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Importance: There is significant concern regarding increasing long-term antidepressant treatment for depression beyond an evidence-based duration. Objective: To determine whether adding internet and telephone support to a family practitioner review to consider discontinuing long-term antidepressant treatment is safe and more effective than a practitioner review alone. Design, Setting, and Participants: In this cluster randomized clinical trial, 131 UK family practices were randomized between December 1, 2018, and March 31, 2022, with remote computerized allocation and 12 months of follow-up. Participants and researchers were aware of allocation, but analysis was blind. Participants were adults who were receiving antidepressants for more than 1 year for a first episode of depression or more than 2 years for recurrent depression who were currently well enough to consider discontinuation and wished to do so and who were at low risk of relapse. Of 6725 patients mailed invitations, 330 (4.9%) were eligible and consented. Interventions: Internet and telephone self-management support, codesigned and coproduced with patients and practitioners. Main Outcomes and Measures: The primary (safety) outcome was depression at 6 months (prespecified complete-case analysis), testing for noninferiority of the intervention to under 2 points on the 9-item Patient Health Questionnaire (PHQ-9). Secondary outcomes (testing for superiority) were antidepressant discontinuation, anxiety, quality of life, antidepressant withdrawal symptoms, mental well-being, enablement, satisfaction, use of health care services, and adverse events. Analyses for the main outcomes were performed on a complete-case basis, and multiple imputation sensitivity analysis was performed on an intention-to-treat basis. Results: Of 330 participants recruited (325 eligible for inclusion; 178 in intervention practices and 147 in control practices; mean [SD] age at baseline, 54.0 [14.9] years; 223 women [68.6%]), 276 (83.6%) were followed up at 6 months, and 240 (72.7%) at 12 months. The intervention proved noninferior; mean (SD) PHQ-9 scores at 6 months were slightly lower in the intervention arm than in the control arm in the complete-case analysis (4.0 [4.3] vs 5.0 [4.7]; adjusted difference, -1.1; 95% CI, -2.1 to -0.1; P = .03) but not significantly different in an intention-to-treat multiple imputation sensitivity analysis (adjusted difference, -0.9 (95% CI, -1.9 to 0.1; P = .08). By 6 months, antidepressants had been discontinued by 66 of 145 intervention arm participants (45.5%) who provided discontinuation data and 54 of 129 control arm participants (41.9%) (adjusted odds ratio, 1.02; 95% CI, 0.52-1.99; P = .96). In the intervention arm, antidepressant withdrawal symptoms were less severe, and mental well-being was better compared with the control arm; differences were small but significant. There were no significant differences in the other outcomes; 28 of 179 intervention arm participants (15.6%) and 22 of 151 control arm participants (14.6%) experienced adverse events. Conclusions and Relevance: In this cluster randomized clinical trial of adding internet and telephone support to a practitioner review for possible antidepressant discontinuation, depression was slightly better with support, but the rate of discontinuation of antidepressants did not significantly increase. Improvements in antidepressant withdrawal symptoms and mental well-being were also small. There were no significant harms. Family practitioner review for possible discontinuation of antidepressants appeared safe and effective for more than 40% of patients willing and well enough to discontinue. Trial Registration: ISRCTN registry Identifiers: ISRCTN15036829 (internal pilot trial) and ISRCTN12417565 (main trial).
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Antidepresivos , Internet , Teléfono , Humanos , Femenino , Masculino , Antidepresivos/uso terapéutico , Persona de Mediana Edad , Adulto , Depresión/tratamiento farmacológico , Reino UnidoRESUMEN
PURPOSE: Antidepressants are a first-line treatment for depression, yet many patients do not respond. There is a need to understand which patients have greater treatment response but there is little research on patient characteristics that moderate the effectiveness of antidepressants. This study examined potential moderators of response to antidepressant treatment. METHODS: The PANDA trial investigated the clinical effectiveness of sertraline (n = 326) compared with placebo (n = 329) in primary care patients with depressive symptoms. We investigated 11 potential moderators of treatment effect (age, employment, suicidal ideation, marital status, financial difficulty, education, social support, family history of depression, life events, health and past antidepressant use). Using multiple linear regression, we investigated the appropriate interaction term for each of these potential moderators with treatment as allocated. RESULTS: Family history of depression was the only variable with weak evidence of effect modification (p-value for interaction = 0.048), such that those with no family history of depression may have greater benefit from antidepressant treatment. We found no evidence of effect modification (p-value for interactions≥0.29) by any of the other ten variables. CONCLUSION: Evidence for treatment moderators was extremely limited, supporting an approach of continuing discuss antidepressant treatment with all patients presenting with moderate to severe depressive symptoms.
