Title: Antidepressants to prevent relapse in depression
Funder: Department of Health and Social Care

Abstract: There were over 53m prescriptions of antidepressants issued in primary care in England in 2013 and many of these were for repeat prescriptions. Antidepressants are used both for treating the acute episode and for prophylaxis of future episodes of depression, also called maintenance treatment. There is good evidence that maintenance treatment that lasts 9 months is effective. However, there is still uncertainty about long term maintenance treatment. NICE recommends that some people “at risk of relapse” should stay on maintenance antidepressants for 2 years but as the NICE guideline recognised there is currently no evidence to support this policy. Surveys of the general population and in general practice indicate that there are large numbers of patients taking antidepressants in the UK, somewhere between 5% and 8% and up to half of these will be taking them long term and half of them will have relatively few symptoms. There are therefore a substantial proportion of people taking long term maintenance treatment even though there is little evidence for its effectiveness. The proposed study will provide a valid and generalizable estimate of the clinical and cost-effectiveness of long term maintenance treatment with antidepressants in UK primary care. The relevant population is those people who are taking long term maintenance antidepressants and now feel well enough to consider stopping medication. RESEARCH QUESTION “What is the clinical and cost-effectiveness in UK primary care of continuing on long term maintenance antidepressants compared to a placebo in preventing relapse of depression in those who have taken antidepressants for more than 9 months and who are now well enough to consider stopping maintenance treatment?” We propose to identify people in primary care who are on long term antidepressant medication by asking general practitioners to search their electronic patient records. We will include people taking four antidepressants (citalopram, sertraline, fluoxetine and mirtazapine) that between them comprise 75% of all antidepressant prescriptions. We will carry out an individually randomised parallel group controlled trial that will compare (1) continuing with the following antidepressant medication (citalopram 20mg, sertraline 100mg, fluoxetine 20mg or mirtazapine 30mg) with (2) replacement of the medication with an identical placebo that will include a double blind tapering period. We will follow up participants for 12 months as previous research has indicated that the increase in relapse rate occurs within 6 months of medication withdrawal. Our primary outcome will be time to depressive relapse. Secondary outcomes will include depressive and anxiety symptoms, adverse effects including withdrawal symptoms, quality of life and the resources and costs used.

Lay abstract: There were over 53m prescriptions of antidepressants issued in primary care in England in 2013 and many of these were for repeat prescriptions. Antidepressants are used both for treating the acute episode and also for preventing future episodes of depression, also called maintenance treatment. There is good evidence that maintenance treatment that lasts 9 months is effective. However, there is still uncertainty about long term maintenance treatment. The NICE guidelines recommend that some people “at risk of relapse” should stay on maintenance antidepressants for 2 years but as the guideline group recognised themselves there is currently no evidence to support this policy. Surveys of the general population and in general practice indicate that there are large numbers of patients taking antidepressants in the UK, somewhere between 5% and 8% and up to half of these will be taking them long term and half of those will have relatively few symptoms. There are therefore a substantial proportion of people taking long term maintenance antidepressant treatment even though there is little evidence for its effectiveness. The proposed study will investigate the effectiveness of long term maintenance treatment in UK primary care. The participants will be people who have been treated for depression, who are now taking long term (more than 9 months) maintenance antidepressants and now feel well enough to consider stopping medication. RESEARCH QUESTION “What is the clinical and cost-effectiveness in UK primary care of continuing on long term maintenance antidepressants compared to a placebo in preventing relapse of depression in those who have taken antidepressants for more than 9 months and who are now well enough to consider stopping maintenance treatment?” We propose to identify people in primary care who are on long term antidepressant medication by asking general practitioners to search their electronic patient records. We will include people taking four antidepressants (citalopram, sertraline, fluoxetine and mirtazapine) that between them comprise 75% of all antidepressant prescriptions. We will carry out a randomised controlled trial that will compare long term maintenance antidepressants with an identical placebo. We will make sure that the people who are withdrawn from antidepressants have a more gradual reduction in dose to avoid withdrawal symptoms. We will follow up participants for 12 months as previous research has indicated that the increase in relapse rate following withdrawal of maintenance medication occurs within 6 months of medication withdrawal.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH