Yasmina Molero

Varenicline and risk of psychiatric conditions, suicidal behaviour, criminal offending, and transport accidents and offences: population based cohort study

Objective To examine associations between varenicline and the incidence of a range of adverse outcomes. Design Population based cohort study using within person analyses to control for confounding by indication. Setting Whole population of Sweden. Participants 7 917 436 people aged 15 and over, of whom 69 757 were treated with varenicline between 2006 and 2009. Main outcome measures Incidence of new psychiatric conditions, suicidal behaviour, suspected and convicted criminal offending, transport accidents, and suspected and convicted traffic offences. Results In the whole population, 337 393 new psychiatric conditions were diagnosed during follow-up. In addition, 507 823 suspected and 338 608 convicted crimes, 40 595 suicidal events, 124 445 transport accidents, and 99 895 suspected and 57 068 convicted traffic crimes were recorded. Within person analyses showed that varenicline was not associated with significant hazards of suicidal behaviour, criminal offending, transport accidents, traffic offences, or psychoses. However, varenicline was associated with a small increase in the risk of anxiety conditions (hazard ratio 1.23, 95% confidence interval 1.01 to 1.51) and mood conditions (1.31, 1.06 to 1.63), which was only seen in people with pre-existing psychiatric disorders. Conclusions Concerns that varenicline is associated with an increased risk of many adverse outcomes, including suicidality and accidents, are not supported in this observational study. The small increase in risk of two psychiatric conditions in people with pre-existing psychiatric disorders needs to be confirmed using other research designs.

Selective serotonin reuptake inhibitors and violent crime: a cohort study

Background Although selective serotonin reuptake inhibitors (SSRIs) are widely prescribed, associations with violence are uncertain. Methods and Findings From Swedish national registers we extracted information on 856,493 individuals who were prescribed SSRIs, and subsequent violent crimes during 2006 through 2009. We used stratified Cox regression analyses to compare the rate of violent crime while individuals were prescribed these medications with the rate in the same individuals while not receiving medication. Adjustments were made for other psychotropic medications. Information on all medications was extracted from the Swedish Prescribed Drug Register, with complete national data on all dispensed medications. Information on violent crime convictions was extracted from the Swedish national crime register. Using within-individual models, there was an overall association between SSRIs and violent crime convictions (hazard ratio [HR] = 1.19, 95% CI 1.08–1.32, p < 0.001, absolute risk = 1.0%). With age stratification, there was a significant association between SSRIs and violent crime convictions for individuals aged 15 to 24 y (HR = 1.43, 95% CI 1.19–1.73, p < 0.001, absolute risk = 3.0%). However, there were no significant associations in those aged 25–34 y (HR = 1.20, 95% CI 0.95–1.52, p = 0.125, absolute risk = 1.6%), in those aged 35–44 y (HR = 1.06, 95% CI 0.83–1.35, p = 0.666, absolute risk = 1.2%), or in those aged 45 y or older (HR = 1.07, 95% CI 0.84–1.35, p = 0.594, absolute risk = 0.3%). Associations in those aged 15 to 24 y were also found for violent crime arrests with preliminary investigations (HR = 1.28, 95% CI 1.16–1.41, p < 0.001), non-violent crime convictions (HR = 1.22, 95% CI 1.10–1.34, p < 0.001), non-violent crime arrests (HR = 1.13, 95% CI 1.07–1.20, p < 0.001), non-fatal injuries from accidents (HR = 1.29, 95% CI 1.22–1.36, p < 0.001), and emergency inpatient or outpatient treatment for alcohol intoxication or misuse (HR = 1.98, 95% CI 1.76–2.21, p < 0.001). With age and sex stratification, there was a significant association between SSRIs and violent crime convictions for males aged 15 to 24 y (HR = 1.40, 95% CI 1.13–1.73, p = 0.002) and females aged 15 to 24 y (HR = 1.75, 95% CI 1.08–2.84, p = 0.023). However, there were no significant associations in those aged 25 y or older. One important limitation is that we were unable to fully account for time-varying factors. Conclusions The association between SSRIs and violent crime convictions and violent crime arrests varied by age group. The increased risk we found in young people needs validation in other studies.

