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1.
  • Garcia-Argibay, Miguel, 1988-, et al. (författare)
  • Methylphenidate and Short-Term Cardiovascular Risk
  • 2024
  • Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 7:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance:  There are concerns about the safety of medications for treatment of attention-deficit/hyperactivity disorder (ADHD), with mixed evidence on possible cardiovascular risk.Objective:  To assess whether short-term methylphenidate use is associated with risk of cardiovascular events.Design, Setting, and Participants:  This retrospective, population-based cohort study was based on national Swedish registry data. Participants were individuals with ADHD aged 12 to 60 years with dispensed prescriptions of methylphenidate between January 1, 2007, and June 30, 2012. Each person receiving methylphenidate (n = 26 710) was matched on birth date, sex, and county to up to 10 nonusers without ADHD (n = 225 672). Statistical analyses were performed from September 13, 2022, to May 16, 2023.Main Outcomes and Measures:  Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias, 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a bayesian within-individual design. Analyses were stratified by history of cardiovascular events.Results:  The cohort included 252 382 individuals (15 442 [57.8% men]; median age, 20 (IQR, 15-31) years). The overall incidence of cardiovascular events was 1.51 per 10 000 person-weeks (95% highest density interval [HDI], 1.35-1.69) for individuals receiving methylphenidate and 0.77 (95% HDI, 0.73-0.82) for the matched controls. Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41; 95% HDI, 1.09-1.88) compared with matched controls (IRR, 1.18; 95% HDI, 1.02-1.37). The posterior probabilities were 70% for at least a 10% increased risk of cardiovascular events in individuals receiving methylphenidate vs 49% in matched controls. No difference was found in this risk between individuals with and without a history of cardiovascular disease (IRR, 1.11; 95% HDI, 0.58-2.13).Conclusions and Relevance:  In this cohort study, individuals receiving methylphenidate had a small increased cardiovascular risk vs matched controls in the 6 months after treatment initiation. However, there was little evidence for an increased risk of 20% or higher and for differences in risk increase between people with and without a history of cardiovascular disease. Therefore, before treatment initiation, careful consideration of the risk-benefit trade-off of methylphenidate would be useful, regardless of cardiovascular history.
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2.
  • Brikell, Isabell, et al. (författare)
  • Medication treatment for attention-deficit/hyperactivity disorder and the risk of acute seizures in individuals with epilepsy
  • 2019
  • Ingår i: Epilepsia. - : Wiley-Blackwell. - 0013-9580 .- 1528-1167. ; 60:2, s. 284-293
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) affects 10%-30% of individuals with epilepsy, yet concerns remain regarding the safety of ADHD medication in this group. The objective of this study was to examine the risk of acute seizures associated with ADHD medication in individuals with epilepsy.METHODS: A total of 21 557 individuals with a seizure history born between 1987 and 2003 were identified from Swedish population registers. Within this study population, we also identified 6773 youth (<19 years of age) who meet criteria for epilepsy, and 1605 youth with continuous antiepileptic drug (AED) treatment. ADHD medication initiation and repeated medication periods were identified from the Swedish Prescribed Drug Register between January 1, 2006 and December 31, 2013. Acute seizures were identified via unplanned visits to hospital or specialist care with a primary seizure discharge diagnosis in the Swedish National Patient Register during the same period. Conditional Poisson regression was used to compare the seizure rate during the 24 weeks before and after initiation of ADHD medication with the rate during the same 48 weeks in the previous year. Cox regression was used to compare the seizure rate during ADHD medication periods with the rate during nonmedication periods. Comparisons were made within-individual to adjust for unmeasured, time?constant confounding.RESULTS: Among 995 individuals who initiated ADHD medication during follow-up, within-individual analyses showed no statistically significant difference in the rate of seizures during the 24 weeks before and after medication initiation, compared to the same period in the previous year. In the full study population 11 754 seizure events occurred during 136 846 person-years and 1855 individuals had at least one ADHD medication period. ADHD medication periods were associated with a reduced rate of acute seizures (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.57-0.94), compared to nonmedication periods within the same individual. Similar associations were found in youth with epilepsy and continuous AED treatment, when adjusting for AEDs, and across sex, age, and comorbid neurodevelopmental disorders.SIGNIFICANCE: We found no evidence for an overall increased rate of acute seizures associated with ADHD medication treatment among individuals with epilepsy. These results suggest that epilepsy should not automatically preclude patients from receiving ADHD medications.
