ORIGINAL PAPER Factors associated with differential response to online cognitive behavioural therapy Katherine S. Button • Nicola J. Wiles • Glyn Lewis • Tim J. Peters • David Kessler Received: 25 November 2010 / Accepted: 18 April 2011 / Published online: 4 May 2011 Ó Springer-Verlag 2011 Abstract Purpose Patients differ in their response to treatments. There is obvious clinical utility in establishing patient characteristics that are associated with differential treat- ment responses (i.e. are effect modifiers or moderators of treatment response). Factors that moderate response to cognitive behavioural therapy (CBT) remain unclear. This study investigates whether factors prognostic of general depression outcome generally are also moderators of response to online CBT in a sample of depressed patients recruited through UK general practices. Methods Secondary analysis of a randomised controlled trial, internet-based psychotherapy for depression. A total of 297 patients referred from 55 UK general practices and suffering from depression were randomly allocated to receive either online CBT or waiting list control. Treatment effect was measured by comparing depression score at 4 months between randomization groups. Treatment effect modification was assessed using regression analyses focusing on interactions between treatment effect and putative moderator variables. Results Pretreatment severity and marital status moder- ated treatment response. More severe patients, and patients who were separated, widowed, or divorced, benefited most from the intervention. Weak evidence suggested that treatment effectiveness diminished with increasing recent adverse life events. No evidence was found to suggest that educational attainment, age, and history of depression- moderated treatment response. Conclusions Secondary analyses of trials comparing two or more treatments allow factors that may moderate treat- ment response to be distinguished from more general prognostic indicators, although caution is needed in inter- preting such exploratory analyses. Keywords Depression Á Cognitive behavioural therapy Á CBT Á Moderators Á Predictors Á Outcome Introduction Cognitive behavioural therapy (CBT) is an effective treatment for depression [1]. In the UK, depression is typically treated by general practitioners but historically there has been limited access to psychological therapy. The UK Government has launched recent initiatives aiming to increase access to CBT in primary care settings (Depart- ment of Health, 2009), and computers are increasingly seen as a way of improving access to CBT [2]. Results from the recent IPCRESS (internet-based psychotherapy for depression) trial demonstrate that therapist-led CBT delivered over the internet (using a modality similar to an ‘instant messaging service’) is an effective treatment for depression [3]. Individuals differ in their response to treatments. It is useful in clinical research to identify which patients are likely to respond well to which treatments and why. It is also important to distinguish between prognostic factors that predict disease outcomes generally (irrespective of treatment), and moderator or effect modifier variables [4] that predict differential response to treatments [5]. K. S. Button (&) Á N. J. Wiles Á G. Lewis Á D. Kessler School of Social and Community Medicine, Academic Unit of Psychiatry, University of Bristol, Oakfield House, 15-23 Oakfield Grove, Bristol BS8 2BN, UK e-mail: kate.button@bristol.ac.uk T. J. Peters School of Clinical Sciences, University of Bristol, Southmead Hospital, Bristol BS10 5NB, UK 123 Soc Psychiatry Psychiatr Epidemiol (2012) 47:827–833 DOI 10.1007/s00127-011-0389-1