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Skoog, P., Larsson, H., Magnuson, A., Troëng, T. & Norgren, L. (2025). Changes in Sex Related Mortality after Revascularisation for Chronic Limb Threatening Ischaemia: A National Observational Study 1994 - 2018. European Journal of Vascular and Endovascular Surgery, 69(1), 130-137
Open this publication in new window or tab >>Changes in Sex Related Mortality after Revascularisation for Chronic Limb Threatening Ischaemia: A National Observational Study 1994 - 2018
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2025 (English)In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 69, no 1, p. 130-137Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The aim of this study was compare all cause mortality across three time periods with a focus on sex differences after revascularisation for chronic limb threatening ischaemia between 1994 and 2013 in Sweden.

METHODS: In this observational registry study, patients registered in the Swedish vascular registry (Swedvasc), revascularised between 1994 and 2013 with open or endovascular infra-inguinal procedures, were divided into three time periods: 1994 - 1999, 2000 - 2006, and 2007 - 2013. Patients were followed for five years. Poisson regression was used to compare 30 day mortality, presented as adjusted relative risk ratio (aRR). Adjusted restricted mean survival time (aRMST) differences at five years were compared with a generalised linear model. The analyses were adjusted for age, comorbidities, and endovascular or open surgery. Comparison with the general Swedish population was also conducted with age adjusted standardised mortality ratios. Results are presented with the 95% confidence intervals (CI).

RESULTS: The study showed increasing 30 day mortality, with an aRR of 1.47 (95% CI 1.31 - 1.65) for women and aRR of 1.20 (95% CI 1.06 - 1.35) for men, per time period. In women, the five year RMST decreased from the first to the third period, with an aRMST of -45 (95% CI -59 - -32) days per period. In men, the aRMST increased 32 (95% CI 18 - 47) days per period. When comparing sexes, women showed lower 30 day mortality and higher five year survival than men in the first time period, but a significantly worse development over time periods than for men. Corresponding findings were observed in comparison with the general Swedish population.

CONCLUSION: This study showed an increased 30 day mortality in women and men across the periods, most evident in women. Men showed an increased five year survival across the periods, whereas opposite findings were recorded for women. The dismal trend over time for women could not be explained by increased age or a higher prevalence of comorbidities.

Place, publisher, year, edition, pages
Elsevier, 2025
Keywords
Chronic limb threatening ischaemia, Longitudinal studies, Mortality, Revascularisation
National Category
Surgery
Identifiers
urn:nbn:se:oru:diva-115800 (URN)10.1016/j.ejvs.2024.08.046 (DOI)39237054 (PubMedID)2-s2.0-85204545255 (Scopus ID)
Available from: 2024-09-06 Created: 2024-09-06 Last updated: 2025-01-15Bibliographically approved
Garcia-Argibay, M., Chang, Z., Brikell, I., Kuja-Halkola, R., D'Onofrio, B. M., Lichtenstein, P., . . . Cortese, S. (2025). Evaluating ADHD medication trial representativeness: a Swedish population-based study comparing hypothetically trial-eligible and trial-ineligible individuals. Paper presented at 2025/01/06. Lancet psychiatry
Open this publication in new window or tab >>Evaluating ADHD medication trial representativeness: a Swedish population-based study comparing hypothetically trial-eligible and trial-ineligible individuals
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2025 (English)In: Lancet psychiatry, ISSN 2215-0374, E-ISSN 2215-0366Article in journal (Refereed) Published
Abstract [en]

Background

Randomised controlled trials (RCTs) evaluating ADHD medications often use strict eligibility criteria, potentially limiting generalisability to patients in real-world clinical settings. We aimed to identify the proportion of individuals with ADHD who would be ineligible for medication RCTs and evaluate differences in treatment patterns and clinical and functional outcomes between RCT-eligible and RCT-ineligible individuals.

Methods

We used multiple Swedish national registries to identify individuals with ADHD, aged at least 4 years at the age of diagnosis, initiating pharmacological treatment between Jan 1, 2007, and Dec 31, 2019, with follow-up up to Dec 31, 2020. Hypothetical RCT ineligibility was established using exclusion criteria from the international MED-ADHD dataset, including 164 RCTs of ADHD medications. Cox models evaluated differences in medication switching and discontinuation within 1 year between eligible and ineligible individuals. Quasi-Poisson models compared eligible and ineligible individuals on rates of psychiatric hospitalisations, injuries or accidents, and substance use disorder within 1 year of initiating ADHD medications. People with lived experience of ADHD were not involved in the research and writing process.

