Mental health

If 'drugs don’t work' for depression, CBT may

“Cognitive behavioural therapy (CBT) can reduce symptoms of depression in people who fail to respond to drug treatment“ BBC News has reported.

The claim follows the publication of a well conducted trial in which 469 adults in the UK with depression whose symptoms had not responded to six months of antidepressants were split into two randomised groups:

  • continued usual care (including continued antidepressants)
  • usual care with the addition of cognitive behavioural therapy (CBT)

CBT is already an established ‘talking therapy’ for depression and takes a more pragmatic and problem solving approach than more traditional forms of psychotherapy. It is based on the principle that there is a link between thinking and behaviour – unhelpful and unrealistic thinking (such as, ‘if I am not perfect then others will reject me’) can lead to unhelpful and sometimes self-destructive behaviour. This in turn can reinforce the unhelpful patterns of thinking.

CBT aims to break through this ‘vicious cycle’ by setting practical, real-world tasks, designed to challenge both patterns of thinking and behaviour.

The study found that people who received CBT in addition to antidepressants, rather than continuing to receive antidepressants alone, had around a three-fold increased chance of responding to treatment and having a reduction in their depression symptoms over the following 12 months.

The study provides further evidence on the effectiveness of CBT to treat depression, particularly in those who have not responded to antidepressants alone.

Where did the story come from?

The study was carried out by researchers from University of Bristol, University of Exeter and several other academic institutions in the UK and was funded by National Institute for Health Research – Health Technology Assessment programme. The study was published in the peer-reviewed medical journal The Lancet.

The BBC’s reporting on the study’s findings is accurate, and includes an insightful quote from Paul Farmer, chief executive at the mental health charity Mind "We welcome this research because it recognises that patients should have the right to a wide range of treatment options based on individual needs".

What kind of research was this?

This was a randomised controlled trial (RCT) which aimed to investigate whether CBT is an effective add-on (or in medical terms – adjunct) to standard care (including ongoing drug treatment with antidepressants) for people whose depression is resistant to standard care alone.

The researchers explained that only one third of patients with depression respond well to antidepressant medications.

It is unclear what the best next step forward for the other two-thirds is.

CBT is one of the most widely used ‘talking therapies’ for depression (and certain other mental health problems, such as anxiety or stress).

It is an established first-line treatment for milder depression, before the use of antidepressants and is sometimes used alongside antidepressants for more severe depression.

The National Institute for Health and Clinical Excellence (NICE) has recommended its use for the treatment of depression (as well as a number of other mental health conditions).

This particular trial aimed to see how effective CBT is when used as an add-on to usual care, including antidepressants, when usual care alone has not worked. The researchers reported that this has not been assessed in a large RCT before.

They compared CBT plus usual care with continued usual care alone. A well conducted RCT such as this is the best way of examining the effectiveness of an intervention.           

What did the research involve?

The trial recruited participants from 73 general practices in Bristol, Exeter and Glasgow. Eligible adults met valid diagnostic criteria for depression and had taken an adequate antidepressant dose for six weeks and still had symptoms of depression (scoring above a certain threshold on an accepted measure of depressive symptoms called the Beck Depression Inventory, BDI).

They excluded people with more significant mental health problems, such as co-existing bipolar disorder, psychosis or substance use.

They also excluded people who were currently receiving CBT or other ‘talking therapies’ or had done so in the past three years.

The 469 participants were randomly assigned to one of two groups, either continued usual care or CBT in addition to usual care. Participants in the intervention group received 12, one-hour sessions of individual CBT with up to a further six sessions if judged to be clinically appropriate by the therapist.

CBT was provided by trained therapists who worked according to standard CBT treatment manuals for depression.

CBT was provided in addition to usual care from their general practitioner.

The researchers report that no restriction was placed upon what treatments could be allowed in the ‘usual care’ group.

For instance, while this typically involved continued antidepressant treatment, if their treating doctor felt that they wanted to refer them on for ‘talking therapies’, including CBT, they were free to do so.

Due to the nature of the intervention, it was not possible to blind participants, therapists or researchers to treatment allocation – that is, everyone involved in the trial was aware of whether the person had received CBT or not. 

Participants were followed up at 3, 6, 9, and 12 months after randomisation. The main outcome of interest was their depression symptom score on the BDI at six months, with a treatment response defined as a reduction in depressive symptoms of at least 50% from the start of the study. Other outcomes of interest included improved quality of life and symptoms such as panic and anxiety.

What were the basic results?

Of the 469 participants, 72% were women, their average age was 49.6 years and 44% were employed. Over half of the participants (59%) had been experiencing their current episode of depression for over two years. Most participants were classified as having moderate depression (58%), with 28% classified as having severe depression, and 14% mild depression.

Three-quarters had a diagnosis of anxiety alongside their depression and 43% reported having other long-term illnesses (such as diabetes or heart disease) or disability.

There were some imbalances between the treatment groups, with the CBT group including a higher proportion of men, more people in paid employment and fewer with longer term illnesses or disability.

At six months, 88% of those in the CBT group and 91% of those in the usual care group were assessed for the main study outcome of treatment response. By 12 months, assessment was completed by 85% and 84%, respectively. (The ‘drop-outs’ occured for a number of reasons, such as people saying they no longer wished to continue with the study or not responding to any follow-up messages.)

At six months, 46% of the CBT group had responded to treatment compared with 22% in the usual care group (odds ratio [OR] 3.26, 95% confidence interval [CI] 2.10 to 5.06).

Adjustment for the imbalances between the two groups had little effect on the results. The researchers calculated that four people would need to be treated with CBT in order for one to benefit. This is known as the number needed to treat or NNT, and compared to some drugs on the market, an NNT of four is reasonably good.

Benefits were maintained to 12 months, when 55% of the CBT group compared with 31% of the usual care group responded to treatment (OR 2.89, 95% CI 2.03 to 4.10).

The secondary outcomes of symptoms of panic and anxiety also improved in the CBT group.

At six months, 93% of both groups were receiving antidepressant treatment. At 12 months, 88% of the CBT group and 92% of the usual care group were still taking antidepressants; the difference between the two groups was not statistically significant.

How did the researchers interpret the results?

The researchers conclude that their study provides strong evidence that CBT as an add-on to usual care (including antidepressants) is an effective treatment for reducing depressive symptoms in people with antidepressant-resistant depression.


This is a well-designed study which has many strengths, including its large sample size, long duration of follow-up with low drop-out rates, and using valid symptom scales to assess outcomes.

As the researchers say, previous research has led to CBT becoming an established treatment for depression.

But this large-scale randomised controlled trial arguably provides the strongest evidence to date about the effectiveness of adding CBT to antidepressant medication for people whose symptoms have not responded to six months of medication.

However, the study does contain some minor limitations. For example, participants and researchers were aware of treatment allocation – an unvoidable constraint with this type of study – you can’t give people ‘placebo’ CBT.

This study nevertheless provides further evidence on the effectiveness of CBT to treat depression, particularly in those who have not responded to antidepressants alone.

NHS Attribution