

Background Earlier studies of patients with schizophrenia have investigated suicide risk in relation to specific psychiatric symptoms, but it remains to be better understood how suicide risk relates to the diagnostic profile in these patients. Methods We identified all patients with a first clinical ICD-diagnosis of schizophrenia, schizophreniform or schizoaffective disorder in Stockholm County between 1984 and 2000. Patients who died by suicide within five years from diagnosis were defined as cases (n = 84) and were individually matched with a similar number of living controls from the same population. Sociodemographic and clinical variables were retrieved from hospital records through a blind process. DSM-IV lifetime diagnoses for cases and controls were derived using the OPCRIT algorithm. Results A schizophrenia spectrum diagnosis (i.e. schizophrenia, schizophreniform or schizoaffective disorder) was assigned by OPCRIT to 50% of the suicide cases and 62% of the controls. Criteria for schizophrenia were met by 41% of the cases and 51% of the controls; for schizoaffective disorder by 8% of the cases and 10% of the controls; for other psychosis by 23% of the cases and 25% of the controls; and for mood disorder by 26% of the cases and 12% of the controls. Using the schizophrenia diagnosis as a reference, suicide risk was significantly higher in patients meeting criteria for a mood disorder diagnosis with an adjusted odds ratio of 3.3 (95% CI 1.2–9.0). Conclusion In patients with a clinical schizophrenia spectrum diagnosis, a DSM-IV mood disorder diagnosis increases the suicide risk more than three-fold.

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.

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.

Objective The objectives of this study were to (1) analyze the prevalence of diabetes, prediabetes, and antidiabetic medication in patients with psychosis compared with control subjects and (2) determine what factors in patients with psychosis were associated with antidiabetic medication. Method We studied 977 patients with psychosis recruited from outpatient clinics in Stockholm County, Sweden, and they were compared with 3908 non-psychotic control subjects for fasting plasma glucose levels; prevalence of diabetes, prediabetes, antidiabetic treatment, and tobacco use; and blood pressure, weight, height, and waist circumference. Group differences were evaluated with analysis of variance and χ 2 test, and factors associated with antidiabetic treatment were evaluated with logistic regression. Results Diabetes was observed in 94 (10%) patients with psychosis, 2.7 times the prevalence observed in control subjects. Among patients with psychosis, 87 (10%) had prediabetes (fasting glucose, 6.1–6.9 mmol/L) compared with 149 (3.8%) control subjects. Most patients with psychosis (77%) who had prediabetes fulfilled criteria for metabolic syndrome. In patients with psychosis, both lipid-lowering medication and fasting glucose were significantly associated with antidiabetic treatment. There was no significant relation between antidiabetic treatment and lifestyle factors such as smoking or degree of psychiatric illness. Conclusions The high prevalence of impaired fasting glucose and metabolic syndrome in patients with psychosis warrants further clinical research in preventing or delaying the onset of diabetes in these patients by pharmacotherapy and/or lifestyle intervention.

Earlier research has indicated a positive association between coeliac disease (CD) and some mental disorders. Studies on CD and depression have inconsistent findings and we know of no study of CD and the risk of bipolar disorder (BD).We used Cox regression to investigate the risk of subsequent mood disorders (MD); depression and BD in 13,776 individuals with CD and 66,815 age- and sex-matched reference individuals in a general population-based cohort study in Sweden. We also studied the association between prior MD and CD through conditional logistic regression.CD was associated with an increased risk of subsequent depression (Hazard ratio (HR)=1.8; 95% CI=1.6-2.2; p0.001, based on 181 positive events in individuals with CD and 529 positive events in reference individuals). CD was not associated with subsequent BD (HR=1.1; 95% CI=0.7-1.7; p=0.779, based on 22 and 99 positive events). Individuals with prior depression (OR=2.3; 95% CI=2.0-2.8; p0.001) or prior BD (OR=1.7; 95% CI=1.2-2.3; p=0.001) were at increased risk of a subsequent diagnosis of CD.Study participants with CD and MD may have more severe disease than the average patient with these disorders since they were identified through a hospital-based register.CD is positively associated with subsequent depression. The risk increase for CD in individuals with prior depression and BD may be due to screening for CD among those with MD.

Background:Several studies from different countries demonstrate that cardiovascular mortality is the main cause of death for schizophrenia patients as well as for the population although patients with schizophrenia have a doubled cardiovascular mortality risk. The general population of Sweden has during recent years experienced remarkable declines in mortality from cardiovascular disease resulting in increased overall life expectancy. It is unclear whether patients with schizophrenia have experienced these benefits.Methods:Standardized mortality ratios (SMR) for schizophrenia patients in Sweden during 1970 through 2003 were analyzed, using data from national registers on diagnosis and causes of death. Secular trends for SMR were calculated in Poisson regression models.Results:SMR was for schizophrenia patients for all causes of death 2.33 for men and 2.35 for women, cardiovascular death 2.08 for men and 2.15 for women, coronary heart disease 1.91 for men and 2.06 for women, and for myocardial infarction 1.75 for men and 1.86 for women. Age-standardized mortality ratios for schizophrenia patients increased significantly (p

