Understanding Australian general practice patients' decisions to deprescribe antidepressants in the WiserAD trial: a realist informed approach.

OBJECTIVES: To evaluate how an approach to antidepressant deprescribing works, for whom, and in what contexts by (1) examining the experiences and perceptions of the approach for antidepressant users, (2) identifying the mechanisms of the approach and (3) describing what contexts are associated with antidepressant tapering. DESIGN: This mixed methods study was informed by the principles of realist evaluation and was conducted in the first 3 months of participation in the WiserAD randomised control trial. SETTING: General practice, Victoria, Australia. PARTICIPANTS: 13 antidepressant users from general practice participating in the WiserAD trial for antidepressant deprescribing. INTERVENTION: A patient-facing, web-based structured support tool that consists of a personalised tapering schedule, an action plan for managing withdrawal symptoms, a daily mood, sleep and activity tracker and mental health nurse support. PRIMARY/SECONDARY OUTCOME MEASURES: The outcomes of the study were revealed on data analysis as per a realist evaluation approach which tests and refines an initial programme theory. RESULTS: The contexts of learnt coping skills, knowledge and perceptions of antidepressants and feeling well were evident. Outcomes were intention to commence, initiation of deprescribing and successful completion of deprescribing. Key mechanisms for antidepressant deprescribing were (1) initiation of the deprescribing discussion; (2) patient self-efficacy; (3) provision of structured guidance; (4) coaching; (5) mood, sleep and activity tracking and (6) feelings of safety during the tapering period. CONCLUSIONS: The WiserAD approach to antidepressant deprescribing supported participants to commence and/or complete tapering. The refined programme theory presents the WiserAD pragmatic framework for the application of antidepressant deprescribing in clinical practice. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT05355025; ACTRN12622000567729; ISRCTN11562922; Pre-results.

Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders.

OBJECTIVE: Blood biomarkers of neuronal injury such as neurofilament light (NfL) show promise to improve diagnosis of neurodegenerative disorders and distinguish neurodegenerative from primary psychiatric disorders (PPD). This study investigated the diagnostic utility of plasma NfL to differentiate behavioural variant frontotemporal dementia (bvFTD, a neurodegenerative disorder commonly misdiagnosed initially as PPD), from PPD, and performance of large normative/reference data sets and models. METHODS: Plasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), bvFTD (n = 22), and compared to the reference cohort (Control Group 2, n = 1926, using GAMLSS modelling), and age-matched controls (Control Group 1, n = 96, using general linear models). RESULTS: Large differences were seen between bvFTD (mean NfL 34.9 pg/mL) and all PPDs and controls (all < 11 pg/mL). NfL distinguished bvFTD from PPD with high accuracy, sensitivity (86%), and specificity (88%). GAMLSS models using reference Control Group 2 facilitated precision interpretation of individual levels, while performing equally to or outperforming models using local controls. Slightly higher NfL levels were found in BPAD, compared to controls and TRS. CONCLUSIONS: This study adds further evidence on the diagnostic utility of NfL to distinguish bvFTD from PPD of high clinical relevance to a bvFTD differential diagnosis, and includes the largest cohort of BPAD to date. Using large reference cohorts, GAMLSS modelling and the interactive Internet-based application we developed, may have important implications for future research and clinical translation. Studies are underway investigating utility of plasma NfL in diverse neurodegenerative and primary psychiatric conditions in real-world clinical settings.

A mixed-methods evaluation of the impacts of an online Carer wellbeing and connection program.

Objective: To evaluate a facilitated, 90-min session, delivered for four weeks, Online Carer Wellbeing and Connection Program in Victoria, Australia. Methods: One hundred and three carers took part in the evaluation. Eighty-six completed both pre- and post-program surveys evaluating program impacts on psychological distress, perceived loneliness, and social support. Qualitative interviews were conducted (n = 76) post-program for experiential data. Findings: Paired samples t-tests showed significant decreases between pre- and post-program for psychological distress (M = 25.10, SD = 7.08; M = 22.00, SD = 6.57; t(85) = 4.88, p = 0.000), perceived loneliness (M = 6.69, SD = 1.89; M = 6.14, SD = 1.76; t(85) = 3.45, p = 0.000) and perceived social support (M = 8.31, SD = 2.48; M = 8.83, SD = 2.21; t(85) = -2.54, p = 0.013). Thematic analysis identified positive experiences and the mechanisms of action (or the ingredients for program success) as: 1. Delivery by a trained facilitator; 2. Provision of respite for person being cared for during meetings; 3. Technical assistance; 4. Online modality; 5. Inclusivity; 6. Diversity of experience; 7. Shared understanding; 8. Safety; 9. Emotional release; 10. Reflection, and; 11. Self-care practices. Innovation: A model illustrating the mechanisms of action based on the findings of the mixed-methods evaluation is presented to support wider implementation and translation. Conclusion: The online program effectively reduced psychological distress and loneliness and improved carer wellbeing.

