Marc Serfaty1,2, Michael King1,3, Irwin Nazareth3, Stirling Moorey4,5, Trefor Aspden1, Adrian Tookman6, Kathryn Mannix7, Anna Gola3,8, Sarah Davis1,7, John Wood3, Louise Jones1,6. 1. Division of Psychiatry, University College London, London, UK. 2. Priory Hospital North London, London, UK. 3. Research Department of Primary Care & Population Health, University College London, London, UK. 4. South London and Maudsley NHS Foundation Trust, London, UK. 5. Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. 6. Marie Curie Hospice, Royal Free Hampstead NHS Trust, London, UK. 7. Palliative Care Service, Newcastle upon Tyne Hospital NHS Foundation Trust, Newcastle upon Tyne, UK. 8. Marie Curie Palliative Care Research Department, University College London, London, UK.
Abstract
BACKGROUND: With a prevalence of up to 16.5%, depression is one of the commonest mental disorders in people with advanced cancer. Depression reduces the quality of life (QoL) of patients and those close to them. The National Institute for Health and Care Excellence (NICE) guidelines recommend treating depression using antidepressants and/or psychological treatments, such as cognitive-behavioural therapy (CBT). Although CBT has been shown to be effective for people with cancer, it is unclear whether or not this is the case for people with advanced cancer and depression. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of treatment as usual (TAU) plus manualised CBT, delivered by high-level Improving Access to Psychological Therapy (IAPT) practitioners, versus TAU for people with advanced cancer and depression, measured at baseline, 6, 12, 18 and 24 weeks. DESIGN: Parallel-group, single-blind, randomised trial, stratified by whether or not an antidepressant was prescribed, comparing TAU with CBT plus TAU. SETTING: Recruitment took place in oncology, hospice and primary care settings. CBT was delivered in IAPT centres or/and over the telephone. PARTICIPANTS: Patients (N = 230; n = 115 in each arm) with advanced cancer and depression. Inclusion criteria were a diagnosis of cancer not amenable to cure, a DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnosis of depressive disorder using the Mini-International Neuropsychiatric Interview, a sufficient understanding of English and eligibility for treatment in an IAPT centre. Exclusion criteria were an estimated survival of < 4 months, being at high risk of suicide and receiving, or having received in the last 2 months, a psychological intervention recommended by NICE for treating depression. INTERVENTIONS: (1) Up to 12 sessions of manualised individual CBT plus TAU delivered within 16 weeks and (2) TAU. OUTCOME MEASURES: The primary outcome was the Beck Depression Inventory, version 2 (BDI-II) score at 6, 12, 18 and 24 weeks. Secondary outcomes included scores on the Patient Health Questionnaire-9, the Eastern Cooperative Oncology Group Performance Status, satisfaction with care, EuroQol-5 Dimensions and the Client Services Receipt Inventory, at 12 and 24 weeks. RESULTS:A total of 80% of treatments (185/230) were analysed: CBT (plus TAU) (n = 93) and TAU (n = 92) for the BDI-II score at all time points using multilevel modelling. CBT was not clinically effective [treatment effect -0.84, 95% confidence interval (CI) -2.76 to 1.08; p = 0.39], nor was there any benefit for other measures. A subgroup analysis of those widowed, divorced or separated showed a significant effect of CBT on the BDI-II (treatment effect -7.21, 95% CI -11.15 to -3.28; p < 0.001). Economic analysis revealed that CBT has higher costs but produces more quality-adjusted life-years (QALYs) than TAU. The mean service costs for participants (not including the costs of the interventions) were similar across the two groups. There were no differences in EQ-5D median scores at baseline, nor was there any advantage of CBT over TAU at 12 weeks or 24 weeks. There was no statistically significant improvement in QALYs at 24 weeks. LIMITATIONS: Although all participants satisfied a diagnosis of depression, for some, this was of less than moderate severity at baseline, which could have attenuated treatment effects. Only 64% (74/115) took up CBT, comparable to the general uptake through IAPT. CONCLUSIONS:Cognitive-behavioural therapy (delivered through IAPT) does not achieve any clinical benefit in advanced cancer patients with depression. The benefit of CBT for people widowed, divorced or separated is consistent with other studies. Alternative treatment options for people with advanced cancer warrant evaluation. Screening and referring those widowed, divorced or separated to IAPT for CBT may be beneficial. Whether or not improvements in this subgroup are due to non-specific therapeutic effects needs investigation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN07622709. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 19. See the NIHR Journals Library website for further project information.
