TY - BOOK
T1 - Randomised controlled trial to determine the clinical effectiveness and costeffectiveness of selective serotonin reuptake inhibitors plus supportive care, versus supportive care alone, for mild to moderate depression with somatic symptoms in primary care:
T2 - the THREAD (THREshold for AntiDepressant response) study.
AU - Kendrick, Tony
AU - Chatwin, Judy
AU - Dowrick, Chris
AU - Tylee, Andre
AU - Morriss, Richard
AU - Peveler, Robert
AU - Leese, Mike
AU - McCrone, Paul
AU - Harris, Tirril
AU - Moore, Michael
AU - Byng, Richard
AU - Brown, George
AU - Barthel, S
AU - Mander, Helen
AU - Ring, Adele
AU - Kelly, V
AU - Wallace, Vuokko
AU - Gabbay, Mark
AU - Craig, Tom
AU - Mann, Anthony
N1 - All NIHR Journals Library reports have been produced under the terms of a commissioning contract issued by the Secretary of State for Health. Reports may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Permission to reproduce material from a published report is covered by the UK government’s non-commercial licence for public sector information.
PY - 2009/4/30
Y1 - 2009/4/30
N2 - 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
Abstract
iv
significant improvement (HDRS reduction ≥ 50%) were
7 (95% CI 4 to 83) and 5 (95% CI 3 to 13) respectively.
Incremental cost-effectiveness ratios and costeffectiveness
planes suggested that adding an SSRI to
supportive care was probably cost-effective. The costeffectiveness
acceptability curve for utility suggested that
adding an SSRI to supportive care was cost-effective at
the values of £20,000–£30,000 per quality-adjusted lifeyear.
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 ≥ 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.
AB - 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
Abstract
iv
significant improvement (HDRS reduction ≥ 50%) were
7 (95% CI 4 to 83) and 5 (95% CI 3 to 13) respectively.
Incremental cost-effectiveness ratios and costeffectiveness
planes suggested that adding an SSRI to
supportive care was probably cost-effective. The costeffectiveness
acceptability curve for utility suggested that
adding an SSRI to supportive care was cost-effective at
the values of £20,000–£30,000 per quality-adjusted lifeyear.
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 ≥ 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.
U2 - 10.3310/hta13220
DO - 10.3310/hta13220
M3 - Commissioned report
SN - 1366-5278
VL - 13
T3 - Health Technology Assessment (HTA)
BT - Randomised controlled trial to determine the clinical effectiveness and costeffectiveness of selective serotonin reuptake inhibitors plus supportive care, versus supportive care alone, for mild to moderate depression with somatic symptoms in primary care:
PB - National Institute for Health Research (NIHR)
ER -