title: Long-term effectiveness and cost-effectiveness of cognitive behavioural therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care: follow-up of the CoBalT randomised controlled trial.
abstract: BACKGROUND
  Cognitive behavioural therapy (CBT) is an effective treatment for people whose depression has not responded to antidepressants. However, the long-term outcome is unknown. In a long-term follow-up of the CoBalT trial, we examined the clinical and cost-effectiveness of cognitive behavioural therapy as an adjunct to usual care that included medication over 3-5 years in primary care patients with treatment-resistant depression.
  
  
  METHODS
  CoBalT was a randomised controlled trial done across 73 general practices in three UK centres. CoBalT recruited patients aged 18-75 years who had adhered to antidepressants for at least 6 weeks and had substantial depressive symptoms (Beck Depression Inventory [BDI-II] score ≥14 and met ICD-10 depression criteria). Participants were randomly assigned using a computer generated code, to receive either usual care or CBT in addition to usual care. Patients eligible for the long-term follow-up were those who had not withdrawn by the 12 month follow-up and had given their consent to being re-contacted. Those willing to participate were asked to return the postal questionnaire to the research team. One postal reminder was sent and non-responders were contacted by telephone to complete a brief questionnaire. Data were also collected from general practitioner notes. Follow-up took place at a variable interval after randomisation (3-5 years). The primary outcome was self-report of depressive symptoms assessed by BDI-II score (range 0-63), analysed by intention to treat. Cost-utility analysis compared health and social care costs with quality-adjusted life-years (QALYs). This study is registered with isrctn.com, number ISRCTN38231611.
  
  
  RESULTS
  Between Nov 4, 2008, and Sept 30, 2010, 469 eligible participants were randomised into the CoBalT study. Of these, 248 individuals completed a long-term follow-up questionnaire and provided data for the primary outcome (136 in the intervention group vs 112 in the usual care group). At follow-up (median 45·5 months [IQR 42·5-51·1]), the intervention group had a mean BDI-II score of 19·2 (SD 13·8) compared with a mean BDI-II score of 23·4 (SD 13·2) for the usual care group (repeated measures analysis over the 46 months: difference in means -4·7 [95% CI -6·4 to -3·0, p<0·001]). Follow-up was, on average, 40 months after therapy ended. The average annual cost of trial CBT per participant was £343 (SD 129). The incremental cost-effectiveness ratio was £5374 per QALY gain. This represented a 92% probability of being cost effective at the National Institute for Health and Care Excellence QALY threshold of £20 000.
  
  
  CONCLUSIONS
  CBT as an adjunct to usual care that includes antidepressants is clinically effective and cost effective over the long-term for individuals whose depression has not responded to pharmacotherapy. In view of this robust evidence of long-term effectiveness and the fact that the intervention represented good value-for-money, clinicians should discuss referral for CBT with all those for whom antidepressants are not effective.
  
  
  BACKGROUND
  National Institute for Health Research Health Technology Assessment.
authors.affiliation: Centre for Academic Mental Health, University of Bristol, Bristol, UK. Electronic address: nicola.wiles@bristol.ac.uk.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Wiles
authors.affiliation: Centre for Academic Mental Health, University of Bristol, Bristol, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Thomas
authors.affiliation: Centre for Academic Mental Health, University of Bristol, Bristol, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Turner
authors.affiliation: Bristol Randomised Trials Collaboration, University of Bristol, Bristol, UK.
authors.forename: Kirsty
authors.initials: K
authors.lastname: Garfield
authors.affiliation: Centre for Academic Mental Health, University of Bristol, Bristol, UK.
authors.forename: Daphne
authors.initials: D
authors.lastname: Kounali
authors.affiliation: Primary Care Research Group, University of Exeter Medical School, Exeter, UK.
authors.forename: John
authors.initials: J
authors.lastname: Campbell
authors.affiliation: Centre for Academic Primary Care, University of Bristol, Bristol, UK.
authors.forename: David
authors.initials: D
authors.lastname: Kessler
authors.affiliation: Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: Willem
authors.initials: W
authors.lastname: Kuyken
authors.affiliation: Division of Psychiatry, University College London, London, UK.
authors.forename: Glyn
authors.initials: G
authors.lastname: Lewis
authors.affiliation: Institute of Health and Wellbeing, General Practice and Primary Care Group, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: Jill
authors.initials: J
authors.lastname: Morrison
authors.affiliation: Institute of Health and Wellbeing, University of Glasgow, Gartnavel Royal Hospital, Glasgow, Scotland, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Williams
authors.affiliation: School of Social and Community Medicine and School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Peters
authors.affiliation: Centre for Academic Primary Care, University of Bristol, Bristol, UK.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hollinghurst
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015928:Cognitive Behavioral Therapy / Q000191:economics; D003131:Combined Modality Therapy; D003362:Cost-Benefit Analysis; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy / Q000628:therapy*; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D011320:Primary Health Care / Q000191:economics*; D019057:Quality-Adjusted Life Years; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents