Title: What are the indications for prescribing antidepressants that will lead to a clinical benefit?
Funder: Department of Health and Social Care

Abstract: BACKGROUND There were 36m prescriptions for an antidepressant in 2009. There is still much uncertainty about when people with depression might benefit from antidepressant medication and concern that they are prescribed when it is not really necessary. AIMS AND OBJECTIVES The overall objective of the programme is to provide general practitioners or other clinicians with a structured assessment and clinical algorithm that will enable them to make recommendations about the likely response to selective serotonin reuptake inhibitor (SSRI) antidepressants for patients with depression in primary care. The main hypothesis is that the response to antidepressants (compared to placebo) increases with both the severity and duration of depressive symptoms Phase 1: Using previously collected data Aim1a: To carry out a systematic review and individual patient data meta-analysis to investigate the relationship between the severity of depressive symptoms and the response to antidepressants Aim 1b: We will “map” the relationship between different depression scales so we can estimate the scores on each scale corresponding to the same severity of symptoms Phase 2: Cohort study: Using both quantitative and qualitative methods Aim 2a: To estimate a clinically important difference on commonly used self-administered questionnaires for depressive symptoms Aim 2b: To investigate the changes reported by patients as they recover from depression Aim 2c: To investigate any mismatch between quantitative reports of symptom change in people recovering from depression Phase 3: Randomised controlled trial (RCT) Aim 3: To investigate the severity and duration of depressive symptoms that are associated with a clinically important response to citalopram in people with depression RESEARCH PLANS Phase 1: Aim 1a: We will carry out a systematic review and request individual patient data (IPD) for a meta-analysis. As we expect this sample of trials to be potentially biased, we will analyse the data to simultaneously model both the aggregate data from trials and the IPD data Aim 1b: We have access to a large number of studies that will allow us to accurately “map” the scores on the different depression measures using novel statistical methods Phase 2: Aim 2a: We will carry out a cohort study of depressed people presenting in primary care. We will ask them to rate their own improvement on a “global rating of change” scale and compare with the results of self-administered questionnaires of depression. This will allow us to calculate the difference in scores corresponding to an improvement in their “global rating of change” scale Aim 2b: On a cohort of 25 people sampled in the same way we will conduct repeated qualitative interviews along with quantitative measures to hear people’s own accounts of recovery and compare these with the results of the quantitative measures. Aim 2c: We will sample 30 people who have different responses to the “global rating of change” scale and the depression questionnaires. This will allow us to investigate, using qualitative methods, the reasons for this discrepancy. Phase 3: Aim 3: We will carry out a randomised controlled trial in which we will examine the hypothesis that the severity and duration of depressive symptoms is related to antidepressant response. We will provide an algorithm based upon a self-administered computerised assessment that can be used in primary care to provide guidance on when someone might benefit from an antidepressant RESEARCH TEAM We have a very experience team of psychiatrists, general practitioners, service users and methodologists in statistics, epidemiology, health economics and social science. The team has worked together before and has carried out relevant research PROGRAMME MANAGEMENT The programme will be led by Glyn Lewis from Bristol with Chris Dowrick, Liverpool and Simon Gilbody, York being responsible for their centres RESEARCH ENVIRONMENT We have an excellent environment in all the centres. The RCT will have the support of the UKCRC/NCRI accredited Bristol Randomised Trials Collaboration OUTPUTS, OUTCOMES, AND IMPACT We expect the programme to have a major impact on the prescription of antidepressants. The research will result in a simple computerised assessment that will give them advice on when someone is likely to respond to an antidepressant JUSTIFICATION OF RESOURCES We have a comprehensive costing for all stages of the programme PATIENT AND PUBLIC INVOLVEMENT We have a service users as a co-applicant and a collaborator. We plan to create a service user group that will have the opportunity, also, of influencing all stages of the research ETHICAL IMPLICATIONS Participants in the RCT will have given their full informed consent to be randomised to placebo or active drug. Clinical supervision will be maintained by the GP and they will be able to withdraw at any time DISSEMINATION The results will be disseminated to a wide audience.

Lay abstract: There were 36m prescriptions for an antidepressant in 2009. There is still much uncertainty about when people wilt depression might benefit from antidepressant medication and concern that they are prescribed when it is not really necessary. The overall objective of the programme is to provide general practitioners with a structured assessment and clinical algorithm that will enable them to make recommendations about the likely response to selective serotonin reuptake inhibitor (SSRI) antidepressants for patients with depression in primary care. Before we can carry out a definitive randomised trial to answer this question, we also plan to use existing data to get an estimate of the likely threshold and to “map” the different questionnaires used to assess depression so that we can interpret the previous results. We also need to estimate a meaningful clinical difference in this population so that we know what size of difference is worth investigating and the way that participants answer questions on the questionnaires that are used. Once these have been established we can plan and carry out the randomised controlled trial. Our hypothesis is that the severity and duration of depressive symptoms is related to antidepressant response though the main aim will be to establish the thresholds on severity and duration that will indicate likely benefit of antidepressants. We will use a self-administered computerised assessment so the results can be implemented easily within primary care.

Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: MENTAL HEALTH