Do adding CBT improve depression while on antidepressants? Lancet:Dec 7:2012


Depression continue to climb up the ladder of disorders that contribute to disability world-wide. Only a third of patients respond fully to pharmacotherapy ie achieve remission .Resistant depression is common and affect individuals , families and services negatively. Adding psychological therapies to standard antidepressant have not always produced extra benefit as well.

No large-scale randomised controlled trials 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. CoBalT trial by Nicola Wiles and colleagues ( University of Bristol) report the results of such a study. They examined 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.  This is a multicentre pragmatic randomised controlled trial with two parallel groups. Adults who have adhered to an adequate dose of antidepressant medication for at least 6 weeks and had a Beck depression inventory (BDI-II)17 score of 14 or more were recruited from 73 general practices  and randomised to usual care or CBT. There were no restriction on treatment as usual group. Intervention group received 12 sessions of  individual CBT(each lasting 50–60min), with (up to) a further six sessions if needed in addition to usual care from their general practitioner.  Therapists were experienced ( mean nearly 10 yrs) ,they used depression treatment manuals, but had flexibility to address other issues ( eg : anxiety ) as well and received regular weekly supervision . Participants were followed up 3, 6, 9, and 12 months after randomisation.The primary outcome was BDI score at 6 months, with response defined as a reduction in depressive symptoms of at least 50% compared with baseline.


 912 patients  were identified as having treatment-resistant depression,  18% declined .  Of the 749 who attended a baseline appointment, 63% (469) were eligible to participate.  72%  of participants were women, mean age was 49·6 years .Mean BDI score at baseline was 31·8 . 28% (129) of participants fulfilled ICD-10 criteria for a severe depressive episode. The intervention group included more men, more individuals in paid employment,fewer individuals with caring responsibilities or long- standing illness or disability, and better physical function.At 6 months, 93% of both groups  were taking antidepressant medication.44% reported taking a different type or dose of medication from that at baseline at 12 months.

It is notable that more than 99% of patients invited for baseline assessment elected to participate. However after entering the study , both groups had similar drop-outs ( withdrawal from study , unable to follow-up etc).

 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). So  the intervention group had three-fold increased odds of response at 6 months.   The results imputing missing data were consistent with the findings of the primary complete-case analysis .Beneficial effect of the intervention was confirmed for the secondary outcomes at 6 months . There was no  evidence of clustering of outcomes by therapist .Subgroup analyses did not show  evidence for patient expectation of outcome  or degree of treatment resistance on outcome. Adjustment for baseline imbalances did not affect any of these findings though data for this is not provided. Individuals in the intervention group had about three-fold increased odds of response and remission over 12 months.


There is  no  ‘attention control’  for treatment as usual group. ( ie  to balance the time spent with the  therapist in active treatment group). Authors wanted to know about the value of addition of CBT to antidepressants in this population in a pragmatic design. Patients and researchers were not  masked.  Adherence to medication was assessed by self report alone.

Also of note is that therapists were experienced, and had the flexibility to tailor the treatment approach to the individual needs and beliefs.


CBT is an effective treatment when used along with medications in treatment resistant primary care patients.

Comment: Definition of treatment resistance in this study is different from usual definition ie   lack of response  from two different antidepressants.  Patients on antidepressant for 6 weeks with BDI score 14 or more were defined as treatment resistance in this study. It is also unclear how many of these patients were on the  ‘recovery path’ ie change in scores from before starting antidepressants to the present point. Also of note is that only 28% of participants had severe depression.

This study clearly show that patients with depression in primary care would benefit substantially from receiving CBT if they are still reporting depressed after 6 weeks on being on an antidepressant.

Summary of the article:

Pharmacotherapy for primary care based patients with treatment resistant depression: results of the CoBalT randomised controlled trial ,Nicola Wiles, Laura Thomas, Anna Abel, Nicola Ridgway, Nicholas Turner, John Campbell, Anne Garland, Sandra Hollinghurst, Bill Jerrom, David Kessler, Willem Kuyken, Jill Morrison, Katrina Turner, Chris Williams, Tim Peters, Glyn Lewis  Lancet, Dec, 2012. Published online December 7, 2012

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