European Comparative Effectiveness Research on Internet-based Depression Treatment (E-COMPARED)

To compare the clinical impact and cost-effectiveness of blended Cognitive Behavioural Therapy (CBT) for adults with major depressive disorder (MDD) with treatment as usual (TAU). Within the French context the TAU is considered as the traditional face to face CBT.

Background: Depression is a common mental disorder with a negative impact on mental well-being, quality of life, and social and work-related functioning both in the short and longer term. Additionally, depression is associated with increased morbidity, mortality, health care utilization and health care costs. On a population level, depression is one of the most costly diseases. The economic costs of depression were estimated at €136.3 billion (EU25) in 2010 in the EU and are still rising. European health care systems face the challenge of improving access to cost-effective treatments while simultaneously working to sustain budgetary stability in times of economic austerity. Internet-based depression treatment appears a very promising alternative to current routine depression treatment strategies. Meta-analyses have demonstrated the clinical effectiveness and potential cost-effectiveness of Internet-based treatment for depression in controlled research setting. Internet-based treatment thus has the potential to keep depression treatment affordable, as it enables mental health care providers to reach out to large populations needing depression treatment at a better cost-effectiveness than those of standard treatment as usual (TAU), but with similar levels of clinical efficacy and quality of care. The trials will be conducted in 8 European countries. Objective: To compare the clinical impact and cost-effectiveness of blended Cognitive Behavioural Therapy (CBT) for adults with major depressive disorder (MDD) with treatments as usual (TAU)-face to face CBT in expert centres specialized in depression. Study design: The study is a two-arm randomized controlled non-inferiority and cost-effectiveness trial. The trial will be conducted in expert centres in France. A total of 150 patients with MDD will be assigned to one of two treatment arms: 1) blended CBT, 2) TAU. Respondents in both arms will be followed until 12 months after baseline (measures will be taken at baseline, 3 months, post- treatment (17 weeks), 6 months and 12 months).

Internet based blended depression treatment combines individual face-to-face cognitive behavioural therapy (CBT) with CBT delivered through an Internet based treatment platform with smart phone components. The core components of the CBT treatment are: (1) psycho-education, (2) cognitive restructuring, (3) behavioural activation, and (4) relapse prevention. These will be delivered over 16 sessions (8 online and 8 face-to-face), once a week. The online platform is called Moodbuster. The trial will not interfere with regular medication treatment, and patient's care will be monitored throughout the study.

In order to increase the comparability between the two arms, we defined TAU as a traditional face to face CBT of 16 sessions. These sessions will be administered over a course of 16 weeks. The trial will not interfere with regular medication treatment, and patient's care will be monitored throughout the study.

The primary outcome measure is symptoms of depression as assessed with Patient Health Questionnaire-9 (PHQ-9; Kroenke, Spitzer, & Williams, 2001). The PHQ-9 is a nine-item mood module that can be used to screen and to diagnose patients with depressive disorders. The 9 items are each scored on a 0-3 scale with the total score ranging from 0-27 and higher scores indicating more severe depression. The PHQ-9 has shown to have good psychometric properties (Wittkampf, Naeije, Schene, Huyser, & van Weert, 2007).

The 16 item self-report version of the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-16-SR) US Translation (Rush et al., 2003) is used in addition to the PHQ-9 because it is a promising questionnaire for assessing depressive symptoms especially in specialized mental health care whereas the PHQ-9 is developed for use in primary care.The QIDS is a questionnaire that screens for depressive symptoms and assesses depression severity. The QIDS is available in both clinician-rated (IDS-C) and patient self-report (IDS-SR) forms. The QIDS consists of 16 items (each item scores 0-3) and includes symptom domains of MDD based on DSM-IV and Research Diagnostic Criteria (RDC).

The full M.I.N.I. 5.0,with exception of section M (Anorexia Nervosa), N (Bulimia nervosa), and P (Antisocial personality disorder), will be assessed at baseline to assess lifetime and current depression, and current comorbid disorders that often co-occur with and predict the onset of depression (anxiety disorders and PTSD) and other comorbid disorders that are an exclusion criteria in this study (i.e. substance dependence, bipolar affective disorder, psychotic illness, and obsessive compulsive disorder). At 12 months follow-up, the depression, anxiety and PTSD sections will be assessed again.

The MADRS (Montgomery and Asberg Depression Rating Scale) is a hetero-assessment of depressive symptoms evaluated by clinicians.

Quality of life will be assessed with the EQ-5D-5L (EuroQol).The EQ-5D-5L is a self-report questionnaire which measures health related quality of life and enables conversion to utility scores to calculate Quality-Adjusted Life-Years (QALYs). The EQ-5D-5L consists of five dimensions: mobility, self-care, ordinary activities, discomfort, and mood state related to anxiety or depression. Each item consists of five categories ranging from no problems to a lot of problems (Van Agt, Essink-Bot, Krabbe, & Bonsel, 1994).

Health-Related Quality of Life will optionally be measured with the Assessment of Quality of Life instrument (AQoL) (Hawthorne, Richardson, & Osborne, 1999). For the current study the AQoL-6D (Richardson, Peacock, Hawthorne, Lezzi, Elsworth, & Day, 2012) which consists of 20 questions measured on a 5 point scale will be used. The AQoL-6D includes the six dimensions: independent living, mental health, coping, relationships, pain, and senses.

Health service uptake and production loss due to illness will be measured with the Trimbos and iMTA Questionnaires on Costs Associated with Psychiatric Illness (TiC-P; Hakkaart-van Rooijen, van Straten, Donker, Tiemens, 2002). The TiC-P is a self-report questionnaire and consists of two different parts that can be administrated separately. Part I will be used to assess the participants' healthcare utilization and medication use. Part II (short form health and labor questionnaire [SF-HLQ]) measures lost productivity costs resulting from absenteeism (being absent from work because of illness) and presenteeism (being present at work while ill which may lead to reduced efficiency) and consists of 11 items. Healthcare utilization and productivity losses will be valued using country-specific prices.

Inclusion Criteria: Being 18 years of age or older Meet DSM-IV diagnostic criteria for MDD confirmed by MINI International Neuropsychiatric Interview version 5.0 Having a PHQ-9 score greater than 5 Having access to a PC and Internet connection Having ( or accepting to be loaned) a smartphone that is compatible with the mobile component of the intervention Understanding of the French language spoken and written Exclusion Criteria: Current high risk for suicide according to the MINI Interview section C Serious psychiatric co-morbidity: substance dependence, bipolar affective disorder, psychotic illness, obsessive compulsive disorder, and suicide risks, as established at the MINI interview Currently receiving psychological treatment for depression

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Kleiboer A, Smit J, Bosmans J, Ruwaard J, Andersson G, Topooco N, Berger T, Krieger T, Botella C, Banos R, Chevreul K, Araya R, Cerga-Pashoja A, Cieslak R, Rogala A, Vis C, Draisma S, van Schaik A, Kemmeren L, Ebert D, Berking M, Funk B, Cuijpers P, Riper H. European COMPARative Effectiveness research on blended Depression treatment versus treatment-as-usual (E-COMPARED): study protocol for a randomized controlled, non-inferiority trial in eight European countries. Trials. 2016 Aug 3;17(1):387. doi: 10.1186/s13063-016-1511-1.