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Purpose To assess the impact on exposure time and outcome misclassifications, and consequent impact on exposure-outcome associations from treatment episode construction. We investigated the dosage assumptions of 1 unit per day, and 1 DDD per day, versus actual prescribed dosage under different handling of gaps and overlaps of prescriptions. Methods Data on mirtazapine and citalopram exposure (years 2006–2014) from the Swedish Prescribed Drug register were used. Via a within individuals design we compared method A, based on actual dosage, with methods B and C based on 1 unit of drug per day and 1 DDD per day assumptions, respectively, including consideration of gaps and overlaps. Four outcomes were used, hospitalizations and outpatient visits for all and for psychiatric causes. Results Relative to method A, both alternative methods lead to misclassification of exposure time. With regard to outcome misclassifications, method B overestimates the effect of the exposure on the outcome in 77% and 100% of exposure definition comparisons for mirtazapine and citalopram respectively, while 23% of the comparisons for mirtazapine results in underestimation of exposure-outcome associations. Conversely, treatment episodes based on DDD (method C) result in underestimation of the exposure-outcome association in 100% and 87.5% of exposure definition comparisons for mirtazapine and citalopram respectively, while 12.5% of the comparisons for citalopram results in overestimation of the exposure-outcome associations. Conclusions The study provides results that have consistent clinical relevance. We have showed that a non-accurate construction of exposure time may lead to errors on outcome detection during exposed time, and consequently affect conclusions on safety or efficacy profile of a treatment.

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.

PURPOSE When defining exposure to pharmacological treatments in pharmacoepidemiology, register data often do not provide information regarding if a pharmacological treatment is a switch or an add-on. This study aims to compare two methods defining switching and add-on therapies and their impact on exposure-outcome associations. Additionally, to guide bias reduction, it aims to describe how the methods relate to immortal time bias and selection bias. METHODS Cohort study using Swedish population-based health registers to identify antidepressant (AD) prescriptions as exposures while hospitalizations for psychiatric reasons were used as an empirical outcome example. The first method for exposure definition used conditioning on future exposure (FE), the second used the concept of uncertain exposure (UE). To estimate associations between outcome and exposure categories "Use of one AD," "Use of two or more ADs", and "UE" compared to "Unexposed," hazard ratios (HRs) and 95% confidence intervals were estimated using Cox regression adjusted for age and sex. RESULTS Using the UE method, 7.2% of time periods were classified as "UE" with a notable proportion of psychiatric hospitalizations (7.7%) occurring during this time, while when using the FE method these hospitalizations were distributed over unexposed time and AD use time. The FE method resulted in slightly higher associations than the UE method. The highest HR was found during "UE": HR (95% CI) 5.54 (5.06-6.07). CONCLUSIONS This study suggests that to reduce the potential immortal time bias, selection bias, and exposure misclassification inherent to the FE method, the UE method could be used for identifying switching and add-on therapies. If not used as a main exposure definition, the UE method may be used to investigate the impact of UE time in a sensitivity analysis.

Background/Objectives Despite profound weight loss after bariatric surgery, some patients are dissatisfied with the results. Pre-surgery expectations, as well as post-surgery items of satisfaction, need to be clarified. The main objective in this study was to investigate the primary reasons to seek bariatric surgery and assess items of satisfaction 1-year post-surgery. Subjects/Methods This is a prospective cohort study of women (n = 50) undergoing bariatric surgery in Stockholm, Sweden. Presurgery assessment included reasons to seek surgery, expected weight loss, co-morbidities, and quality of life. Post-surgery assessment included items of satisfaction, weight loss, co-morbidities, and quality of life. In total, two women did not undergo surgery, and 40 women had complete data from all pre- and post-surgery assessments. Results Mean change in body mass index (BMI) pre- and post-surgery was -12.9 (3.7) kg/m(2). At 1-year post-surgery, the mean percent of excess weight loss (% EWL) was 86.9 (26.3). Pre-surgery, the most reported reason to seek surgery was "weight loss" (47.9%), while the most reported item of satisfaction post-surgery was "improved self-esteem" (55.6%). Satisfaction with the result 1-year post-surgery was associated with the extent of % EWL. Satisfied patients (n = 32) had a mean % EWL of 94.6 (22.9), while those not satisfied (n = 8) had a mean % EWL of 59.9 (17.6). Conclusions The primary reason to seek bariatric surgery was weight loss. However, despite profound weight loss, improved self-esteem was the item of most satisfaction post-surgery. Our findings may be useful in the clinical setting when informing patients pre- surgery about what to expect as well as when meeting a patient post-surgery to discuss results.