A study of the possible association between adenosine A2A receptor gene polymorphisms and attention-deficit hyperactivity disorder traits

The adenosine A2A receptor (ADORA2A) is linked to the dopamine neurotransmitter system and is also implicated in the regulation of alertness, suggesting a potential association with attention‐deficit hyperactivity disorder (ADHD) traits. Furthermore, animal studies suggest that the ADORA2A may influence ADHD‐like behavior. For that reason, the ADORA2A gene emerges as a promising candidate for studying the etiology of ADHD traits. The aim of this study was to examine the relationship between ADORA2A gene polymorphisms and ADHD traits in a large population‐based sample. This study was based on the Child and Adolescent Twin Study in Sweden (CATSS), and included 1747 twins. Attention‐deficit hyperactivity disorder traits were assessed through parental reports, and samples of DNA were collected. Associations between six single nucleotide polymorphisms (SNPs) and ADHD traits were examined, and results suggested a nominal association between ADHD traits and three of these SNPs: rs3761422, rs5751876 and rs35320474. For one of the SNPs, rs35320474, results remained significant after correction for multiple comparisons. These results indicate the possibility that the ADORA2A gene may be involved in ADHD traits. However, more studies replicating the present results are warranted before this association can be confirmed.

Association Between Deliberate Self-harm and Violent Criminality

Importance Individuals who self-harm may have an increased risk of aggression toward others, but this association has been insufficiently investigated. More conclusive evidence may affect assessment, treatment interventions, and clinical guidelines. Objective To investigate the association between nonfatal self-harm and violent crime. Design, Setting, and Participants This population-based longitudinal cohort study, conducted from January 1, 1997, through December 31, 2013, studied all Swedish citizens born between 1982 and 1998 who were 15 years and older (N = 1 850 252). Individuals who emigrated from Sweden before the age of 15 years (n = 104 051) or immigrated to Sweden after the age of 13 years (ie, <2 years before the beginning of the follow-up; n = 22 009) were excluded. Data analysis was performed from April 21, 2016, to June 4, 2016. Exposures Receipt of self-harm–associated clinical care. Main Outcomes and Measures Conviction of a violent crime according to the Swedish penal code. Results The study cohort consisted of 1 850 525 individuals (950 382 males and 900 143 females), and the mean (SD) follow-up time was 8.1 (4.7) years (range, 0-17.0 years; minimum age, 15 years; maximum age, 32 years). During a mean follow-up period of 8.1 years, 55 185 individuals (3.0%) received clinical care for self-harm. The crude hazard ratio was 4.9 (95% CI, 4.8-5.0) for violent crime conviction in exposed individuals compared with the unexposed group. Women who self-harm were at particularly high risk for expressing violent behaviors. After adjustment for relevant psychiatric comorbidities and socioeconomic status, an almost doubled hazard of violent offense remained (hazard ratio, 1.8; 95% CI, 1.8-1.9). Conclusions and Relevance Self-harm is associated with an increased risk of conviction for a violent offense in both sexes. The risk of violence, as well as the risk of suicide and self-harm, should be assessed among offending and self-harming individuals.

Subthreshold and threshold attention deficit hyperactivity disorder symptoms in childhood: psychosocial outcomes in adolescence in boys and girls

To examine the association between different levels of childhood attention deficit hyperactivity disorder (ADHD) symptoms and sex differences in psychosocial outcomes during adolescence.

Violent, nonviolent, and substance-related offending over the life course in a cohort of males and females treated for substance misuse as youths

Most studies on adolescent offending heterogeneity are based on general population samples, and few include individuals with substance misuse or look specifically at substance-related offending. It is also unclear how offender subtypes develop after young adulthood or how offending heterogeneity varies between genders. This study aimed to identify subgroups of offending among adolescents with misuse problems and to examine associations with offending in adulthood. The study included 1,992 females and males that consulted a clinic for adolescents with misuse problems between 1968 and 1971. Latent Class Analyses were conducted to identify subgroups based on violent and nonviolent offending before age 20. Participants were then followed until age 50 and reexamined regarding violent, nonviolent, and substance-related crimes. Associations between subgroups before age 20 and subgroups age 21-50 were examined. Before age 20, three subgroups were identified among the females and six among the males. Males were more specialized in their offending and demonstrated higher levels of offending. Results pointed to both stability and decrease of violent and nonviolent offending, and to the emergence of substance-related offending in adulthood in both genders. The connection between substance-related crimes and general delinquency in adulthood among individuals treated for substance misuse suggests that interventions should also address substance misuse for reducing the overall volume of crime. This study also highlights the importance of including females in research on offending heterogeneity.

