| 1. |
- Lagerberg, Tyra
(författare)
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Behavioural outcomes of treatment with selective serotonin reuptake inhibitors
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mood and anxiety disorders are some of the biggest contributors to morbidity worldwide, and may be lethal. Appropriate treatment is therefore paramount. Antidepressant medications constitute the primary pharmacological treatment for these disorders, with selective serotonin reuptake inhibitors (SSRIs) as the most common type in several Western countries. While developed to treat disorders that increase the risk of violence and suicide, there is concern that SSRI treatment may in itself increase the risk for these behavioural outcomes, especially among young people. The overarching aim of this thesis is therefore to contribute to the understanding of the risks and benefits of treatment with SSRIs in relation to severe behavioural outcomes in different age groups, including when SSRIs are combined with other central nervous system (CNS) drugs. We also document antidepressant prescription patterns in young individuals – the age group where the balance between benefits and risks of antidepressant treatment is least clear. In study I, we described the prevalence of antidepressant use and polypharmacy of CNS drugs with antidepressants over time in children, adolescents, and young adults living in Sweden. We found that, over time, there was an increasing trend in antidepressant use and an increase in the co-prescription of antidepressants with other CNS drugs. We also found that antidepressant users had higher likelihood than population controls of collecting other CNS drug classes additionally to antidepressants. In Study II, we investigated the hazard of conviction for violent crimes during treatment with SSRIs, including in different time periods since start and end of treatment. In a follow-up of up to 8 years, we found that the hazard of violent crime was statistically significantly elevated throughout treatment periods, and for up to 12 weeks after the end of treatment. This was true in youths as well as older adults, which adds to prior research that has found elevated risk of aggression outcomes during SSRI treatment in young adults but not older individuals. In Study III, we explored the incidence rate of suicide attempts or deaths (suicidal behaviour) in time periods before and after initiation of SSRI treatment. We found that the month immediately prior to SSRI treatment initiation was associated with the greatest incidence rate of suicidal behaviour, that treatment periods up to one year after treatment initiation were associated with lower incidence rate compared to the month immediately before initiation, and that the incidence rate gradually decreased over treatment time. However, all treated periods had higher incidence rates than the month one year before treatment start. These patterns were consistent across age categories, including among children and young adults. In Study IV, we applied a data-driven screening approach to compare the incidence rate of suicidal behaviour in periods after and before initiation of additional CNS drugs during continuous SSRI treatment. We found several drugs that were associated with statistically significantly reduced incidence rate of suicidal behaviour when initiated during SSRI treatment, and only two associated with increased risk of suicidal behaviour. We found no evidence of harmful effects of combining SSRIs with additional CNS drugs. Many of the signals of reduced suicidal behaviour correspond to prior evidence; novel signals could be further investigated to evaluate the use of these drugs concurrently with SSRI treatment. In conclusion, the presented thesis has documented: the increasing prevalence of antidepressant use and polypharmacy of antidepressants with other CNS drugs in young individuals resident in Sweden; the associations between SSRI use and violent crime and suicidal behaviour; and the impact of initiating other CNS drugs during SSRI treatment on the risk for suicidal behaviour. The findings are expected to help guide future research and clinical decision making.
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| 2. |
- Leone, Marica, et al.
(författare)
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MELATONIN USE AND THE RISK OF SELF-HARM AND UNINTENTIONAL INJURIES IN YOUTHS
- 2022
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Ingår i: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 63, s. E113-E113
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Sleep disorders in youth have been associated with increased risks of injury, including suicidal behavior. This study investigated whether melatonin, which is themost common medication for sleep disturbances in youth in Sweden, is associated with a decreased risk of injury.Methods: This population-based cohort study included 25,575 youths who initiated melatonin treatment between ages 6 and 18. Poisson regression was used to estimate rate of injuries in the year prior to and following melatonin-treatment initiation. A within-individual design was used to estimate relative risks by comparing injury risk in the last unmedicated month with injury risks in the 12 months after medication initiation. Analyses were stratified by sex, in-jury type, psychiatric comorbidities, and age at melatonin-treatment initiation.Results: While body injuries, falls, and transport accident rates were comparable in the year before and after melatonin-treatment initiation, the risk of self-injurious behavior was highest in the months immediately prior medication and decreased thereafter. This was particularly prominent among adolescents with depression and/or anxiety, with females displaying greater absolute risks than males. Compared to the last unmedicated month, the 12 months post medication initiation had decreased relative risks for self-harm, with an IRR [95% CI] in the month following melatonin-treatment initiation of 0.46 [0.27-0.76] among adolescent females with psychiatric disorders, after excluding antidepressant users.Discussion: Decreased risk of intentional injury was observed following melatonin-treatment initiation among females with depression and anxiety, suggesting that sleep interventions could be considered in an effort to reduce risk of self-injurious behavior in this population.
