Elsevier

The Lancet

Volume 381, Issue 9864, 2–8 February 2013, Pages 375-384
The Lancet

Articles
Cognitive behavioural therapy as an adjunct to pharmacotherapy for primary care based patients with treatment resistant depression: results of the CoBalT randomised controlled trial

https://doi.org/10.1016/S0140-6736(12)61552-9Get rights and content

Summary

Background

Only a third of patients with depression respond fully to antidepressant medication but little evidence exists regarding the best next-step treatment for those whose symptoms are treatment resistant. The CoBalT trial aimed to examine the effectiveness of cognitive behavioural therapy (CBT) as an adjunct to usual care (including pharmacotherapy) for primary care patients with treatment resistant depression compared with usual care alone.

Methods

This two parallel-group multicentre randomised controlled trial recruited 469 patients aged 18–75 years with treatment resistant depression (on antidepressants for ≥6 weeks, Beck depression inventory [BDI] score ≥14 and international classification of diseases [ICD]-10 criteria for depression) from 73 UK general practices. Participants were randomised, with a computer generated code (stratified by centre and minimised according to baseline BDI score, whether the general practice had a counsellor, previous treatment with antidepressants, and duration of present episode of depression) to one of two groups: usual care or CBT in addition to usual care, and were followed up for 12 months. Because of the nature of the intervention it was not possible to mask participants, general practitioners, CBT therapists, or researchers to the treatment allocation. Analyses were by intention to treat. The primary outcome was response, defined as at least 50% reduction in depressive symptoms (BDI score) at 6 months compared with baseline. This trial is registered, ISRCTN38231611.

Findings

Between Nov 4, 2008, and Sept 30, 2010, we assigned 235 patients to usual care, and 234 to CBT plus usual care. 422 participants (90%) were followed up at 6 months and 396 (84%) at 12 months, finishing on Oct 31, 2011. 95 participants (46%) in the intervention group met criteria for response at 6 months compared with 46 (22%) in the usual care group (odds ratio 3·26, 95% CI 2·10–5·06, p<0·001).

Interpretation

Before this study, no evidence from large-scale randomised controlled trials was available for the effectiveness of augmentation of antidepressant medication with CBT as a next-step for patients whose depression has not responded to pharmacotherapy. Our study has provided robust evidence that CBT as an adjunct to usual care that includes antidepressants is an effective treatment, reducing depressive symptoms in this population.

Funding

National Institute for Health Research Health Technology Assessment.

Introduction

Depression is a major public health problem. It is predicted to be the leading cause of disability in high-income countries by 2030, with only HIV/AIDS and perinatal disorders ranking higher for low-income and middle-income countries.1 Antidepressants are often the first-line treatment for depression and prescriptions for such drugs have increased substantially in the past 20 years.2, 3 However, only a third of patients respond fully to pharmacotherapy and half do not have at least a 50% reduction in depressive symptoms after 12–14 weeks of medication.4 When an adequate dose and duration of treatment has been given, such non-response can be termed treatment resistance. No agreed definition of treatment resistance exists5 but, in view of the extent of non-response, treatment-resistant depression clearly has a substantial effect on individuals, health services, and society.

No standard approach to the management of treatment-resistant depression exists. Options include increasing the dose of pharmacotherapy, switching to a different antidepressant, or augmentation with another pharmacological or psychological treatment. However, evidence that these approaches improve outcome is scarce.6, 7

Evidence shows that cognitive behavioural therapy (CBT), the most widely available structured psychotherapy for depression, is effective for previously untreated episodes of depression. CBT and its variants have been investigated for treatment of chronic and treatment-resistant depression but previous trials have not included a comparison group of patients who continued with their existing medication,8 meaning that the effectiveness of augmentation of antidepressant medication with CBT has not been assessed as a next-step treatment option. Some researchers have investigated a variant of CBT—cognitive behavioural analysis system of psychotherapy (CBASP)9, 10—which puts more emphasis on behavioural and interpersonal factors than does standard CBT. However, these trials in patients with chronic depression have provided inconsistent results as to the effectiveness of CBASP combined with medication compared with medication alone.9, 10

Scarce access to psychological treatment in the UK and elsewhere has meant that, in clinical practice, CBT has often been reserved for individuals who have not responded to antidepressants. No large-scale randomised controlled trials6, 7 have assessed the effectiveness of CBT after non-response to pharmacotherapy compared with continuing pharmacotherapy as part of usual care for patients with treatment-resistant depression. We chose to investigate CBT rather than CBASP because some evidence suggests that CBT might reduce rates of relapse,11 including among individuals with residual depressive symptoms.12 Furthermore, some models of more persistent depression put emphasis on cognitive rather than behavioural aspects of treatment.13

The aim of the CoBalT trial was to examine the effectiveness of CBT as an adjunct to usual care including pharmacotherapy for primary care patients with treatment resistant depression compared with usual care alone. The economic evaluation will be reported separately.

Section snippets

Study design and participants

CoBalT was a multicentre pragmatic randomised controlled trial with two parallel groups.14 We recruited participants from 73 general practices in urban and rural settings in three UK centres: Bristol, Exeter, and Glasgow. Most participants were identified through a search of practice computerised medical records, although general practitioners (family doctors) were able to refer patients directly to the research team.

Eligible patients were those aged 18–75 years who had adhered15, 16 to an

Results

We did the first record search for eligible patients on Nov 4, 2008, and randomised the last patient on Sept 30, 2010 (appendix pp 2–3). We obtained follow-up data between March 16, 2009, and Oct 31, 2011. We identified 912 patients as having treatment-resistant depression and invited them to attend a baseline appointment, but 163 (18%) declined (figure). We identified no age or gender differences between individuals who declined and those who agreed to attend such an appointment (data not

Discussion

CBT as an adjunct to usual care that included pharmacotherapy was effective in reducing depressive symptoms and improving quality of life in primary care patients with treatment-resistant depression. The beneficial effect of the intervention was also identified for the more stringent criteria of remission and improvements were maintained over 12 months.

No one definition of treatment-resistant depression is accepted, hence we used an inclusive and pragmatic definition that would be generalisable

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