Title: A pilot RCT of drug treatment for depression in patients undergoing Haemodialysis
Funder: Department of Health (England)

Abstract: Background End Stage Renal Disease (ESRD) treated with Haemodialysis (HD) places many demands on the patient (both medical and social). For ESRD depression is the most common comorbid psychiatric pathology, and is known to have an impact on quality of life (QoL), adherence, morbidity and mortality. Despite the existence of treatments for depression in chronically ill, including SSRIs, there is little work testing these drugs among ESRD patients. Previous studies have been small with no control groups. The clinical and psychosocial demands on this patient group present many risks for treatment, including drug safety and pharmacokinetics (PK), adherence, and unique psychological issues that may interfere with treatment adherence and efficacy. To address these issues a pilot RCT is proposed. Aims The main aim is to enable a later large, well powered trial to establish the efficacy of SSRIs in HD patients. Therefore the practical aims are to estimate the proportion of: eligible patients who agree to take part; enrolled patients adhering to the prescribed medication regime; enrolled patients completing the study; enrolled patients with complete data (with assessment of the nature of missing data). We will also quantify the variability in the treatment and placebo control arms, allowing the calculation of effect sizes, estimation of centre effect, evaluation of adverse events, and of bias due to missing data. A qualitative sub-study will document factors facilitating participation and adherence to treatment. In addition, the PK of the SSRI will be studied in a further subgroup. Plan of Investigation The proposed study is a pilot placebo controlled RCT with 2 arms (SSRI treated versus placebo). Patients will be recruited from 4 UK centres (N=2000 treated patients), and after consent and screeing (with diagnosis) randomly allocated to one of the study arms Patients will be assessed (Depression, QoL, demographic and clinical measures) at baseline, 3 months and 6 months, with health checks and monitoring for self harm risk monthly. The qualitative substudy will sample patients at different time points to capture the patients experience across the study design, and semi structured interviews used. The pk study will sample levels of the drug at 3 time points. Data analysis will establish participation, treatment adherence, drop-out, missing data, variability, and safety. Potential Impact The study will generate the necessary data to conduct a full scale RCT. The full RCT will then be able to determine how effective SSRIs are at treating depression in ESRD patients. If effective, then promoting increased use of these drugs can alleviate depressive symptoms, and improve quality of life and adherence among the thousands of depressed ESRD patients in the UK, and the rest of the world. If ineffective, the NICE guidelines can be amended to reflect this and divert resources to other methods of tackling the issue. The pharmacokinetics sub-study will allow the formulation of guidelines for prescribing SSRIs to HD patients in the future, potentially increasing efficacy and reducing the chance of adverse effects.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH;RENAL AND UROGENITAL