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 Treatment resistant depression (TRD) is common among patients with depression, and is associated with clinical and functional disability. However, the risk and risk factors for being granted disability pension (DP) among patients with TRD have not been investigated. Methods All antidepressant initiators in Sweden with a diagnosis of depression in specialized care were identified in nationwide registers 2006–2013 and followed regarding treatment trials. TRD was defined as the start of a third sequential trial. Patients with TRD who were not on DP (N = 3204) were matched by age, sex, history of depression, calendar year, and time for treatment start with 3204 comparators with depression and ongoing antidepressant treatment. A proportional Cox Regression was performed with DP as outcome, adjusted for various sociodemographic and clinical covariates. Results Compared to the comparison cohort, TRD was associated with a doubled risk for all-cause DP (aHR 2.07; 95%CI 1.83–2.35), DP due to depression (2.28; 1.82–2.85) and to any mental disorder (2.24; 1.95–2.57) but not due to somatic diagnoses (1.25; 0.84–1.86). Among significant risk factors for DP in TRD were female sex, being > 29 years of age, unemployment and a diagnosis of comorbid personality disorder (ICD-10 codes F60.0–9). Conclusion TRD is associated with an elevated risk for DP compared to other patients with depression, with large potential costs for the affected patients and for society. Clinical and therapeutic implications for patients with TRD who are granted DP should be further investigated. Limitation: No clinical data, e.g. type of depression or reason for treatment switch, was available for this study.

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

Background Gastric bypass (GBP) surgery is considered a safe and effective treatment for obesity. However, there is uncertainty regarding the impact of preexisting psychiatric comorbidity on GBP complications. We have investigated whether a psychiatric diagnosis before GBP surgery is associated with delayed discharge (the odds of being in the 90th percentile of length of stay) and rate of reoperation in a nationwide Swedish cohort. Methods Patients undergoing GBP surgery during 2008–2012 were identified and followed up through the National Patient Register and the Prescribed Drug Register. Logistic regression models were fitted to the studied outcomes. Results Among the 22,539 patients identified, a prior diagnosis of bipolar disorder, schizophrenia, depression, neurotic disorders, ADHD (attention deficit hyperactivity disorder), substance use disorder, eating disorder, personality disorder, or self-harm since 1997 (n = 9480) was found to be associated with delayed discharge after GBP surgery (odds ratio [OR] = 1.47, confidence interval [CI] 1.34–1.62), especially in patients with psychiatric hospitalization exceeding 1 week in the 2 years preceding GBP surgery (OR = 2.06, CI 1.30–3.28), compared with those not hospitalized within psychiatry. Likewise, patients with a prior psychiatric diagnosis were more likely to be reoperated within 30 days (OR = 1.25, CI 1.11–1.41), with twice the likelihood OR 2.23 (CI 1.26–3.92) for patients with psychiatric hospitalization of up to a week in the 2 years preceding GBP surgery, compared with patients who had not been hospitalized within psychiatry. Conclusions A psychiatric diagnosis before GBP surgery was associated with delayed discharge and increased likelihood of reoperation within 30 days. Patients with a prior psychiatric diagnosis may, therefore, need additional attention and support.

Introduction This post-authorization safety study (PASS) was a commitment to the European Medicines Agency. Objective This PASS investigated quetiapine as antidepressant treatment in Swedish registers with regard to the risk for all-cause mortality, self-harm and suicide, acute myocardial infarction, stroke, diabetes mellitus, extrapyramidal disorders, and somnolence. Methods Users of quetiapine and antidepressants (2011‒2014) who had changed treatment in the past year were included. Conditional logistic regression models were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) for each outcome in nested case–control studies for quetiapine as combination therapy and monotherapy, monotherapy with antidepressants, and no medication, versus the use of combinations of antidepressants (reference group). Results Overall, 7421 quetiapine users and 281,303 antidepressant users were included. For quetiapine in combination, risks were increased for all-cause mortality [adjusted OR (aOR) 1.31, 95% CI 1.12–1.54] compared with combinations of antidepressants; however, when stratified by age, only patients ≥ 65 years of age had an increased mortality, and, in a post hoc analysis excluding patients with Parkinson’s disease, no mortality increase remained. Furthermore, the risk for self-harm and suicide was increased (aOR 1.53, 95% CI 1.31–1.79), but when stratified by age, the risk increase was found only among patients aged 18–64 years. Risks were also increased for stroke among patients ≥ 65 years of age (aOR 1.47, 95% CI 1.01–2.12), for extrapyramidal disorder (aOR 6.15, 95% CI 3.57–10.58), and for somnolence (aOR 2.41, 95% CI 1.42–4.11). Conclusion Risks for all-cause mortality, self-harm and suicide, and stroke in older patients may be higher among patients treated with quetiapine and antidepressant combination therapy. Electronic supplementary material The online version of this article (10.1007/s40264-019-00889-0) contains supplementary material, which is available to authorized users.

