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Background: There is an increasing demand for mental health services for young people, which may vary across the year., Objective: To determine whether there are seasonal patterns in primary care antidepressant prescribing and mental health issues in adolescents and young adults., Methods: This cohort study used anonymised electronic health records from general practices in England contributing to QResearch. It included 5 081 263 males and females aged 14-18 (adolescents), 19-23 and 24-28 years between 2006 and 2019. The incidence rates per 1000 person-years and the incidence rate ratios (IRRs) were calculated for the first records of a selective serotonin reuptake inhibitor (SSRI) prescription, depression, anxiety and self-harm. The IRRs were adjusted for year, region, deprivation, ethnic group and number of working days., Findings: There was an increase in SSRI prescribing, depression and anxiety incidence in male and female adolescents in the autumn months (September-November) that was not seen in older age groups. The IRRs for SSRI prescribing for adolescents peaked in November (females: 1.75, 95% CI 1.67 to 1.83, p<0.001; males: 1.72, 95% CI 1.61 to 1.84, p<0.001, vs in January) and for depression (females: 1.29, 95% CI 1.25 to 1.33, p<0.001; males: 1.29, 95% CI 1.23 to 1.35, p<0.001). Anxiety peaked in November for females aged 14-18 years (1.17, 95% CI 1.13 to 1.22, p<0.001) and in September for males (1.19, 95% CI 1.12 to 1.27, p<0.001)., Conclusions: There were higher rates of antidepressant prescribing and consultations for depression and anxiety at the start of the school year among adolescents., Clinical Implications: Support around mental health issues from general practitioners and others should be focused during autumn., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Studies report an increased risk of self-harm or suicide in people prescribed mirtazapine compared with other antidepressants., Objectives: To compare the risk of serious self-harm in people prescribed mirtazapine versus other antidepressants as second-line treatments., Design and Setting: Cohort study using anonymised English primary care electronic health records, hospital admission data and mortality data with study window 1 January 2005 to 30 November 2018., Participants: 24 516 people diagnosed with depression, aged 18-99 years, initially prescribed a selective serotonin reuptake inhibitor (SSRI) and then prescribed mirtazapine, a different SSRI, amitriptyline or venlafaxine., Main Outcome Measures: Hospitalisation or death due to deliberate self-harm. Age-sex standardised rates were calculated and survival analyses were performed using inverse probability of treatment weighting to account for baseline covariates., Results: Standardised rates of serious self-harm ranged from 3.8/1000 person-years (amitriptyline) to 14.1/1000 person-years (mirtazapine). After weighting, the risk of serious self-harm did not differ significantly between the mirtazapine group and the SSRI or venlafaxine groups (HRs (95% CI) 1.18 (0.84 to 1.65) and 0.85 (0.51 to 1.41) respectively). The risk was significantly higher in the mirtazapine than the amitriptyline group (3.04 (1.36 to 6.79)) but was attenuated after adjusting for dose., Conclusions: There was no evidence for a difference in risk between mirtazapine and SSRIs or venlafaxine after accounting for baseline characteristics. The higher risk in the mirtazapine versus the amitriptyline group might reflect residual confounding if amitriptyline is avoided in people considered at risk of self-harm., Clinical Implications: Addressing baseline risk factors and careful monitoring might improve outcomes for people at risk of serious self-harm., Competing Interests: Competing interests: All authors have completed the ICMJE declaration of interest form and declare support from the National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, NIHR School for Primary Care Research, and NIHR MindTech MedTech Co-operative. JHC is a shareholder and former director of ClinRisk Ltd, outside of the submitted work. JHC is an unpaid director of QResearch which is an alternative database to CPRD run as a partnership between the University of Oxford and EMIS (commercial supplier of GP computer systems) outside the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objectives: Previous pandemics have resulted in significant consequences for mental health. Here, we report the mental health sequelae of the COVID-19 pandemic in a UK cohort and examine modifiable and non-modifiable explanatory factors associated with mental health