Project description:ObjectivesWe aimed to examine the temporal association between selective serotonin reuptake inhibitors (SSRI) and tricyclic antidepressant (TCA) prescriptions and suicide-related events in children and adolescents.DesignSelf-controlled case series.SettingElectronic health records were used from 479 general practices in The Health Improvement Network (THIN) UK primary care database from 1995 to 2009.Participants81 young people aged 10-18 years with a record of completed suicide, 1496 who attempted suicide, 1178 with suicidal ideation and 2361 with intentional self-harm.Main outcome measuresIncidence Rate Ratios (IRRs) for completed and attempted suicide, suicidal ideation and intentional self-harm.ResultsFor non-fatal suicide-related behaviour, IRRs were similar for the time the person was prescribed either SSRIs or TCAs: IRRs increased during pre-exposure, peaked on prescription day, were stable up to the fourth prescription-week, and decreased after the prescriptions were stopped. For both types of antidepressants, IRRs were lower or similar to pre-exposure levels during the period of prescription. For SSRIs, there was an increase in the IRR for completed suicide on the day of prescription (N=5; IRR=42.5, 95% CI 4.5 to 403.4), and during the fourth week of SSRI prescription (N=2; IRR=11.3, 95% CI 1.1 to 115.6).ConclusionsWe found that a very small number of young people were prescribed antidepressants and that there was an absence of a sustained increase in rates of suicide-related events in this group. There were no systematic differences between the association of TCAs and SSRIs and the incidence risk ratios for attempted suicide, suicidal ideation or intentional self-harm and, apart from the day of prescription, rates did not exceed pre-exposure levels. The pattern of IRR for suicide for SSRIs was similar to that found in non-fatal suicide-related events. Our results warrant a re-evaluation of the current prescription of SSRIs in young people. We recommend the creation of a pragmatic registry for active pharmacovigilance.

Project description:BackgroundAntidepressants may be used to manage a number of conditions in children and young people including depression, anxiety, and obsessive-compulsive disorder. UK guidelines for the treatment of depression in children and young people recommend that antidepressants should only be initiated following assessment and diagnosis by a child and adolescent psychiatrist. The aim of this study was to summarise visits to mental health specialists and indications recorded around the time of antidepressant initiation in children and young people in UK primary care.MethodsThe study used linked English primary care electronic health records and Hospital Episode Statistics secondary care data. The study included 5-17-year-olds first prescribed antidepressants between January 2006 and December 2017. Records of visits to paediatric or psychiatric specialists and potential indications (from a pre-specified list) were extracted. Events were counted if recorded less than 12?months before or 6?months after the first antidepressant prescription. Results were stratified by first antidepressant type (all, selective serotonin reuptake inhibitors (SSRIs), tricyclic and related antidepressants) and by age group (5-11?years, 12-17?years).ResultsIn total, 33,031 5-17-year-olds were included. Of these, 12,149 (37%) had a record of visiting a paediatrician or a psychiatric specialist in the specified time window. The majority of recorded visits (7154, 22%) were to paediatricians. Of those prescribed SSRIs, 5463/22,130 (25%) had a record of visiting a child and adolescent psychiatrist. Overall, 17,972 (54%) patients had a record of at least one of the pre-specified indications. Depression was the most frequently recorded indication (12,501, 38%), followed by anxiety (4155, 13%).ConclusionsThe results suggest many children and young people are being prescribed antidepressants without the recommended involvement of a relevant specialist. These findings may justify both greater training for GPs in child and adolescent mental health and greater access to specialist care and non-pharmacological treatments. Further research is needed to explore factors that influence how and why GPs prescribe antidepressants to children and young people and the real-world practice barriers to adherence to clinical guidelines.