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| 3. |
- Leone, Marica, et al.
(författare)
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Melatonin use and the risk of self-harm and unintentional injuries in youths with and without psychiatric disorders
- 2023
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Ingår i: Journal of Child Psychology and Psychiatry. - : John Wiley & Sons. - 0021-9630 .- 1469-7610. ; 64:7, s. 1027-1036
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sleep disorders in youth have been associated with increased risks of injury, including suicidal behavior. This study investigated whether melatonin, which is the most common medication for sleep disturbances in youth in Sweden, is associated with a decreased risk of injury.METHODS: This population-based cohort study included 25,575 youths who initiated melatonin treatment between ages 6 and 18. Poisson regression was used to estimate rate of injuries in the year prior to and following melatonin treatment initiation. A within-individual design was used to estimate relative risks by comparing injury risk in the last unmedicated month with injury risks in the 12 months after medication initiation. Analyses were stratified by sex, injury type, psychiatric comorbidities and age at melatonin-treatment initiation.RESULTS: While body injuries, falls and transport accident rates were comparable in the year before and after melatonin-treatment initiation, the risk of self-harm was highest in the months immediately prior to medication, and decreased thereafter. This was particularly prominent among adolescents with depression and/or anxiety, with females displaying greater absolute risks than males. Compared to the last unmedicated month, the 12 months post medication initiation had decreased relative risks for self-harm, with an IRR [95% CI] in the month following melatonin-treatment initiation of 0.46 [0.27-0.76] among adolescent females with psychiatric disorders, after excluding antidepressant users.CONCLUSIONS: Decreased risk of intentional self-harm was observed following melatonin-treatment initiation among females with depression and anxiety, suggesting that sleep interventions could be considered in an effort to reduce risk of self-harm in this population.
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| 4. |
- Li, Lin, 1989-, et al.
(författare)
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Maternal pre-pregnancy overweight/obesity and the risk of attention-deficit/hyperactivity disorder in offspring : a systematic review, meta-analysis and quasi-experimental family-based study
- 2020
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 49:3, s. 857-875
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Previous studies are inconclusive concerning the association between maternal pre-pregnancy overweight/obesity and risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. We therefore conducted a systematic review and meta-analysis to clarify this association. To address the variation in confounding adjustment between studies, especially inadequate adjustment of unmeasured familial confounding in most studies, we further performed cousin and sibling comparisons in a nationwide population-based cohort in Sweden.METHODS: We searched PubMed, Embase and PsycINFO during 1975-2018. We used random-effects models to calculate pooled risk ratios (RRs) with 95% confidence interval. In the population-based study, Cox proportional hazard models were used to calculate the unadjusted hazard ratios (HRs) and HRs adjusted for all confounders identified in previous studies. Stratified Cox models were applied to data on full cousins and full siblings to further control for unmeasured familial confounding.RESULTS: Eight cohorts with a total of 784 804 mother-child pairs were included in the meta-analysis. Maternal overweight [RRoverweight = 1.31 (1.25-1.38), I2 = 6.80%] and obesity [RRobesity = 1.92 (1.84-2.00), I2 = 0.00%] were both associated with an increased risk of ADHD in offspring. In the population-based cohort of 971 501 individuals born between 1992 and 2004, unadjusted Cox models revealed similar associations [HRoverweight = 1.30 (1.28-1.34), HRobesity = 1.92 (1.87-1.98)]. These associations gradually attenuated towards the null when adjusted for measured confounders [HRoverweight = 1.21 (1.19-1.25), HRobesity = 1.60 (1.55-1.65)], unmeasured factors shared by cousins [HRoverweight = 1.10 (0.98-1.23), HRobesity = 1.44 (1.22-1.70)] and unmeasured factors shared by siblings [HRoverweight = 1.01 (0.92-1.11), HRobesity = 1.10 (0.94-1.27)].CONCLUSION: Pre-pregnancy overweight/obesity is associated with an increased risk of ADHD in offspring. The observed association is largely due to unmeasured familial confounding.
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| 5. |
- Liu, Shengxin, et al.
