Title: Targeting insomnia to treat depression: A randomised controlled trial of sleep restriction therapy
Funder: Medical Research Council

Abstract: WHY IS THIS RESEARCH IMPORTANT?_x000D_ Depression is a very common and impairing condition. Current treatments include antidepressant medication and psychological therapy. Both can be effective but more than one-third of people do not benefit from these treatments. There are reasons to think that poor sleep is an important contributor to depression, and that if sleep could be improved, depression would improve too. _x000D_ _x000D_ WHAT DO WE WANT TO FIND OUT?_x000D_ Previous research has shown that we can improve sleep quality using a behavioural treatment called ‘sleep scheduling therapy’. This treatment involves reviewing the patient’s current sleep pattern and supporting them to follow a new, personalised sleep schedule. We want to find out whether using this treatment to improve sleep will also improve depression and, if so, how it works._x000D_ _x000D_ HOW WILL WE DO THIS? _x000D_ We plan to recruit patients from general practice who experience symptoms of both sleep disruption (insomnia) and depression. We will identify people in two main ways. GPs will search medical records and send out study invitations. They will also make patients aware of the study during consultations. Patients who are interested in taking part in the study will be asked to complete two short questionnaires and a phone interview with a member of the research team to determine if the study is suitable for them._x000D_ _x000D_ Eligible participants will be allocated at random, by a computer, to one of two groups. One group will receive the behavioural sleep treatment alongside any existing treatment they are receiving for depression or sleep. This will involve meeting with a nurse each week for 6 weeks and following a personalised daily sleep schedule. The treatment aims to reduce awakenings during the night and encourage a more regular sleep pattern. The second group will not receive a specific treatment as part of the study but will continue to receive any existing treatment for depression or sleep. _x000D_ _x000D_ All participants will complete assessments at baseline (before treatment begins), and at 1 month, 2 months and 6 months. This will help us determine whether the treatment has worked. We will measure symptoms of depression using a questionnaire, and ask participants to complete computerised tasks that assess responses to emotional words and images. We will measure sleep quality using questionnaires, daily sleep diaries and actigraphy (a watch-like device that measures movement and therefore can indicate when one is asleep or awake). We will also collect information on medication prescriptions and any other treatments participants may access during the study. _x000D_ _x000D_ Importantly, at all stages of the study, five members of the public with experience of poor sleep and depression will act as advisors to the research team. This will ensure that our research takes into account the needs and views of patients, and that our findings can be translated to the NHS in a meaningful way. At the end of the study, we will send all participants a summary of the findings, publish our results in scientific journals, and work with the university’s media office and the Mental Health Foundation to share our work with the broader public. _x000D_ _x000D_ WHAT MIGHT BE THE IMPACT OF OUR RESEARCH?_x000D_ Our study will provide clear evidence on whether improving sleep quality improves depression. Our research may lead to new ways of treating depression in the future, and provide important knowledge on how sleep and mental health are connected.

Lay abstract: Background: Depression is a highly prevalent and impairing condition. Effective treatments exist but a significant minority of patients do not respond to pharmacotherapy or psychological therapy; there is a clear need for innovation with a focus on novel targets. Insomnia characterises 85% of patients with depression. Mounting clinical and experimental evidence suggests that insomnia is involved in both the causation and perpetuation of depression. _x000D_ _x000D_ Aims and objectives: Our primary objective is to test if adding an effective behavioural sleep intervention to existing depression care improves depression outcomes. Our secondary objectives are to assess whether the intervention improves depression via change in insomnia symptoms, and to assess whether the intervention drives change in mechanistic processes presumed to underlie the causal association between insomnia and depression._x000D_ _x000D_ Design: Individually randomised, parallel group, explanatory clinical trial design to compare sleep restriction therapy (SRT+treatment as usual; TAU) with TAU on its own. Participants will be randomised (1:1) to SRT+TAU or TAU using a validated web-based randomisation programme._x000D_ _x000D_ Setting: Participants will be recruited through 13 general practices in Thames Valley._x000D_ _x000D_ Target population: Adults aged 18 yrs and over who meet criteria for major depression and insomnia._x000D_ _x000D_ Interventions/control: All participants in the trial will continue to receive TAU. In addition, the SRT arm will receive six nurse-delivered treatment sessions (three in-person at the practice and three over the phone). Participants will be supported by the nurse to implement a new sleep schedule according to weekly review of their sleep pattern._x000D_ _x000D_ Outcomes: We will collect outcomes at baseline, 4, 8, and 26 weeks post-randomisation. The primary outcome is depression severity at 26 weeks measured with the PHQ-9. Insomnia severity (measured with the ISI at 4 weeks) is the mediator of interest. Mechanistic outcomes include objective sleep and circadian rest-activity rhythms (actigraphy), negative emotion processing bias (Oxford Emotional Test Battery), affect (Positive and Negative Affect Schedule) and repetitive negative thinking (Perseverative Thinking Questionnaire). _x000D_ _x000D_ Sample size and analysis: Assuming a minimum between-group standardised effect size difference of 0.50, with power set at 90%, significance level at 5%, and accounting for up to 20% attrition, a sample size of 212 participants (106 in each group) is required to detect effects on the primary depression outcome at 26 weeks. The primary analysis will be according to randomised group and will use a linear mixed model to estimate treatment differences in depression severity at 26 weeks, adjusting for minimisation factors._x000D_ _x000D_ Timetable: Prior to funded period=recruit team, finalise protocol, submit to ethics; M1-M6=trial set-up and nurse training; M7-M22=recruitment period (including 4 month internal pilot), randomising ~13 patients per month; M23-M30=complete follow-up; M31-M36=trial close-out, analysis, and final report. _x000D_ _x000D_ Anticipated impact and dissemination: Results have the potential to 1) identify a new pathway to treating depression (through insomnia reduction); and 2) elucidate mechanisms linking sleep improvement and mental health. We will work with our PPI advisory group, University media office, and partner charity (Mental Health Foundation) to disseminate trial findings through social media and seminar events.

Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MENTAL HEALTH