258 research outputs found
Attention-deficit/hyperactivity disorder medication and seizures
OBJECTIVE:
Individuals with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of seizures, but there is uncertainty about whether ADHD medication treatment increases risk among patients with and without preexisting seizures.
METHODS:
We followed a sample of 801,838 patients with ADHD who had prescribed drug claims from the Truven Health MarketScan Commercial Claims and Encounters databases to examine whether ADHD medication increases the likelihood of seizures among ADHD patients with and without a history of seizures. First, we assessed overall risk of seizures among patients with ADHD. Second, within-individual concurrent analyses assessed odds of seizure events during months when a patient with ADHD received ADHD medication compared with when the same individual did not, while adjusting for antiepileptic medications. Third, within-individual long-term analyses examined odds of seizure events in relation to the duration of months over the previous 2 years patients received medication.
RESULTS:
Patients with ADHD were at higher odds for any seizure compared with non-ADHD controls (odds ratio [OR] = 2.33, 95% confidence interval [CI] = 2.24-2.42 males; OR = 2.31, 95% CI = 2.22-2.42 females). In adjusted within-individual comparisons, ADHD medication was associated with lower odds of seizures among patients with (OR = 0.71, 95% CI = 0.60-0.85) and without (OR = 0.71, 95% CI = 0.62-0.82) prior seizures. Long-term within-individual comparisons suggested no evidence of an association between medication use and seizures among individuals with (OR = 0.87, 95% CI = 0.59-1.30) and without (OR = 1.01, 95% CI = 0.80-1.28) a seizure history.
CONCLUSIONS:
Results reaffirm that patients with ADHD are at higher risk of seizures. However, ADHD medication was associated with lower risk of seizures within individuals while they were dispensed medication, which is not consistent with the hypothesis that ADHD medication increases risk of seizures
Health, behavior, and social outcomes among offspring of parents with criminal convictions: a registerābased study from Sweden
Background: There is currently insufficient understanding of the health and behavior of children whose parents engage in criminal behavior. We examined associations between parental criminal convictions and wide range of offspring health, behavioral, and social outcomes by age 18 in a large, national sample, aiming to get a comprehensive picture of the risks among children of offending parents. Methods: We studied 1,013,385 individuals born in Sweden between 1987 and 1995, and their parents. Using data from several longitudinal nationwide registers, we investigated parental convictions and 85 offspring outcomes until the end of 2013, grouped into birthārelated conditions, psychiatric and somatic disorders, accidents and injuries, mortality, school achievement, violent victimization, and criminality. Cox proportional hazards regression and logistic regression models were used to examine the associations. The role of genetic factors in intergenerational associations was studied in childrenāofāsiblings analyses. We also examined the coāoccurrence of multiple outcomes using Poisson regression. Results: A total of 223,319 (22.0%) individuals had one parent convicted and 31,241 (3.1%) had both parents convicted during the first 18 years of their life. The strongest associations were found between parental convictions and offspring behavioral problems, substance use disorders, poor school achievement, violent victimization, and criminality, with an approximately 2 to 2.5āfold increased risk in children with one convicted parent and 3ā to 4āfold increased risk in children with two convicted parents. The risks were particularly elevated among children of incarcerated parents with a history of violent convictions. The associations appeared to be at least partly explained by genetic influences. Parental convictions were also associated with an increased likelihood of experiencing multiple outcomes. Conclusions: Our findings help to calibrate the risks of a wide range of adverse outcomes associated with parental convictions and may be used to guide prevention efforts and identify key areas for future research
Associations between Ī²-blockers and psychiatric and behavioural outcomes: a population-based cohort study of 1.4 million individuals in Sweden
Background
Ī²-blockers are widely used for treating cardiac conditions and are suggested for the treatment of anxiety and aggression, although research is conflicting and limited by methodological problems. In addition, Ī²-blockers have been associated with precipitating other psychiatric disorders and suicidal behaviour, but findings are mixed. We aimed to examine associations between Ī²-blockers and psychiatric and behavioural outcomes in a large population-based cohort in Sweden.
Methods and findings
We conducted a population-based longitudinal cohort study using Swedish nationwide high-quality healthcare, mortality, and crime registers. We included 1,400,766 individuals aged 15 years or older who had collected Ī²-blocker prescriptions and followed them for 8 years between 2006 and 2013. We linked register data on dispensed Ī²-blocker prescriptions with main outcomes, hospitalisations for psychiatric disorders (not including self-injurious behaviour or suicide attempts), suicidal behaviour (including deaths from suicide), and charges of violent crime. We applied within-individual Cox proportional hazards regression to compare periods on treatment with periods off treatment within each individual in order to reduce possible confounding by indication, as this model inherently adjusts for all stable confounders (e.g., genetics and health history). We also adjusted for age as a time-varying covariate. In further analyses, we adjusted by stated indications, prevalent users, cardiac severity, psychiatric and crime history, individual Ī²-blockers, Ī²-blocker selectivity and solubility, and use of other medications. In the cohort, 86.8% (n = 1,215,247) were 50 years and over, and 52.2% (n = 731,322) were women. During the study period, 6.9% (n = 96,801) of the Ī²-blocker users were hospitalised for a psychiatric disorder, 0.7% (n = 9,960) presented with suicidal behaviour, and 0.7% (n = 9,405) were charged with a violent crime. There was heterogeneity in the direction of results; within-individual analyses showed that periods of Ī²-blocker treatment were associated with reduced hazards of psychiatric hospitalisations (hazard ratio [HR]: 0.92, 95% confidence interval [CI]: 0.91 to 0.93, p < 0.001), charges of violent crime (HR: 0.87, 95% CI: 0.81 to 0.93, p < 0.001), and increased hazards of suicidal behaviour (HR: 1.08, 95% CI: 1.02 to 1.15, p = 0.012). After stratifying by diagnosis, reduced associations with psychiatric hospitalisations during Ī²-blocker treatment were mainly driven by lower hospitalisation rates due to depressive (HR: 0.92, 95% CI: 0.89 to 0.96, p < 0.001) and psychotic disorders (HR: 0.89, 95% CI: 0.85 to 0.93, p < 0.001). Reduced associations with violent charges remained in most sensitivity analyses, while associations with psychiatric hospitalisations and suicidal behaviour were inconsistent. Limitations include that the within-individual model does not account for confounders that could change during treatment, unless measured and adjusted for in the model.
Conclusions
In this population-wide study, we found no consistent links between Ī²-blockers and psychiatric outcomes. However, Ī²-blockers were associated with reductions in violence, which remained in sensitivity analyses. The use of Ī²-blockers to manage aggression and violence could be investigated further
Association of parental substance use disorder with offspring cognition : a population family-based study
Aims To assess whether parental substance use disorder (SUD) is associated with lower cognitive ability in offspring, and whether the association is independent of shared genetic factors. Design A population family-based cohort study utilizing national Swedish registries. Linear regression with increased adjustment of covariates was performed in the full population. In addition, the mechanism of the association was investigated with children-of-sibling analyses using fixed-effects regression with three types of sibling parents with increasing genetic relatedness (half-siblings, full siblings and monozygotic twins). Setting and participants A total of 3 004 401 people born in Sweden between 1951 and 1998. Measurements The exposure variable was parental SUD, operationalized as having a parent with life-time SUD diagnosis or substance-related criminal conviction in the National Patient Register or Crime Register, respectively. Outcomes were cognitive test score at military conscription and final school grades when graduating from compulsory school. Covariates included in the analyses were sex, birth year, parental education, parental migration status and parental psychiatric comorbid diagnoses. Findings In the full population, parental SUD was associated with decreased cognitive test stanine scores at conscription [4.56, 95% confidence interval (CI) = 4.55-4.57] and lower Z-standardized school grades (-0.43, 95% CI = -0.43 to -0.42) compared to people with no parental SUD (cognitive test: 5.17, 95% CI = 5.17-5.18; grades: 0.09, 95% CI = 0.08-0.09). There was evidence of a dose-response relationship, in that having two parents with SUD (cognitive test: 4.17, 95% CI = 4.15-4.20; grades: -0.83, 95% CI = -0.84 to -0.82) was associated with even lower cognitive ability than having one parent with SUD (cognitive test: 4.60, 95% CI = 4.59-4.60; grades: -0.38, 95% CI = -0.39 to -0.380). In the children-of-siblings analyses when accounting for genetic relatedness, these negative associations were attenuated, suggestive of shared underlying genetic factors. Conclusions There appear to be shared genetic factors between parental substance use disorder (SUD) and offspring cognitive function, suggesting that cognitive deficits may constitute a genetically transmitted risk factor in SUD.Peer reviewe
Familial Liability for Eating Disorders and Suicide Attempts: Evidence From a Population Registry in Sweden
IMPORTANCE: Suicide attempts are common in individuals with eating disorders. More precise understanding of the mechanisms underlying their concomitant occurrence is needed.