(författare)
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Psychotropic Medication Use in Children and Adolescents With Type 1 Diabetes
- 2023
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Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Children and adolescents with type 1 diabetes (T1D) face elevated risks of psychiatric disorders. Despite their nonnegligible adverse effects, psychotropic medications are a common cost-effective approach to alleviating psychiatric symptoms, but evidence regarding their dispensation to children and adolescents with T1D remains lacking. OBJECTIVE: To examine the trends and patterns of psychotropic medication dispensation among children and adolescents with T1D in Sweden between 2006 and 2019.DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from multiple Swedish registers. The main study cohort included children and adolescents residing in Sweden from 2006 to 2019 and was followed up until the earliest of December 31, 2019, 18th birthday, emigration, or death. Data analyses were conducted from November 1, 2022, to April 30, 2023.EXPOSURES: Type 1 diabetes.MAIN OUTCOMES AND MEASURES: The primary outcomes were trends and patterns of psychotropic medication dispensation (including antipsychotics, antidepressants, anxiolytics, hypnotics, mood stabilizers, and medications for attention-deficit/hyperactivity disorder [ADHD]), psychotropic medication initiation, and history of neurodevelopmental and psychiatric diagnosis. Cumulative incidence curves and Cox proportional hazard models were used to estimate the aggregated incidence and hazard ratios of medication initiation after diabetes onset. RESULTS: Of 3 723 745 children and adolescents (1 896 199 boys [50.9%]), 13 200 (0.4%; 7242 boys [54.9%]) had T1D (median [IQR] age at diagnosis, 11.1 [7.6-14.7] years). Between 2006 and 2019, psychotropic medication dispensation increased from 0.85% (95% CI, 0.65%-1.10%) to 3.84% (3.11%-4.69%) among children and from 2.72% (95% CI, 2.15%-3.39%) to 13.54% (95% CI, 12.88%-14.23%) among adolescents with T1D, consistently higher than their peers without T1D. The most commonly dispensed medications included hypnotics, ADHD medications, anxiolytics, and selective serotonin reuptake inhibitors, and all exhibited increasing trends. For those with T1D, psychiatric care was the primary prescription source, and up to 50.1% of treatments lasted more than 12 months. In addition, children and adolescents with T1D showed higher cumulative incidence and hazard ratios of medication initiation after diabetes onset than their same-age and same-sex counterparts.CONCLUSIONS AND RELEVANCE: This cohort study found an increasing trend in psychotropic medication dispensation among children and adolescents with T1D from 2006 to 2019, persistently higher than those without T1D. These findings call for further in-depth investigations into the benefits and risks of psychotropic medications within this population and highlight the importance of integrating pediatric diabetes care and mental health care for early detection of psychological needs and careful monitoring of medication use.
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| 6. |
- Virtanen, Suvi, et al.
(författare)
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Antidepressant Use and Risk of Manic Episodes in Children and Adolescents With Unipolar Depression
- 2024
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Ingår i: JAMA Psychiatry. - 2168-622X .- 2168-6238. ; 8081:111, s. 25-33
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Antidepressants are increasingly prescribed to pediatric patients with unipolar depression, but little is known about the risk of treatment-emergent mania. Previous research suggests pediatric patients may be particularly vulnerable to this adverse outcome. OBJECTIVE To estimate whether pediatric patients treated with antidepressants have an increased incidence of mania/hypomania compared with patients not treated with antidepressants and to identify patient characteristics associated with the risk of mania/hypomania. DESIGN, SETTING, AND PARTICIPANTS In a cohort study applying the target trial emulation framework, nationwide inpatient and outpatient care in Sweden from July 1, 2006, to December 31, 2019, was evaluated. Follow-up was conducted for 12 and 52 weeks after treatment initiation, with administrative follow-up ending December 31, 2020. Data were analyzed between May 1, 2022, and June 28, 2023. Individuals aged 4 to 17 years with a diagnosis of depression, but without a prior diagnosis of mania/hypomania, bipolar disorder, or psychosis or treatment with mood stabilizer (lithium, valproate, or carbamazepine), prescriptions were included. EXPOSURES The treatment group included patients who initiated any antidepressant medication within 90 days of diagnosis. The control group included patients who did not initiate antidepressants within 90 days. MAIN OUTCOMES AND MEASURES Diagnosis of mania/hypomania or initiation of mood stabilizer therapy. Incidences were estimated with Kaplan-Meier estimator, and inverse probability of treatment weighting was used to adjust for group differences at baseline. RESULTS The cohort included 43 677 patients (28 885 [66%] girls); 24 573 in the treatment group and 19 104 in the control group. The median age was 15 (IQR, 14-16) years. The outcome occurred in 96 individuals by 12 weeks and in 291 by 52 weeks. The cumulative incidence of mania was 0.26% (95% CI, 0.19%-0.33%) in the treatment group and 0.20% (95% CI, 0.13%-0.27%) in the control group at 12 weeks, with a risk difference of 0.06% (95% CI, −0.04% to 0.16%). At 52 weeks, the cumulative incidence was 0.79% (95% CI, 0.68%-0.91%) in the treatment group and 0.52% (95% CI, 0.40%-0.63%) in the control group (risk difference, 0.28%; 95% CI, 0.12%-0.44%). Hospitalizations, parental bipolar disorder, and use of antipsychotics and antiepileptics were the most important predictors of mania/hypomania by 12 weeks. CONCLUSION This cohort study found no evidence of treatment-emergent mania/hypomania by 12 weeks in children and adolescents. This corresponds to the time frame for antidepressants to exert their psychotropic effect. A small risk difference was found only with longer follow-up. Certain patient characteristics were associated with mania/hypomania, which warrants clinical attention.
