Scientific background and review of current literature

Clinical depression is one of the most common and debilitating of the psychiatric disorders. It accounts for the greatest burden of disease among all mental health problems, and is the second largest cause of global disability.³ Lifetime prevalence has been estimated at 16.2% and rates of comorbidity and risk for suicide are high.^4–6 Depression is often recurrent, and without treatment many cases become chronic, lasting > 2 years in one-third of individuals. Over three-quarters of all people who recover from one episode will go on to have at least one more.⁷ In the UK, depression and anxiety are estimated to cost the economy £17B in lost output and direct health-care costs annually, with a £9B impact on the Exchequer through benefit payments and lost tax receipts.⁸ Globally, the economic impact of depression on aggregate economic output is predicted to be US$5.36 trillion between 2011 and 2030.⁹

Reducing these substantial costs is a key objective for low-, medium- and high-income countries alike. Antidepressant medication (ADM) and cognitive–behavioural therapy (CBT) are the two treatments with most evidence of effectiveness, both of which are recommended by the National Institute for Health and Care Excellence (NICE).¹⁰ Problems with ADM include side effects, poor patient adherence and relapse risk on ADM discontinuation. Service user organisations and policy think tanks advocate greater availability of psychological therapies, which many people prefer.¹¹ CBT, which is of similar efficacy to ADM,¹² has several advantages: (1) it reflects the desire of many service users for non-pharmacological treatment; (2) it has no physical side effects; and (3) it modifies the illness trajectory in that benefits continue after the end of treatment, preventing recurrence.¹³ However, CBT has several disadvantages: (1) its complexity makes it difficult to learn to implement in a competent fashion; (2) its efficacy is dependent on the skill of the individual practitioner; (3) patients are required to learn quite high-level skills; and (4) the high cost of training and employing sufficient therapists limits access to CBT.

As a consequence of the disadvantages above, many people do not receive adequate treatment, and, even when treatment is given, many respond only partially or not at all.¹⁴ Despite the recent government initiative in England – ‘Improving Access to Psychological Therapies’ (IAPT; URL: www.iapt.nhs.uk/) – no more than 15% of people with depression will receive NHS-delivered CBT, and only 50% receiving CBT will recover.¹⁵ It is therefore important to continue to test promising new treatments, especially if there are indications that such treatments reduce the risk of symptom return, are applicable to a wide range of depressed people including those with severe disease, are easy to implement in clinical practice and are therefore potentially more accessible,¹⁶ and are a cost-effective use of resources.

Globally, health services require effective, easily implemented and cost-effective psychological treatments for depression that can be delivered by less specialist health workers in order to close a treatment gap that can be as much as 80–90% in some low-income countries.¹⁷ The English NHS, in order to meet public and professional expectations, requires a simple, equivalently effective, easily implemented psychological treatment for depression which can be delivered by less specialist (albeit appropriately competent) junior mental health workers (MHWs) to treat many more people with depression in a more cost-effective manner.

Rationale for the research

Behavioural activation (BA) is a psychological treatment based on behavioural theory that alleviates depression by focusing directly on changing behaviour.^18–20 This theory states that depression is maintained by avoidance of normal activities. As people withdraw and disrupt their basic routines, they become isolated from positive reinforcement opportunities in their environment. The combination of increased negative reinforcement with reduced positive reinforcement results in a cycle of depressed mood, decreased activity and avoidance which maintains depression.¹⁹ BA systematically disrupts this cycle, initiating action in the presence of negative mood, when people’s natural tendency is to withdraw or avoid.^21,22 Although CBT incorporates some behavioural elements, these focus on increasing rewarding activity and initiating behavioural experiments to test specific beliefs. In contrast, BA targets avoidance from a contextual, functional approach not found in CBT (i.e. BA focuses on understanding the function of behaviour and replacing it accordingly). BA also explicitly prioritises the treatment of negatively reinforced avoidance and rumination. Furthermore, the BA rationale is easier to understand and operationalise for both patients and MHWs than CBT, which also focuses on increasing activity, but primarily on changing maladaptive beliefs.²³ Moreover, there is some evidence that CBT is less effective when delivered by less competent therapists.^12,24

In the UK, CBT is delivered by professionally qualified senior MHWs (mainly clinical psychology, nursing, occupational therapy, social work or counselling), who have obtained a further 1-year, full-time postgraduate qualification in CBT. Their training is long and expensive and their employment grade is costly compared with junior MHWs, who deliver much of the routine mental health care in the UK. The relative simplicity of BA treatment may make it easier and cheaper to train junior MHWs in its application than CBT, the argument of ‘parsimony’ first advanced by one of the early proponents of this approach, Neil Jacobson.¹⁹ However, this is appropriate only if BA delivered in this way is as effective as, and more cost-effective than, CBT.