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Antidepresivos , Depresión , Atención Primaria de Salud , Sertralina , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológico , Análisis de Datos Secundarios , Sertralina/uso terapéutico , Resultado del TratamientoRESUMEN
INTRODUCTION: Long-term antidepressant (AD) use, much longer than recommended, is very common and can lead to potential harms. OBJECTIVE: To investigate the existing literature on perspectives of health professionals (HPs) regarding long-term AD treatment, focusing on barriers and facilitators to discontinuation. METHODS: A systematic review with thematic synthesis. Eight electronic databases were searched until August 2023 including MEDLINE, PubMed, Embase, PsycINFO, CINAHL, AMED, Health Management Information Consortium, and the Networked Digital Library of Theses and Dissertation. RESULTS: Thirteen studies were included in the review. Of these, nine focused on general practitioner perspectives, one on psychiatrist perspectives, and three on a mix of HPs perspectives. Barriers and facilitators to discontinuing long-term ADs emerged within eight themes, ordered chronologically based on HP considerations during an AD review: perception of AD use, fears, HP role and responsibility, HPs' perception of AD discontinuation, HPs' confidence regarding their ability to manage discontinuation, perceived patient readiness to stop, support from patient's trusted people, and support from other HPs. LIMITATIONS: Coding and development of subthemes and themes was performed by one researcher and further developed through discussion within the research team. CONCLUSION: Deprescribing long-term ADs is a challenging concept for HPs. The review found evidence that the barriers far outweigh the facilitators with fear of relapse as a main barrier. HP education, reassurance and confidence-building is essential to increase the initiation of the discontinuation process. Further research into the perspectives of pharmacists and mental health workers is needed as well as exploring the role of trusted people.
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Antidepresivos , Humanos , Antidepresivos/uso terapéutico , Actitud del Personal de Salud , Personal de SaludRESUMEN
Background: Guidelines on the management of depression recommend that practitioners use patient-reported outcome measures for the follow-up monitoring of symptoms, but there is a lack of evidence of benefit in terms of patient outcomes. Objective: To test using the Patient Health Questionnaire-9 questionnaire as a patient-reported outcome measure for monitoring depression, training practitioners in interpreting scores and giving patients feedback. Design: Parallel-group, cluster-randomised superiority trial; 1 : 1 allocation to intervention and control. Setting: UK primary care (141 group general practices in England and Wales). Inclusion criteria: Patients aged ≥ 18 years with a new episode of depressive disorder or symptoms, recruited mainly through medical record searches, plus opportunistically in consultations. Exclusions: Current depression treatment, dementia, psychosis, substance misuse and risk of suicide. Intervention: Administration of the Patient Health Questionnaire-9 questionnaire with patient feedback soon after diagnosis, and at follow-up 10-35 days later, compared with usual care. Primary outcome: Beck Depression Inventory, 2nd edition, symptom scores at 12 weeks. Secondary outcomes: Beck Depression Inventory, 2nd edition, scores at 26 weeks; antidepressant drug treatment and mental health service contacts; social functioning (Work and Social Adjustment Scale) and quality of life (EuroQol 5-Dimension, five-level) at 12 and 26 weeks; service use over 26 weeks to calculate NHS costs; patient satisfaction at 26 weeks (Medical Informant Satisfaction Scale); and adverse events. Sample size: The original target sample of 676 patients recruited was reduced to 554 due to finding a significant correlation between baseline and follow-up values for the primary outcome measure. Randomisation: Remote computerised randomisation with minimisation by recruiting university, small/large practice and urban/rural location. Blinding: Blinding of participants was impossible given the open cluster design, but self-report outcome measures prevented observer bias. Analysis was blind to allocation. Analysis: Linear mixed models were used, adjusted for baseline depression, baseline anxiety, sociodemographic factors, and clustering including practice as random effect. Quality of life and costs were analysed over 26 weeks. Qualitative interviews: Practitioner and patient interviews were conducted to reflect on trial processes and use of the Patient Health Questionnaire-9 using the Normalization Process Theory framework. Results: Three hundred and two patients were recruited in intervention arm practices and 227 patients were recruited in control practices. Primary outcome data were collected for 252 (83.4%) and 195 (85.9%), respectively. No significant difference in Beck Depression Inventory, 2nd edition, score was found at 12 weeks (adjusted mean difference -0.46, 95% confidence interval -2.16 to 1.26). Nor were significant differences found in Beck Depression Inventory, 2nd Edition, score at 26 weeks, social functioning, patient satisfaction or adverse events. EuroQol-5 Dimensions, five-level version, quality-of-life scores favoured the intervention arm at 26 weeks (adjusted mean difference 0.053, 95% confidence interval 0.013 to 0.093). However, quality-adjusted life-years over 26 weeks were not significantly greater (difference 0.0013, 95% confidence interval -0.0157 to 0.0182). Costs were lower in the intervention arm but, again, not significantly (-£163, 95% confidence interval -£349 to £28). Cost-effectiveness and cost-utility analyses, therefore, suggested that the intervention was dominant over usual care, but with considerable uncertainty around the point estimates. Patients valued using the Patient Health Questionnaire-9 to compare scores at baseline and follow-up, whereas practitioner views were more mixed, with some considering it too time-consuming. Conclusions: We found no evidence of improved depression management or outcome at 12 weeks from using the Patient Health Questionnaire-9, but patients' quality of life was better at 26 weeks, perhaps because feedback of Patient Health Questionnaire-9 scores increased their awareness of improvement in their depression and reduced their anxiety. Further research in primary care should evaluate patient-reported outcome measures including anxiety symptoms, administered remotely, with algorithms delivering clear recommendations for changes in treatment. Study registration: This study is registered as IRAS250225 and ISRCTN17299295. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/42/02) and is published in full in Health Technology Assessment; Vol. 28, No. 17. See the NIHR Funding and Awards website for further award information.
