Major new research published in the Lancet last week gives hope to those struggling with antidepressant-resistant depression.  Nicola Wiles and 15 co-authors have just reported on this two year study involving 469 patients with treatment-resistant depression seen in 73 UK general practices.  The abstract of their paper "Cognitive behavioural therapy as an adjunct to pharmacotherapy for primary care based patients with treatment resistant depression: Results of the CoBalT randomised controlled trial" states "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."

The more I look at this research paper, the more I impressed I am by it.  What a huge amount of high quality work has gone into addressing an extremely important area of need.  As the authors note "Depression ... 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." Many sufferers will be treated with antidepressants, but "half do not have at least a 50% reduction in depressive symptoms after 12-14 weeks of medication."  What should one do in this situation?  Choices include increasing antidepressant dose, switching to an alternative antidepressant, or adding additional medication or psychological help. Surprisingly - when one considers the importance of the question and the amount of research on CBT & psychotherapy more generally - good evidence-based answers to the simple question "How valuable is it to add psychotherapy to failed/partial antidepressant response?" have been surprisingly thin on the ground.  The very exciting major CBASP study - "A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression" - published with so much hope in 2000, was followed nine years later by the saddening "Cognitive Behavioral Analysis System of Psychotherapy and brief supportive psychotherapy for augmentation of antidepressant nonresponse in chronic depression: The REVAMP trial."   I'm still holding my breath for more news emerging after the tantalising 2008 paper "Treatment of chronically depressed patients: A multisite randomized controlled trial testing the effectiveness of 'cognitive behavioral analysis system of psychotherapy' (CBASP) for chronic depressions versus usual secondary care" let us know more good evidence about CBASP's effectiveness was on the way (I am getting a little impatient though).  Of the cluster of interesting papers that emerged from the eye-opening 2000 study, there was both a strong suggestion that quite a few chronic depression medication non-responders might do pretty well if they were simply swapped to psychotherapy (and vice-versa) - see "Chronic depression: medication (nefazodone) or psychotherapy (CBASP) is effective when the other is not."  Also fascinating and potentially genuinely helpful was the indication that chronic depression sufferers with abusive childhoods may well respond to psychotherapy much better than they respond to pharmacotherapy - "Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma" - and it does seem to be to be childhood trauma rather than just difficult "life events" that matter here - "Childhood life events and childhood trauma in adult patients with depressive, anxiety and comorbid disorders vs. controls."

In tomorrow's post I'll give a bit more context & detail of this important recent Lancet study on CBT augmentation for antidepressant-resistant depression.