OBJECTIVE: To examine the association between eating disorders and suicide attempts and whether familial risk factors contribute to the association.
DESIGN, SETTING, AND PARTICIPANTS: A Swedish birth cohort including individuals born in Sweden between January 1, 1979, and December 31, 2001, was followed up from age 6 years to December 31, 2009 (N = 2,268,786). Information was acquired from Swedish national registers. All individuals were linked to their biological full siblings, maternal half siblings, paternal half siblings, full cousins, and half cousins. Data analysis was conducted from October 5, 2014, to April 28, 2015.
MAIN OUTCOMES AND MEASURES: Eating disorders were captured by 3 variables (any eating disorder, anorexia nervosa, and bulimia nervosa) identified by any lifetime diagnoses recorded in the registers. Suicide attempts were defined as any suicide attempts, including death by suicide, recorded in the registers. We examined the association between eating disorders and death by suicide separately, but the study was underpowered to explore familial liability for this association.
RESULTS: Of 2,268,786 individuals, 15,457 females (1.40% of all females) and 991 males (0.09% of all males) had any eating disorder, 7680 females (0.70%) and 453 males (0.04%) had anorexia nervosa, and 3349 females (0.30%), and 61 males (0.01%) had bulimia nervosa. Individuals with any eating disorder had an increased risk (reported as odds ratio [95% CI]) of suicide attempts (5.28 [5.04-5.54]) and death by suicide (5.39 [4.00-7.25]). The risks were attenuated but remained significant after adjusting for comorbid major depressive disorder, anxiety disorder, and substance use disorder (suicide attempts: 1.82 [1.72-1.93]; death by suicide: 2.04 [1.49-2.80]). Similar results were found for anorexia nervosa (suicide attempts: crude, 4.42 [4.12-4.74] vs adjusted, 1.70 [1.56-1.85]; death by suicide: crude, 6.46 [4.38-9.54] vs adjusted, 2.67 [1.78-4.01]) and bulimia nervosa (suicide attempts: crude, 6.26 [5.73-6.85] vs adjusted, 1.88 [1.68-2.10]; death by suicide: crude, 4.45 [2.44-8.11] vs adjusted, 1.48 [0.81-2.72]). Individuals (index) who had a full sibling with any eating disorder had an increased risk of suicide attempts (1.41 [1.29-1.53]). The risk was attenuated for any eating disorder in more-distant relatives (maternal half siblings, 1.10 [0.90-1.34]; paternal half siblings, 1.21 [0.98-1.49]; full cousins, 1.11 [1.06-1.18]; half cousins, 0.90 [0.78-1.03]). This familial pattern remained stable after adjusting for the index individuals' eating disorders. Similar patterns were found for anorexia nervosa and bulimia nervosa.
CONCLUSIONS AND RELEVANCE: These results suggest an increased risk of suicide attempts in individuals with lifetime eating disorders and their relatives. The pattern of familial coaggregation suggests familial liability for the association between eating disorders and suicide. Psychiatric comorbidities partially explain this association, suggesting particularly high-risk presentations
Use of central nervous system drugs in combination with selective serotonin reuptake inhibitor treatment: a Bayesian screening study for risk of suicidal behavior
Background: Using other central nervous system (CNS) medications in combination with selective serotonin reuptake inhibitor (SSRI) treatment is common. Despite this, there is limited evidence on the impact on suicidal behavior of combining specific medications. We aim to provide evidence on signals for suicidal behavior risk when initiating CNS drugs during and outside of SSRI treatment.