Depression is common, can be disabling and costs the nation billions. The National Health Service recommends general practitioners who treat people with depression use symptom questionnaires to help assess whether those people are getting better over time. A symptom questionnaire is one type of patient-reported outcome measure. Patient-reported outcome measures appear to benefit people having therapy and mental health care, but this approach has not been tested thoroughly in general practice. Most people with depression are treated in general practice, so it is important to test patient-reported outcome measures there, too. In this study, we tested whether using a patient-reported outcome measure helps people with depression get better more quickly. The study was a 'randomised controlled trial' in general practices, split into two groups. In one group, people with depression completed the Patient Health Questionnaire, or 'PHQ-9', patient-reported outcome measure, which measures nine symptoms of depression. In the other group, people with depression were treated as usual without the Patient Health Questionnaire-9. We fed the results of the Patient Health Questionnaire-9 back to the people with depression themselves to show them how severe their depression was and asked them to discuss the results with the practitioners looking after them. We found no differences between the patient-reported outcome measure group and the control group in their level of depression; their work or social life; their satisfaction with care from their practice; or their use of medicines, therapy or specialist care for depression. However, we did find that their quality of life was improved at 6 months, and the costs of the National Health Service services they used were lower. Using the Patient Health Questionnaire-9 can improve patients' quality of life, perhaps by making them more aware of improvement in their depression symptoms, and less anxious as a result. Future research should test using a patient-reported outcome measure that includes anxiety and processing the answers through a computer to give practitioners clearer advice on possible changes to treatment for depression.
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Depresión , Calidad de Vida , Humanos , Análisis Costo-Beneficio , Depresión/terapia , Medición de Resultados Informados por el Paciente , Atención Primaria de Salud , Adulto Joven , AdultoRESUMEN
BACKGROUND: Primary care clinicians see people experiencing the full range of mental health problems. Determining when symptoms reflect disorder is complex. The Four-Dimensional Symptom Questionnaire (4DSQ) uniquely distinguishes general distress from depressive and anxiety disorders. It may support diagnostic conversations and targeting of treatment. AIM: To explore peoples' experiences of completing the 4DSQ and their perceptions of their resulting score profile across distress, depression, anxiety, and physical symptoms. DESIGN AND SETTING: A qualitative study was conducted in the UK with people recruited from primary care and community settings. METHOD: Participants completed the 4DSQ then took part in semi-structured telephone interviews. They were interviewed about their experience of completing the 4DSQ, their perceptions of their scores across four dimensions, and the perceived utility if used with a clinician. Interviews were transcribed verbatim and data were analysed thematically. RESULTS: Twenty-four interviews were conducted. Most participants found the 4DSQ easy to complete and reported that scores across the four dimensions aligned well with their symptom experience. Distinct scores for distress, depression, and anxiety appeared to support improved self-understanding. Some valued the opportunity to discuss their scores and provide relevant context. Many felt the use of the 4DSQ with clinicians would be helpful and likely to support treatment decisions, although some were concerned about time-limited consultations. CONCLUSION: Distinguishing general distress from depressive and anxiety disorders aligned well with people's experience of symptoms. Use of the 4DSQ as part of mental health consultations may support targeting of treatment and personalisation of care.