Childhood Symptoms of ADHD Overrule Comorbidity in Relation to Psychosocial Outcome at Age 15: A Longitudinal Study

Objective Neurodevelopmental problems (NDPs) may influence the transition from childhood to adolescence. Our aim was to study long-term psychosocial outcomes of NDPs, focusing on ADHD. Method Data was collected through a telephone interview with parents of twins at ages 9 or 12 years. NDP screen-positive children were clinically assessed at age 15; N = 450. Psychosocial outcome concerning peers, school, internalizing problems, antisocial behavior, alcohol misuse, drug misuse, and impaired daily functioning was examined. Results Even after controlling for other NDP comorbidity, screen-positivity for ADHD doubled or tripled the odds of later psychosocial problems. When controlling for parental education level, the significant effect of ADHD remained only for antisocial behavior and impaired daily functioning. Conclusions Signs of NDPs as well as other psychiatric diagnoses at ages 9 or 12 years are associated with a more problematic adolescence. However, despite the presence of comorbidity, early ADHD symptoms stand out as the most important risk factor for later antisocial development and impaired daily functioning.

Effectiveness and implementation of a community-based prevention programme targeting anabolic androgenic steroid use in gyms: study protocol of a quasi-experimental control group study

BackgroundDuring the past decades, concerns about increased anabolic androgenic steroid (AAS) use among recreational sportspeople have been raised, yet there is a paucity of AAS prevention efforts targeting this group. Accordingly, doping prevention efforts aimed at gyms have been recommended. The overall objective of the present project is to examine a prevention programme named 100% Pure Hard Training (100% PHT), which targets AAS use among recreational sportspeople training in gyms. Specifically, the project aims to: 1) assess the prevalence of AAS, and its associations with alcohol, illicit drugs, and nutritional supplements use; 2) examine whether 100% PHT can decrease AAS use in gyms, and 3) provide insights into which factors facilitate and/or impede implementation of the programme.Methods/designThe intervention group consists of 27 gyms, and 27 gyms serve as controls. Intervention gyms take part in 100% PHT, a community-based programme involving several components: (a) training of key stakeholders (i.e., gym staff, gym owners, local police, and municipal prevention coordinators) regarding AAS use; (b) developing an action plan for AAS prevention for each gym; (c) certification of gyms that follow 100% PHT; (d) cooperative relationship between stakeholders; (e) annual follow-up of gyms. The project consists of two studies: Study A will examine the prevalence of AAS use and the effectiveness of 100% PHT (aims 1 and 2), and data for Study A will be collected using questionnaires distributed to gym attendees at two assessment points: baseline (pre-intervention) and follow-up (post-intervention). Study B will evaluate the implementation of 100% PHT (aim 3), and semi-structured interviews with participating stakeholders will be carried out post-intervention.DiscussionKnowledge gained from the present project can be used to develop community-based doping prevention efforts aimed at recreational sportspeople training in gyms. Furthermore, it can provide insights into which factors are important for successful implementation of AAS prevention programmes that target gyms. Results are also expected to yield information on the prevalence of AAS use as well as associations between the use of AAS and other licit and illicit substances, including nutritional supplements, among recreational sportspeople.Trial registrationThe study was registered retrospectively at isrctn.com (Identifier: ISRCTN11655041; Registration date: 3 November 2016;).

Benzodiazepine prescribing for children, adolescents, and young adults from 2006 through 2013: A total population register-linkage study

