Title: REviewing long term anti-Depressant Use by Careful monitoring in Everyday practice (REDUCE) programme
Funder: Department of Health and Social Care

Abstract: Aim: To identify feasible, safe, effective, and cost-effective ways of helping patients taking long-term antidepressants withdraw from treatment when appropriate. Objectives: Conduct a systematic review of interventions used to help patients successfully withdraw from antidepressant treatment. Identify factors promoting or inhibiting treatment withdrawal, through interviews with patients, and focus groups with practitioners. Develop an internet-supported CBT-based intervention to support treatment withdrawal, through co-design and co-production with practitioners and patients. Determine the effectiveness of the intervention through a randomised controlled trial, and estimate cost-effectiveness from a health/social service perspective. Build a translational framework addressing how the intervention should be delivered, including overcoming practitioner and patient related barriers, to facilitate implementation. Background: Antidepressant prescriptions have risen steadily, due to GPs prescribing longer courses, and the average length of treatment is now >2yrs. Some people need long-term antidepressants to prevent relapse, but surveys suggest 30-50% have no indication for long-term use. However stopping is not easy, due to withdrawal symptoms including anxiety and mood changes which feel similar to the reason why treatment was started in the first place. Patients on long-term treatment are often given repeat prescriptions and reviewed only infrequently. When GPs are prompted to review patients and advise withdrawal where appropriate, only 7% successfully withdraw. Practitioners need guidance to provide support for withdrawal, and patients need 24hr support. Research plan: WS1. Systematic review of interventions facilitating antidepressant withdrawal (months 1-9). Papers will be identified through comprehensive searches (Medline/Embase/DARE/CINAHL/PsycINFO). Selection for inclusion, based on a priori criteria, will be by two independent researchers. A thematic synthesis will be performed, and if appropriate data will be combined through meta-analysis. WS2. Intervention planning (months 1-12). This will draw on our PPI and team's expertise, informed by theoretical modelling based on identified literature, and insights gained from CBT-based internet programmes for anxiety and depression. Planning will also be informed by 15-20 qualitative patient interviews, and focus groups with 15-20 practitioners. Thematic analysis will be used, checking agreement between analysts, and discussing emerging themes with the whole team. WS3. Co-production of internet-supported withdrawal intervention (months 10-24). Internet-supported advice for patients on dealing with withdrawal symptoms and when to seek help will be delivered using LifeGuide software developed in Southampton. Clinical support will be provided by a primary care mental health worker (PCMHW) by telephone. Other interventions identified in WS1-2, e.g. buddying, may be added. The website will be iteratively developed, through qualitative interviews with 15-20 patients, and 15-20 practitioners. Once a prototype is created, qualitative research with another 15-20 patients will explore whether it is acceptable, interesting, persuasive, and feasible. Think-aloud interviews will be employed, and thematic analysis used to identify improvements, iteratively. WS4. Feasibility RCT, to assess acceptability, recruitment, and outcome measures (months 22-36). We will recruit 20 patients per arm, from 14 practices over 3 months, and follow them up for 6 months. We will assess recruitment; attrition; choice of outcome questionnaires; and adherence (automatically recorded by LifeGuide). We will explore burden of treatment, need for mental health worker telephone support, and technical support. A qualitative process evaluation will be conducted through interviewing 15-20 patients and 15-20 practitioners. WS5. Fully powered RCT to demonstrate effectiveness, and cost-effectiveness (months 37-72). Inclusion criteria: having received treatment for >1 year for a first episode or >2 years for a recurrent episode; no longer depressed; not at significant risk of relapse. Cluster randomising practices (stratifying by size, location, and deprivation) to avoid contamination between arms arising from practitioner training. Baseline measures: socio-demographics; internet experience; work status; comorbidities; symptoms (PHQ-9/GAD-7); QoL (EQ-5D-5L and SF-12); NHS/SS resource use over previous 3 months. Patients in both arms will have treatment reviewed by their GP/NP, with appointments for follow-up. Intervention arm practitioners will be trained in supporting withdrawal, and patients helped to engage with the web-based support package. Follow-up will be by post, with telephone back-up, blind to allocation, at 3,6,9 and 12m. Primary outcome: depression at 6m, powered to demonstrate non-inferiority ( ITT (and PP) analyses will use logistic/linear regression, controlling for baseline values, stratification variables, practice, and appropriate confounders. Patterns of missing data will be explored, with imputation if appropriate, and CACE analyses conducted. Process evaluation: quantitative assessment of effects of baseline patient characteristics and psychological factors; qualitative interviews to understand patients perspectives and influences on trial outcomes. Projected outputs & dissemination: Translational framework on implementing internet-supported intervention to support antidepressant withdrawal, disseminated through patient groups. Publications: systematic reviews; Markov modelling; patient numbers; intervention development; feasibility study; trial results; cost-effectiveness; implementation framework. Benefits to patients/the NHS Reductions in inappropriate treatment of patients, costs of drugs, and monitoring.

Lay abstract: There is considerable concern about increasing antidepressant use in England. GPs are giving out more than 50 million prescriptions a year, to more than 1-in-10 adults. Some people need long-term antidepressants to stop them getting depressed, but a third-to-a-half could probably stop them without relapsing. However, stopping is not easy, due to withdrawal symptoms including anxiety and low mood which are usually temporary but feel similar to the reason why patients were first put on antidepressants. So understandably some people restart their antidepressant quickly. Others are reluctant to try stopping because they feel well on medication and are afraid their symptoms may come back. People taking antidepressants have told us their GPs often do not review them and just give repeat prescriptions. Studies show that when GPs review patients on long-term antidepressants and advise them where appropriate to withdraw, only 1-in-14 is able to stop. Patients can be fearful and withdrawal can be tricky so GPs and Nurse Practitioners (NPs) who prescribe antidepressants need to guide patients who want to withdraw, and patients need around the clock support. &bull; We aim to identify feasible, safe, reliable and cost-effective (value for money) ways of helping patients withdraw from long-term antidepressants, where this is appropriate. &bull; We will first review all published relevant research, to identify successful ways to help patients withdraw from treatment. &bull; We will identify the difficulties in withdrawing, and things that patients and practitioners think might help withdrawal, through interviews with patients taking antidepressants long-term, and through focus groups with GPs, NPs and primary care mental health workers (PCMHWs). &bull; We will try out support through the Internet for patients, and their GPs, to help them. &bull; An interactive programme will be developed to help support patient withdrawal from antidepressants, available around the clock. &bull; It will be developed through a process of 'co-design' and 'coproduction' which means taking the views of patients and practitioners into account throughout its development and initial trial run. &bull; We will also explore whether 'buddying' support from people who have come off antidepressants might help. &bull; We will check the usefulness of the programme in helping patients stop treatment through a randomised controlled trial in three centres, and estimate financial benefits for the NHS. &bull; If the programme works we will spread it throughout the NHS, publishing practical guidance for professionals, and advice for patients to follow, publicised through patient support groups. We have developed the ideas for this project with the help of people having long-term treatment for depression. They will continue to work with us to help make sense of the information we gather, and advise on the support we develop for antidepressant withdrawal, from the patient s point of view.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: MENTAL HEALTH