Major depression is a prevalent mental disorder associated with significant disability and economic costs . In this sense, it is known that 25% of all human beings will suffer from a depression at any moment over their lives  and, according to the World Health Organization , depression will become the second most important cause of disability in 2020. From the perspective of the health system, 25-35% of the patients attending primary care settings suffer from a psychiatric disorder and more than 80% of them are depression and/or anxiety . This percentage is higher at the Spanish Primary Care where 45% of the patients have had a mental disorder during their life, with 31% experiencing a mental disorder in the past 12 months . Almost 30% attendees reported a lifetime history of major depressive disorder, with 9.6% experiencing major depression in the past year. In most countries, general practitioners refer only 5-10% of the patients with psychiatric disorders to specialized services  and, despite of that, mental health services are collapsed all over the world.
Major depression can be treated effectively using antidepressants, but relapse is high following cessation, and many patients prefer psychological therapies , which are as effective as pharmacological treatment . Although evidence-based treatments exist, rates of treatment seeking are low, and many patients with depression do not receive adequate management, being the main barriers the limited availability of trained clinicians with consequent long waiting lists, direct and indirect costs of treatment, stigma, and difficulty attending therapy during business hours . These reasons, expected to get worse in the future, had convinced international health authorities to search for new cost-effective treatment alternatives for depression .
It has been defined “Computer-delivered psychotherapy” (CDP) as any psychotherapy program that uses patients’ inputs to take decisions regarding treatment [10–12]. This excludes videoconferences, self-help programs exclusively based on bibliotherapy, chats, help groups, etc. Patients receive therapy using their computers at home and the sessions are usually short (20–30 min.), on a weekly basis and the treatment lasts 3–6 months [10–12]. At this moment, there exist evidence of the effectiveness of CDP in depression , anxiety , and other psychiatric disorders such as alcohol abuse, psychosomatic disorders  or even pain . Recently, cost-effectiveness studies on CDP have been published with satisfactory results [17–20]. The results has lead to British NICE to support the use of a computer-delivered psychotherapy program for the treatment of depression ("Beating the Blues") to be widely used by the patients of the British National Health Service [11, 21]. Other studies show that CDP is so effective that it should be used not only at primary care level, but even in mental health services. In these specialized settings, it would be recommended as a self-help first step for depression and anxiety, before being attended by a psychologist or psychiatrist . Recently, other CDP programs without the presence of a psychotherapist, such as "Blues Begone", have been evaluated with adequate effectiveness not only in randomized controlled trials  but in naturalistic studies as well .
Internet-delivered psychotherapy (iPT) is a form of CDP delivered by internet. According to NICE , iPT programs are highly structured and comprises systematically presented online lessons, homework, and supplementary resources. Programs may be entirely self-guided, or patients may receive therapist contact via asynchronous e-mails or synchronous online chat or telephone calls. Depending on the time devoted by the psychotherapist to the patient, iPT programs can be broadly divided into low-intensity (<3 h) and high-intensity iPT (>3 h of therapist time in total) . Although an Internet connection and basic computer hardware are required, some of the advantages of iPT include convenience, treatment fidelity, and accessibility. That is, patients and therapists may logon to the program at anytime, every patient receives exactly the same materials, and barriers relating to stigma, geography and limited therapist resources are minimized .
While there is consensus about the effectiveness of iPT for major depression, it is still unknown how these interventions work and for whom they work. This holds true for other types of intervention as well, despite some exploratory studies on this subject [26, 27]. For this reason, it is relevant to examine potential mediating and moderating variables that explain the effect of these treatments. Another key challenge is how to successfully adapt and disseminate iPT programs developed and evaluated in a research environment to the heterogeneous health services of developed and developing countries. One recent example is a program that was effective in reducing depressive symptoms in an RCT , but which did not improve treatment outcomes when added to treatment as usual in primary care settings . Regarding this, it is recommendable to develop studies in which iPT be integrated within usual primary care services. The efficacy and reliability of iPT have been demonstrated for depression in different countries and different languages, especially English, but as far as we know, there is no validated internet delivery program in Spanish. Since Spanish is, after English one of the most used languages in the world, it seems highly relevant that an online treatment program in Spanish for depressive patients in primary care could be tested. Finally, an unresearched question is the attitude towards iPT not only of the patients that receive it, but of the health professionals (both general practitioners and psychologists/psychiatrists) and stakeholders. Curiously, the attitudes of professionals are usually more negative than patients’ [30, 31], but both are moderated by their experience with iPT [32, 33]. To better tailor the programs to the environment in which they are intended to be used and about the acceptability to stakeholders, in order to facilitate the integration of these programs into the health system, qualitative studies to identify attitudes and barriers are systematically recommended.
The main objective of this study will be to compare the effectiveness of a low intensity vs. a self-guided Internet-delivered psychotherapy program compared with ITAU for the treatment of major depression in primary care in Spain, with a multicenter, randomized, controlled trial. The secondary objective will be the cost-effectiveness of those programs, to identify the patients that most benefit of these programs and to examine the potential mediators and moderators. In this article we describe the design of the study.