Materials and methods: Using a linkage of Swedish national registers, we identified a national cohort of SSRI users aged 6ā59 years residing in Sweden 2006ā2013. We used a two-stage Bayesian Poisson model to estimate the incidence rate ratio (IRR) of suicidal behavior in periods up to 90 days before and after a CNS drug initiation during SSRI treatment, while accounting for multiple testing. For comparison, and to assess whether there were interactions between SSRIs and other CNS drugs, we also estimated the IRR of initiating the CNS drug without SSRI treatment.
Results: We identified 53 common CNS drugs initiated during SSRI treatment, dispensed to 262,721 individuals. We found 20 CNS drugs with statistically significant IRRs. Of these, two showed a greater risk of suicidal behavior after versus before initiating the CNS drug (alprazolam, IRR = 1.39; flunitrazepam, IRR = 1.83). We found several novel signals of drugs that were statistically significantly associated with a reduction in the suicidal behavior risk. We did not find evidence of harmful interactions between SSRIs and the selected CNS drugs.
Conclusion: Several of the detected signals for reduced risk correspond to drugs where there is previous evidence of benefit for antidepressant augmentation (e.g., olanzapine, quetiapine, lithium, buspirone, and mirtazapine). Novel signals of reduced suicidal behavior risk, including for lamotrigine, valproic acid, risperidone, and melatonin, warrant further investigation
Longitudinal Associations of Childhood Internalizing Psychopathology With Substance Misuse : A Register-Based Twin and Sibling Study
Objective: The pathways from internalizing psychopathology to substance misuse remain largely unclear. We estimated associations between childhood internalizing problems and subsequent substance misuse in 2 family-based samples. We also investigated sex differences and the role of externalizing comorbidity. Method: We studied associations of childhood internalizing psychopathology with register-based substance misuse after age 13 years. Sample 1 included all individuals born in Sweden from 1984 to 2000 (N = 1,768,516). Depressive and anxiety disorders were included as register-based International Classification of Diseases Ninth Revision (ICD-9) or Tenth Revision (ICD-10) diagnoses before age 13. Sample 2 was a subsample within the population sample, the Child and Adolescent Twin Study in Sweden (CATSS) twin cohort (n = 12,408; born 1992-1998), with mood and anxiety problems assessed at age 9/12 by parents. In both samples, substance misuse was defined as an ICD-9/10 alcohol/drug use disorder or an alcohol/drug-related criminal conviction until December 2013. To account for familial effects, stratified analyses were conducted within siblings and twin pairs. Results: In the population sample, both depressive (hazard ratio [HR] = 2.75, 95% CI = 2.36-3.20) and anxiety disorders (HR = 1.52, 95% CI = 1.35-1.73) were associated with substance misuse. Childhood mood problems (HR = 2.28, 95% CI = 1.69-3.08) were associated with substance misuse in the CATSS sample. The associations were partially explained by familial factors, and comorbid externalizing disorders explained the associations in men but not in women. Conclusion: Childhood mood problems were associated with substance misuse, but familial factors shared by siblings partially explained the associations. The relationship of anxiety with substance misuse was complex and depended on measurement and the type of anxiety disorder. Internalizing problems may be especially important for substance misuse risk in women.Peer reviewe
Risk of death by suicide following self-harm presentations to healthcare: development and validation of a multivariable clinical prediction rule (OxSATS)
Background Assessment of suicide risk in individuals who have self-harmed is common in emergency departments, but is often based on tools developed for other purposes.
Objective We developed and validated a predictive model for suicide following self-harm.
Methods We used data from Swedish population-based registers. A cohort of 53 172 individuals aged 10+ years, with healthcare episodes of self-harm, was split into development (37 523 individuals, of whom 391 died from suicide within 12 months) and validation (15 649 individuals, 178 suicides within 12 months) samples. We fitted a multivariable accelerated failure time model for the association between risk factors and time to suicide. The final model contains 11 factors: age, sex, and variables related to substance misuse, mental health and treatment, and history of self-harm. Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis guidelines were followed for the design and reporting of this work.