Findings

Of 189 699 individuals included in the study cohort (112 153 men and boys [59%] and 77 546 women and girls [41%]; mean age 21·52 years [SD 12·83; range 4–68]) initiating ADHD medication, 53% (76 477 [74%] of 103 023 adults [aged >17 years], 12 658 [35%] of 35 681 adolescents [aged 13–17 years], and 10 643 [21%] of 50 995 children [aged <13 years]) would have been ineligible for RCT participation. Ethnicity data were not available. Ineligible individuals had a higher likelihood of treatment switching (hazard ratio 1·14, 95% CI 1·12–1·16) and a decreased likelihood of medication discontinuation (0·96, 0·94–0·98) compared with eligible individuals. Individuals ineligible for RCTs had significantly higher rates of psychiatric hospitalisations (ncidence rate ratio 9·68, 95% CI 9·57–9·78) and specialist care visits related to substance use disorder (14·78, 14·64–14·91), depression (6·00, 5·94–6·06), and anxiety (11·63, 11·56–11·69).

Interpretation

Individuals ineligible for ADHD medication trials face higher risks of adverse outcomes. This study provides the first empirical evidence for the limited generalisability of ADHD RCTs to real-world clinical populations, by applying eligibility criteria extracted from a comprehensive dataset of RCTs to a large real-world cohort. Triangulating evidence from RCTs and real-world studies is crucial to inform rigorous evidence-based treatment guidelines.

Place, publisher, year, edition, pages
Elsevier, 2025
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-118003 (URN)10.1016/S2215-0366(24)00396-1 (DOI)39788146 (PubMedID)
Conference
2025/01/06
Funder
Swedish Research Council, 2022–01119EU, Horizon 2020, 965381
Available from: 2025-01-07 Created: 2025-01-07 Last updated: 2025-01-10Bibliographically approved
Nguyen, T.-D., Meijsen, J. J., Sigström, R., Kuja-Halkola, R., Xiong, Y., Harder, A., . . . Lu, Y. (2025). Genetic insights into psychotic major depressive disorder: bridging the mood-psychotic disorder spectrum. EBioMedicine, 112, Article ID 105576.
Open this publication in new window or tab >>Genetic insights into psychotic major depressive disorder: bridging the mood-psychotic disorder spectrum
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2025 (English)In: EBioMedicine, E-ISSN 2352-3964, Vol. 112, article id 105576Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND: Psychotic major depressive disorder (MDD), a subtype of MDD characterised by psychotic symptoms that occur exclusively during mood episode, is clinically significant yet underexplored genetically due to its rarity. This study comprehensively examines the genetic basis of psychotic MDD and elucidates its position within the mood-psychotic spectrum.

METHODS: This population-based cohort study used Swedish and Danish registry data for over 5.1 M individuals born between 1958 and 1993/1996. Specialist-diagnosed psychotic MDD was defined using ICD-10 sub-codes of MDD, F32.2/F32.3. We estimated familial aggregation/coaggregation using generalised estimating equations, heritability and genetic correlations using structural equation modelling. We also analysed ∼30,000 genotyped MDD cases from the UK Biobank and a Swedish cohort to explore which polygenic risk score (PRS) may predispose individuals to psychotic MDD.

FINDINGS: With over 10,000 psychotic MDD identified from the two nationwide patient registers, this study highlights the familial aggregation of psychotic MDD, co-aggregation with mood and psychotic disorders, and its stronger genetic correlation with schizophrenia compared to non-psychotic MDD. The familial risks increased with closer biological relatedness, suggesting genetic influence. Pedigree-heritability of psychotic MDD was 30.17% (95% CI 23.53-36.80%). While the genetic correlation between psychotic and non-psychotic MDD was high (0.82, 95% CI 0.73-0.92), the psychotic subgroup showed a higher genetic correlation with schizophrenia than non-psychotic MDD (0.67 vs 0.46, p-value 7.55∗10-4). Within 30,000 genotyped MDD cases, individuals with psychotic MDD had higher mean PRS for schizophrenia and BD but a lower MDD PRS than non-psychotic MDD. PRS for BD type-I was associated with increased odds of psychotic MDD, while BD type-II PRS showed no significant association with psychotic MDD.