Project description:Background: The clinical impact of the functional CYP2C19 and CYP2D6 gene variants on antidepressant treatment in people with depression is not well studied. Here, we evaluate the utility of pharmacogenetic (PGx) testing in psychiatry by investigating the association between the phenotype status of the cytochrome P450 (CYP) 2C19/2D6 enzymes and the one-year risks of clinical outcomes in patients with depression with incident new-use of (es)citalopram, sertraline, or fluoxetine. Methods: This study is a population-based cohort study of 17,297 individuals who were born between 1981 and 2005 with a depression diagnosis between 1996 and 2012. Using array-based single-nucleotide-polymorphism genotype data, the individuals were categorized according to their metabolizing status of CYP2C19/CYP2D6 as normal (NM, reference group), ultra-rapid- (UM), rapid- (RM), intermediate- (IM), or poor-metabolizer (PM). The outcomes were treatment switching or discontinuation, psychiatric emergency department contacts, and suicide attempt/self-harm. By using Poisson regression analyses, we have estimated the incidence rate ratios (IRR) with 95% confidence intervals (95% CI) that were adjusted for covariates and potential confounders, by age groups (<18 (children and adolescents), 19−25 (young adults), and 26+ years (adults)), comparing the outcomes in individuals with NM status (reference) versus the mutant metabolizer status. For statistically significant outcomes, we have calculated the number needed to treat (NNT) and the number needed to genotype (NNG) in order to prevent one outcome. Results: The children and adolescents who were using (es)citalopram with CYP2C19 PM status had increased risks of switching (IRR = 1.64 [95% CI: 1.10−2.43]) and suicide attempt/self-harm (IRR = 2.67 [95% CI; 1.57−4.52]). The young adults with CYP2C19 PM status who were using sertraline had an increased risk of switching (IRR = 2.06 [95% CI; 1.03−4.11]). The young adults with CYP2D6 PM status who were using fluoxetine had an increased risk of emergency department contacts (IRR = 3.28 [95% CI; 1.11−9.63]). No significant associations were detected in the adults. The NNG for preventing one suicide attempt/suicide in the children who were using (es)citalopram was 463, and the NNT was 11. Conclusion: The CYP2C19 and CYP2D6 PM phenotype statuses were associated with outcomes in children, adolescents, and young adults with depression with incident new-use of (es)citalopram, sertraline, or fluoxetine, therefore indicating the utility of PGx testing, particularly in younger people, for PGx-guided antidepressant treatment.

Project description:BackgroundWeb-based interventions are a promising approach to support youth at risk of suicide, and those incorporating peer-to-peer social networking may have the added potential to target interpersonal states of perceived burdensomeness and thwarted belongingness. Owing to feasibility and safety concerns, including fear of contagion, this had not been tested until recently. In 2018, we conducted a pilot evaluation to test the feasibility, safety, and acceptability of a Moderated Online Social Therapy intervention, called Affinity, with a sample of young people with active suicidal ideation.ObjectiveThe aim of this study is to report qualitative data collected from study participants regarding their experience of the web-based social network and the consequent safety features.MethodsAffinity is a closed website incorporating 3 key components: therapeutic content delivered via comics, peer-to-peer social networking, and moderation by peers and clinicians. Semistructured interviews were conducted with 17 young people who participated in the pilot study after 8 weeks of exposure to the intervention. Interview data from 2 young people who did not use Affinity were excluded from the analysis. The interviews were analyzed using thematic analysis, with the frequency of responses characterized using the consensual qualitative research method. The results are reported in accordance with the Consolidated Criteria for Reporting Qualitative Research checklist.ResultsA total of 4 overarching themes were identified: a safe and supportive environment, the importance of mutual experiences, difficulty engaging and connecting, and the pros and cons of banning discussions about suicide. Interestingly, although Affinity was perceived to be safe and free of judgment, concerns about negative evaluation and triggering others were significant barriers to posting on the social network. Participants generally supported the banning of conversations about suicide, although for some this was perceived to reinforce stigma or was associated with frustration and distress.ConclusionsThe results not only support the safety and potential therapeutic benefit of the social networking aspect of Affinity but also highlight several implementation challenges. There is a need to carefully balance the need for stringent safety and design features while ensuring that the potential for therapeutic benefit is maximized.

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Psychological therapy must accompany antidepressants in young people.

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