Self-reported reasons for reducing or stopping antidepressant medications in primary care: thematic analysis of the diamond longitudinal study.

BACKGROUND: Current treatment guidelines advise that the deprescribing of antidepressants should occur around 6 months post-remission of symptoms. However, this is not routinely occurring in clinical practice, with between 30% and 50% of antidepressant users potentially continuing treatment with no clinical benefit. To support patients to deprescribe antidepressant treatment when clinically appropriate, it is important to understand what is important to patients when making the decision to reduce or cease antidepressants in a naturalistic setting. AIM: The current study aimed to describe the self-reported reasons primary care patients have for reducing or stopping their antidepressant medication. METHODS: Three hundred and seven participants in the diamond longitudinal study reported taking an SSRI/SNRI over the life of the study. Of the 307, 179 reported stopping or tapering their antidepressant during computer-assisted telephone interviews and provided a reason for doing so. A collective case study approach was used to collate the reasons for stopping or tapering. FINDINGS: Reflexive thematic analysis of patient-reported factors revealed five overarching themes; 1. Depression; 2. Medication; 3. Healthcare system; 4. Psychosocial, and; 5. Financial. These findings are used to inform suggestions for the development and implementation of antidepressant deprescribing discussions in clinical practice.

General Practice Patients' Experiences and Perceptions of the WiserAD Structured Web-Based Support Tool for Antidepressant Deprescribing: Protocol for a Mixed Methods Case Study With Realist Evaluation.

BACKGROUND: Research suggests that the rapid increase in worldwide antidepressant use is mainly due to a rise in long-term and potentially inappropriate use. It has been suggested that 1 in 3 antidepressant users among general practice patients are no longer experiencing clinical benefits from their medication and should commence deprescribing. However there are many barriers to antidepressant deprescribing for both patients and clinicians, which adds to the complex nature of reducing or ceasing the medication. As such, antidepressant deprescribing does not routinely occur in clinical practice. Evidence-based supports and interventions for safe and successful antidepressant deprescribing are needed to assist patients and their doctors. Interventions should also include an understanding of how an intervention works, why it works, and whom it is for. OBJECTIVE: This study aims to evaluate how the WiserAD approach to antidepressant deprescribing works, whom it is for, and the underlying circumstances by (1) examining the experiences and perceptions of WiserAD among antidepressant users, (2) identifying the underlying mechanisms of the WiserAD approach to antidepressant deprescribing, and (3) describing in what contexts and to what extent the underlying mechanisms of WiserAD are suited for antidepressant users. METHODS: A mixed methods case study with realist evaluation will be conducted among participants in the WiserAD randomized controlled trial for antidepressant deprescribing. Quantitative data will be obtained from up to 12 participants from the intervention and control arms at baseline and 3-month follow-up. Baseline data will be used to characterize the sample using descriptive statistics. Paired samples t tests will also be performed to compare responses between baseline and 3-month follow-up for participant self-management, skills, confidence and knowledge, beliefs about medicines, current emotional health, and well-being symptoms. Qualitative data from the same participants will be collected via narrative interview at 3-month follow-up. Quantitative and qualitative data will be converged to form a "case," and analysis will be conducted within each case with comparisons made across multiple cases. RESULTS: Recruitment of participants commenced in October 2022 and will be completed by March 2023. Analysis will be completed by June 2023. CONCLUSIONS: To our knowledge, this will be the first realist evaluation of an antidepressant deprescribing intervention in general practice. Findings from this evaluation may assist in the implementation of the WiserAD approach to antidepressant deprescribing in routine clinical practice. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/42526.

