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expert reaction to ‘no treatment difference’ between some antidepressants and CBT for severe depression

The use of second generation antidepressants or cognitive behavioural therapies (CBT) to treat severe depression in adults is the subject of a paper published in The BMJ, with the authors reporting no difference in the effectiveness of the two treatments.

The SMC also produced a Factsheet on depression.


Prof. Shirley Reynolds, Director, Charlie Waller Institute at the University of Reading, said:

“This is important research for doctors and patients. The researchers have carefully integrated the results of randomised controlled trials that compared ‘second generation’ anti-depressants and cognitive behaviour therapy for the treatment of moderate to severe depression in adults.

“The results are consistent with previous studies on this important topic and have direct implications for doctors and patients.

“The review is careful and well conducted – the authors’ conclusion that anti-depressants and cognitive behaviour therapy are equally effective therefore seems valid.

“This research is important because it suggests that, when possible, patients should be given the opportunity to choose what treatment they would prefer. When choice is not possible, patients can be reassured that either treatment is likely to be equally helpful.  This may encourage patients to seek help sooner and GPs to offer treatment promptly.

“It is believed by most doctors and therapists that the way that each treatment works is quite different. However, recent research suggests that both treatments change patients’ underlying ‘cognitive biases’ and there may be shared mechanisms of change at the level of neuroscience.

“Despite these positive results there is much that we still do not understand about depression and its treatment. For example, we need more research on the possible side effects of both drugs and psychological therapies; we need better understanding of how treatments work and for whom each (drugs or CBT) will work best. It is also very important to be aware that these results only apply to adult patients aged under 65 years.  They do not apply, and should not be generalised, to children and adolescents, or to older adults who often have other complex physical health problems.”


Prof. Guy Goodwin, President of European College of Neuropsychopharmacology (ECNP) and Professor of Psychiatry, University of Oxford, said:

“The claim that CBT is equal to antidepressants for ‘severe’ depression, is highly misleading. In the real world patients with severe depression are rarely able to engage with demanding talking therapies. What this paper regurgitates is the finding from a very small series of clinical trials in moderately ill patients, many of whom appear to respond to either CBT or an antidepressant. On a technical point none of these trials appear to have been powered to show equivalence and meta-analysis adds nothing when it includes small trials of questionable quality.”


Prof. Phil Cowen, Professor of Psychopharmacology, University of Oxford, said:

“The studies included in this review and meta-analysis mostly concerned patients with moderate to severe depression (as defined by the Hamilton Depression Rating Scale), i.e. it included those in the range between moderate and severe. Therefore the press release stating that CBT is effective in ‘severe depression’ is misleading. However, in the kind of depressed patients recruited for the described trials, the paper’s findings are in line with previous meta-analyses and current guidelines and it seems perfectly reasonable to offer such patients CBT first (if it is available without too much delay) and to reserve antidepressants for those not responding well to it.

“Patients with severe depression (which in practice is identified clinically rather than by a point on a rating scale) often have significant problems with concentration, learning and memory. This can make using psychotherapy difficult and it’s important that patients who need medication because CBT doesn’t work for them shouldn’t feel in some way that they have ‘failed’.”


Prof. Sir Simon Wessely, President of the Royal College of Psychiatrists and Professor of Psychological Medicine, King’s College London’s Institute of Psychiatry, Psychology & Neuroscience, said:

“This confirms what many have been saying for some time.  Both antidepressants and talking therapies such as CBT should be offered for patients with depressive illnesses.  Both seem equally effective, and like all interventions across the whole of medicine, both have side effects. So the decision is going to be made on issues such as patient preference and of course availability. This study will reassure GPs that it is reasonable to prescribe antidepressants as a first line treatment for patients who wish it, whilst also arranging for talking treatments where available.  In this country we have made major strides in making CBT more available but there is still more to be done.  Finally we should remember that it’s not either/or here – the evidence repeatedly shows that the best outcomes comes from both together.  If I were to develop depression I would want both antidepressants and talking therapies.”


Prof. Anthony Cleare, Professor of Psychiatry, King’s College London’s Institute of Psychiatry, Psychology & Neuroscience, said:

“This research is essentially a summary of all the previous trials that have been done comparing modern antidepressants and modern psychological treatments (cognitive therapies) for depression. It uses data from these previous trials, but is unfortunately limited by the small number of trials that have been undertaken and by the variable and often poor quality of the trials themselves.