Introduction Suicide seasonality with a peak incidence in spring or early summer has been consistently reported. Although a quite robust finding this spring peak of suicides is poorly understood. The effect of climate parameters such as sunlight, temperature, humidity etc. on hormones and neurotransmitters such as serotonin has been hypothesized to explain the seasonal variation in suicide. Objective To examine the amplitude of suicide seasonality in relation to sunlight duration and serotonergic medication. Methods By using Swedish Registers we gathered information including forensic data on antidepressive medication for 11,845 suicides during 1992 to 2003. Moreover, data for sunlight duration for the same period for all Swedish counties was obtained from the Swedish Meteorological and Hydrological Institute. The presence of suicide seasonality was estimated with a Poisson regression variant, in three groups, as defined by tertiles of sunlight duration. Results In regions with low sunlight duration no statistically significant seasonality pattern was found for men independently of medication. In regions with middle or high sunlight duration an increased amplitude of seasonality was observed among men treated with SSRIs in a dose dependent pattern. Such a pattern was not observed among suicide victims on other antidepressant medication or those without an antidepressant. Women on the other hand showed a seasonal variation in suicide only in regions with low sunlight duration. Conclusions Suicide seasonality amplitude increases with higher sunlight duration especially in men treated with SSRIs. In women, the highest suicide seasonality was observed in regions with the lowest sunshine duration.

IntroductionSuicide risk is increased in patients with a history of psychiatric hospitalization.AimTo explore how suicide risk varies by age during psychiatric hospitalization and in the year post-discharge.MethodsThis is a population-based case-control study of all suicides (n = 20,675; 70% male) in Sweden aged ≥18 years during 1991–2003. Each suicide was individually matched to 10 population controls by age, sex, and county of residence. Discharge diagnoses of a mental disorder (except dementia and other organic disorders) in the year prior to suicide were identified by register linkage. Odds ratios (OR) were calculated by conditional logistic regression to estimate the relative risk of suicide in those with psychiatric diagnoses compared to the general population. ORs were estimated by age group (18–34 years, 35–49 years, 50–64 years, and ≥ 65 years) and timing of the suicide in relation to discharge.ResultsDuring hospitalization, the youngest age group had the greatest suicide risk elevation [OR 64 (95% CI 44-92)]. In the first month post-discharge, the oldest age group had the highest suicide risk elevation [OR 162 (95% 66–399) in the first week and OR 127 (95% 67–242) in the second to fourth weeks]. In the remaining eleven months, suicide risk elevation was lower and relatively similar in different age groups.ConclusionsDuring the year following psychiatric hospitalization, an especially high attention should be paid to the suicide risk of the elderly patients in the first month post-discharge.

IntroductionPatients with schizophrenia are at increased risk of suicide, but data from controlled studies of how pharmacotherapy is related to suicide risk is limited.AimTo explore suicide risk in relation to prescription of antipsychotics and antidepressants.MethodsOf all patients with a first clinical discharge diagnosis of schizophrenia or schizoaffective disorder in Stockholm County between 1984 and 2000 (n = 4,000), patients who died by suicide within five years from diagnosis were defined as cases (n = 84; 54% male). Individual matching was performed with schizophrenia controls from the same population. Information on prescribed medication was retrieved from psychiatric records in a blinded way. Odds ratios (OR) of the association between medication and suicide risk were calculated by conditional logistic regression.ResultsNo significant association was observed between suicide and having ever been prescribed any antidepressant (33 cases and 30 controls) or any antipsychotic (83 cases and 82 controls). A lower suicide risk was found in patients who had ever been prescribed a second generation antipsychotic (risperidone, ziprazidone, olanzapine or clozapine; 12 cases and 23 controls): OR 0.2 (95% confidence interval [CI], 0.1–0.7). When the 6 cases and 8 controls who had been prescribed clozapine were excluded, the OR was 0.1 (95% CI, 0.03–0.6).ConclusionsThe lower suicide risk for patients who had been prescribed second generation antipsychotics may be related to a pharmacological effect of these medications, to differences in compliance, or to differences in other characteristics associated with a lower suicide risk.

Antidepressants; Comorbidity; Drug utilization study; Europe Antidepresivos; Comorbilidad; Estudio de utilización de medicamentos; Europa Antidepressius; Comorbiditat; Estudi d'utilització de medicaments; Europa Background We aimed to describe patterns of use and characteristics of 10 commonly used antidepressants for the period 2009–2014 in Denmark, Germany, Spain, and Sweden. Methods Adult initiators from 2009 to 2014 of each study antidepressant were identified in four countries using five data sources: the Danish National registers, GePaRD (Germany), EpiChron (Aragon, Spain), SIDIAP (Catalonia, Spain), and the Swedish National Registers. The study included 10 study antidepressants: citalopram, escitalopram, fluoxetine, paroxetine, sertraline, duloxetine, venlafaxine, amitriptyline, mirtazapine, and agomelatine. Results Citalopram was the most prescribed study antidepressant, followed by mirtazapine. Paroxetine and agomelatine were the least prescribed antidepressants. Mirtazapine was widely used among older antidepressant initiators with higher percentages of comorbidities at baseline, and fluoxetine was used among young patients. Citalopram and amitriptyline had the lowest percentage of multiple antidepressant use in the 12 months prior to the current treatment episode, while agomelatine, duloxetine, and venlafaxine had the highest percentage of multiple antidepressant use in the year prior to the current treatment episode. Limitations The most important limitations are exposure information based on filled prescriptions, focus on antidepressant initiators only, lack of information on the indication, and heterogeneity of the type of data across data sources. Conclusions Results of this study including 4.8 million study antidepressant initiators of study antidepressants suggest that citalopram and mirtazapine are the most commonly prescribed antidepressants. Agomelatine and paroxetine were the least used antidepressants in the participating populations. Mirtazapine was the antidepressant most commonly prescribed among older antidepressant initiators with high percentage of comorbidities at baseline, whereas fluoxetine was commonly used among young patients.