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 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.

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 aim of this study was to examine risk of self-harm, hospitalization for depression and death by suicide after gastric bypass surgery (GBP).Concerns regarding severe adverse psychiatric outcomes after GBP have been raised.This nationwide, longitudinal, self-matched cohort encompassed 22,539 patients who underwent GBP during 2008 to 2012. They were identified through the Swedish National Patient Register, the Prescribed Drug Register, and the Causes of Death Register. Follow-up time was up to 2 years. Main outcome measures were hazard ratios (HRs) for post-surgery self-harm or hospitalization for depression in patients with presurgery self-harm and/or depression compared to patients without this exposure; and standardized mortality ratio (SMR) for suicide post-surgery.A diagnosis of self-harm in the 2 years preceding surgery was associated with an HR of 36.6 (95% confidence interval [CI] 25.5-52.4) for self-harm during the 2 years of follow up, compared to GBP patients who had no self-harm diagnosis before surgery. Patients with a diagnosis of depression preceding GBP surgery had an HR of 52.3 (95% CI 30.6-89.2) for hospitalization owing to depression after GBP, compared to GBP patients without a previous diagnosis of depression. The SMR for suicide after GBP was increased among females (n = 13), 4.50 (95% CI 2.50-7.50). The SMR among males (n = 4), was 1.71 (95% CI 0.54-4.12).The increased risk of post-surgery self-harm and hospitalization for depression is mainly attributable to patients who have a diagnosis of self-harm or depression before surgery. Raised awareness is needed to identify vulnerable patients with history of self-harm or depression, which may be in need of psychiatric support after GBP.

Despite profound weight loss after bariatric surgery, some patients are dissatisfied with the results. Pre-surgery expectations, as well as post-surgery items of satisfaction, need to be clarified. The main objective in this study was to investigate the primary reasons to seek bariatric surgery and assess items of satisfaction 1-year post-surgery.This is a prospective cohort study of women (n = 50) undergoing bariatric surgery in Stockholm, Sweden. Pre-surgery assessment included reasons to seek surgery, expected weight loss, co-morbidities, and quality of life. Post-surgery assessment included items of satisfaction, weight loss, co-morbidities, and quality of life. In total, two women did not undergo surgery, and 40 women had complete data from all pre- and post-surgery assessments.Mean change in body mass index (BMI) pre- and post-surgery was - 12.9 (3.7) kg/mThe primary reason to seek bariatric surgery was weight loss. However, despite profound weight loss, improved self-esteem was the item of most satisfaction post-surgery. Our findings may be useful in the clinical setting when informing patients pre-surgery about what to expect as well as when meeting a patient post-surgery to discuss results.

Acute liver injury; Antidepressants; Case-control Lesió hepàtica aguda; Antidepressius; Control de casos Lesión hepática aguda; Antidepresivos; Control de casos Background Agomelatine is a melatonin receptor agonist and serotonin 5-HT2C receptor antagonist indicated for depression in adults. Hepatotoxic reactions like acute liver injury (ALI) are an identified risk in the European risk management plan for agomelatine. Hepatotoxic reactions have been reported for other antidepressants, but population studies quantifying these risks are scarce. Antidepressants are widely prescribed, and users often have risk factors for ALI (e.g. metabolic syndrome). Objective The goal was to estimate the risk of ALI associated with agomelatine and other antidepressants (fluoxetine, paroxetine, sertraline, escitalopram, mirtazapine, venlafaxine, duloxetine, and amitriptyline) when compared with citalopram in routine clinical practice. Method A nested case–control study was conducted using data sources in Denmark, Germany, Spain, and Sweden (study period 2009–2014). Three ALI endpoints were defined using International Classification of Diseases (ICD) codes: primary (specific codes) and secondary (all codes) endpoints used only hospital discharge codes; the tertiary endpoint included both inpatient and outpatient settings (all codes). Validation of endpoints was implemented. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for current use were estimated for each data source and combined. Results We evaluated 3,238,495 new antidepressant and 74,440 agomelatine users. For the primary endpoint, the OR for agomelatine versus citalopram was 0.48 (CI 0.13–1.71). Results were also

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.