Economic evaluation of the Target-D platform to match depression management to severity prognosis in primary care: A within-trial cost-utility analysis.

BACKGROUND: Target-D, a new person-centred e-health platform matching depression care to symptom severity prognosis (minimal/mild, moderate or severe) has demonstrated greater improvement in depressive symptoms than usual care plus attention control. The aim of this study was to evaluate the cost-effectiveness of Target-D compared to usual care from a health sector and partial societal perspective across 3-month and 12-month follow-up. METHODS AND FINDINGS: A cost-utility analysis was conducted alongside the Target-D randomised controlled trial; which involved 1,868 participants attending 14 general practices in metropolitan Melbourne, Australia. Data on costs were collected using a resource use questionnaire administered concurrently with all other outcome measures at baseline, 3-month and 12-month follow-up. Intervention costs were assessed using financial records compiled during the trial. All costs were expressed in Australian dollars (A$) for the 2018-19 financial year. QALY outcomes were derived using the Assessment of Quality of Life-8D (AQoL-8D) questionnaire. On a per person basis, the Target-D intervention cost between $14 (minimal/mild prognostic group) and $676 (severe group). Health sector and societal costs were not significantly different between trial arms at both 3 and 12 months. Relative to a A$50,000 per QALY willingness-to-pay threshold, the probability of Target-D being cost-effective under a health sector perspective was 81% at 3 months and 96% at 12 months. From a societal perspective, the probability of cost-effectiveness was 30% at 3 months and 80% at 12 months. CONCLUSIONS: Target-D is likely to represent good value for money for health care decision makers. Further evaluation of QALY outcomes should accompany any routine roll-out to assess comparability of results to those observed in the trial. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616000537459).

Deprescribing intervention activities mapped to guiding principles for use in general practice: a scoping review.

OBJECTIVE: To identify and characterise activities for deprescribing used in general practice and to map the identified activities to pioneering principles of deprescribing. SETTING: Primary care. DATA SOURCES: Medline, EMBASE (Ovid), CINAHL, Australian New Zealand Clinical Trials Registry (ANZCTR), Clinicaltrials.gov, ISRCTN registry, OpenGrey, Annals of Family Medicine, BMC Family Practice, Family Practice and British Journal of General Practice (BJGP) from inception to the end of June 2021. STUDY SELECTION: Included studies were original research (randomised controlled trial, quasi-experimental, cohort study, qualitative and case studies), protocol papers and protocol registrations. DATA EXTRACTION: Screening and data extraction was completed by one reviewer; 10% of the studies were independently reviewed by a second reviewer. Coding of full-text articles in NVivo was conducted and mapped to five deprescribing principles. RESULTS: Fifty studies were included. The most frequently used activities were identification of appropriate patients for deprescribing (76%), patient education (50%), general practitioners (GP) education (48%), and development and use of a tapering schedule (38%). Six activities did not align with the five deprescribing principles. As such, two principles (engage practice staff in education and appropriate identification of patients, and provide feedback to staff about deprescribing occurrences within the practice) were added. CONCLUSION: Activities and guiding principles for deprescribing should be paired together to provide an accessible and comprehensive guide to deprescribing by GPs. The addition of two principles suggests that practice staff and practice management teams may play an instrumental role in sustaining deprescribing processes within clinical practice. Future research is required to determine the most of effective activities to use within each principle and by whom.

Is peripartum maternal fever alone a reliable predictor of neonatal sepsis? A single-centre, retrospective cohort study.