RCT Entities:
BACKGROUND: With a prevalence of up to 16.5%, depression is one of the commonest mental disorders in people with advanced cancer. Depression reduces the quality of life (QoL) of patients and those close to them. The National Institute for Health and Care Excellence (NICE) guidelines recommend treating depression using antidepressants and/or psychological treatments, such as cognitive-behavioural therapy (CBT). Although CBT has been shown to be effective for people with cancer, it is unclear whether or not this is the case for people with advanced cancer and depression. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of treatment as usual (TAU) plus manualised CBT, delivered by high-level Improving Access to Psychological Therapy (IAPT) practitioners, versus TAU for people with advanced cancer and depression, measured at baseline, 6, 12, 18 and 24 weeks. DESIGN: Parallel-group, single-blind, randomised trial, stratified by whether or not an antidepressant was prescribed, comparing TAU with CBT plus TAU. SETTING: Recruitment took place in oncology, hospice and primary care settings. CBT was delivered in IAPT centres or/and over the telephone. PARTICIPANTS: Patients (N = 230; n = 115 in each arm) with advanced cancer and depression. Inclusion criteria were a diagnosis of cancer not amenable to cure, a DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnosis of depressive disorder using the Mini-International Neuropsychiatric Interview, a sufficient understanding of English and eligibility for treatment in an IAPT centre. Exclusion criteria were an estimated survival of < 4 months, being at high risk of suicide and receiving, or having received in the last 2 months, a psychological intervention recommended by NICE for treating depression. INTERVENTIONS: (1) Up to 12 sessions of manualised individual CBT plus TAU delivered within 16 weeks and (2) TAU. OUTCOME MEASURES: The primary outcome was the Beck Depression Inventory, version 2 (BDI-II) score at 6, 12, 18 and 24 weeks. Secondary outcomes included scores on the Patient Health Questionnaire-9, the Eastern Cooperative Oncology Group Performance Status, satisfaction with care, EuroQol-5 Dimensions and the Client Services Receipt Inventory, at 12 and 24 weeks. RESULTS: A total of 80% of treatments (185/230) were analysed: CBT (plus TAU) (n = 93) and TAU (n = 92) for the BDI-II score at all time points using multilevel modelling. CBT was not clinically effective [treatment effect -0.84, 95% confidence interval (CI) -2.76 to 1.08; p = 0.39], nor was there any benefit for other measures. A subgroup analysis of those widowed, divorced or separated showed a significant effect of CBT on the BDI-II (treatment effect -7.21, 95% CI -11.15 to -3.28; p < 0.001). Economic analysis revealed that CBT has higher costs but produces more quality-adjusted life-years (QALYs) than TAU. The mean service costs for participants (not including the costs of the interventions) were similar across the two groups. There were no differences in EQ-5D median scores at baseline, nor was there any advantage of CBT over TAU at 12 weeks or 24 weeks. There was no statistically significant improvement in QALYs at 24 weeks. LIMITATIONS: Although all participants satisfied a diagnosis of depression, for some, this was of less than moderate severity at baseline, which could have attenuated treatment effects. Only 64% (74/115) took up CBT, comparable to the general uptake through IAPT. CONCLUSIONS: Cognitive-behavioural therapy (delivered through IAPT) does not achieve any clinical benefit in advanced cancerpatients with depression. The benefit of CBT for people widowed, divorced or separated is consistent with other studies. Alternative treatment options for people with advanced cancer warrant evaluation. Screening and referring those widowed, divorced or separated to IAPT for CBT may be beneficial. Whether or not improvements in this subgroup are due to non-specific therapeutic effects needs investigation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN07622709. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 19. See the NIHR Journals Library website for further project information.