Adherence to treatment is one of the most consistent factors associated with a favorable addiction treatment outcome. Little is known about factors associated with treatment adherence in individuals affected with comorbid attention-deficit/hyperactivity disorder and substance use disorders (SUD). This study aimed to explore whether treatment-associated factors, such as the prescribing physician's (sub)specialty and methylphenidate (MPH) dose, or patient-related factors, such as sex, age, SUD subtype, and psychiatric comorbidity, were associated with adherence to MPH treatment. Swedish national registers were used to identify adult individuals with prescriptions of MPH and medications specifically used in the treatment of SUD or a diagnosis of SUD and/or coexisting psychiatric diagnoses. Primary outcome measure was days in active MPH treatment in stratified dose groups (≤36 mg, ≥37 mg to ≤54 mg, ≥55 mg to ≤72 mg, ≥73 mg to ≤90 mg, ≥91 mg to ≤108 mg, and ≥109 mg). Lower MPH doses (ie, ≤36 mg day 100) were associated with treatment discontinuation between days 101 and 830 (HR≤36 mg, 1.67; HR37-54mg, 1.37; HR55-72mg, 1.36; HR73-90mg, 1.19; HR≥108mg, 1.09). The results showed a linear trend (P < 0.0001) toward decreased risk of treatment discontinuation along with increase of MPH doses. In conclusion, this study shows that higher MPH doses were associated with long-term treatment adherence in individuals with attention-deficit/hyperactivity disorder and SUD.

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

Behavioral differences between native and introduced species may contribute to the invasiveness of certain species. This includes differences at the species level, consistent variation among individuals (“personality”) and within-individual variation (e.g., behavioral plasticity). Here, we investigated swimming activity of individuals from four different amphipod species occurring in the river Rhine system, three of which were native or naturalized (>100 years present) while one is a recent invader (Dikerogammarus villosus

In recent years, the use of atypical antipsychotics and combination therapy for relapse prevention in bipolar disorder has increased substantially. However, real-world data on the comparative effectiveness of these treatment options are largely non-existent. We conducted a population-based cohort study, using data from Swedish national registers. All patients aged 18–75 years who were hospitalized for mania 2006–2014 and filled at least one prescription of lithium, valproate, olanzapine, quetiapine, aripiprazole or any combination of these drugs were included, and followed for up to one year after hospital discharge, generating follow-up data from 5 713 hospitalizations. We used Cox proportional hazard regression models to study time to treatment failure for each individual drug and combination therapy, using lithium as comparator. Treatment failure was defined as treatment discontinuation, switch, or rehospitalization, and the results were adjusted for clinical and sociodemographic factors. We found that treatment failure occurred in 85% of cases and that the majority of combination therapies were associated with lower risks of treatment failure compared to monotherapies. Patients combining lithium + valproate + quetiapine had the lowest risk of treatment failure (adjusted HR [AHR] 0.40, 95% CI 0.30–0.54), followed by patients on lithium + valproate + olanzapine (AHR 0.55, 95% CI 0.45–0.68). In contrast, monotherapies with antipsychotics were associated with significantly higher risks of treatment failure compared to single use of lithium. In conclusion, our results support experimental findings, suggesting that combination therapy is more effective than monotherapy after a manic episode.