outcomes. We focus on the first wave of data collection, which examined short-term consequences for mental health, as reported during the first 4-6 weeks of social distancing measures being introduced., Design: Cross-sectional online survey., Setting: Community cohort study., Participants: N=3097 adults aged ≥18 years were recruited through a mainstream and social media campaign between 3 April 2020 and 30 April 2020. The cohort was predominantly female (n=2618); mean age 44 years; 10% (n=296) from minority ethnic groups; 50% (n=1559) described themselves as key workers and 20% (n=649) identified as having clinical risk factors putting them at increased risk of COVID-19., Main Outcome Measures: Depression, anxiety and stress scores., Results: Mean scores for depression ([Formula: see text] =7.69, SD=6.0), stress ([Formula: see text] =6.48, SD=3.3) and anxiety ([Formula: see text] = 6.48, SD=3.3) significantly exceeded population norms (all p<0.0001). Analysis of non-modifiable factors hypothesised to be associated with mental health outcomes indicated that being younger, female and in a recognised COVID-19 risk group were associated with increased stress, anxiety and depression, with the final multivariable models accounting for 7%-14% of variance. When adding modifiable factors, significant independent effects emerged for positive mood, perceived loneliness and worry about getting COVID-19 for all outcomes, with the final multivariable models accounting for 54%-57% of total variance., Conclusions: Increased psychological morbidity was evident in this UK sample and found to be more common in younger people, women and in individuals who identified as being in recognised COVID-19 risk groups. Public health and mental health interventions able to ameliorate perceptions of risk of COVID-19, worry about COVID-19 loneliness and boost positive mood may be effective., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Antidepressants are one of the most commonly prescribed medications in young and middle-aged adults, but there is relatively little information on their safety across a range of adverse outcomes in this age group. This study aimed to assess associations between antidepressant treatment and several adverse outcomes in people aged 20-64 years diagnosed with depression., Methods: We conducted a cohort study in 238,963 patients aged 20-64 years registered with practices across the UK contributing to the QResearch primary care database. Only patients with a first diagnosis of depression were included. Outcomes were falls, fractures, upper gastrointestinal bleed, road traffic accidents, adverse drug reactions and all-cause mortality recorded during follow-up. Cox proportional hazards models were used to estimate hazard ratios associated with antidepressant exposure adjusting for potential confounding variables., Results: During 5 years of follow-up, 4651 patients had experienced a fall, 4796 had fractures, 1066 had upper gastrointestinal bleeds, 3690 had road traffic accidents, 1058 had experienced adverse drug reactions, and 3181 patients died. Fracture rates were significantly increased for selective serotonin reuptake inhibitors (adjusted hazard ratio 1.30, 95% CI 1.21-1.39) and other antidepressants (1.28, 1.11-1.48) compared with periods when antidepressants were not used. All antidepressant drug classes were associated with significantly increased rates of falls. Rates of adverse drug reactions were significantly higher for tricyclic and related antidepressants (1.54, 1.25-1.88) and other antidepressants (1.61, 1.22-2.12) compared with selective serotonin reuptake inhibitors. Trazodone was associated with a significantly increased risk of upper gastrointestinal bleed. All-cause mortality rates were significantly higher for tricyclic and related antidepressants (1.39, 1.22-1.59) and other antidepressants (1.26, 1.08-1.47) than for selective serotonin reuptake inhibitors over 5 years but not 1 year, and were significantly reduced after 85 or more days of treatment with selective serotonin reuptake inhibitors. Mirtazapine was associated with significantly increased mortality rates over 1 and 5 years of follow-up., Conclusions: Selective serotonin reuptake inhibitors had higher rates of fracture than tricyclic and related antidepressants but lower mortality and adverse drug reaction rates than the other antidepressant drug classes. The association between mirtazapine and increased mortality merits further investigation. These risks should be carefully considered and balanced against potential benefits for individual patients when the decision to prescribe an antidepressant is made.

