Clinical effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: the CoBalT randomised controlled trial

Health technology assessment (Winchester, England) 05/2014; 18(31):1-168. DOI: 10.3310/hta18310
Source: PubMed

ABSTRACT Only one-third of patients with depression respond fully to treatment with antidepressant medication. However, there is little robust evidence to guide the management of those whose symptoms are 'treatment resistant'.
The CoBalT trial examined the clinical effectiveness and cost-effectiveness of cognitive behavioural therapy (CBT) as an adjunct to usual care (including pharmacotherapy) for primary care patients with treatment-resistant depression (TRD) compared with usual care alone.
Pragmatic, multicentre individually randomised controlled trial with follow-up at 3, 6, 9 and 12 months. A subset took part in a qualitative study investigating views and experiences of CBT, reasons for completing/not completing therapy, and usual care for TRD.
General practices in Bristol, Exeter and Glasgow, and surrounding areas.
Patients aged 18-75 years who had TRD [on antidepressants for ≥ 6 weeks, had adhered to medication, Beck Depression Inventory, 2nd version (BDI-II) score of ≥ 14 and fulfilled the International Classification of Diseases and Related Health Problems, Tenth edition criteria for depression]. Individuals were excluded who (1) had bipolar disorder/psychosis or major alcohol/substance abuse problems; (2) were unable to complete the questionnaires; or (3) were pregnant, as were those currently receiving CBT/other psychotherapy/secondary care for depression, or who had received CBT in the past 3 years.
Participants were randomised, using a computer-generated code, to usual care or CBT (12-18 sessions) in addition to usual care.
The primary outcome was 'response', defined as ≥ 50% reduction in depressive symptoms (BDI-II score) at 6 months compared with baseline. Secondary outcomes included BDI-II score as a continuous variable, remission of symptoms (BDI-II score of < 10), quality of life, anxiety and antidepressant use at 6 and 12 months. Data on health and social care use, personal costs, and time off work were collected at 6 and 12 months. Costs from these three perspectives were reported using a cost-consequence analysis. A cost-utility analysis compared health and social care costs with quality adjusted life-years.
A total of 469 patients were randomised (intervention: n = 234; usual care: n = 235), with 422 participants (90%) and 396 (84%) followed up at 6 and 12 months. Ninety-five participants (46.1%) in the intervention group met criteria for 'response' at 6 months compared with 46 (21.6%) in the usual-care group {odds ratio [OR] 3.26 [95% confidence interval (CI) 2.10 to 5.06], p < 0.001}. In repeated measures analyses using data from 6 and 12 months, the OR for 'response' was 2.89 (95% CI 2.03 to 4.10, p < 0.001) and for a secondary 'remission' outcome (BDI-II score of < 10) 2.74 (95% CI 1.82 to 4.13, p < 0.001). The mean cost of CBT per participant was £910, the incremental health and social care cost £850, the incremental QALY gain 0.057 and incremental cost-effectiveness ratio £14,911. Forty participants were interviewed. Patients described CBT as challenging but helping them to manage their depression; listed social, emotional and practical reasons for not completing treatment; and described usual care as mainly taking medication.
Among patients who have not responded to antidepressants, augmenting usual care with CBT is effective in reducing depressive symptoms, and these effects, including outcomes reflecting remission, are maintained over 12 months. The intervention was cost-effective based on the National Institute for Health and Care Excellence threshold. Patients may experience CBT as difficult but effective. Further research should evaluate long-term effectiveness, as this would have major implications for the recommended treatment of depression.
Current Controlled Trials ISRCTN38231611.
This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 31. See the NIHR Journals Library website for further project information.

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Available from: David Kessler, May 19, 2014
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    ABSTRACT: Objective To assess the role that treatment response plays in a randomized clinical trial of an anti-depressant among people with spinal cord injury (SCI) diagnosed with major depression disorder (MDD) in explaining quality of life (QOL), assessed both globally as life satisfaction and in terms of physical and mental health-related QOL. Design Multivariable analyses were conducted, controlling for demographic, neurological and participatory factors as well as perceived functional limitations. Setting A 12-week randomized clinical trial of venlafaxine XR conducted at 6 centers around the U.S. Participants 124 of the 133 persons who were randomized into the “Project to Improve Symptoms and Mood after Spinal Cord Injury” randomized clinical trial. All were between the ages of 18 and 64, at least one month post SCI, met the DSM IV criteria for MDD and completed the core measures used in this study. Main Outcome Measures The Satisfaction with Life Scale and the SF-12’s Physical and Mental Component Summary scores. Results Reduction in depressive symptoms over the course of a 12 week trial was predictive of increased QOL, measured as life satisfaction and mental well-being, within the context of other explanatory factors. Reduction in symptoms did not explain differences in physical well-being among those with MDD, however. Perceived functional disability, explained all three indices of QOL. Conclusions Greater recognition has been given to QOL outcomes as endpoints of clinical trials as these often reflect participants’ reported outcomes. Our findings support the association of QOL to reduction of depression symptoms among trial participants. This association differs depending upon how QOL is defined and measured, with stronger relationships observed with life satisfaction and mental well-being among those diagnosed with MDD. The lack of association between depression with physical well-being may be explained by participants’ subjective interpretation of physical well-being following SCI, their expectations and perceptions of improved physical health related QOL based on the use of assistive technology. Consistent with our findings, pain is likely to play a role in decreasing physical QOL among those with incomplete injuries. The authors suggest caution in using physical well-being as an endpoint in trials among people with SCI.
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