New RCT shows that adding CBT to usual care helps people with treatment resistant depression


The CoBalT trial was published last week in the Lancet. This important randomised controlled trial (RCT) examined the effectiveness of cognitive behavioural therapy (CBT) as an add-on treatment to usual care for people with treatment resistant depression.

Previous studies have shown that only around one third of people with depression respond well to treatment with antidepressant drugs.

This new RCT provides the most reliable evidence yet that it’s worth adding CBT to antidepressant treatment in order to reduce symptoms of depression.

The researchers recruited 469 participants from 73 general practices in Bristol, Exeter and Glasgow. Patients had been taking antidepressants for 6 weeks and continued to show symptoms of depression (measured by the Beck Depression Inventory).

The researchers excluded people with bipolar disorder, psychosis or substance misuse, as well as those who had received CBT within the last 3 years.

The patients in the trial were:

  • 44% employed
  • 72% female
  • Average age 49.6 years old
  • 28% had severe depression, 58% moderate depression and 14% mild depression
  • 43% reported suffering from another disability or chronic disease like heart disease or diabetes
  • Three-quarters also had anxiety

Patients were randomised to one of two treatments:

  1. Continued usual GP care (including antidepressants and any other appropriate treatment)
  2. Usual care plus CBT (12-18 one hour sessions with a trained therapist)

Patients were followed up at 3 monthly intervals for one year. Outcomes included:

  • 50% reduction in depression symptoms (measured by the Beck Depression Inventory)
  • Quality of life
  • Reduction in symptoms of anxiety and panic

Here’s what they found:

  • After 6 months:
    • 46% of the CBT group had responded to treatment
    • 22% in the usual care group had responded to treatment
    • Odds ratio [OR] 3.26, 95% confidence interval [CI] 2.10 to 5.06
  • After 12 months:
    • 55% of the CBT group had responded to treatment
    • 31% of the usual care group had responded to treatment
    • OR 2.89, 95% CI 2.03 to 4.10
  • There was relatively little drop out in the study:
    • At 6 months, 88% of the CBT group and 91% of the usual care group were assessed
    • At 12 months, 85% of the CBT group and 84% of the usual care group were assessed
  • The NNT (number needed to treat for one person to benefit) for CBT was 4
  • Secondary outcomes of anxiety and panic also improved in the CBT group

The authors concluded:

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.

This is a well-conducted and reliable piece of evidence that adds considerably to what we already know about using CBT to help people with treatment resistant depression. It’s encouraging to see how well CBT performs given that such a significant investment has been made in the treatment through the Improving Access to Psychological Therapies programme.

The trial is not perfect, but it has a large sample size, reliable outcome assessment measures, relatively long follow-up and low drop out rate.

Limitations included:

  • The CBT group had more men, more employed and fewer patients with other long-term illnesses
  • Patients and researchers were not blind to the treatment being given (it’s possible to give placebo pills but placebo CBT is more of a challenge!)

Overall though, this is a useful addition to the evidence base, showing that people with depression who have not responded to drug treatment may well respond if CBT is added to their treatment plan.


Wiles N, Thomas L, Abel A, Ridgway N, Turner N, Campbell J, Garland A, Hollinghurst S, Jerrom B, Kessler D, Kuyken W, Morrison J, Turner K, Williams C, Peters T, Lewis G. Cognitive behavioural therapy as an adjunct to pharmacotherapy for primary care based patients with treatment resistant depression: results of the CoBalT randomised controlled trial. The Lancet – 7 December 2012 DOI: 10.1016/S0140-6736(12)61552-9 [Abstract]

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Andre Tomlin

André Tomlin is an Information Scientist with 20 years experience working in evidence-based healthcare. He's worked in the NHS, for Oxford University and since 2002 as Managing Director of Minervation Ltd, a consultancy company who do clever digital stuff for charities, universities and the public sector. Most recently André has been the driving force behind the Mental Elf and the National Elf Service; an innovative digital platform that helps professionals keep up to date with simple, clear and engaging summaries of evidence-based research. André is a Trustee at the Centre for Mental Health and an Honorary Research Fellow at University College London Division of Psychiatry. He lives in Bristol, surrounded by dogs, elflings and lots of woodland!

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