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Atención Primaria de Salud , Investigación Cualitativa , Humanos , Femenino , Masculino , Encuestas y Cuestionarios , Adulto , Persona de Mediana Edad , Distrés Psicológico , Diagnóstico Diferencial , Reino Unido , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/psicología , Trastornos Mentales/diagnósticoRESUMEN
BACKGROUND: Outcome monitoring of depression treatment is recommended but there is a lack of evidence on patient benefit in primary care. AIM: To test monitoring depression using the Patient Health Questionnaire (PHQ-9) with patient feedback. DESIGN AND SETTING: An open cluster-randomised controlled trial was undertaken in 141 group practices. METHOD: Adults with new depressive episodes were recruited through record searches and opportunistically. The exclusion criteria were as follows: dementia; psychosis; substance misuse; and suicide risk. The PHQ-9 was administered soon after diagnosis, and 10-35 days later. The primary outcome was the Beck Depression Inventory (BDI-II) score at 12 weeks. The secondary outcomes were as follows: BDI-II at 26 weeks; Work and Social Adjustment Scale (WSAS) and EuroQol EQ-5D-5L quality of life at 12 and 26 weeks; antidepressant treatment; mental health and social service contacts; adverse events, and Medical Interview Satisfaction Scale (MISS) over 26 weeks. RESULTS: In total, 302 patients were recruited to the intervention arm and 227 to the controls. At 12 weeks, 254 (84.1%) and 199 (87.7%) were followed-up, respectively. Only 40.9% of patients in the intervention had a GP follow-up PHQ-9 recorded. There was no significant difference in BDI-II score at 12 weeks (mean difference -0.46; 95% confidence interval [CI] = -2.16 to 1.26; adjusted for baseline depression, baseline anxiety, sociodemographic factors, and clustering by practice). EQ-5D-5L quality-of-life scores were higher in the intervention arm at 26 weeks (adjusted mean difference 0.053; 95% CI = 0.013 to 0.093. A clinically significant difference in depression at 26 weeks could not be ruled out. No significant differences were found in social functioning, adverse events, or satisfaction. In a per-protocol analysis, antidepressant use and mental health contacts were significantly greater in patients in the intervention arm with a recorded follow-up PHQ-9 (P = 0.025 and P = 0.010, respectively). CONCLUSION: No evidence was found of improved depression outcome at 12 weeks from monitoring. The findings of possible benefits over 26 weeks warrant replication, investigating possible mechanisms, preferably with automated delivery of monitoring and more instructive feedback.
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Calidad de Vida , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios de Seguimiento , Antidepresivos/uso terapéutico , Atención Primaria de Salud , Cuestionario de Salud del Paciente , Depresión/diagnóstico , Escalas de Valoración PsiquiátricaRESUMEN
BACKGROUND: This paper investigates whether age of onset of depression, duration of the last episode, number of episodes, and residual symptoms of depression and anxiety are associated with depression relapse in primary care patients who have been on long-term maintenance antidepressant treatment and no longer meet ICD10 criteria for depression. METHODS: An observational cohort using data from ANTLER (N = 478), a double-blind placebo-controlled trial. The primary outcome was time to relapse using the retrospective CIS-R. Participants were followed for 12 months. RESULTS: Primary outcome was available for 468 participants. Time to relapse in those with more than five previous episodes of depression was shorter, hazard ratio (HR) 1.84 (95% confidence interval [CI] 1.23-2.75) compared to people with two episodes; HR 1.57 (95% CI 1.01-2.43) after adjustment. The residual symptoms of depression at baseline were also associated with increased relapse: HR 1.05 (95% CI 1.01-1.09) and HR 1.06 (95% CI 1.01-1.12) in the adjusted model. There was evidence of reduced rate of relapse in older age of onset group: HR 0.86 (95% CI 0.78-0.95); HR attenuated after adjustment HR 0.91 (95% CI 0.81-1.02). There was no evidence of an association between duration of the current episode and residual anxiety symptoms with relapse. CONCLUSIONS: The number of previous episodes and residual symptoms of depression were associated with increased likelihood of relapse. These factors could inform joint decision making when patients are considering tapering off maintenance antidepressant treatment or considering other treatments to prevent relapse.
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Antidepresivos , Depresión , Humanos , Depresión/terapia , Estudios Retrospectivos , Antidepresivos/uso terapéutico , Recurrencia , Atención Primaria de Salud , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Progress feedback, also known as measurement-based care (MBC), is the routine collection of patient-reported measures to monitor treatment progress and inform clinical decision-making. Although a key ingredient to improving mental health care, sustained use of progress feedback is poor. Integration into everyday workflow is challenging, impacted by a complex interrelated set of factors across patient, clinician, organizational, and health system levels. This study describes the development of a qualitative coding scheme for progress feedback implementation that accounts for the dynamic nature of barriers and facilitators across multiple levels of use in mental health settings. Such a coding scheme may help promote a common language for researchers and implementers to better identify barriers that need to be addressed, as well as facilitators that could be supported in different settings and contexts. METHODS: Clinical staff, managers, and leaders from two Dutch, three Norwegian, and four mental health organizations in the USA participated in semi-structured interviews on how intra- and extra-organizational characteristics interact to influence the use of progress feedback in clinical practice, supervision, and program improvement. Interviews were conducted in the local language, then translated to English prior to qualitative coding. RESULTS: A team-based consensus coding approach was used to refine an a priori expert-informed and literature-based qualitative scheme to incorporate new understandings and constructs as they emerged. First, this hermeneutic approach resulted in a multi-level coding scheme with nine superordinate categories and 30 subcategories. Second-order axial coding established contextually sensitive categories for barriers and facilitators. CONCLUSIONS: The primary outcome is an empirically derived multi-level qualitative coding scheme that can be used in progress feedback implementation research and development. It can be applied across contexts and settings, with expectations for ongoing refinement. Suggestions for future research and application in practice settings are provided. Supplementary materials include the coding scheme and a detailed playbook.