Background: The benefits of work for physical, psychological, and financial wellbeing are well documented. Return to work (RTW) after unintentional injury is often delayed, and psychological morbidity may contribute to this delay. The impact of psychological morbidity on RTW after a wide range of unintentional injuries in the UK has not been adequately quantified., Aim: To quantify the role of psychological factors, including anxiety, depression, and post-traumatic distress, on RTW following unintentional injuries., Design and Setting: A longitudinal multicentre prospective study was undertaken in Nottingham, Bristol, Leicester, and Guildford, UK., Method: Participants ( n = 273) were 16-69-year-olds admitted to hospital following unintentional injury, who were in paid employment prior to injury. They were surveyed at baseline, then at 1, 2, 4, and 12 months following injury; demographic data were collected along with injury characteristics, psychological morbidity, and RTW status. Associations between demographic, injury and psychological factors, and RTW between 2 and 12 months after injury were quantified using random effects logistic regression., Results: The odds of RTW between 2 and 12 months after injury reduced as depression scores early in the recovery period (1 month after injury) increased (odds ratio [OR] 0.87, 95% confidence interval [CI] = 0.79 to 0.95) and as length of hospital stay increased (OR 0.91, 95% CI] = 0.86 to 0.96). For those experiencing threatening life events following injury (OR 0.27, 95% CI = 0.10 to 0.72) and with higher scores on the Crisis Support Scale (OR 0.93, 95% CI] = 0.88 to 0.99), the odds of RTW between 2 and 12 months after injury were lower. Multiple imputation analysis found similar results, but those relating to crisis support did not remain statistically significant., Conclusion: Primary care professionals can identify patients at risk of delayed RTW who may benefit from management of psychological morbidity and support to RTW., (© British Journal of General Practice 2017.)

Objective: To assess associations between different antidepressant treatments and rates of three cardiovascular outcomes (myocardial infarction, stroke or transient ischaemic attack, and arrhythmia) in people with depression., Design: Cohort study., Setting: UK general practices contributing to the QResearch primary care database., Participants: 238,963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011., Exposures: Antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, duration of use, and commonly prescribed individual antidepressant drugs., Main Outcome Measures: First diagnoses of myocardial infarction, stroke or transient ischaemic attack, and arrhythmia during five years' follow-up. Cox proportional hazards models were used to estimate hazard ratios, adjusting for potential confounding variables., Results: During five years of follow-up, 772 patients had a myocardial infarction, 1106 had a stroke or transient ischaemic attack, and 1452 were diagnosed as having arrhythmia. No significant associations were found between antidepressant class and myocardial infarction over five years' follow-up. In the first year of follow-up, patients treated with selective serotonin reuptake inhibitors had a significantly reduced risk of myocardial infarction (adjusted hazard ratio 0.58, 95% confidence interval 0.42 to 0.79) compared with no use of antidepressants; among individual drugs, fluoxetine was associated with a significantly reduced risk (0.44, 0.27 to 0.72) and lofepramine with a significantly increased risk (3.07, 1.50 to 6.26). No significant associations were found between antidepressant class or individual drugs and risk of stroke or transient ischaemic attack. Antidepressant class was not significantly associated with arrhythmia over five years' follow-up, although the risk was significantly increased during the first 28 days of treatment with tricyclic and related antidepressants (adjusted hazard ratio 1.99, 1.27 to 3.13). Fluoxetine was associated with a significantly reduced risk of arrhythmia (0.74, 0.59 to 0.92) over five years, but citalopram was not significantly associated with risk of arrhythmia even at high doses (1.11, 0.72 to 1.71 for doses ≥ 40 mg/day)., Conclusions: This study found no evidence that selective serotonin reuptake inhibitors are associated with an increased risk of arrhythmia or stroke/transient ischaemic attack in people diagnosed as having depression between the ages of 20 to 64 or that citalopram is associated with a significantly increased risk of arrhythmia. It found some indication of a reduced risk of myocardial infarction with selective serotonin reuptake inhibitors, particularly fluoxetine, and of an increased risk with lofepramine., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To assess the associations between different antidepressant treatments and the rates of suicide and attempted suicide or self harm in people with depression., Design: Cohort study., Setting: Patients registered with UK general practices contributing data to the QResearch database., Participants: 238,963 patients aged 20 to 64 years with a first diagnosis of depression between 1 January 2000 and 31 July 2011, followed up until 1 August 2012., Exposures: Antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, and duration of use, and commonly prescribed individual antidepressant drugs. Cox proportional hazards models were used to calculate hazard ratios adjusting for potential confounding variables., Main