ArticlesCognitive behavioural therapy as an adjunct to pharmacotherapy for primary care based patients with treatment resistant depression: results of the CoBalT randomised controlled trial
Introduction
Depression is a major public health problem. It 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.1 Antidepressants are often the first-line treatment for depression and prescriptions for such drugs have increased substantially in the past 20 years.2, 3 However, only a third of patients respond fully to pharmacotherapy and half do not have at least a 50% reduction in depressive symptoms after 12–14 weeks of medication.4 When an adequate dose and duration of treatment has been given, such non-response can be termed treatment resistance. No agreed definition of treatment resistance exists5 but, in view of the extent of non-response, treatment-resistant depression clearly has a substantial effect on individuals, health services, and society.
No standard approach to the management of treatment-resistant depression exists. Options include increasing the dose of pharmacotherapy, switching to a different antidepressant, or augmentation with another pharmacological or psychological treatment. However, evidence that these approaches improve outcome is scarce.6, 7
Evidence shows that cognitive behavioural therapy (CBT), the most widely available structured psychotherapy for depression, is effective for previously untreated episodes of depression. CBT and its variants have been investigated for treatment of chronic and treatment-resistant depression but previous trials have not included a comparison group of patients who continued with their existing medication,8 meaning that the effectiveness of augmentation of antidepressant medication with CBT has not been assessed as a next-step treatment option. Some researchers have investigated a variant of CBT—cognitive behavioural analysis system of psychotherapy (CBASP)9, 10—which puts more emphasis on behavioural and interpersonal factors than does standard CBT. However, these trials in patients with chronic depression have provided inconsistent results as to the effectiveness of CBASP combined with medication compared with medication alone.9, 10
Scarce access to psychological treatment in the UK and elsewhere has meant that, in clinical practice, CBT has often been reserved for individuals who have not responded to antidepressants. No large-scale randomised controlled trials6, 7 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. We chose to investigate CBT rather than CBASP because some evidence suggests that CBT might reduce rates of relapse,11 including among individuals with residual depressive symptoms.12 Furthermore, some models of more persistent depression put emphasis on cognitive rather than behavioural aspects of treatment.13
The aim of the CoBalT trial was to examine 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. The economic evaluation will be reported separately.
Section snippets
Study design and participants
CoBalT was a multicentre pragmatic randomised controlled trial with two parallel groups.14 We recruited participants from 73 general practices in urban and rural settings in three UK centres: Bristol, Exeter, and Glasgow. Most participants were identified through a search of practice computerised medical records, although general practitioners (family doctors) were able to refer patients directly to the research team.
Eligible patients were those aged 18–75 years who had adhered15, 16 to an
Results
We did the first record search for eligible patients on Nov 4, 2008, and randomised the last patient on Sept 30, 2010 (appendix pp 2–3). We obtained follow-up data between March 16, 2009, and Oct 31, 2011. We identified 912 patients as having treatment-resistant depression and invited them to attend a baseline appointment, but 163 (18%) declined (figure). We identified no age or gender differences between individuals who declined and those who agreed to attend such an appointment (data not
Discussion
CBT as an adjunct to usual care that included pharmacotherapy was effective in reducing depressive symptoms and improving quality of life in primary care patients with treatment-resistant depression. The beneficial effect of the intervention was also identified for the more stringent criteria of remission and improvements were maintained over 12 months.
No one definition of treatment-resistant depression is accepted, hence we used an inclusive and pragmatic definition that would be generalisable
References (41)
- et al.
What is the meaning of treatment resistant/refractory major depression (TRD)? A systematic review of current randomized trials
Eur Neuropsychopharmacol
(2007) - et al.
Cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment resistant depression in primary care: the CoBalT randomised controlled trial protocol
Control Clin Trials
(2012) - et al.
Projections of global mortality and burden of disease from 2002 to 2030
PLoS Med
(2006) - et al.
Secular trends in antidepressant prescribing in the UK, 1975–1998
J Public Health Med
(2001) - et al.
Recent trends in the use of antidepressant drugs in Australia
Med J Aust
(2000) - et al.
Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice
Am J Psychiatry
(2006) - et al.
Randomised controlled trials investigating pharmacological and psychological interventions for treatment-refractory depression. Systematic review
Br J Psychiatry
(2002) - et al.
The effectiveness of psychological treatments for treatment-resistant depression: a systematic review
Acta Psychiatr Scand
(2005) - et al.
Cognitive therapy versus medication in augmentation and switch strategies as second-step treatments: a STAR*D report
Am J Psychiatry
(2007) - et al.
A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression
N Engl J Med
(2000)
Cognitive behavioral analysis system of psychotherapy and brief supportive psychotherapy for augmentation of antidepressant nonresponse in chronic depression: the REVAMP Trial
Arch Gen Psychiatry
Prevention of relapse following cognitive therapy vs medications in moderate to severe depression
Arch Gen Psychiatry
Prevention of relapse in residual depression by cognitive therapy: a controlled trial
Arch Gen Psychiatry
Cognitive therapy for chronic and persistent depression
Concurrent and predictive validity of a self-reported measure of medication adherence
Med Care
Compliance with tricyclic antidepressants: the value of four different methods of assessment
Br J Clin Pharmacol
Beck depression inventory—second edition: manual
Assessing psychiatric disorder with a human interviewer or a computer
J Epidemiol Community Health
Measuring psychiatric disorder in the community: a standardized assessment for use by lay interviewers
Psychol Med
Minimization—reducing predictability for multi-centre trials whilst retaining balance within centre
Stat Med
Cited by (255)
Low dose pipamperone therapy for major depression: A randomized controlled clinical trial comparison with citalopram
2024, Personalized Medicine in PsychiatrySpecialist treatment for persistent depression in secondary care: Sustained effects from a multicentre UK study at 24 and 36 months
2024, Journal of Affective DisordersEfficacy and Acceptability of Remote Cognitive Behavioral Therapy for Patients With Major Depressive Disorder in Japanese Clinical Settings: A Case Series
2023, Cognitive and Behavioral PracticeA mathematical formula of plasticity: Measuring susceptibility to change in mental health and data science
2023, Neuroscience and Biobehavioral ReviewsPotential advantages of combining randomized controlled trials with qualitative research in mood and anxiety disorders - A systematic review
2023, Journal of Affective Disorders