Randomised controlled trial to determine the clinical effectiveness and cost-effectiveness of selective serotonin reuptake inhibitors plus supportive care, versus supportive care alone, for mild to moderate depression with somatic symptoms in primary care: the THREAD (THREshold for AntiDepressant response) study.

OBJECTIVES: To determine (1) the effectiveness and cost-effectiveness of selective serotonin reuptake inhibitor (SSRI) treatment plus supportive care, versus supportive care alone, for mild to moderate depression in patients with somatic symptoms in primary care; and (2) the impact of the initial severity of depression on effectiveness and relative costs. To investigate the impact of demographic and social variables.
DESIGN: The study was a parallel group, open-label, pragmatic randomised controlled trial.
SETTING: The study took place in a UK primary care setting. Patients were referred by 177 GPs from 115 practices around three academic centres. PARTICIPANTS: Patients diagnosed with new episodes of depression and potentially in need of treatment. In total, 602 patients were referred to the study team, of whom 220 were randomised.
INTERVENTIONS: GPs were asked to provide supportive care to all participants in follow-up consultations 2, 4, 8 and 12 weeks after the baseline assessment, to prescribe an SSRI of their choice to patients in the SSRI plus supportive care arm and to continue treatment for at least 4 months after recovery. They could switch antidepressants during treatment if necessary. They were asked to refrain from prescribing an antidepressant to those in the supportive care alone arm during the first 12 weeks but could prescribe to these patients if treatment became necessary. MAIN OUTCOME MEASURES: The primary outcome measure was Hamilton Depression Rating Scale (HDRS) score at 12-week follow-up. Secondary outcome measures were scores on HDRS at 26-week follow-up, Beck Depression Inventory, Medical Outcomes Study Short Form-36 (SF-36), Medical Interview Satisfaction Scale (MISS), modified Client Service Receipt Inventory and medical record data.
RESULTS: SSRIs were received by 87% of patients in the SSRI plus supportive care arm and 20% in the supportive care alone arm. Longitudinal analyses demonstrated statistically significant differences in favour of the SSRI plus supportive care arm in terms of lower HDRS scores and higher scores on the SF-36 and MISS. Significant mean differences in HDRS score adjusted for baseline were found at both follow-up points when analysed separately but were relatively small. The numbers needed to treat for remission (to HDRS > 8) were 6 [95% confidence interval (CI) 4 to 26)] at 12 weeks and 6 (95% CI 3 to 31) at 26 weeks, and for significant improvement (HDRS reduction > or = 50%) were 7 (95% CI 4 to 83) and 5 (95% CI 3 to 13) respectively. Incremental cost-effectiveness ratios and cost-effectiveness planes suggested that adding an SSRI to supportive care was probably cost-effective. The cost-effectiveness acceptability curve for utility suggested that adding an SSRI to supportive care was cost-effective at the values of 20,000 pounds-30,000 pounds per quality-adjusted life-year. A poorer outcome on the HDRS was significantly related to greater severity at baseline, a higher physical symptom score and being unemployed.
CONCLUSIONS: Treatment with an SSRI plus supportive care is more effective than supportive care alone for patients with mild to moderate depression, at least for those with symptoms persisting for 8 weeks and an HRDS score of > or = 12. The additional benefit is relatively small, and may be at least in part a placebo effect, but is probably cost-effective at the level used by the National Institute for Health and Clinical Excellence to make judgements about recommending treatments within the National Health Service. However, further research is required.

RCT Entities:   Population Interventions Outcomes