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Introduction: Multidomain interventions to address modifiable risk factors for dementia are promising, but require more cost-effective, scalable delivery. This study investigated the feasibility of the "Active Brains" digital behavior change intervention and its trial procedures. Materials and methods: Active Brains aims to reduce cognitive decline by promoting physical activity, healthy eating, and online cognitive training. We conducted 12-month parallel-design randomized controlled feasibility trials of "Active Brains" amongst "lower cognitive scoring" (n = 180) and "higher cognitive scoring" (n = 180) adults aged 60-85. Results: We collected 67.2 and 76.1% of our 12-month primary outcome (Baddeley verbal reasoning task) data for the "lower cognitive score" and "higher cognitive score" groups, respectively. Usage of "Active Brains" indicated overall feasibility and satisfactory engagement with the physical activity intervention content (which did not require sustained online engagement), but engagement with online cognitive training was limited. Uptake of the additional brief telephone support appeared to be higher in the "lower cognitive score" trial. Preliminary descriptive trends in the primary outcome data might indicate a protective effect of Active Brains against cognitive decline, but further investigation in fully-powered trials is required to answer this definitively. Discussion: Whilst initial uptake and engagement with the online intervention was modest, it was in line with typical usage of other digital behavior change interventions, and early indications from the descriptive analysis of the primary outcome and behavioral data suggest that further exploration of the potential protective benefits of Active Brains are warranted. The study also identified minor modifications to procedures, particularly to improve online primary-outcome completion. Further investigation of Active Brains will now seek to determine its efficacy in protecting cognitive performance amongst adults aged 60-85 with varied levels of existing cognitive performance.
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Disfunción Cognitiva , Encéfalo , Cognición , Disfunción Cognitiva/prevención & control , Disfunción Cognitiva/psicología , Ejercicio Físico , Estudios de Factibilidad , HumanosRESUMEN
Importance: Socioeconomic factors are associated with the prevalence of depression, but their associations with prognosis are unknown. Understanding this association would aid in the clinical management of depression. Objective: To determine whether employment status, financial strain, housing status, and educational attainment inform prognosis for adults treated for depression in primary care, independent of treatment and after accounting for clinical prognostic factors. Data Sources: The Embase, International Pharmaceutical Abstracts, MEDLINE, PsycINFO, and Cochrane (CENTRAL) databases were searched from database inception to October 8, 2021. Study Selection: Inclusion criteria were as follows: randomized clinical trials that used the Revised Clinical Interview Schedule (CIS-R; the most common comprehensive screening and diagnostic measure of depressive and anxiety symptoms in primary care randomized clinical trials), measured socioeconomic factors at baseline, and sampled patients with unipolar depression who sought treatment for depression from general physicians/practitioners or who scored 12 or more points on the CIS-R. Exclusion criteria included patients with depression secondary to a personality or psychotic disorder or neurologic condition, studies of bipolar or psychotic depression, studies that included children or adolescents, and feasibility studies. Studies were independently assessed against inclusion and exclusion criteria by 2 reviewers. Data Extraction and Synthesis: Data were extracted and cleaned by data managers for each included study, further cleaned by multiple reviewers, and cross-checked by study chief investigators. Risk of bias and quality were assessed using the Quality in Prognosis Studies (QUIPS) and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) tools, respectively. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses-Individual Participant Data (PRISMA-IPD) reporting guidelines. Main Outcomes and Measures: Depressive symptoms at 3 to 4 months after baseline. Results: This systematic review and individual patient data meta-analysis identified 9 eligible studies that provided individual patient data for 4864 patients (mean [SD] age, 42.5 (14.0) years; 3279 women [67.4%]). The 2-stage random-effects meta-analysis end point depressive symptom scale scores were 28% (95% CI, 20%-36%) higher for unemployed patients than for employed patients and 18% (95% CI, 6%-30%) lower for patients who were homeowners than for patients living with family or friends, in hostels, or homeless, which were equivalent to 4.2 points (95% CI, 3.6-6.2 points) and 2.9 points (95% CI, 1.1-4.9 points) on the Beck Depression Inventory II, respectively. Financial strain and educational attainment were associated with prognosis independent of treatment, but unlike employment and housing status, there was little evidence of associations after adjusting for clinical prognostic factors. Conclusions and Relevance: Results of this systematic review and meta-analysis revealed that unemployment was associated with a poor prognosis whereas home ownership was associated with improved prognosis. These differences were clinically important and independent of the type of treatment received. Interventions that address employment or housing difficulties could improve outcomes for patients with depression.