Background Pharmacoepidemiological studies have long raised concerns on widespread use of benzodiazepines and benzodiazepine-related drugs (BZDs), in particular long-term use, among adults and the elderly. In contrast, evidence pertaining to the rates of BZD use at younger ages is still scarce, and the factors that influence BZD utilisation and shape the different prescribing patterns in youths remain largely unexplored. We examined the prevalence rates, relative changes in rates over time, and prescribing patterns for BZD dispensation in young people aged 0–24 years in Sweden during the period January 1, 2006–December 31, 2013, and explored demographic, clinical, pharmacological, and prescriber-related attributes of BZD prescribing in this group. Methods and findings Through the linkage of 3 nationwide Swedish health and administrative registers, we collected data on 17,500 children (0–11 years), 15,039 adolescents (12–17 years), and 85,200 young adults (18–24 years) with at least 1 dispensed prescription for a BZD during 2006–2013, out of 3,726,818 Swedish inhabitants aged 0–24 years. Age-specific annual prevalence rates of BZD dispensations were adjusted for population growth, and relative changes in rates were calculated between 2006 and 2013. We analysed how BZD dispensation varied by sex, psychiatric morbidity and epilepsy, concurrent dispensation of psychotropic medication, type of dispensed BZD, and type of healthcare provider prescribing the BZD. Prescribing patterns were established in relation to duration (3 months, >3 to ≤6 months, or >6 months), dosage (<0.5 defined daily dosage [DDD]/day, ≥0.5 to <1.5 DDD/day, or ≥1.5 DDD/day), and “user category” (“regular users” [≥0.5 to <1.5 DDD/day for ≥1 year], “heavy users” [≥1.5 DDD/day for ≥1 year], or otherwise “occasional users”). Multinomial regression models were fitted to test associations between BZD prescribing patterns and individual characteristics of study participants. Between 2006 and 2013, the prevalence rate of BZD dispensation among individuals aged 0–24 years increased by 22% from 0.81 per 100 inhabitants to 0.99 per 100 inhabitants. This increase was mainly driven by a rise in the rate among young adults (+20%), with more modest increases in children (+3%) and adolescents (+7%). Within each age category, overall dispensation of BZD anxiolytics and clonazepam decreased over time, while dispensation of BZD hypnotics/sedatives, including Z-drugs, showed an increase between 2006 and 2013. Out of 117,739 study participants with dispensed BZD prescriptions, 65% initiated BZD prescriptions outside of psychiatric services (92% of children, 60% of adolescents, 60% of young adults), and 76% were dispensed other psychotropic drugs concurrently with a BZD (46% of children, 80% of adolescents, 81% of young adults). Nearly 30% of the participants were prescribed a BZD for longer than 6 months (18% of children, 31% of adolescents, 31% of young adults). A high dose prescription (≥1.5 DDD/day) and heavy use were detected in 2.6% and 1.7% of the participants, respectively. After controlling for potential confounding by demographic and clinical characteristics, the characteristics age above 11 years at the first BZD dispensation, lifetime psychiatric diagnosis or epilepsy, and concurrent dispensation of other psychotropic drugs were found to be associated with higher odds of being prescribed a BZD for longer than 6 months, high dose prescription, and heavy use. Male sex was associated with a higher likelihood of high dose prescription and heavy use, but not with being prescribed a BZD on a long-term basis (> 6 months). The study limitations included lack of information on actual consumption of the dispensed BZDs and unavailability of data on the indications for BZD prescriptions. Conclusions The overall increase in prevalence rates of BZD dispensations during the study period and the unexpectedly high proportion of individuals who were prescribed a BZD on a long-term basis at a young age indicate a lack of congruence with international and national guidelines. These findings highlight the need for close monitoring of prescribing practices, particularly in non-psychiatric settings, in order to build an evidence base for safe and efficient BZD treatment in young persons.

Parental nicotine replacement therapy and offspring bronchitis/bronchiolitis and asthma – a nationwide population-based cohort study

Background Prior evidence shows that environmental tobacco smoke is a risk factor for respiratory tract infections, wheeze, and asthma. Nicotine replacement therapy has been shown to increase smoking cessation. However, no prior studies have explored if parental use decreases the risk of bronchitis/bronchiolitis and asthma in the offspring. Objective To examine whether nicotine replacement therapy varenicline, given to parents, was associated with a reduction in bronchitis/bronchiolitis and/or asthma in their children. Methods This study is a population-based cohort study, linking data from nationwide registers, and using a within-individual design that minimizes selection effects and controls for time-invariant confounding factors. Participants included 37,420 parents with a collected prescription of varenicline with 72,392 offspring <18 years of age. Exposure was defined as collected prescriptions of varenicline among the parents. Primary outcomes were offspring hospital visits for bronchitis/bronchiolitis (ICD10: J20 or J21) and offspring hospital visits for asthma (ICD10: J45). Results Parental varenicline treatment was associated with a lower rate of visits for bronchitis/bronchiolitis in their children (incidence rate ratio [IRR]=0.67; 95% CI=0.50–0.91), but no association was found for asthma (IRR=1.08; 95% CI=0.97–1.19). The rate reduction of bronchitis/bronchiolitis was similar when we restricted data to children aged 0–3 years (IRR=0.71; 95% CI=0.52–0.97) and to maternal varenicline treatment (IRR=0.64; 95% CI=0.43–0.96). When restricting the outcomes to unplanned visits only (ie, excluding booked appointments, followups, and referrals), no associations were found (IRR=0.72, 95% CI=0.51–1.02). Conclusion In this cohort study, nicotine replacement treatment in parents was associated with reduced hospital visits for bronchitis/bronchiolitis in their children.