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3.
  • Chang, Zheng, et al. (författare)
  • Association Between Prescription of Major Psychotropic Medications and Violent Reoffending After Prison Release
  • 2016
  • Ingår i: Journal of the American Medical Association (JAMA). - Chicago, USA : American Medical Association. - 0098-7484 .- 1538-3598. ; 316:17, s. 1798-1807
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Individuals released from prison have high rates of violent reoffending, and there is uncertainty about whether pharmacological treatments reduce reoffending risk.Objective: To investigate the associations between major classes of psychotropic medications and violent reoffending.Design, Setting, and Participants: This cohort study included all released prisoners in Sweden from July 1, 2005, to December 31, 2010, through linkage of population-based registers. Rates of violent reoffending during medicated periods were compared with rates during nonmedicated periods using within-individual analyses. Follow-up ended December 31, 2013.Exposures: Periods with or without dispensed prescription of psychotropic medications (antipsychotics, antidepressants, psychostimulants, drugs used in addictive disorders, and antiepileptic drugs) after prison release. Prison-based psychological treatments were investigated as a secondary exposure.Main Outcomes and Measures: Violent crime after release from prison.Results: The cohort included 22 275 released prisoners (mean [SD] age, 38 [13] years; 91.9% male). During follow-up (median, 4.6 years; interquartile range, 3.0-6.4 years), 4031 individuals (18.1%) had 5653 violent reoffenses. The within-individual hazard ratio (HR) associated with dispensed antipsychotics was 0.58 (95% CI, 0.39-0.88), based on 100 events in 1596 person-years during medicated periods and 1044 events in 11 026 person-years during nonmedicated periods, equating to a risk difference of 39.7 (95% CI, 11.3-57.7) fewer violent reoffenses per 1000 person-years. The within-individual HR associated with dispensed psychostimulants was 0.62 (95% CI, 0.40-0.98), based on 94 events in 1648 person-years during medicated periods and 513 events in 4553 person-years during nonmedicated periods, equating to a risk difference of 42.8 (95% CI, 2.2-67.6) fewer violent reoffenses per 1000 person-years. The within-individual HR associated with dispensed drugs for addictive disorders was 0.48 (95% CI, 0.23-0.97), based on 46 events in 1168 person-years during medicated periods and 1103 events in 15 725 person-years during nonmedicated periods, equating to a risk difference of 36.4 (95% CI, 2.1-54.0) fewer violent reoffenses per 1000 person-years. In contrast, antidepressants and antiepileptics were not significantly associated with violent reoffending rates (HR = 1.09 [95% CI, 0.83-1.43] and 1.14 [95% CI, 0.79-1.65], respectively). The most common prison-based program was psychological treatments for substance abuse, associated with an HR of 0.75 (95% CI, 0.63-0.89), which equated to a risk difference of 23.2 (95% CI, 10.3-34.1) fewer violent reoffenses per 1000 person-years.Conclusions and Relevance: Among released prisoners in Sweden, rates of violent reoffending were lower during periods when individiduals were dispensed antipsychotics, psychostimulants, and drugs for addictive disorders, compared with periods in which they were not dispensed these medications. Further research is needed to understand the causal nature of this association.
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4.
  • Chang, Zheng, et al. (författare)
  • Developmental twin study of attention problems : high heritabilities throughout development.