Outcome Measures: Suicide and attempted suicide or self harm during follow-up., Results: During follow-up, 87.7% (n = 209,476) of the cohort received one or more prescriptions for antidepressants. The median duration of treatment was 221 days (interquartile range 79-590 days). During the first five years of follow-up 198 cases of suicide and 5243 cases of attempted suicide or self harm occurred. The difference in suicide rates during periods of treatment with tricyclic and related antidepressants compared with selective serotonin reuptake inhibitors was not significant (adjusted hazard ratio 0.84, 95% confidence interval 0.47 to 1.50), but the suicide rate was significantly increased during periods of treatment with other antidepressants (2.64, 1.74 to 3.99). The hazard ratio for suicide was significantly increased for mirtazapine compared with citalopram (3.70, 2.00 to 6.84). Absolute risks of suicide over one year ranged from 0.02% for amitriptyline to 0.19% for mirtazapine. There was no significant difference in the rate of attempted suicide or self harm with tricyclic antidepressants (0.96, 0.87 to 1.08) compared with selective serotonin reuptake inhibitors, but the rate of attempted suicide or self harm was significantly higher for other antidepressants (1.80, 1.61 to 2.00). The adjusted hazard ratios for attempted suicide or self harm were significantly increased for three of the most commonly prescribed drugs compared with citalopram: venlafaxine (1.85, 1.61 to 2.13), trazodone (1.73, 1.26 to 2.37), and mirtazapine (1.70, 1.44 to 2.02), and significantly reduced for amitriptyline (0.71, 0.59 to 0.85). The absolute risks of attempted suicide or self harm over one year ranged from 1.02% for amitriptyline to 2.96% for venlafaxine. Rates were highest in the first 28 days after starting treatment and remained increased in the first 28 days after stopping treatment., Conclusion: Rates of suicide and attempted suicide or self harm were similar during periods of treatment with selective serotonin reuptake inhibitors and tricyclic and related antidepressants. Mirtazapine, venlafaxine, and trazodone were associated with the highest rates of suicide and attempted suicide or self harm, but the number of suicide events was small leading to imprecise estimates. As this is an observational study the findings may reflect indication biases and residual confounding from severity of depression and differing characteristics of patients prescribed these drugs. The increased rates in the first 28 days of starting and stopping antidepressants emphasise the need for careful monitoring of patients during these periods., (© Coupland et al 2015.)

Highlights: What We Already Know? The COVID-19 pandemic has caused substantial disruption to daily life. The pandemic increased anxiety and depression in the general population of New Zealand in its first 3 months. What This Article Adds? This study found that depression and anxiety reduced over the first year of the pandemic in New Zealanders. However, even in a country with low transmission, anxiety and depression remained elevated compared to pre-pandemic norms. Younger age, being a pet owner, negative life events, and having mental health disorder increased the risk of anxiety and depression. This longitudinal study investigated changes in and risk factors for anxiety and depression during the COVID-19 pandemic in a New Zealand cohort. Online surveys were distributed to 681 participants at three time-points: May 2020 (Time 1), August–September 2020 (Time 2), and March–April 2021 (Time 3). Participants completed measures of anxiety and depression, alongside measures of possible risk/protective factors. A total of 261 participants completed all three surveys and were included in analyses. Depression and anxiety reduced over time; however, levels were still significantly higher than pre-pandemic norms. Being younger, having a prior mental health disorder, experiencing negative life events due to COVID-19, and being a pet owner were risk factors for poorer depression and anxiety, whereas having higher positive mood was protective. This study demonstrates persisting negative effects of the pandemic on anxiety and depression in a context of low transmission and highlights the importance of providing psychological help to those most at risk. [ABSTRACT FROM AUTHOR]

Background: Psychological factors can influence susceptibility to viral infections. We examined whether such influences are evident in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.Methods: Participants (n = 102) completed measures of anxiety, depression, positive mood, and loneliness and provided a blood sample for the measurement of antibodies to the SARS-CoV-2 spike and nucleocapsid proteins.Results: SARS-CoV-2 was significantly negatively associated with anxiety and depression. The model remained significant after adjustment for age and gender, although anxiety and depression were no longer significant independent predictors.Conclusions: These findings offer early support for the hypothesis that psychological factors may influence susceptibility to SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Background: Previous research has shown that psychological factors, such as stress and social support, are associated with greater susceptibility to viral respiratory illnesses and more severe symptoms. During the COVID-19 pandemic there has been a well-documented deterioration in psychological well-being and increased social isolation. This raises questions