Real-world outcomes of concomitant antidepressant and statin use in primary care patients with depression: a population-based cohort study

Background Antidepressants are licensed for use in depressive disorders, but non-response and poor adherence to treatment affect a considerable number of patients. Pre-clinical and clinical evidence suggest that statins can augment the effects of antidepressants. However, the acceptability and tolerability of combining statins with antidepressants are unclear, and their add-on efficacy has only been shown in small, short-term clinical trials. Observational data can provide complementary information about treatment effects on larger samples over longer follow-ups. In this study, we therefore assessed the real-world acceptability, tolerability, and efficacy of concomitant antidepressant and statin treatment in depression. Methods We conducted a population-based cohort study investigating QResearch primary care research database, which comprises the anonymised electronic healthcare records of 35 + million patients over 1574 English general practices. Patients aged 18–100 years, registered between January 1998 and August 2020, diagnosed with a new episode of depression, and commencing an antidepressant were included. Using a between-subject design, we identified two study groups: antidepressant + statin versus antidepressant-only prescriptions. Outcomes of interest included the following: antidepressant treatment discontinuations due to any cause (acceptability) and due to any adverse event (tolerability) and effects on depressive symptoms (efficacy) measured as response, remission, and change in depression score on the Patient Health Questionnaire-9. All outcomes were assessed at 2, 6, and 12 months using multivariable regression analyses, adjusted for relevant confounders, to calculate adjusted odds ratios (aORs) or mean differences (aMDs) with 99% confidence intervals (99% CIs). Results Compared to antidepressant-only (N 626,335), antidepressant + statin (N 46,482) was associated with higher antidepressant treatment acceptability (aOR2months 0.88, 99% CI 0.85 to 0.91; aOR6months 0.81, 99% CI 0.79 to 0.84; aOR12months 0.78, 99% CI 0.75 to 0.81) and tolerability (aOR2months 0.92, 99% CI 0.87 to 0.98; aOR6months 0.94, 99% CI 0.89 to 0.99, though not long term aOR12 months 1.02, 99% CI 0.97 to 1.06). Efficacy did not differ between groups (range aOR2-12 months 1.00 and 1.02 for response and remission, range aOR2-12 months − 0.01 and − 0.02 for change in depression score). Conclusions On real-world data, there is a positive correlation between antidepressant treatment adherence and statin use, partly explained by fewer dropouts due to adverse events. The main limitation of our study is its observational design, which restricts the potential to make causal inferences

Mortality and adverse events associated with statin use in primary care patients with depression: a real-world, population-based cohort study

Background: New National Institute for Health and Care Excellence (NICE) guidance endorses the prescription of statins in larger population groups for the prevention of cardiovascular and cerebrovascular morbidity and mortality, especially in people with severe mental illness. However, the evidence base for their safety and risk/benefit balance in depression is not established. Objectives: This study aims to assess the real-world mortality and adverse events of statins in depressive disorders. Methods: Population-based, nationwide (England), between-subject, cohort study. We used electronic health records (QResearch database) of people aged 18–100 years with first-episode depression, registered with English primary care practices over January 1998–August 2020 for 12(+) months, divided into statin users versus non-users. Primary safety outcomes included all-cause mortality and any adverse event measured at 2, 6 and 12 months. Multivariable logistic regression was employed to control for several potential confounders and calculate adjusted ORs (aORs) with 99% CIs. Findings: From over 1 050 105 patients with depression (42.64% males, mean age 43.23±18.32 years), 21 384 (2.04%) died, while 707 111 (67.34%) experienced at least one adverse event during the 12-month follow-up. Statin use was associated with lower mortality over 12 months (range aOR2–12months 0.66–0.67, range 99% CI 0.60 to 0.73) and with lower adverse events over 6 months (range aOR2–6months 0.90–0.96, range 99% CI 0.91 to 0.99), but not at 1 year (aOR12months 0.99, 99% CI 0.96 to 1.03). No association with any other individual outcome measure (ie, any other neuropsychiatric symptoms) was identified. Conclusions: We found no evidence that statin use among people with depression increases mortality or other adverse events. Clinical implications: Our findings support the safety of updated NICE guidelines for prescribing statins in people with depressive disorders

Real-world effect of antidepressants for depressive disorder in primary care: protocol of a population-based cohort study

Introduction: Clinical guidelines recommend antidepressants as the first line of treatment for adults with moderate-to-severe depression. Randomised trials provide the best evidence on the comparative effectiveness of antidepressants for depression, but are limited by a short follow-up and a highly selected population. We aim to conduct a cohort study on a large database to assess acceptability, efficacy, safety and tolerability of antidepressant monotherapy in people with depressive disorder in primary care.Methods and analysis: This is a protocol for a cohort study using data from the QResearch primary care research database, which is the largest general practice research database in the UK. We will include patients registered for at least 1 year from 1 January 1998, diagnosed with a new episode of depression and on antidepressant and a comparison group not on antidepressant. The exposure of interest will be treatment with antidepressant medications. Our outcomes will be acceptability (treatment discontinuation due to any cause), efficacy (clinical response and remission); safety (adverse events (AEs) and all-cause mortality); and tolerability (dropouts due to any AE) measured at 2 months, 6 months and 1 year. For each outcome, we will estimate the absolute risks for all antidepressants, and relative effects between antidepressants using Cox’s proportion hazards models. We will calculate HRs and 99.9% CIs for each outcome of interest.Discussion: The main limitation is the observational nature of our study, while the major strengths include the large representative population contained in QResearch and the possibly high generalisability

Development and validation of a meta-learner for combining statistical and machine learning prediction models in individuals with depression.