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| 7. |
- Virtanen, Suvi, et al.
(författare)
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Association of selective serotonin reuptake inhibitor (SSRI) treatment with acute substance misuse outcomes
- 2022
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Ingår i: Addiction. - : Blackwell Publishing. - 0965-2140 .- 1360-0443. ; 117:1, s. 234-242
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed medications for patients with anxiety/depression. These patients often have problems with substance use, but it remains unclear whether the risk of substance misuse is influenced by SSRI treatment. We aimed to determine whether SSRI treatment is associated with a decreased risk of acute substance misuse-related outcomes.DESIGN: Cohort study following individuals through Swedish nationwide registers between July 2005 and December 2013 and comparing the risk of substance misuse outcomes during periods on- versus off-treatment within the same individual.SETTING: Swedish general population.PARTICIPANTS: Individuals with a new dispensed prescription of SSRIs between July 2006 and December 2013, and an ICD-10 diagnosis of anxiety/depressive disorder before the first treatment initiation. The cohort included 146,114 individuals (60.7% women).MEASUREMENTS: Substance misuse outcomes included ICD-10 diagnoses of acute intoxications (F10.0-F19.0), accidental poisonings by alcohol or drugs (X41-X42, X45-X46), and substance-related criminal offenses.FINDINGS: The absolute rate of substance misuse increased sharply before the onset of SSRI treatment and decreased after treatment initiation. Stratified Cox regression models showed an elevated risk (hazard ratio (HR)=1.70, 95% confidence interval (CI): 1.62-1.78) of substance misuse outcomes during a 1-month period preceding treatment initiation, compared with the reference period of more than 1 month before treatment start. The on-treatment estimates (1-30 days [HR=1.29, 95% CI: 1.23-1.37], 31-120 days [HR=1.30, 95% CI: 1.24-1.35], and >120 days [HR=1.24, 95% CI: 1.18-1.30] after treatment initiation) were consistently lower than the 1-month pre-treatment estimate, but still elevated compared with the reference period.CONCLUSIONS: For people with anxiety/depression, the risk of substance misuse appears to be particularly elevated right before initiating selective serotonin reuptake inhibitor (SSRI) treatment, which may reflect the emergence or worsening of substance use problems concurrently with anxiety/depression. SSRI treatment appears to be associated with a lower risk of substance misuse compared with the 1-month period preceding treatment initiation, but causality remains uncertain.
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| 8. |
- Wiggs, Kelsey K., et al.