Findings An 11-item risk model to predict suicide was developed using sociodemographic and clinical risk factors, and showed good discrimination (c-index 0.77, 95% CI 0.75 to 0.78) and calibration in external validation. For risk of suicide within 12 months, using a 1% cut-off, sensitivity was 82% (75% to 87%) and specificity was 54% (53% to 55%). A web-based risk calculator is available (Oxford Suicide Assessment Tool for Self-harm or OxSATS).
Conclusions OxSATS accurately predicts 12-month risk of suicide. Further validations and linkage to effective interventions are required to examine clinical utility.
Clinical implications Using a clinical prediction score may assist clinical decision-making and resource allocation
Selective serotonin re-uptake inhibitor use during pregnancy: association with offspring birth size and gestational age.
BACKGROUND: Depression around the time of pregnancy affects at least 1 in 8 women
and treatment with selective serotonin re-uptake inhibitors (SSRIs) in pregnant
women has been increasing, but research on adverse effects on the fetus have so
far commonly used designs unable to account for confounding. We aimed to examine
the effects of prenatal SSRI exposure on offspring size outcomes and gestational
age, and disentangle whether associations observed were due to the medication or
other factors. METHODS: We used a Swedish population-based cohort of 392,029
children and national registers to estimate the associations between prenatal
exposure to SSRIs and depression on the outcomes birthweight, birth length, birth
head circumference, gestational age at birth and preterm birth. A sub-sample of
1007 children was analysed in a within-family design that accounts for unmeasured
parental genetic and environmental confounders. RESULTS: Crude analyses revealed
associations between prenatal SSRI exposure, and offspring birth size and
gestational age. However, in the within-family analyses, only the association
between SSRI exposure and reduced gestational age (-2.3 days; 95% confidence
interval -3.8 to -0.8) was observed. CONCLUSIONS: This study indicates that
prenatal SSRI exposure may not be causally related to offspring birth size.
Rather, our analyses suggest that the association could be caused by other
underlying differences instead of the medication per se. A small reduction of
gestational age was associated with SSRI exposure in the within-family analysis
and could be due to either the exposure, or other factors changing between
pregnancies.The Swedish Research CouncilSwedish Initiative for Research on Microdata in the Social and Medical Sciences (SIMSAM).The Swedish Medical Research CouncilThe Swedish foundation for Strategic ResearchThe Swedish Brain FoundationManuscrip
Maternal and infant outcomes associated with lithium use in pregnancy
Background Concerns about teratogenicity and offspring complications limit use of lithium in pregnancy. We aimed to investigate the association between in-utero lithium exposure and risk of pregnancy complications, delivery outcomes, neonatal morbidity and congenital malformations. Methods Meta-analysis of primary data analyzed using a shared protocol. Six study sites participated: Denmark, Canada, Netherlands, Sweden, UK, and US, totaling 727 lithium-exposed pregnancies compared to 21,397 reference pregnancies in mothers with a mood disorder, but unexposed to lithium. Main outcome measures included: (1) pregnancy complications, (2) delivery outcomes, (3) neonatal readmission to hospital within 28 days of birth, and (4) congenital malformations (major malformations and cardiac malformations). Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were generated using logistic regression models. Site-specific prevalence rates and ORs were pooled using random-effects meta-analytic models. Findings Lithium exposure was not associated with any of the pre-defined pregnancy complications or delivery outcomes. There was an increased risk for neonatal readmission in lithium exposed (27Ā·5%) versus reference group (14Ā·3%) (Pooled aOR1Ā·62; 95% CI: 1Ā·12ā2Ā·33). Lithium exposure during first trimester was associated with increased risk of major malformations (7Ā·4% versus 4Ā·3%; pooled aOR 1Ā·71, 95% CI: 1Ā·07ā2Ā·72). Similarly, more lithium exposed children had major cardiac malformations, albeit not stasticially significant (2Ā·1% versus 1Ā·6%; pooled aOR 1Ā·54, 95% CI: 0Ā·64ā3Ā·70). Limitations in our study include: Serum lithium 5 levels were not available, hence no analyses related to dose-response effects could be performed, and residual confounding from e.g. substance abuse cannot be ruled out. Interpretation Treatment decisions must weigh the potential for increased risks, considering both effct sizes and the precision of the estimates, in particular associated with first-trimester lithium use against its effectiveness at reducing relapse
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