as to whether those experiencing psychological adversity during the pandemic are more at risk of contracting and/or experiencing COVID-19 symptoms.Purpose: To examine the relationship between psychological factors and the risk of COVID-19 self-reported infection and the symptomatic experience of SARS-CoV-2 (indicated by the number and severity of symptoms).Methods: As part of a longitudinal prospective observational cohort study, 1,087 adults completed validated measures of psychological well-being during April 2020 and self-reported incidence of COVID-19 infection and symptom experience across the pandemic through to December 2020. Regression models were used to explore these relationships controlling for demographic and occupational factors.Results: Greater psychological distress during the early phase of the pandemic was significantly associated with subsequent self-reported SARS-CoV-2 infection as well as the experience of a greater number and more severe symptoms.Conclusions: COVID-19 infection and symptoms may be more common among those experiencing elevated psychological distress. Further research to elucidate the mechanisms underlying these associations is needed. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is a serious condition which can profoundly affect an individual's life. While there is some evidence to suggest an association between antidepressant use and epilepsy and seizures it is conflicting and not conclusive. Antidepressant prescribing is rising in the UK so it is important to quantify absolute risks with individual antidepressants to enable shared decision making with patients. In this study we assess and quantify the association between antidepressant treatment and the risk of epilepsy and seizures in a large cohort of patients diagnosed with depression aged between 20 and 64 years. Methods: Data on 238,963 patients with a diagnosis of depression aged 20 to 64 from 687 UK practices were extracted from the QResearch primary care database. We used Cox's proportional hazards to analyse the time to the first recorded diagnosis of epilepsy/seizures, excluding patients with a prior history and estimated hazard ratios for antidepressant exposure adjusting for potential confounding variables. Results: In the first 5 years of follow-up, 878 (0.37%) patients had a first diagnosis of epilepsy/seizures with the hazard ratio (HR) significantly increased (P < 0.01) for all antidepressant drug classes and for 8 of the 11 most commonly prescribed drugs. The highest risks (in the first 5 years) compared with no treatment were for trazodone (HR 5.41, 95% confidence interval (CI) 3.05 to 9.61, number needed to harm (NNH) 65), lofepramine (HR 3.09, 95% CI 1.73 to 5.50, NNH 138), venlafaxine (HR 2.84, 95% CI 1.97 to 4.08, NNH 156) and combined antidepressant treatment (HR 2.73, 95% CI 1.52 to 4.91, NNH 166). Conclusions: Risk of epilepsy/seizures is significantly increased for all classes of antidepressant. There is a need for individual risk-benefit assessments in patients being considered for antidepressant treatment, especially those with ongoing mild depression or with additional risk factors. Residual confounding and indication bias may influence our results, so confirmation may be required from additional studies. [ABSTRACT FROM AUTHOR]

Background: Antidepressants are among the most commonly prescribed drugs in primary care in England and their use is increasing. This is largely due to longer durations of treatment of depression. Observational studies have shown some differences in adverse outcomes associated with different antidepressant drugs but relatively little is known about their relative safety particularly with long term use. The primary aim of this study is to determine the relative and absolute risks of pre-defined adverse events comparing different classes of antidepressant drugs in adults aged under 65 years and diagnosed with depression. Methods/design: The study will identify a cohort of patients with a first recorded diagnosis of depression between 1/1/2000 and 31/07/2011, and made between the ages of 20 to 64 years using a large primary care database (QResearch). Patients will be followed up until 1/08/2012. Details of all prescriptions for antidepressants in patients in the cohort will be extracted, including the date of each prescription, the type of antidepressant drug, the dose and total quantity prescribed. Prospectively recorded data will be used to ascertain information on adverse outcomes that occurred during follow-up and after entry into the cohort. These are: all-cause mortality, suicide, attempted suicide/self-harm, sudden death, antidepressant overdose/poisoning, myocardial infarction, stroke/ transient ischaemic attack, cardiac arrhythmia, epilepsy/seizures, upper gastrointestinal bleeding, falls, fractures, adverse drug reactions and motor vehicle crashes. Cox proportional hazard models will be used to estimate the association of the outcomes with class of antidepressant drug adjusting for potential confounding variables. The analyses will also examine associations by duration and dose and with the most frequently prescribed individual antidepressant drugs. Self-controlled case series analyses will be used to estimate the relative incidence of the outcomes of interest for defined time periods of antidepressant use. Discussion: The results of this study will help to establish the relative safety and balance of risks for different antidepressant drugs in people aged under 65. [ABSTRACT FROM AUTHOR]