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Depresión , Trastorno Depresivo Mayor , Adolescente , Adulto , Ansiedad/terapia , Niño , Depresión/diagnóstico , Depresión/terapia , Femenino , Humanos , Masculino , Pronóstico , Factores SocioeconómicosRESUMEN
OBJECTIVE: To investigate associations between major life events and prognosis independent of treatment type: (1) after adjusting for clinical prognostic factors and socio-demographics; (2) amongst patients with depressive episodes at least six-months long; and (3) patients with a first life-time depressive episode. METHODS: Six RCTs of adults seeking treatment for depression in primary care met eligibility criteria, individual patient data (IPD) were collated from all six (n = 2858). Participants were randomized to any treatment and completed the same baseline assessment of life events, demographics and clinical prognostic factors. Two-stage random effects meta-analyses were conducted. RESULTS: Reporting any major life events was associated with poorer prognosis regardless of treatment type. Controlling for baseline clinical factors, socio-demographics and social support resulted in minimal residual evidence of associations between life events and treatment prognosis. However, removing factors that might mediate the relationships between life events and outcomes reporting: arguments/disputes, problem debt, violent crime, losing one's job, and three or more life events were associated with considerably worse prognoses (percentage difference in 3-4 months depressive symptoms compared to no reported life events =30.3%(95%CI: 18.4-43.3)). CONCLUSIONS: Assessing for clinical prognostic factors, social support, and socio-demographics is likely to be more informative for prognosis than assessing self-reported recent major life events. However, clinicians might find it useful to ask about such events, and if they are still affecting the patient, consider interventions to tackle problems related to those events (e.g. employment support, mediation, or debt advice). Further investigations of the efficacy of such interventions will be important.
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Depresión , Atención Primaria de Salud , Humanos , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Apoyo SocialRESUMEN
BACKGROUND: Depression is a common mental health condition with considerable negative impact on health and well-being. Although antidepressants are recommended as first-line treatment, there is limited evidence regarding the cost effectiveness of long-term maintenance antidepressants for preventing relapse. OBJECTIVES: Our objective was to calculate the mean incremental costs and quality-adjusted life-years (QALYs) over 12 months of discontinuing long-term antidepressant medication in well patients compared with maintenance, using patient-level trial data. METHODS: We conducted a cost-utility analysis of 478 participants from 150 UK general practices recruited to a randomised, double-blind trial (ANTLER). QALYs were calculated from EQ-5D-5L and 12-Item Short Form survey (SF-12) results, with primary analysis using the EQ-5D-5L value set for England. Resource use was collected from primary care patient electronic medical records and self-completed questionnaires capturing mental-health-related resource use. Costs were calculated by applying standard UK unit costs to resource use. Adjustments were made for baseline variables. RESULTS: Participants randomised to discontinuation had significantly worse utility scores at 3 months (- 0.032; 95% confidence interval [CI] - 0.053 to - 0.011) but no significant difference in QALYs (- 0.011; 95% CI - 0.026 to 0.003) or costs (£3.11; 95% CI - 41.28 to 47.50) at 12 months. The probability that discontinuation was cost effective compared with maintenance was 12.9% at a threshold of £20,000 per QALY gained. CONCLUSIONS: Discontinuation of antidepressants was unlikely to be cost effective compared with maintenance for currently well patients on long-term antidepressants. However, this analysis provides no information on the wider impact of antidepressants. Our findings provide information on the potential impact of discontinuing long-term maintenance antidepressants and facilitate improving guidance for shared patient-clinician decision making. TRIAL REGISTRATION: EudraCT number 2015-004210-26; ISRCTN number ISRCTN15969819.
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Antidepresivos , Atención Primaria de Salud , Antidepresivos/uso terapéutico , Análisis Costo-Beneficio , Inglaterra , Humanos , Calidad de Vida , Años de Vida Ajustados por Calidad de VidaRESUMEN
BACKGROUND: Subgrouping methods have the potential to support treatment decision making for patients with depression. Such approaches have not been used to study the continued course of depression or likelihood of relapse following treatment. METHOD: Data from individual participants of seven randomised controlled trials were analysed. Latent profile analysis was used to identify subgroups based on baseline characteristics. Associations between profiles and odds of both continued chronic depression and relapse up to one year post-treatment were explored. Differences in outcomes were investigated within profiles for those treated with antidepressants, psychological therapy, and usual care. RESULTS: Seven profiles were identified; profiles with higher symptom severity and long durations of both anxiety and depression at baseline were at higher risk of relapse and of chronic depression. Members of profile five (likely long durations of depression and anxiety, moderately-severe symptoms, and past antidepressant use) appeared to have better outcomes with psychological therapies: antidepressants vs. psychological therapies (OR (95% CI) for relapse = 2.92 (1.24-6.87), chronic course = 2.27 (1.27-4.06)) and usual care vs. psychological therapies (relapse = 2.51 (1.16-5.40), chronic course = 1.98 (1.16-3.37)). CONCLUSIONS: Profiles at greater risk of poor outcomes could benefit from more intensive treatment and frequent monitoring. Patients in profile five may benefit more from psychological therapies than other treatments.