BACKGROUND The debate of whether machine learning models offer advantages over standard statistical methods when making predictions is ongoing. We discuss the use of a meta-learner model combining both approaches as an alternative. METHODS To illustrate the development of a meta-learner, we used a dataset of 187,757 people with depression. Using 31 variables, we aimed to predict two outcomes measured 60 days after initiation of antidepressant treatment: severity of depressive symptoms (continuous) and all-cause dropouts (binary). We fitted a ridge regression and a multi-layer perceptron (MLP) deep neural network as two separate prediction models ("base-learners"). We then developed two "meta-learners", combining predictions from the two base-learners. To compare the performance across the different methods, we calculated mean absolute error (MAE, for continuous outcome) and the area under the receiver operating characteristic curve (AUC, for binary outcome) using bootstrapping. RESULTS Compared to the best performing base-learner (MLP base-learner, MAE at 4.63, AUC at 0.59), the best performing meta-learner showed a 2.49% decrease in MAE at 4.52 for the continuous outcome and a 6.47% increase in AUC at 0.60 for the binary outcome. CONCLUSIONS A meta-learner approach may effectively combine multiple prediction models. Choosing between statistical and machine learning models may not be necessary in practice

Primary duodenal follicular lymphoma: 6-years complete remission after combined radio-immunotherapy

Primary gastrointestinal lymphoma (PGL) is known to account for 40% of all extranodal non-Hodgkin's lymphomas (NHLs) and between 4% to 12% of all NHLs. The small intestine is the site of presentation in 20-30% of cases, with the terminal ileum usually involved. Duodenal localizations have always been thought to be rare, but are presently growing in incidence. We herein report on a case of Stage IV primary duodenal FCL, located to the second portion of the duodenum with concomitant minimal bone marrow involvement. The patient was frontline approached with a conservative combined modality treatment consisting of 4 weekly infusions of the chimeric human-murine IgG1 mono-clonal antibody against the B-cell surface antigen CD-20, Rituximab (375 mg/m2) and consolidation 3D conformal external beam radiotherapy up to a total dose of 36 Gy given into 20 fractions to the involved duodenal portion. Six years after treatment has been completed, the patient is free from disease with no treatment-related toxicity. (Acta gastroenterol. belg., 2011, 74, 337-342)

Comparative efficacy and acceptability of pharmacological treatments for insomnia in adults: a systematic review and network meta-analysis

This is the protocol for a review and there is no abstract. The objectives are as follows: 1) To compare individual pharmacological treatments for insomnia in adults in terms of: efficacy, measured as self-rated quality of sleep or satisfaction with sleep; and acceptability of treatment. 2) To generate a clinically-useful hierarchy of available pharmacological treatments for insomnia in adults, according to their efficacy and acceptability

Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis.