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

Background The impact of treatment resistant depression (TRD) on mortality is not established. Methods Using Swedish national registers, 118,774 patients between 18–69 years of age who had been prescribed an antidepressant and been diagnosed with depression in specialized care were identified. Patients with at least two additional treatment trials during the same depressive episode were classified as having TRD. Data on the covariates of sex, age, history of depression, self-harm, substance use disorders, and other psychiatric and somatic comorbidities was also used. Relative risks comparing TRD patients with other depressed patients were calculated as hazard ratios (HR) for all-cause mortality and for external and non-external causes of death, as well as excess mortality rate ratios (EMRR), with 95% confidence intervals (CI). Results In total 15,013 patients (13%) were classified with TRD. Adjusted HR for all-cause mortality was 1.35 (95% CI 1.21–1.50). Mortality from external causes (including suicides and accidents) was markedly higher in TRD patients than in other depressed patients (HR 1.97; 1.69–2.29), while mortality from non-external causes was similar. The adjusted EMRR was 1.52 (1.31–1.76), highest among patients 18–29 years old (EMRR 2.03; 1.31–1.76) and patients without somatic comorbidity (EMRR 1.99; 1.63–2.43). Limitations Severity of depression and adherence to treatment were not available in the data. Conclusions Patients with TRD may have an increased all-cause mortality compared to other depressed patients, mainly for external causes of death. The relative mortality is highest among young and physically healthy patients.

Background: Breast milk is associated with a lower risk of neonatal morbidity in very preterm infants. Despite the benefits, the duration of breastfeeding is shorter in very preterm infants than in term infants. Objective: This study aimed to investigate how early provision of mother’s own milk (MOM) and maternal and infant characteristics are related to breast milk feeding (BMF) between 36 and 40 weeks postmenstrual age (PMA) after very preterm birth. Methods: A regional observational study of 138 singleton infants born at < 32 weeks of gestation in Stockholm, Sweden, was conducted. Data were derived from medical charts to investigate the association between early provision of MOM; maternal and infant characteristics; and exclusive, partial, or no BMF at 36 weeks PMA. Moreover, changes in BMF between 36 and 40 weeks PMA were studied. Results: Most infants (80%) received MOM at 36 weeks PMA (55% exclusively, 25% partial). High provision of MOM at postnatal day 7 was associated with exclusive BMF at 36 weeks PMA, odds ratio (OR) 1.18 per 10 mL/kg MOM (95% confidence interval [CI], 1.06-1.32). Mothers born in non-Nordic countries provided MOM exclusively less often, adjusted OR 0.27 (95% CI, 0.10-0.69), compared to Nordic mothers. Between 36 and 40 weeks PMA, BMF decreased overall. This change was not associated with investigated predictors. Conclusion: It is possible to achieve high rates of BMF in very preterm infants. High intake of MOM early in the postnatal period is strongly related to exclusive BMF at 36 weeks PMA.

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.

Objective To compare the incidence of hypertension, stroke, coronary heart disease, and diabetes in women who have delivered after in vitro fertilization (IVF) with those who delivered after natural conception. Design A cohort study in Sweden between 1990 and 2008. Setting Sweden. Patient(s) 23,498 women who had given birth to a child after IVF and 116,960 individually matched women. Intervention(s) None. Main Outcome Measure(s) Incidence rates of hypertension, diabetes, stroke, and coronary heart disease in both groups. Result(s) Inpatient and outpatient diagnoses of hypertension, stroke, coronary heart disease, and diabetes were identified by linkage to the Swedish National Patient Register. The mean time of follow-up was 8.6 years in both groups. Multivariable analysis showed that hypertension had a higher incidence in IVF mothers with a hazard ratio (HR) of 1.27, 95% confidence interval (CI) 1.13–1.41, as compared with mothers from the Medical Birth Register. There was a trend to a higher incidence of stroke (HR 1.27; 95% CI, 0.96–1.68), but the incidence of coronary heart disease and diabetes did not differ. Conclusion(s) Hypertension was more prevalent in the IVF group, which suggests that these women should be aware of their blood pressure and cardiovascular risk profile.

Objective. To investigate whether interventions that have positive effects on psychological symptoms and quality of life compared with usual care would also reduce days on sick leave. Design. A randomized controlled trial. Setting. A large primary health care centre in Stockholm, Sweden. Intervention. Patients with common mental disorders were recruited by their GPs and randomized into one of two group interventions that took place in addition to usual care. These group interventions were: (a) group cognitive behavioural therapy (CBT), and (b) group multimodal intervention (MMI). Both types of intervention had previously shown significant effects on quality of life, and MMI had also shown significant effects on psychological symptoms. Patients. Of the 245 randomized patients, 164 were employed and had taken sick leave periods of at least two weeks in length during the study period of two years. They comprised the study group. Main outcome measures. The odds, compared with usual care, for being sick-listed at different times relative to the date of randomization. Results. The mean number of days on sick leave increased steadily in the two years before randomization and decreased in the two years afterwards, showing the same pattern for all three groups .The CBT and MMI interventions did not show the expected lower odds for sick-listing compared with usual care during the two-year follow-up. Conclusion. Reduction in psychological symptoms and increased well-being did not seem to be enough to reduce sickness absence for patients with common mental problems in primary care. The possibility of adding workplace-oriented interventions is discussed.