  • 2013
  • Ingår i: JAMA psychiatry. - Chicago, USA : American Medical Association. - 2168-6238 .- 2168-622X. ; 70:3, s. 311-318
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: The genetic and environmental link between attention-deficit/hyperactivity disorder in childhood and the adult manifestation of the disorder is poorly understood because of a lack of longitudinal studies with cross-informant data.Objective: To explore the relative contribution of genetic and environmental influences on symptoms of attention problems from childhood to early adulthood.Design: Analysis was conducted using longitudinal structural equation modeling with multiple informants.Setting The Swedish Twin Study of Child and Adolescent Development.Participants: One thousand four hundred eighty twin pairs were prospectively followed up from childhood to young adulthood.Main outcome measures: Symptoms were obtained using parent and self-ratings of the Attention Problems Scale at ages 8 to 9, 13 to 14, 16 to 17, and 19 to 20 years.Results: The best-fitting model revealed high heritability of attention problems as indexed by parent and self-ratings from childhood to early adulthood (h² = 0.77-0.82). Genetic effects operating at age 8 to 9 years continued, explaining 41%, 34%, and 24% of the total variance at ages 13 to 14, 16 to 17, and 19 to 20 years. Moreover, new sets of genetic risk factors emerged at ages 13 to 14, 16 to 17, and 19 to 20 years.Conclusions: The shared view of self- and informant-rated attention problems is highly heritable in childhood, adolescence, and early adulthood, suggesting that the previous reports of low heritability for attention-deficit/hyperactivity disorder in adults are best explained by rater effects. Both genetic stability and genetic innovation were present throughout this developmental stage, suggesting that attention problems are a developmentally complex phenotype characterized by both continuity and change across the life span.
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5.
  • Chang, Zheng, et al. (författare)
  • Maternal age at childbirth and risk for ADHD in offspring : a population-based cohort study
  • 2014
  • Ingår i: International Journal of Epidemiology. - Oxford, United Kingdom : Oxford University Press. - 0300-5771 .- 1464-3685. ; 43:6, s. 1815-1824
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Women who give birth at younger ages (e.g. teenage mothers) are more likely to have children who exhibit behaviour problems, such as attention-deficit/hyperactivity disorder (ADHD). However, it is not clear whether young maternal age is causally associated with poor offspring outcomes or confounded by familial factors.Methods: The association between early maternal age at childbirth and offspring ADHD was studied using data from Swedish national registers. The sample included all children born in Sweden between 1988 and 2003 (N = 1 495 543), including 30 674 children with ADHD. We used sibling- and cousin-comparisons to control for unmeasured genetic and environmental confounding. Further, we used a children-of-siblings model to quantify the genetic and environmental contribution to the association between maternal age and offspring ADHD.Results: Maternal age at first birth (MAFB) was associated with offspring ADHD. Teenage childbirth (<20 years) was associated with 78% increased risk of ADHD. The association attenuated in cousin-comparison, suggesting unmeasured familial confounding. The children-of-siblings model indicated that the association between MAFB and ADHD was mainly explained by genetic confounding.Conclusions: All children born to mothers who bore their first child early in their reproductive lives were at increased risk of ADHD. The association was mainly explained by genetic factors transmitted from mothers to their offspring that contribute to both age at childbirth and ADHD in offspring. Our results highlight the importance of using family-based designs to understand how early life circumstances affect child development.
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6.
  • Chang, Zheng, et al. (författare)
  • Medication for Attention-Deficit/Hyperactivity Disorder and Risk for Depression : A Nationwide Longitudinal Cohort Study
  • 2016
  • Ingår i: Biological Psychiatry. - New York : Elsevier. - 0006-3223 .- 1873-2402. ; 80:12, s. 916-922
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Attention-deficit/hyperactivity disorder (ADHD) is associated with high rates of psychiatric comorbidity, including depression. However, it is unclear whether ADHD medication increases or decreases the risk for depression.Methods: We studied all individuals with a diagnosis of ADHD born between 1960 and 1998 in Sweden (N = 38,752). We obtained data for prescription of ADHD medication, diagnosis of depression and other psychiatric disorders, and sociodemographic factors from population-based registers. The association between ADHD medication and depression was estimated with Cox proportional hazards regression.Results: After adjustment for sociodemographic and clinical confounders, ADHD medication was associated with a reduced long-term risk (i.e., 3 years later) for depression (hazard ratio = 0.58; 95% confidence interval, 0.51-0.67). The risk was lower for longer duration of ADHD medication. Also, ADHD medication was associated with reduced rates of concurrent depression; within-individual analysis suggested that occurrence of depression was 20% less common during periods when patients received ADHD medication compared with periods when they did not (hazard ratio = 0.80; 95% confidence interval, 0.70-0.92).Conclusions Our study suggests that ADHD medication does not increase the risk of later depression; rather, medication was associated with a reduced risk for subsequent and concurrent depression.