INTERPRETATION: This study provides evidence for the genetic basis of psychotic MDD, underscoring its unique position bridging the spectrum of mood and psychotic disorders. These findings advance our understanding of the aetiology of psychotic MDD and contribute to the limited body of evidence on this phenotype by utilising large-scale population-based data.

Place, publisher, year, edition, pages
Elsevier, 2025
Keywords
Epidemiology, Genetic, Psychotic disorders, Psychotic major depressive disorder
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-119177 (URN)10.1016/j.ebiom.2025.105576 (DOI)39889373 (PubMedID)2-s2.0-85216379962 (Scopus ID)
Funder
EU, European Research CouncilEU, Horizon 2020Swedish Research CouncilSwedish Foundation for Strategic ResearchThe Swedish Brain Foundation
Note

Funding Agencies:

European Research Council

US National Institutes of Mental Health

European Union Horizon 2020 Program

Swedish Research Council

Research Council of Norway

Swedish Foundation for Strategic Research

Hjärnfonden

Available from: 2025-02-07 Created: 2025-02-07 Last updated: 2025-02-07Bibliographically approved
Holmberg, A., Pol-Fuster, J., Kuja-Halkola, R., Larsson, H., Lichtenstein, P., Chang, Z., . . . Fernández de la Cruz, L. (2025). Multigenerational family coaggregation study of obsessive-compulsive disorder and cardiometabolic disorders. BMJ Mental Health, 28(1), Article ID e301323.
Open this publication in new window or tab >>Multigenerational family coaggregation study of obsessive-compulsive disorder and cardiometabolic disorders
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2025 (English)In: BMJ Mental Health, E-ISSN 2755-9734, Vol. 28, no 1, article id e301323Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Obsessive-compulsive disorder (OCD) is associated with an increased risk of morbidity and mortality due to cardiometabolic disorders. Whether this association is driven by familial factors is unknown. This population-based family study explored the familial co-aggregation of OCD and cardiometabolic disorders.

METHODS: We identified 6 049 717 individuals born in Sweden between 1950 and 2008, including 50 212 individuals with OCD, and followed them up to 2020. These individuals were linked to their mothers, fathers, full siblings, maternal and paternal half siblings, aunts, uncles and cousins. We estimated the risk of cardiovascular diseases (CVD) and metabolic disorders (including obesity, type 2 diabetes and hyperlipidaemia), comparing the relatives of probands with and without OCD. Cox proportional hazards regression models, incorporating time-varying exposures, estimated HRs.

RESULTS: OCD was associated with an increased risk of CVD (HR 1.47; 95% CI 1.43 to 1.51), obesity (HR 1.69; 95% CI 1.63 to 1.74), type 2 diabetes (HR 2.01; 95% CI 1.90 to 2.12) and hyperlipidaemia (HR 1.42; 95% CI 1.33 to 1.52). The relatives of probands with OCD exhibited small increased risks of CVD (HRs from 1.01 to 1.11) and obesity (HRs from 1.03 to 1.20). Slightly increased risks for type 2 diabetes were observed in mothers (HR 1.11; 95% CI 1.07 to 1.15) and full siblings (HR 1.12; 95% CI 1.05 to 1.20), while for hyperlipidaemia it was only observed in mothers (HR 1.06; 95% CI 1.02 to 1.10).

CONCLUSIONS: Our results do not support a major contribution of familial factors to the association between OCD and cardiometabolic disorders, suggesting a more prominent role of unique environmental factors.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2025
Keywords
PSYCHIATRY
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-118754 (URN)10.1136/bmjment-2024-301323 (DOI)001400780300001 ()39832837 (PubMedID)2-s2.0-85215868577 (Scopus ID)
Funder
Swedish Research Council, 2022-00510_VR
Available from: 2025-01-22 Created: 2025-01-22 Last updated: 2025-01-31Bibliographically approved
Madsen, M. G., Zhu, J. L., Munk-Olsen, T., Wimberley, T., Larsson, H., Rommel, A.-S., . . . Madsen, K. B. (2025). Prevalence and Temporal Trends of Attention Deficit Hyperactivity Disorder Medication Fills During Pregnancy and Breastfeeding in Denmark. Pediatric Drugs
Open this publication in new window or tab >>Prevalence and Temporal Trends of Attention Deficit Hyperactivity Disorder Medication Fills During Pregnancy and Breastfeeding in Denmark
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2025 (English)In: Pediatric Drugs, ISSN 1174-5878, E-ISSN 1179-2019Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND AND OBJECTIVES: Females of reproductive age are increasingly using attention deficit hyperactivity disorder (ADHD) medication, but its use during pregnancy and breastfeeding is largely unknown. The aim of this study is to examine the prevalence of ADHD medication fills during pregnancy and breastfeeding, including characteristics of these females and cohort differences over time.