AIM: To determine the incidence rate of early-onset neonatal sepsis (EONS) among term neonates (gestation greater than 37 weeks) admitted to the neonatal intensive care unit for suspected sepsis and the association of EONS with maternal fever (temperature greater than 38°C). METHODS: A single-centre retrospective cohort study of all term neonates (gestation >37 weeks) admitted to and treated in the neonatal unit at the Townsville University Hospital between March 2015 and March 2020. Neonatal sepsis was confirmed with positive neonatal blood culture. Data on neonatal birth/stay and maternal pregnancy were collected from the electronic medical records and neonatal database. RESULTS: Data from 737 neonates who were admitted for treatment of EONS were analysed. Sixty % (426) reported maternal intrapartum fever, with 1.1% (5) of neonates developing blood culture-proven sepsis. Forty % did not report intrapartum fever (311), with 3% (9) of neonates developing sepsis. As such, the sensitivity and specificity of maternal fever are 1.14% and 97%, respectively. The positive predictive value was 35.7%, and the negative predictive value was 40.1%. Fourteen neonates developed EONS, and all of them were symptomatic. Seventy-eight % (334/426) of the women in the febrile group received epidural analgesia compared to 5% (16/311) in the afebrile group. Of the 95 neonates born to women with chorioamnionitis, one (1.0%) of the neonates born to women with chorioamnionitis developed sepsis. CONCLUSIONS: Intrapartum maternal fever is an unreliable predictor for EONS and leads to unnecessary antibiotic treatment. Symptoms in the neonate are a more reliable indicator of an ill neonate with blood culture-proven sepsis.

Matching depression management to severity prognosis in primary care: results of the Target-D randomised controlled trial.

BACKGROUND: Mental health treatment rates are increasing, but the burden of disease has not reduced. Tools to support efficient resource distribution are required. AIM: To investigate whether a person-centred e-health (Target-D) platform matching depression care to symptom severity prognosis can improve depressive symptoms relative to usual care. DESIGN AND SETTING: Stratified individually randomised controlled trial in 14 general practices in Melbourne, Australia, from April 2016 to February 2019. In total, 1868 participants aged 18-65 years who had current depressive symptoms; internet access; no recent change to antidepressant; no current antipsychotic medication; and no current psychological therapy were randomised (1:1) via computer-generated allocation to intervention or usual care. METHOD: The intervention was an e-health platform accessed in the GP waiting room, comprising symptom feedback, priority-setting, and prognosis-matched management options (online self-help, online guided psychological therapy, or nurse-led collaborative care). Management options were flexible, neither participants nor staff were blinded, and there were no substantive protocol deviations. The primary outcome was depressive symptom severity (9-item Patient Health Questionnaire [PHQ-9]) at 3 months. RESULTS: In intention to treat analysis, estimated between- arm difference in mean PHQ-9 scores at 3 months was -0.88 (95% confidence interval [CI] = -1.45 to -0.31) favouring the intervention, and -0.59 at 12 months (95% CI = -1.18 to 0.01); standardised effect sizes of -0.16 (95% CI = -0.26 to -0.05) and -0.10 (95% CI = -0.21 to 0.002), respectively. No serious adverse events were reported. CONCLUSION: Matching management to prognosis using a person-centred e-health platform improves depressive symptoms at 3 months compared to usual care and could feasibly be implemented at scale. Scope exists to enhance the uptake of management options.

Development of a Mobile Clinical Prediction Tool to Estimate Future Depression Severity and Guide Treatment in Primary Care: User-Centered Design.

BACKGROUND: Around the world, depression is both under- and overtreated. The diamond clinical prediction tool was developed to assist with appropriate treatment allocation by estimating the 3-month prognosis among people with current depressive symptoms. Delivering clinical prediction tools in a way that will enhance their uptake in routine clinical practice remains challenging; however, mobile apps show promise in this respect. To increase the likelihood that an app-delivered clinical prediction tool can be successfully incorporated into clinical practice, it is important to involve end users in the app design process. OBJECTIVE: The aim of the study was to maximize patient engagement in an app designed to improve treatment allocation for depression. METHODS: An iterative, user-centered design process was employed. Qualitative data were collected via 2 focus groups with a community sample (n=17) and 7 semistructured interviews with people with depressive symptoms. The results of the focus groups and interviews were used by the computer engineering team to modify subsequent protoypes of the app. RESULTS: Iterative development resulted in 3 prototypes and a final app. The areas requiring the most substantial changes following end-user input were related to the iconography used and the way that feedback was provided. In particular, communicating risk of future depressive symptoms proved difficult; these messages were consistently misinterpreted and negatively viewed and were ultimately removed. All participants felt positively about seeing their results summarized after completion of the clinical prediction tool, but there was a need for a personalized treatment recommendation made in conjunction with a consultation with a health professional. CONCLUSIONS: User-centered design led to valuable improvements in the content and design of an app designed to improve allocation of and engagement in depression treatment. Iterative design allowed us to develop a tool that allows users to feel hope, engage in self-reflection, and motivate them to treatment. The tool is currently being evaluated in a randomized controlled trial.