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BACKGROUND: There has been a steady increase in the number of primary care patients receiving long-term maintenance antidepressant treatment, despite limited evidence of a benefit of this treatment beyond 8 months. OBJECTIVE: The ANTidepressants to prevent reLapse in dEpRession (ANTLER) trial investigated the clinical effectiveness and cost-effectiveness of antidepressant medication in preventing relapse in UK primary care. DESIGN: This was a Phase IV, double-blind, pragmatic, multisite, individually randomised parallel-group controlled trial, with follow-up at 6, 12, 26, 39 and 52 weeks. Participants were randomised using minimisation on centre, type of antidepressant and baseline depressive symptom score above or below the median using Clinical Interview Schedule - Revised (two categories). Statisticians were blind to allocation for the outcome analyses. SETTING: General practices in London, Bristol, Southampton and York. PARTICIPANTS: Individuals aged 18-74 years who had experienced at least two episodes of depression and had been taking antidepressants for ≥ 9 months but felt well enough to consider stopping their medication. Those who met an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis of depression or with other psychiatric conditions were excluded. INTERVENTION: At baseline, participants were taking citalopram 20 mg, sertraline 100 mg, fluoxetine 20 mg or mirtazapine 30 mg. They were randomised to either remain on their current medication or discontinue medication after a tapering period. MAIN OUTCOME MEASURES: The primary outcome was the time, in weeks, to the beginning of the first depressive episode after randomisation. This was measured by a retrospective Clinical Interview Schedule - Revised that assessed the onset of a depressive episode in the previous 12 weeks, and was conducted at 12, 26, 39 and 52 weeks. The depression-related resource use was collected over 12 months from medical records and patient-completed questionnaires. Quality-adjusted life-years were calculated using the EuroQol-5 Dimensions, five-level version. RESULTS: Between 9 March 2017 and 1 March 2019, we randomised 238 participants to antidepressant continuation (the maintenance group) and 240 participants to antidepressant discontinuation (the discontinuation group). The time to relapse of depression was shorter in the discontinuation group, with a hazard ratio of 2.06 (95% confidence interval 1.56 to 2.70; p < 0.0001). By 52 weeks, relapse was experienced by 39% of those who continued antidepressants and 56% of those who discontinued antidepressants. The secondary analysis revealed that people who discontinued experienced more withdrawal symptoms than those who remained on medication, with the largest difference at 12 weeks. In the discontinuation group, 37% (95% confidence interval 28% to 45%) of participants remained on their randomised medication until the end of the trial. In total, 39% (95% confidence interval 32% to 45%) of participants in the discontinuation group returned to their original antidepressant compared with 20% (95% confidence interval 15% to 25%) of participants in maintenance group. The health economic evaluation demonstrated that participants randomised to discontinuation had worse utility scores at 3 months (-0.037, 95% confidence interval -0.059 to -0.015) and fewer quality-adjusted life-years over 12 months (-0.019, 95% confidence interval -0.035 to -0.003) than those randomised to continuation. The discontinuation pathway, besides giving worse outcomes, also cost more [extra £2.71 per patient over 12 months (95% confidence interval -£36.10 to £37.07)] than the continuation pathway, although the cost difference was not significant. CONCLUSIONS: Patients who discontinue long-term maintenance antidepressants in primary care are at increased risk of relapse and withdrawal symptoms. However, a substantial proportion of patients can discontinue antidepressants without relapse. Our findings will give patients and clinicians an estimate of the likely benefits and harms of stopping long-term maintenance antidepressants and improve shared decision-making. The participants may not have been representative of all people on long-term maintenance treatment and we could study only a restricted range of antidepressants and doses. Identifying patients who will not relapse if they discontinued antidepressants would be clinically important. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15969819 and EudraCT 2015-004210-26. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 69. See the NIHR Journals Library website for further project information.
Antidepressants are used to treat depression when someone is unwell, but are also used as maintenance treatment to prevent the reoccurrence of depression. There has been a large increase in the use of long-term maintenance antidepressant treatment, but the evidence for the benefits of maintenance beyond 8 months is very poor. The ANTidepressants to prevent reLapse in dEpRession (ANTLER) trial was a randomised controlled trial that examined the effectiveness of long-term maintenance treatment with antidepressants. The participants were well enough to consider stopping antidepressant medication, were recruited from primary care and had taken antidepressants for ≥ 9 months. In total, 238 participants were randomised to continue taking antidepressants and 240 were randomised to receive a visually identical tablet that contained no active ingredients after a period when the antidepressants were gradually reduced. Neither the participants nor those interviewing them knew which group they had been placed in, and they were followed up for 1 year. Participants who discontinued antidepressants were more likely to experience relapse than those who continued antidepressants. By 52 weeks, 39% of those who continued antidepressants had experienced a relapse, compared with 56% in the group that discontinued antidepressants. In other words, over a 52-week period, one in every six patients who stopped antidepressants would experience a relapse that may not have occurred if they had remained on their antidepressants. Patients in the discontinuation group reported more symptoms of anxiety and depression and experienced more withdrawal symptoms than those in the maintenance group, mostly in the first 34 months after stopping the antidepressants. Participants in the discontinuation group also reported lower quality of life than those in the maintenance group but both groups used similar amounts of health-care and social care resources over the 12-month period. About one-third of participants who were allocated to the discontinuation group in the ANTLER trial decided to restart their antidepressants. However, another one-third of participants in that group remained on trial medication for 12 months and managed without antidepressants. Long-term maintenance treatment with antidepressants is effective in reducing the rate of relapses. For those who are considering stopping their antidepressant, our findings will provide estimates of the likely benefits and harms, to improve shared decision-making and support the regular review of long-term antidepressant prescription.