METHODS: We conducted a descriptive study using Danish nationwide registers. Within cohorts of pregnant and breastfeeding females, we calculated the prevalence of ADHD medication (methylphenidate, amphetamine, dexamfetamine, lisdexamfetamine, modafinil, atomoxetine, clonidine and guanfacine) fills and described sociodemographic and clinical characteristics across groups with fills, no fills and previous fills. Cohort differences in ADHD medication fills during pregnancy for 2005-2010, 2011-2016 and 2017-2022 were examined.

RESULTS: In this cohort of 1,077,279 pregnancies, ADHD medication fills increased from 0.08 to 7.71 per 1000 individuals between 2005 and 2022. Among 446,485 breastfeeding females, fills increased from 0.55 to 3.67 per 1000 individuals from 2012 to 2022. Compared with the group with no fills, females filling ADHD medication during pregnancy and breastfeeding were younger, had lower levels of education, were more often smoking during pregnancy, utilised more psychiatric healthcare and had concurrent fills of other psychotropic medication. Cohort differences over time revealed that females filling ADHD medication during pregnancy in 2017-2022 were older, had higher levels of education, smoked less during pregnancy, had fewer psychiatric contacts and were less likely to fill other psychotropic medications compared with females in the earlier cohorts.

CONCLUSIONS: Results showed an increasing prevalence of ADHD medication fills during pregnancy and breastfeeding in Denmark over time, surpassing the increase observed generally in females of reproductive age filling ADHD medication. Results revealed a difference in characteristics of females filling ADHD medication during pregnancy over time, suggesting a shift in pregnancy treatment patterns.

Place, publisher, year, edition, pages
Adis International Ltd., 2025
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-118352 (URN)10.1007/s40272-024-00671-5 (DOI)001395854000001 ()39806199 (PubMedID)
Note

Funding Agencies:

Open access funding provided by Aarhus Universitet. This study was funded by Sygeforsikring ‘danmark’ (journalnr. 2021–0139). Partial financial support was also received from the National Institute of Mental Health (NIMH) (R01MH122869).

Available from: 2025-01-14 Created: 2025-01-14 Last updated: 2025-01-28Bibliographically approved
Kuja-Halkola, R., Henningsohn, L., Zietsch, B., Larsson, H. & Cederlöf, M. (2025). Risk of childlessness in help-seeking men with Peyronie's disease: A Swedish longitudinal study. PLOS ONE, 20(1), Article ID e0315948.
Open this publication in new window or tab >>Risk of childlessness in help-seeking men with Peyronie's disease: A Swedish longitudinal study
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2025 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 20, no 1, article id e0315948Article in journal (Refereed) Published
Abstract [en]

Peyronie's disease (PD) is a disorder of the penis that is associated with poor mental health, lowered psychosocial- and sexual wellbeing, which may increase the risk of childlessness in men affected by the disorder. Although this is an issue of significant clinical importance, it has not been addressed in research to date. We conducted a longitudinal cohort study based on data from Swedish national registers utilizing a large sample of help-seeking men with PD, along with matched subjects from the general population. We assessed the probability and odds ratio of childlessness, modeled with logistic regressions, and offspring rate ratio, modeled with Poisson regression. We found that the probability of childlessness was somewhat lowered for men with PD aged between 35 and 71 years at end of follow-up. Men with PD aged 35 or less showed slightly elevated probabilities of childlessness. Specifically, odds ratios for childlessness were between 0.5 and 1.0 for men aged above 35, and between 1 and 1.5 for men aged less than 35, although the confidence intervals for increased odds partly included the null. Analyses of men's rate of offspring showed similar pattern, with higher rate ratios for older men and lower for younger men. Although more research is needed, the findings of this study suggest that clinical urological practice may be enhanced by a proactive discussions about the potential issue of childlessness in younger men with PD.