“It is particularly difficult to separate out what are non-specific, “placebo” effects of cognitive therapy – such as having a compassionate listening ear – and what may be specific to the therapy itself – such as changing thought patterns or behaviours.

“Since patients receiving antidepressants in these studies did not receive as much contact with health professionals, the non-specific placebo effects of therapist contact will have been higher in those receiving cognitive therapy.

“Similarly, as those receiving cognitive therapy were rarely given a dummy pill as well, the known additional placebo effects of taking a pill would have been larger in the antidepressant group.

“Thus, it is still not completely clear whether antidepressants or cognitive therapies are more effective.

“But arguments over which type of treatment is most effective should not obscure the fact that too many patients are currently not getting adequate treatment for depression. Indeed, the Royal College of Psychiatrists recently found that over half of those with depression go untreated.

“The good news from this study is that patients can be reassured that both antidepressants and psychological therapies like CBT are likely to be effective treatments for depression.

“Some patients tell us they would prefer antidepressants and some psychological therapies. We know from other work that this is very important: patients show substantially higher recovery rates if they can have their preferred treatment.

“The key message is that a choice of treatments should be available to all patients with depression.”


Dr Michael Bloomfield, Clinical Lecturer in Psychiatry, MRC Clinical Sciences Centre and UCL, said:

“Depression is a leading global cause of illness and it is therefore very important that we understand how to best help the millions of people suffering from depression all over the world.  This new analysis combines existing studies comparing antidepressants with one type of psychotherapy called cognitive-behavioural therapy (CBT) to see what is most helpful in patients suffering from depression.  It is important to make clear that the authors use the term ‘major depression’ as this is in the American diagnostic guidelines, and should not be confused with ‘severe depression’ as compared to ‘mild depression’, which has a different meaning in the international diagnostic guidelines used in the United Kingdom.

“There are many different possible treatment outcomes that could be chosen for these studies.  In the outcome measures assessed in this study, the authors found no significant difference between antidepressant medicines and antidepressant CBT.  Previous studies have shown that these two treatments are effective for people with depression.  We must be extremely cautious in the conclusions we can draw from this new analysis given the low strength of evidence of the studies included in this new analysis.  As the authors of this analysis rightly point out themselves, “Results should be interpreted cautiously given the low strength of evidence”.  There are several limitations of the current research, particularly as placebo groups were not used, leading the authors to describe some of their own results as “circumstantial”.

“There is some evidence that antidepressant medicines and psychotherapies may be working in similar ways, by helping people improve patterns of depressed thinking called emotional processing biases, for example.  It is not an exaggeration to say that for many people these treatments are life-saving.  As a field, we should be moving away from a repeated debate about medicines vs. psychotherapy, and move towards research looking at how to predict who will respond to what type or combination of treatments. Furthermore, future research must also include other types of psychotherapy and also examine combinations of psychotherapies, particularly for patients with a more severe or complex illness.  No one should stop either a medicine or psychotherapy without discussing this with their doctor or therapist first.

“In clinical practice today one of the biggest barriers to recovery is a toxic combination of sustained funding cuts together with a fractured dismantling of services, particularly for patients with more severe and long-term mental illnesses. Outcomes for patients with mental illnesses will remain challenging unless this is urgently addressed.”


Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis’ by Amick et al. published in The BMJ on Tuesday 8th December. 


Declared interests

Prof. Goodwin: “I have advised companies on the development of drugs to treat depression.”

Prof. Cowen: “PJ Cowen has no current conflict of interest. In the last three years he has been an advisor to Lundbeck.”

Prof. Wessely: “I gave a non-promotional talk on psychological therapies for CFS three years ago sponsored by Jansen.”

Prof. Cleare: “A.J.C. has within the past 3 years: (a) spoken about his clinical and research interests at numerous conferences and unrestricted educational programmes; of these one was funded by Astra Zeneca and one was funded by an organisation sponsored by Pfizer, neither of whom had any input into the content of his talks.  (b) been a co-investigator on one research grant from Lundbeck from which he did not gain financially. (c) received honoraria for consulting on antidepressant treatments made by Allergan and Livanova. (d) been lead author on the 2015 British Association for Psychopharmacology Guidelines on antidepressant treatment which advise on the evidence base for the optimal treatment of depression (”

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