Introduction and aims To assess opioid-related mortality and correlation with filled prescriptions for buprenorphine and methadone. Design and methods A register study, including data from the Swedish Forensic Pathology and Forensic Toxicology databases 2003-2010, the Prescribed Drug Register and the National Patient Register. Results A total of 1301 deaths, assessed as related to buprenorphine, methadone or heroin, or a combination of them, were studied. The largest number of fatalities was related to intake of heroin (n = 776), followed by methadone (n = 342) and buprenorphine (n = 168). The total annual number of fatal cases related to the studied drugs more than doubled (116 to 255) during the study period. There were increases in mortality related to both buprenorphine and methadone: from 1 to 49 cases for buprenorphine, and from 19 to 81 cases for methadone. Only one-fifth of the fatal cases had a filled prescription for the maintenance drug assessed as the cause of death. Discussion and conclusion This study showed that most fatalities were not related to filled prescriptions of maintenance drugs, and a substantial illicit use of buprenorphine and methadone resulting in deaths was revealed. To prevent opioid toxicity deaths it is important to make efforts not only to reduce drug diversion from maintenance programs, but also to improve the control of drug trafficking and other illegal sources.

Background. The purpose was to test the effectiveness of two transdiagnostic group interventions compared to care as usual (CAU) for patients with anxiety, depressive or stress-related disorders within a primary health care context. Objectives. To compare the effects of cognitive-based-behavioural therapy (CBT) and multimodal intervention (MMI) on the quality of life and relief of psychological symptoms of patients with common mental disorders or problems attending primary health care centre. Methods. Patients (n = 278), aged 18–65 years, were referred to the study by the GPs and 245 were randomized to CAU or one of two group interventions in addition to CAU: (i) group CBT administered by psychologists and (ii) group MMI administered by assistant nurses. The primary outcome measure was the Mental Component Summary score of short form 36. Secondary outcome measures were Perceived Stress Scale and Self-Rating Scale for Affective Syndromes. The data were analysed using intention-to-treat with a linear mixed model. Results. On the primary outcome measure, the mean improvement based on mixed model analyses across post- and follow-up assessment was significantly larger for the MMI group than for the CBT (4.0; P = 0.020) and CAU (7.5; P = .001) groups. Participants receiving CBT were significantly more improved than those in the CAU group. On four of the secondary outcome measures, the MMI group was significantly more improved than the CBT and CAU groups. The course of improvement did not differ between the CBT group and the CAU group on these measures. Conclusions. Transdiagnostic group treatment can be effective for patients with common mental disorders when delivered in a primary care setting. The group format and transdiagnostic approach fit well with the requirements of primary care.

Introduction: In Scandinavia, portable monitoring has virtually replaced standard polysomnography for diagnosis of obstructive sleep apnea syndrome (OSAS). Because waiting times for specialized OSA ...

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.

Caloric restriction in animals is an effective way to reduce carcinogenesis. Anorexia nervosa (AN) is considered a model of extreme caloric restriction in humans. The aim of our study was to assess cancer incidence and mortality in women with AN. A total of 6,009 women with at least one inpatient treatment for AN during the period 1973-2003 were included in the study. Standardized incidence ratios (SIR) and standardized mortality ratios (SMR) were calculated. Overall, there was no statistically significant difference in cancer incidence compared to women in the general population. At a statistically significant or borderline significant level, a higher incidence for lung cancer and cancer of lymphoid, hematopoietic and related tissue was observed along with a reduced breast cancer incidence. Women with AN had twice as high mortality from cancer in general, and more specifically from melanoma, cancers of genital organs and cancers of ill-defined, secondary and unspecified sites. The increased lung cancer incidence may be due to smoking habits among women with AN. The worse prognosis with higher mortality from melanoma, cancers of genital organs and cancers of ill-defined, secondary and unspecified sites may be explained by AN-specific attitudes toward seeking medical care, adherence to treatment or worse biological precondition due to starvation and cachexia.