Place, publisher, year, edition, pages
Public Library of Science (PLoS), 2025
National Category
Public Health, Global Health and Social Medicine
Identifiers
urn:nbn:se:oru:diva-118998 (URN)10.1371/journal.pone.0315948 (DOI)39883718 (PubMedID)
Funder
Riksbankens Jubileumsfond, P21-0226
Available from: 2025-01-31 Created: 2025-01-31 Last updated: 2025-01-31Bibliographically approved
Solmi, M., Croatto, G., Fabiano, N., Wong, S., Gupta, A., Fornaro, M., . . . Correll, C. U. (2025). Sex-stratified mortality estimates in people with schizophrenia: A systematic review and meta-analysis of cohort studies of 2,700,825 people with schizophrenia. European Neuropsychopharmacology, 91, 56-66
Open this publication in new window or tab >>Sex-stratified mortality estimates in people with schizophrenia: A systematic review and meta-analysis of cohort studies of 2,700,825 people with schizophrenia
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2025 (English)In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 91, p. 56-66Article, review/survey (Refereed) Published
Abstract [en]

The differential influence of sex on premature mortality in schizophrenia is unclear. This study assessed the differences in all-cause and specific cause mortality risks in people with schizophrenia compared to several control groups stratified by sex. We conducted a PRISMA 2020-compliant systematic review and random-effects meta-analysis of cohort studies assessing mortality relative risk (RR) for people with schizophrenia, comparing by sex. We measured publication bias and conducted a quality assessment through the Newcastle-Ottawa scale. We meta-analyzed 43 studies reporting on 2,700,825 people with schizophrenia. Both males and females with schizophrenia had increased all-cause mortality vs. comparison groups (males, RR=2.62, 95%CI 2.35-2.92; females, RR=2.56, 95%CI 2.27-2.87), suicide (males, RR=9.02, 95%CI 5.96-13.67; females, RR=12.09, 95%CI 9.00-16.25), and natural cause mortality (males, RR=2.11, 95%CI 1.88-2.38; females, RR=2.14, 95%CI 1.93-2.38). No statistically significant differences in sex-dependent mortality risk emerged. There was an age-group-dependent increased mortality risk in females < 40 years vs. >/=40 years old (RR=4.23/2.17), and significantly higher risk of death due to neurological disorders (dementia) in males vs. females (RR=5.19/2.40). Increased mortality risks were often associated with specific modifiable risk factors. The increased mortality risk did not improve over time, calling for more studies to identify modifiable factors, and for better physical healthcare for males and females with schizophrenia.

Place, publisher, year, edition, pages
Elsevier, 2025
Keywords
Antipsychotic, Meta-analysis, Mortality, Schizophrenia, Sex, Systematic review
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-117655 (URN)10.1016/j.euroneuro.2024.11.001 (DOI)001373462600001 ()39626570 (PubMedID)2-s2.0-85210747597 (Scopus ID)
Note

Forskningsöversikt.

Available from: 2024-12-11 Created: 2024-12-11 Last updated: 2025-01-24Bibliographically approved
Pol-Fuster, J., Fernández de la Cruz, L., Beucke, J., Hesselmark, E., Crowley, J. J., de Schipper, E., . . . Mataix-Cols, D. (2024). A population-based multigenerational family co-aggregation study of severe infections and obsessive-compulsive disorder. Biological Psychiatry
Open this publication in new window or tab >>A population-based multigenerational family co-aggregation study of severe infections and obsessive-compulsive disorder
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2024 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND: Postinfectious autoimmune processes have been proposed as potential causal factors for obsessive-compulsive disorder (OCD). This large population-based study aimed to clarify the co-aggregation pattern between severe infections and OCD across clusters of relatives with varying degrees of relatedness.

METHODS: We identified 4,916,898 individuals born in Sweden between 1960 and 2008 and followed them until 2020. Each individual was linked to their first- and second-degree relatives, including monozygotic (MZ) and dizygotic (DZ) twins, mothers, fathers, full siblings, maternal and paternal half siblings, aunts, uncles, and cousins. OCD and infection diagnoses from inpatient and specialized outpatient units were retrieved from the Swedish National Patient Register. We compared the risk of OCD in relatives of probands with severe infections to those of probands without severe infections. Cox proportional hazard regression models, incorporating time-varying exposures, were used to estimate hazard ratios (HRs). Dose-response associations were examined using logistic regression models.

RESULTS: Relatives of probands with severe infections exhibited a higher risk of OCD, increasing with genetic relatedness, with HRs (95% CI) ranging from 1.46 (1.07-1.98) in MZ twins to 1.10 (1.09-1.11) in cousins. The results remained robust after adjusting for severe infections among relatives, OCD in probands, and comorbid autoimmune disorders in both probands and relatives. A dose-response association was observed between the number of infections in the probands and their odds of OCD, as well as in their relatives.

CONCLUSIONS: The results strongly suggest that the association between severe infections and OCD may be largely driven by shared genetic factors.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
OCDTWIN study, Obsessive-compulsive disorder, PANDAS, PANS, co-aggregation study, cohort study, severe infections
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-116090 (URN)10.1016/j.biopsych.2024.09.004 (DOI)39284402 (PubMedID)2-s2.0-85208684690 (Scopus ID)
Funder
The Swedish Brain Foundation, FO2017-0154The Swedish Brain Foundation, FO2020-0139Region Stockholm, 20200137Åke Wiberg Foundation, M19-0401Åke Wiberg Foundation, M20-0013Åke Wiberg Foundation, M21-0097
Note

Funded by a Breakthrough Grant from the International OCD Foundation (Mataix-Cols), the Swedish Brain Foundation (Hjärnfonden; Mataix-Cols, reference numbers FO2017-0154 and FO2020-0139), Region Stockholm, ALF Medicine funding program (Mataix-Cols, reference number 20200137), the Swedish Åke Wiberg’s Foundation (Åke Wibergs Stiftelse; Fernández de la Cruz, reference numbers M19-0401, M20-0013, and M21-0097), and a post-doctoral research grant from the German Research Foundation (Beucke, reference number BE5964/1-1). 

Available from: 2024-09-18 Created: 2024-09-18 Last updated: 2025-01-20Bibliographically approved
Brikell, I., Yao, H., Li, L., Astrup, A., Gao, L., Gillies, M. B., . . . Chang, Z. (2024). ADHD medication discontinuation and persistence across the lifespan: a retrospective observational study using population-based databases. Lancet psychiatry, 11(1), 16-26
Open this publication in new window or tab >>ADHD medication discontinuation and persistence across the lifespan: a retrospective observational study using population-based databases
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2024 (English)In: Lancet psychiatry, ISSN 2215-0374, E-ISSN 2215-0366, Vol. 11, no 1, p. 16-26Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Although often intended for long-term treatment, discontinuation of medication for ADHD is common. However, cross-national estimates of discontinuation are missing due to the absence of standardised measures. The aim of this study was to determine the rate of ADHD treatment discontinuation across the lifespan and to describe similarities and differences across countries to guide clinical practice.

METHODS: We did a retrospective, observational study using population-based databases from eight countries and one Special Administrative Region (Australia, Denmark, Hong Kong, Iceland, the Netherlands, Norway, Sweden, the UK, and the USA). We used a common analytical protocol approach and extracted prescription data to identify new users of ADHD medication. Eligible individuals were aged 3 years or older who had initiated ADHD medication between 2010 and 2020. We estimated treatment discontinuation and persistence in the 5 years after treatment initiation, stratified by age at initiation (children [age 4-11 years], adolescents [age 12-17 years], young adults [age 18-24 years], and adults [age ≥25 years]) and sex. Ethnicity data were not available.

FINDINGS: 1 229 972 individuals (735 503 [60%] males, 494 469 females [40%]; median age 8-21 years) were included in the study. Across countries, treatment discontinuation 1-5 years after initiation was lowest in children, and highest in young adults and adolescents. Within 1 year of initiation, 65% (95% CI 60-70) of children, 47% (43-51) of adolescents, 39% (36-42) of young adults, and 48% (44-52) of adults remained on treatment. The proportion of patients discontinuing was highest between age 18 and 19 years. Treatment persistence for up to 5 years was higher across countries when accounting for reinitiation of medication; at 5 years of follow-up, 50-60% of children and 30-40% of adolescents and adults were covered by treatment in most countries. Patterns were similar across sex.