Target-D: a stratified individually randomized controlled trial of the diamond clinical prediction tool to triage and target treatment for depressive symptoms in general practice: study protocol for a randomized controlled trial.

BACKGROUND: Depression is a highly prevalent and costly disorder. Effective treatments are available but are not always delivered to the right person at the right time, with both under- and over-treatment a problem. Up to half the patients presenting to general practice report symptoms of depression, but general practitioners have no systematic way of efficiently identifying level of need and allocating treatment accordingly. Therefore, our team developed a new clinical prediction tool (CPT) to assist with this task. The CPT predicts depressive symptom severity in three months' time and based on these scores classifies individuals into three groups (minimal/mild, moderate, severe), then provides a matched treatment recommendation. This study aims to test whether using the CPT reduces depressive symptoms at three months compared with usual care. METHODS: The Target-D study is an individually randomized controlled trial. Participants will be 1320 general practice patients with depressive symptoms who will be approached in the practice waiting room by a research assistant and invited to complete eligibility screening on an iPad. Eligible patients will provide informed consent and complete the CPT on a purpose-built website. A computer-generated allocation sequence stratified by practice and depressive symptom severity group, will randomly assign participants to intervention (treatment recommendation matched to predicted depressive symptom severity group) or comparison (usual care plus Target-D attention control) arms. Follow-up assessments will be completed online at three and 12 months. The primary outcome is depressive symptom severity at three months. Secondary outcomes include anxiety, mental health self-efficacy, quality of life, and cost-effectiveness. Intention-to-treat analyses will test for differences in outcome means between study arms overall and by depressive symptom severity group. DISCUSSION: To our knowledge, this is the first depressive symptom stratification tool designed for primary care which takes a prognosis-based approach to provide a tailored treatment recommendation. If shown to be effective, this tool could be used to assist general practitioners to implement stepped mental-healthcare models and contribute to a more efficient and effective mental health system. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR 12616000537459 ). Retrospectively registered on 27 April 2016. See Additional file 1 for trial registration data.

Depression and anger in fathers of unsettled infants: A community cohort study.

AIM: To examine the relationship between unsettled infant behaviour and fathers' depressive symptoms, cognitions surrounding infant sleep (anger, doubt), and personal sleep, in a community cohort. METHODS: Data were collected from 102 fathers of healthy infants at 4 weeks, 4 months and 6 months of age. Measures included father report of infant sleep and crying problems, depressive symptoms, cognitions about infant sleep and own sleep quality and quantity. Data were analysed using adjusted regression models. RESULTS: Sleep problems at 4 months of age were associated with increased depressive symptoms (adjusted mean difference 2.64 (1.27-4.00)), doubt (adjusted mean difference 1.82 (0.40-3.25)), anger (adjusted mean difference 1.86 (0.51-3.20)), poor personal sleep quantity (adjusted odds ratio (OR) 0.21; 95% confidence interval (CI) 0.09-0.51) and quality (adjusted OR 0.20; 95% CI 0.08-0.51); and at 6 months of age, with increased depressive symptoms (adjusted mean difference 2.56 (1.28-3.84)), anger (adjusted mean difference 1.63 (0.40-2.87)), poor personal sleep quantity (adjusted OR 0.14; 95% CI 0.05-0.38) and quality (adjusted OR 0.28; 95% CI 0.11-0.72). Infant cry problems at 4 months were associated with increased anger (adjusted mean difference 1.98 (0.60-3.36)) and doubt (adjusted mean difference 1.55 (0.05-3.05)); and at 6 months, with increased depressive symptoms (adjusted mean difference 3.04 (1.59-4.69)), anger (adjusted mean difference 2.73 (1.29-4.17)) and less personal sleep (adjusted OR 0.22; 95% CI 0.07-0.71). CONCLUSION: Fathers of unsettled infants reported greater anger towards their infant and increased depressive symptoms by 4 months infant age, with these symptoms persisting 2 months later. Evidence-based interventions are needed for these fathers.