(författare)
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A nationwide study of initiation of antidepressant pharmacotherapy and the risk of seizures
- 2023
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Ingår i: Epilepsy Research. - : Elsevier. - 0920-1211 .- 1872-6844. ; 192
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The present study aimed to examine whether antidepressant initiation increases the risk of hospitalizations and unplanned outpatient visits for seizures. Research has provided conflicting evidence as to whether antidepressant initiation causes seizures. Because epilepsy and depression are comorbid, this remains an important question, particularly in the care of those already at-risk for seizures.METHODS: We used Swedish-register data, including 658,766 antidepressant initiators and 1:1 age-, region-, and sex-matched non-initiators, ages 12-65. We used filled prescriptions to identify any antidepressant and serotonergic antidepressant and inpatient hospitalizations and unplanned outpatient (to avoid coding routine epilepsy maintenance as a seizure) visits to identify seizures, respectively. We first compared seizure visit incidence between antidepressant-initiators and matched non-users in the year following initiation from 2006 to 2013. To examine seizure risk over months pre- and post-initiation, within-individual analyses compared risk during the month one year prior to initiation with all subsequent months. We examined associations for any antidepressant and serotonergic antidepressants, as well as for any initiator and initiators with a history of seizures.RESULTS: Our matched-cohort results showed higher incidence of seizure visits among antidepressant users compared with non-users (e.g., adjusted incidence rate ratio [IRR]=3.14, 95% confidence interval [CI]=2.83-3.49). In within-individual analyses, the months after initiation were associated with higher incidence of seizure visits when compared with the month one year prior to initiation (e.g., one month after initiation IRR=1.96, 95%CI=1.64-2.34), but in individuals with a seizure history we observed weaker or no associations in the months after initiation (e.g., two months after initiation IRR=1.12, 95%CI=0.87-1.45). Notably, irrespective of potential seizure history, the months preceding initiation were associated with the greatest risk (e.g., one month before initiation IRR=2.86, 95% CI=2.42-3.38).CONCLUSIONS: Our findings suggest that there may be an elevated risk of seizures during antidepressant treatment, though the period of highest risk was before the initiation of antidepressants. Risk for seizure visits was lower among individuals with a history of prior seizures, which may be reassuring for the clinical care of these patients or indicate lack of treatment seeking following seizures. This study highlights the need to consider seizure risk across time; the failure to account for these dynamics may help account for discrepant findings in previous studies.
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| 9. |
- Zhang, Le, et al.
(författare)
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Comedication and Polypharmacy With ADHD Medications in Adults : A Swedish Nationwide Study
- 2021
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Ingår i: Journal of Attention Disorders. - : Sage Publications. - 1087-0547 .- 1557-1246. ; 25:11, s. 1519-1528
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Evidence regarding comedication among individuals with ADHD is lacking, especially in adults. This study investigated comedication and polypharmacy with ADHD medications in adults.Method: We identified adults dispensed with ADHD medications during 2013 in Sweden and matched them to controls. Logistic regression was used to calculate odds ratios (ORs) of receiving other medications.Results: Individuals receiving ADHD medications had higher risk of receiving any major classes of somatic medications (ORs ranged from 4.1, 95% confidence interval [CI] = [4.0, 4.3], to 7.4, 95% CI = [6.5, 8.5] across age groups). They were more likely to receive respiratory system, alimentary tract and metabolic system, and cardiovascular system medications. In addition, they had higher risk of receiving any other psychotropic medications. The proportion of polypharmacy with five or more medication classes increased from 10.1% to 60.4% from 18 to 64 years. Conclusion: Comedication was more common in adults receiving ADHD medications. Potential benefits and harms of comedication and polypharmacy require further research.
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| 10. |
- Zhang, Le, et al.
(författare)
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Prediction of treatment dosage and duration from free-text prescriptions : an application to ADHD medications in the Swedish prescribed drug register
- 2021
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Ingår i: Evidence-Based Mental Health. - : BMJ Publishing Group Ltd. - 1362-0347 .- 1468-960X. ; 24:4, s. 146-152
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Accurate estimation of daily dosage and duration of medication use is essential to pharmacoepidemiological studies using electronic healthcare databases. However, such information is not directly available in many prescription databases, including the Swedish Prescribed Drug Register.OBJECTIVE: To develop and validate an algorithm for predicting prescribed daily dosage and treatment duration from free-text prescriptions, and apply the algorithm to ADHD medication prescriptions.METHODS: We developed an algorithm to predict daily dosage from free-text prescriptions using 8000 ADHD medication prescriptions as the training sample, and estimated treatment periods while taking into account several features including titration, stockpiling and non-perfect adherence. The algorithm was implemented to all ADHD medication prescriptions from the Swedish Prescribed Drug Register in 2013. A validation sample of 1000 ADHD medication prescriptions, independent of the training sample, was used to assess the accuracy for predicted daily dosage.FINDINGS: In the validation sample, the overall accuracy for predicting daily dosage was 96.8%. Specifically, the natural language processing model (NLP1 and NLP2) have an accuracy of 99.2% and 96.3%, respectively. In an application to ADHD medication prescriptions in 2013, young adult ADHD medication users had the highest probability of discontinuing treatments as compared with other age groups. The daily dose of methylphenidate use increased with age substantially.CONCLUSIONS: The algorithm provides a flexible approach to estimate prescribed daily dosage and treatment duration from free-text prescriptions using register data. The algorithm showed a good performance for predicting daily dosage in external validation.CLINICAL IMPLICATIONS: The structured output of the algorithm could serve as basis for future pharmacoepidemiological studies evaluating utilization, effectiveness, and safety of medication use, which would facilitate evidence-based treatment decision-making.
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