INTERPRETATION: Early medication discontinuation is prevalent in ADHD treatment, particularly among young adults. Although reinitiation of medication is common, treatment persistence in adolescents and young adults is lower than expected based on previous estimates of ADHD symptom persistence in these age groups. This study highlights the scope of medication treatment discontinuation and persistence in ADHD across the lifespan and provides new knowledge about long-term ADHD medication use.

FUNDING: European Union Horizon 2020 Research and Innovation Programme.

Place, publisher, year, edition, pages
Elsevier, 2024
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-110005 (URN)10.1016/S2215-0366(23)00332-2 (DOI)38035876 (PubMedID)2-s2.0-85178365504 (Scopus ID)
Funder
EU, Horizon 2020
Available from: 2023-12-01 Created: 2023-12-01 Last updated: 2024-01-12Bibliographically approved
Li, L., Zhu, N., Zhang, L., Kuja-Halkola, R., D'Onofrio, B. M., Brikell, I., . . . Chang, Z. (2024). ADHD Pharmacotherapy and Mortality in Individuals With ADHD. Journal of the American Medical Association (JAMA), 331(10), 850-860
Open this publication in new window or tab >>ADHD Pharmacotherapy and Mortality in Individuals With ADHD
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2024 (English)In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 331, no 10, p. 850-860Article in journal (Refereed) Published
Abstract [en]

IMPORTANCE: Attention-deficit/hyperactivity disorder (ADHD) is associated with increased risks of adverse health outcomes including premature death, but it is unclear whether ADHD pharmacotherapy influences the mortality risk. OBJECTIVE: To investigate whether initiation of ADHD pharmacotherapy was associated with reduced mortality risk in individuals with ADHD. DESIGN,

SETTING, AND PARTICIPANTS: In an observational nationwide cohort study in Sweden applying the target trial emulation framework, we identified individuals aged 6 through 64 years with an incident diagnosis of ADHD from 2007 through 2018 and no ADHD medication dispensation prior to diagnosis. Follow-up started from ADHD diagnosis until death, emigration, 2 years after ADHD diagnosis, or December 31, 2020, whichever came first.

EXPOSURES: ADHD medication initiation was defined as dispensing of medication within 3 months of diagnosis. MAIN OUTCOMES AND MEASURES: We assessed all-cause mortality within 2 years of ADHD diagnosis, as well as natural-cause (eg, physical conditions) and unnatural-cause mortality (eg, unintentional injuries, suicide, and accidental poisonings).

RESULTS: Of 148 578 individuals with ADHD (61 356 females [41.3%]), 84 204 (56.7%) initiated ADHD medication. The median age at diagnosis was 17.4 years (IQR, 11.6-29.1 years). The 2-year mortality risk was lower in the initiation treatment strategy group (39.1 per 10 000 individuals) than in the noninitiation treatment strategy group (48.1 per 10 000 individuals), with a risk difference of -8.9 per 10 000 individuals (95% CI, -17.3 to -0.6). ADHD medication initiation was associated with significantly lower rate of all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.70 to 0.88) and unnatural-cause mortality (2-year mortality risk, 25.9 per 10 000 individuals vs 33.3 per 10 000 individuals; risk difference, -7.4 per 10 000 individuals; 95% CI, -14.2 to -0.5; HR, 0.75; 95% CI, 0.66 to 0.86), but not natural-cause mortality (2-year mortality risk, 13.1 per 10 000 individuals vs 14.7 per 10 000 individuals; risk difference, -1.6 per 10 000 individuals; 95% CI, -6.4 to 3.2; HR, 0.86; 95% CI, 0.71 to 1.05).

CONCLUSIONS AND RELEVANCE: Among individuals diagnosed with ADHD, medication initiation was associated with significantly lower all-cause mortality, particularly for death due to unnatural causes.

Place, publisher, year, edition, pages
American Medical Association (AMA), 2024
National Category
Psychiatry
Identifiers
urn:nbn:se:oru:diva-112412 (URN)10.1001/jama.2024.0851 (DOI)001217012900004 ()38470385 (PubMedID)2-s2.0-85187789072 (Scopus ID)
Funder
Ekhaga Foundation, 2021-59Olle Engkvists stiftelse, 218-0049Forte, Swedish Research Council for Health, Working Life and Welfare, 2019-01172; 2022-01111EU, Horizon 2020, 965381
Available from: 2024-03-19 Created: 2024-03-19 Last updated: 2024-05-24Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-6851-3297

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