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7.
  • Chang, Zheng, et al. (författare)
  • Psychiatric disorders and violent reoffending : a national cohort study of convicted prisoners in Sweden
  • 2015
  • Ingår i: Lancet psychiatry. - Oxon,United kingdom : Elsevier. - 2215-0374 .- 2215-0366. ; 2:10, s. 891-900
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Reoffending and presence of psychiatric disorders are common in prisoners worldwide. However, whether psychiatric disorders are risk factors for reoffending is still unknown. We aimed to examine the association between psychiatric disorders, including substance use disorder, and violent reoffending.Methods: We did a longitudinal cohort study of 47,326 prisoners who were imprisoned since Jan 1, 2000, and released before Dec 31, 2009, in Sweden. We obtained data for diagnosed psychiatric disorders from both inpatient and outpatient registers, and sociodemographic and criminological factors from other population-based registers. We calculated hazard ratios (HRs) for violent reoffending with Cox regression. To control for potential familial confounding, we compared sibling prisoners with and without psychiatric disorders. We calculated population attributable fraction to assess the population effect.Findings: Diagnosed psychiatric disorders were associated with an increased hazard of violent reoffending in male (adjusted HR 1·63 [95% CI 1·57-1·70]) and female (2·02 [1·54-2·63]) prisoners, and these associations were independent of measured sociodemographic and criminological factors, and, in men, remained substantial after adjustment for unmeasured familial factors (2·01 [1·66-2·43]). However, findings differed between individual diagnoses and sex. We found some evidence of stronger effects on violent reoffending of alcohol and drug use disorders and bipolar disorder than of other psychiatric disorders. Alcohol use disorder seemed to have a greater effect in women than in men (women 2·08 [1·66-2·60]; men 1·63 [1·56-1·71]). The overall effects of psychiatric disorders did not differ with severity of crime. The hazard of violent reoffending increased in a stepwise way with the number of diagnosed psychiatric disorders. Assuming causality, up to 20% (95% CI 19-22) of violent reoffending in men and 40% (27-52) in women was attributable to the diagnosed psychiatric disorders that we investigated.Interpretation Certain psychiatric disorders are associated with a substantially increased hazard of violent reoffending. Because these disorders are prevalent and mostly treatable, improvements to prison mental health services could counteract the cycle of reoffending and improve both public health and safety. National violence prevention strategies should consider the role of prison health.Funding: Wellcome Trust, Swedish Research Council, and Swedish Research Council for Health, Working Life and Welfare.
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8.
  • Chang, Zheng, et al. (författare)
  • Serious transport accidents in adults with attention-deficit/hyperactivity disorder and the effect of medication : a population-based study
  • 2014
  • Ingår i: JAMA psychiatry. - Chicago, USA : American Medical Association. - 2168-6238 .- 2168-622X. ; 71:3, s. 319-325
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Studies have shown that attention-deficit/hyperactivity disorder (ADHD) is associated with transport accidents, but the magnitude of the association remains unclear. Most important, it is also unclear whether ADHD medication reduces this risk.Objectives: To estimate the association between ADHD and the risk of serious transport accidents and to explore the extent to which ADHD medication influences this risk among patients with ADHD.Design, setting and participants: In total, 17,408 patients with a diagnosis of ADHD were observed from January 1, 2006, through December 31, 2009, for serious transport accidents documented in Swedish national registers. The association between ADHD and accidents was estimated with Cox proportional hazards regression. To study the effect of ADHD medication, we used stratified Cox regression to compare the risk of accidents during the medication period with the risk during the nonmedication period within the same patients.Main outcomes and measures: Serious transport accident, identified as an emergency hospital visit or death due to transport accident.Results: Compared with individuals without ADHD, male patients with ADHD (adjusted hazard ratio, 1.47; 95% CI, 1.32-1.63) and female patients with ADHD (1.45; 1.24-1.71) had an increased risk of serious transport accidents. In male patients with ADHD, medication was associated with a 58% risk reduction (hazard ratio, 0.42; 95% CI, 0.23-0.75), but there was no statistically significant association in female patients. Estimates of the population-attributable fractions suggested that 41% to 49% of the accidents in male patients with ADHD could have been avoided if they had been receiving treatment during the entire follow-up.Conclusions and relevance: Attention-deficit/hyperactivity disorder is associated with an increased risk of serious transport accidents, and this risk seems to be possibly reduced by ADHD medication, at least among male patients. This should lead to increased awareness among clinicians and patients of the association between serious transport accidents and ADHD medication.