Asunto(s)
Antidepresivos , Depresión , Adolescente , Adulto , Anciano , Análisis Costo-Beneficio , Depresión/tratamiento farmacológico , Depresión/prevención & control , Humanos , Persona de Mediana Edad , Atención Primaria de Salud , Calidad de Vida , Recurrencia , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Patients with depression who are treated in primary care practices may receive antidepressants for prolonged periods. Data are limited on the effects of maintaining or discontinuing antidepressant therapy in this setting. METHODS: We conducted a randomized, double-blind trial involving adults who were being treated in 150 general practices in the United Kingdom. All the patients had a history of at least two depressive episodes or had been taking antidepressants for 2 years or longer and felt well enough to consider stopping antidepressants. Patients who had received citalopram, fluoxetine, sertraline, or mirtazapine were randomly assigned in a 1:1 ratio to maintain their current antidepressant therapy (maintenance group) or to taper and discontinue such therapy with the use of matching placebo (discontinuation group). The primary outcome was the first relapse of depression during the 52-week trial period, as evaluated in a time-to-event analysis. Secondary outcomes were depressive and anxiety symptoms, physical and withdrawal symptoms, quality of life, time to stopping an antidepressant or placebo, and global mood ratings. RESULTS: A total of 1466 patients underwent screening. Of these patients, 478 were enrolled in the trial (238 in the maintenance group and 240 in the discontinuation group). The average age of the patients was 54 years; 73% were women. Adherence to the trial assignment was 70% in the maintenance group and 52% in the discontinuation group. By 52 weeks, relapse occurred in 92 of 238 patients (39%) in the maintenance group and in 135 of 240 (56%) in the discontinuation group (hazard ratio, 2.06; 95% confidence interval, 1.56 to 2.70; P<0.001). Secondary outcomes were generally in the same direction as the primary outcome. Patients in the discontinuation group had more symptoms of depression, anxiety, and withdrawal than those in the maintenance group. CONCLUSIONS: Among patients in primary care practices who felt well enough to discontinue antidepressant therapy, those who were assigned to stop their medication had a higher risk of relapse of depression by 52 weeks than those who were assigned to maintain their current therapy. (Funded by the National Institute for Health Research; ANTLER ISRCTN number, ISRCTN15969819.).
Asunto(s)
Antidepresivos/uso terapéutico , Trastorno Depresivo/tratamiento farmacológico , Atención Primaria de Salud , Recurrencia , Adulto , Anciano , Antidepresivos/efectos adversos , Trastornos de Ansiedad/epidemiología , Citalopram/uso terapéutico , Trastorno Depresivo/epidemiología , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Quimioterapia de Mantención , Masculino , Persona de Mediana Edad , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Encuestas y Cuestionarios , Reino Unido , Privación de TratamientoRESUMEN
BACKGROUND: By 2050, worldwide dementia prevalence is expected to triple. Affordable, scalable interventions are required to support protective behaviours such as physical activity, cognitive training and healthy eating. This paper outlines the theory-, evidence- and person-based development of 'Active Brains': a multi-domain digital behaviour change intervention to reduce cognitive decline amongst older adults. METHODS: During the initial planning phase, scoping reviews, consultation with PPI contributors and expert co-investigators and behavioural analysis collated and recorded evidence that was triangulated to inform provisional 'guiding principles' and an intervention logic model. The following optimisation phase involved qualitative think aloud and semi-structured interviews with 52 older adults with higher and lower cognitive performance scores. Data were analysed thematically and informed changes and additions to guiding principles, the behavioural analysis and the logic model which, in turn, informed changes to intervention content. RESULTS: Scoping reviews and qualitative interviews suggested that the same intervention content may be suitable for individuals with higher and lower cognitive performance. Qualitative findings revealed that maintaining independence and enjoyment motivated engagement in intervention-targeted behaviours, whereas managing ill health was a potential barrier. Social support for engaging in such activities could provide motivation, but was not desirable for all. These findings informed development of intervention content and functionality that appeared highly acceptable amongst a sample of target users. CONCLUSIONS: A digitally delivered intervention with minimal support appears acceptable and potentially engaging to older adults with higher and lower levels of cognitive performance. As well as informing our own intervention development, insights obtained through this process may be useful for others working with, and developing interventions for, older adults and/or those with cognitive impairment.