Limitations of previous trials

A number of systematic reviews have attempted to address the more general question of BA effectiveness compared with CBT.^10,25–28 All have commented on the relatively poor quality of component studies. We conducted a meta-analysis of randomised controlled trials (RCTs) of BA,²⁵ and identified 12 studies with a total of 476 patients. At the primary end point we found no difference between the groups on depression symptom level [Hedges’ g = 0.102, 95% confidence interval (CI) −0.122 to 0.326; I² = 29%; p = 0.372] (Figure 1). At follow-up we found no difference between the groups on depression symptom level (Hedges’ g = 0.395, 95% CI −0.032 to 0.822; I² = 61%; p = 0.070).

FIGURE 1

Meta-analysis of pre-COBRA (Cost and Outcome of BehaviouRal Activation) trial BA vs. CBT primary outcome point, all included studies. AT, automatic thoughts; LS, low severity.

In a subsequent update of this review²⁶ we found no additional trials comparing BA with CBT. Many of the trials included in our review were of limited methodological quality, all were underpowered for comparing treatments, and most did not utilise diagnostic interviews for trial inclusion. Treatments in many cases did not conform to modern clinical protocols for BA. Long-term outcomes were rarely reported, with average follow-up only to 4 months. These results have been replicated in two recent Cochrane reviews of behavioural therapies,^27,28 which concluded that there was only low- to moderate-quality evidence that behavioural therapies and other psychological therapies were equally effective and called for ‘Studies recruiting larger samples with improved reporting of design and fidelity to treatment to improve the quality of the evidence’.²⁷

Most significantly, NICE¹⁰ reviewed the same evidence and regarded only a small subset of three trials^31,38,40 as of sufficient quality to be able to contribute evidence of effect (Figure 2). In those studies no difference was found between BA and CBT at primary end point (Hedges’ g = 0.139, 95% CI –0.4.00 to 0.122; I² = 1%; p = 0.296) or at follow-up (Hedges’ g = 0.135, 95% CI –0.456 to 0.186; I² = 0%; p = 0.409).

FIGURE 2

Meta-analysis of pre-COBRA (Cost and Outcome of BehaviouRal Activation) trial BA vs. CBT, subset of high-quality included studies in NICE review. AT, automatic thoughts; LS, low severity.

The conclusion of the NICE Guideline Development Group was that that the evidence base for BA was not ‘sufficiently robust’ for it to be recommended as an alternative to CBT. It was suggested that BA could be an option for clinicians, but the limited evidence base should be considered when making this treatment choice.¹⁰ Consequently, NICE made a clear research recommendation ‘to establish whether behavioural activation is an effective alternative to CBT’ using a study which is ‘large enough to determine the presence or absence of clinically important effects using a non-inferiority design’ (p. 256).¹⁰

Pilot work preceding this trial

In order to test uncertainties around our main objectives, we piloted BA in a Phase II RCT to examine whether or not MHWs without previous specialist training in psychological therapy can effectively treat depressed people using BA.⁴¹ We compared BA against usual care. Relatively junior NHS MHWs (‘band 5’ – equivalent to a basic grade, qualified mental health nurse) with no previous formal training or experience in psychotherapy delivered BA. These workers received 5 days’ training in BA and, subsequently, 1 hour of clinical supervision, fortnightly, from a clinical nurse consultant or trained psychotherapist. Intention-to-treat (ITT) analyses indicated a difference in favour of BA of −15.79 points (n = 47, 95% CI −24.55 to −7.02 points) on depression (as measured via the Beck Depression Inventory-II), an effect size of −1.15 standard deviation (SD) units (95% CI −0.45 to −1.85 units). We also found a quality-adjusted life-year (QALY) difference in favour of BA of 0.20 points (95% CI 0.01 to 0.39 points; p = 0.042), incremental cost-effectiveness ratio (ICER) of £5756 per QALY and a 97% probability that BA is cost-effective at a threshold value of £20,000.⁴¹

Conclusion

From our literature reviews and pilot work we concluded that BA was a potentially viable treatment for depression when delivered by junior MHWs, but that, as NICE had suggested, a non-inferiority trial of BA versus CBT was required to test whether or not BA was non-inferior to CBT and if BA could be a potentially cost-effective alternative to CBT for depression. We now report the results of this randomised trial to determine if BA is non-inferior to CBT in the treatment of patients with depression. This report is divided into chapters detailing the methods and results of our primary clinical effectiveness and cost-effectiveness questions followed by a chapter for our process evaluation. We conclude with a discussion chapter summarising our results and considering their implications for the treatment of depression in the UK and internationally.