BACKGROUND Behavioural, cognitive, and pharmacological interventions can all be effective for insomnia. However, because of inadequate resources, medications are more frequently used worldwide. We aimed to estimate the comparative effectiveness of pharmacological treatments for the acute and long-term treatment of adults with insomnia disorder. METHODS In this systematic review and network meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, PsycINFO, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and websites of regulatory agencies from database inception to Nov 25, 2021, to identify published and unpublished randomised controlled trials. We included studies comparing pharmacological treatments or placebo as monotherapy for the treatment of adults (≥18 year) with insomnia disorder. We assessed the certainty of evidence using the confidence in network meta-analysis (CINeMA) framework. Primary outcomes were efficacy (ie, quality of sleep measured by any self-rated scale), treatment discontinuation for any reason and due to side-effects specifically, and safety (ie, number of patients with at least one adverse event) both for acute and long-term treatment. We estimated summary standardised mean differences (SMDs) and odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with Open Science Framework, https://doi.org/10.17605/OSF.IO/PU4QJ. FINDINGS We included 170 trials (36 interventions and 47 950 participants) in the systematic review and 154 double-blind, randomised controlled trials (30 interventions and 44 089 participants) were eligible for the network meta-analysis. In terms of acute treatment, benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more efficacious than placebo (SMD range: 0·36-0·83 [CINeMA estimates of certainty: high to moderate]). Benzodiazepines, eszopiclone, zolpidem, and zopiclone were more efficacious than melatonin, ramelteon, and zaleplon (SMD 0·27-0·71 [moderate to very low]). Intermediate-acting benzodiazepines, long-acting benzodiazepines, and eszopiclone had fewer discontinuations due to any cause than ramelteon (OR 0·72 [95% CI 0·52-0·99; moderate], 0·70 [0·51-0·95; moderate] and 0·71 [0·52-0·98; moderate], respectively). Zopiclone and zolpidem caused more dropouts due to adverse events than did placebo (zopiclone: OR 2·00 [95% CI 1·28-3·13; very low]; zolpidem: 1·79 [1·25-2·50; moderate]); and zopiclone caused more dropouts than did eszopiclone (OR 1·82 [95% CI 1·01-3·33; low]), daridorexant (3·45 [1·41-8·33; low), and suvorexant (3·13 [1·47-6·67; low]). For the number of individuals with side-effects at study endpoint, benzodiazepines, eszopiclone, zolpidem, and zopiclone were worse than placebo, doxepin, seltorexant, and zaleplon (OR range 1·27-2·78 [high to very low]). For long-term treatment, eszopiclone and lemborexant were more effective than placebo (eszopiclone: SMD 0·63 [95% CI 0·36-0·90; very low]; lemborexant: 0·41 [0·04-0·78; very low]) and eszopiclone was more effective than ramelteon (0.63 [0·16-1·10; very low]) and zolpidem (0·60 [0·00-1·20; very low]). Compared with ramelteon, eszopiclone and zolpidem had a lower rate of all-cause discontinuations (eszopiclone: OR 0·43 [95% CI 0·20-0·93; very low]; zolpidem: 0·43 [0·19-0·95; very low]); however, zolpidem was associated with a higher number of dropouts due to side-effects than placebo (OR 2·00 [95% CI 1·11-3·70; very low]). INTERPRETATION Overall, eszopiclone and lemborexant had a favorable profile, but eszopiclone might cause substantial adverse events and safety data on lemborexant were inconclusive. Doxepin, seltorexant, and zaleplon were well tolerated, but data on efficacy and other important outcomes were scarce and do not allow firm conclusions. Many licensed drugs (including benzodiazepines, daridorexant, suvorexant, and trazodone) can be effective in the acute treatment of insomnia but are associated with poor tolerability, or information about long-term effects is not available. Melatonin, ramelteon, and non-licensed drugs did not show overall material benefits. These results should serve evidence-based clinical practice. FUNDING UK National Institute for Health Research Oxford Health Biomedical Research Centre

Sustain and reinforce transition from child to adult mental health care in Switzerland : study protocol

AIM A suboptimal transition in mental health care affects a young person’s wellbeing and health in the long run. We aim to identify a large cohort of young people approaching the transition boundary between child and adolescent and adult mental health services in the canton of Geneva and implement the model of managed transition for a randomly selected subset. METHODS We will perform a nested-cohort randomised controlled trial, which is a modification of the multiple cohort randomised controlled trial, where the allocation to the intervention is conducted by cluster randomisation, with each distinct mental health service constituting a cluster. We will include 387 adolescents with a mental disorder, without intellectual disability and within 18 months of reaching the transition boundary. We will randomly allocate mental health services to the intervention (managed transition) or control group (treatment as usual). The primary outcome is the patient’s health status as measured by Health of the Nation Outcome Scale for Children and Adolescents (HoNOSCA) or Health of the Nation Outcome Scale for adults (HoNOS). CONCLUSIONS This is a protocol of a nested-cohort randomised controlled trial. This study will promote change in health systems management and administration. It will facilitate close collaboration between child and adolescent and adult mental health services, which for decades have been completely separated and differentiated

Mapping child and adolescent mental health services and the interface during transition to adult services in six Swiss cantons

Rationale: Transition in psychiatry refers to the period where young people transit from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS). Discontinuity of care during this period is well-documented but little is known about provisions and transition characteristics and policies across Switzerland. The aim of this article is to describe the architecture of public mental health providers in Switzerland and compare it to EU countries. Method: Two mapping surveys, developed previously for European countries, were adapted and sent to cantonal experts: the adapted European CAMHS Mapping Questionnaire (ECM-Q) assessing the architecture and functioning of CAMHS and the adapted Standardized Assessment Tool for Mental Health Transition (SATMeHT) to map CAMHS-AMHS interface. Results: Data were gathered from six cantons. Activity data and transition policies were comparable between Swiss regions and European countries. The percentage of young people below 19 years who were in care was above 2% in every responding canton with a higher proportion of boys than girls for patients <12 years of age. The transition occurred at the age of 18 years, civil majority, in each canton, and between 0 and 24% (3/7) and 25% and 49% (4/7) of young people were expected to transition. One canton (1/7) benefitted from written guidelines, at the CAMHS level only, regarding transition but none had guidelines for mapping CAMHS/AMHS interface even at the regional level. Conclusion: Despite the availability of resources and even if the possibilities of access to care are on average higher than in many European countries, issues regarding transition remain comparable in six Swiss cantons when compared to Europe. Meaning that beyond resources, it is the coordination between services that needs to be worked on. Importantly, implementing those changes would not require investing financial resources but rather working on the coordination between existing teams