AIM: To assess prescribing patterns, sociodemographic characteristics and previous disease history in patients receiving pregabalin.METHODS: An observational study using register data on dispensed drugs and recorded diagnoses for all patients in Stockholm, Sweden, who filled at least one prescription of pregabalin between July 2005 and December 2009. Analyses focused on prevalence, incidence, diagnosis patterns, prior dispensing of other analgesics/psychotropics and persistence to treatment over time.RESULT: A total of 18,626 patients (mean age 55 years, 63% women) were initiated on treatment between July 2006 and December 2009. Approved indications were recorded in hospital and/or primary care within 1 year prior to the first dispensing for 40% of the patients (epilepsy 1.3%, neuropathic pain 35.5% and generalised anxiety disorder (GAD) 3.6%). Antidepressants were used by 55%, opioids by 49% and sedatives by 48% prior to initiation of pregabalin. One-third (34%) only purchased one prescription and the proportion purchasing pregabalin 1 year after initiation was 42.1% for epilepsy, 36.3% for GAD, 21.5% for neuropathic pain and 25.6% for those without any of the included diagnoses.CONCLUSION: Pregabalin was mainly used as a second-line drug for the treatment of GAD or neuropathic pain and to a lesser extent as add-on therapy in epilepsy. However, a large proportion of all patients only purchased one prescription and the persistence declined rapidly over time. The issue of potential off-label prescribing or poor registration of diagnoses should also be noted as a high proportion had been prescribed the drug without a record of any of the approved indications.

Patients with Attention Deficit/Hyperactivity Disorder (ADHD) and comorbid Substance Use Disorders (SUD) are increasingly being treated with central stimulant medication despite limited evidence for its effectiveness. Lack of longitudinal follow-up studies of dosing and adverse effects has resulted in conflicting treatment guidelines. This study aims to explore whether individuals with ADHD and comorbid SUD are treated with higher stimulant doses than individuals with ADHD only, and whether doses increase over time as a sign of tolerance, a core symptom of addiction. Information on methylphenidate doses for 14 314 Swedish adults, including 4870 individuals with comorbid SUD was obtained through linkages of Swedish national registers between 2006 and 2009. Differences in doses between patients with and without SUD were estimated using logistic regression while a linear regression model calculated time trends in mean doses. Individuals with SUD were prescribed higher methylphenidate doses than those without (OR day365 ; 2.12, 95% CI 1.81–2.47: OR day730 2.65, 95% CI 2.13–3.30). Patients with SUD were, two years after initiating stimulant treatment, prescribed approximately 40% higher doses compared to individuals with ADHD only. The results may suggest a need for increased doses in this population to achieve optimal ADHD symptom control. A tendency towards increasing doses during the first years of treatment, more pronounced in individuals with comorbid SUD, may reflect a reluctance to prescribe adequate doses due to lack of clinical guidelines. Mean doses stabilized after about two years in both groups, which does not lend support to continuously increasing tolerance over time.

Background: Information transfer in mammalian communication networks is often based on the deposition of excreta in latrines. Depending on the intended receiver(s), latrines are either formed at territorial boundaries (between-group communication) or in core areas of home ranges (within-group communication). The relative importance of both types of marking behavior should depend, amongst other factors, on population densities and social group sizes, which tend to differ between urban and rural wildlife populations. Our study is the first to assess (direct and indirect) anthropogenic influences on mammalian latrine-based communication networks along a rural-to-urban gradient in European rabbits (Oryctolagus cuniculus) living in urban, suburban and rural areas in and around Frankfurt am Main (Germany). Results: The proportion of latrines located in close proximity to the burrow was higher at rural study sites compared to urban and suburban ones. At rural sites, we found the largest latrines and highest latrine densities close to the burrow, suggesting that core marking prevailed. By contrast, latrine dimensions and densities increased with increasing distance from the burrow in urban and suburban populations, suggesting a higher importance of peripheral marking. Conclusions: Increased population densities, but smaller social group sizes in urban rabbit populations may lead to an increased importance of between-group communication and thus, favor peripheral over core marking. Our study provides novel insights into the manifold ways by which man-made habitat alterations along a rural-to-urban gradient directly and indirectly affect wildlife populations, including latrine-based communication networks.

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.