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9.
  • Chang, Zheng, et al. (författare)
  • Stimulant ADHD medication and risk for substance abuse
  • 2014
  • Ingår i: Journal of Child Psychology and Psychiatry. - Hoboken, USA : Wiley-Blackwell. - 0021-9630 .- 1469-7610. ; 55:8, s. 878-885
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There are persistent concerns of long-term effects of stimulant ADHD medication on the development of substance abuse.Methods: Using Swedish national registers, we studied all individuals born between 1960 and 1998 and diagnosed with ADHD (26,249 men and 12,504 women). We investigated the association between stimulant ADHD medication in 2006 and substance abuse during 2009. Substance abuse was indexed by substance-related death, crime, or hospital visits.Results: ADHD medication was not associated with increased rate of substance abuse. Actually, the rate during 2009 was 31% lower among those prescribed ADHD medication in 2006, even after controlling for medication in 2009 and other covariates (hazard ratio: 0.69; 95% confidence interval: 0.57-0.84). Also, the longer the duration of medication, the lower the rate of substance abuse. Similar risk reductions were suggested among children and when investigating the association between stimulant ADHD medication and concomitant short-term abuse.Conclusions: We found no indication of increased risks of substance abuse among individuals prescribed stimulant ADHD medication; if anything, the data suggested a long-term protective effect on substance abuse. Although stimulant ADHD medication does not seem to increase the risk for substance abuse, clinicians should remain alert to the potential problem of stimulant misuse and diversion in ADHD patients.
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10.
  • Chang, Zheng, et al. (författare)
  • Substance use disorders, psychiatric disorders, and mortality after release from prison : a nationwide longitudinal cohort study
  • 2015
  • Ingår i: Lancet psychiatry. - : Elsevier. - 2215-0374 .- 2215-0366. ; 2:5, s. 422-430
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: High mortality rates have been reported in people released from prison compared with the general population. However, few studies have investigated potential risk factors associated with these high rates, especially psychiatric determinants. We aimed to investigate the association between psychiatric disorders and mortality in people released from prison in Sweden.METHODS: We studied all people who were imprisoned since Jan 1, 2000, and released before Dec 31, 2009, in Sweden for risks of all-cause and external-cause (accidents, suicide, homicide) mortality after prison release. We obtained data for substance use disorders and other psychiatric disorders, and criminological and sociodemographic factors from population-based registers. We calculated hazard ratios (HRs) by Cox regression, and then used them to calculate population attributable fractions for post-release mortality. To control for potential familial confounding, we compared individuals in the study with siblings who were also released from prison, but without psychiatric disorders. We tested whether any independent risk factors improved the prediction of mortality beyond age, sex, and criminal history.FINDINGS: We identified 47,326 individuals who were imprisoned. During a median follow-up time of 5·1 years (IQR 2·6-7·5), we recorded 2874 (6%) deaths after release from prison. The overall all-cause mortality rate was 1205 deaths per 100,000 person-years. Substance use disorders significantly increased the rate of all-cause mortality (alcohol use: adjusted HR 1·62, 95% CI 1·48-1·77; drug use: 1·67, 1·53-1·83), and the association was independent of sociodemographic, criminological, and familial factors. We identified no strong evidence that other psychiatric disorders increased mortality after we controlled for potential confounders. In people released from prison, 925 (34%) of all-cause deaths in men and 85 (50%) in women were potentially attributable to substance use disorders. Substance use disorders were also an independent determinant of external-cause mortality, with population attributable fraction estimates at 42% in men and 70% in women. Substance use disorders significantly improved the prediction of external-cause mortality, in addition to sociodemographic and criminological factors.INTERPRETATION: Interventions to address substance use disorders could substantially decrease the burden of excess mortality in people released from prison, but might need to be provided beyond the immediate period after release.
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