PERSONAE - a Personalized Online Treatment of Depression

Prevalence and cost of depression

Depression is a highly prevalent disorder in Europe (Alonso et al., 2004). Globally, 280 million are estimated to suffer from depression. In Denmark, 13.2% of the population suffers from depression. The cost of affective disorders in Europe was estimated to be 106 billion euros in 2004. In Denmark, the health board's newest estimates of the cost of depression are 6700 deaths a year, 10 billion DKK for treatment, and 25 billion DKK in lost productivity. Depression has been found to cause 1124 quality-adjusted life years (QALY) lost per 100,000 patients, and compared with the general population, patients with mental disorders experience one standard deviation of lower quality of life.

Although depression is highly prevalent both in Denmark and internationally, not enough individuals with depression receive the help they need. There are barriers that can discourage help-seeking behavior. Some of the most important barriers to help-seeking behavior in Denmark are the high costs of psychotherapy as the service costs the patient pays 40% of the costs of the consultations, even after referral, and long waiting lists for being seen at a private practice psychologist. The stigma associated with mental illness, limited number of trained clinicians, and limited access to low-threshold, low-cost, and evidence-based psychotherapy furthermore present significant barriers. Several researchers have recommended further study of the implementation and dissemination of evidence-based psychotherapies.

Cognitive behavioral therapy

Cognitive behavioral therapy - one of the most used and evidence-based forms of therapy - is a combination of behavioral and cognitive therapy. Behavioral therapy was developed in the 1930's and -40's based on the research by e.g. Skinner, Pavlov, and Watson. The underlying assumption is that the patient repeats conditioned dysfunctional behaviors, which can become extinct or counteracted by behavioral exercises e.g. behavioral activation. Cognitive therapy was originally developed by Aaron Beck and is based on observations of occurrences of cognitive distortions or thought patterns that are not realistic or verifiable, leading to the conclusion that thoughts are the cause of depression. Maladaptive assumptions (thoughts) result in maladaptive behavior strategies and the development of maintenance behavior. According to Beck, cognitive distortions are a common trait in all mental disorders, and the treatment should therefore target distortions, thereby enabling awareness and realistic appraisals.

Today, behavioral and cognitive methods are combined and referred to as Cognitive Behavioral Therapy (CBT), which is often denoted second wave CBT. CBT employs both behavioral interventions and working with cognitive distortions.

CBT has been shown to be a clinically- and cost-effective treatment for depression. CBT demonstrates results equal to antidepressant pharmacotherapy and compared with pharmacotherapy only has a longer lasting effect and higher acceptability.

However, CBT still has some shortcomings, such as lack of focus on contextual influences on the patient, lack of focus on accepting negative thoughts that are not distorted, and lack of focus on emotions and emotion regulation. These shortcomings have given rise to a third wave of CBT.

This third-wave CBT consists of several different approaches, each of which tries to cover some of the lack in second-wave CBT. For example, another approach is Acceptance and Commitment Therapy (ACT), which contextualizes a person's situation, and instead of focusing only on distorted thoughts, the focus on acceptance and diffusion from thoughts and emotion is heightened compared to core CBT. Compassion focused therapy (CFT) is based on an evolutionary framework assuming humans are social beings with pro-social behavior that evolved to enhance in-group cohesion. CFT focuses on enhancing the innate compassionate and altruistic abilities towards the depressed person themselves. The purpose is to overcome the base fear and threat modes such as the inner critical voice. CFT as a tool in depression treatment is focused on shame and guilt and can especially aid people who have had adverse childhoods or other shame-inducing experiences. Positive Affect Treatment (PAT) is designed to address the symptom of anhedonia common in depression. Traditional therapies primarily focus on reducing negative emotions, whereas PAT directly targets deficits in the brain's reward system.

Internet-based self-guided, guided, and blended cognitive behavioral therapy

Over the course of the past two decades, researchers have investigated the possibility of delivering CBT via the internet in a guided self-help format named Internet-based Cognitive Behavioral Therapy (iCBT). The main part of the therapy is delivered in a self-help format through an internet-based computer program. These programs use the same therapeutic interventions, as face-to-face therapy formats; however, the content is adapted for delivery via a web platform largely designed to function as self-help. Since iCBT is still based on evidence-based CBT methods, it is not a new treatment in the classical sense, but rather a different treatment delivery format. The temporal structure also largely mimics face-to-face therapy, so patients typically go through one module in the program per week, after which they are given homework assignments, which they are expected to work on for about a week. Hereafter, they log back into the program again and take the next module, and so on. These programs typically contain 6-10 modules typically taken over approximately three months. However, there is great variation in how many modules are taken. The content of the modules are psychoeducation and exercises delivered via a variety of multimedia elements, e.g. video- and audio clips, text passages, graphics, animations, etc. Several meta-analyses have shown this treatment format to be efficacious for depression - particularly when the patients are assessed for eligibility prior to engaging with the programs and are supported by a clinician with even a minimal level of support. The support is usually comprised of approximately 10-20 minutes per week via either telephone or a secure email-like text medium built into the digital platform delivering the treatment content.

However, guided iCBT only targets a specific group of depressed patients. People with low or high symptom severity may be excluded from treatment as well as conditions with complications such as comorbidities (e.g. anxiety) or social problems interfering with the therapy. To embrace a larger demographic, earlier or stabilizing interventions or the possibility of more contact with a clinician should target these demographics. This can be achieved by including two additional treatment delivery formats: self-guided iCBT (S-iCBT) and blended iCBT (B-iCBT).

Self-guided denotes the fact that there is no actual clinician contact, and the main therapeutic alliance is formed with the program itself. There can be technical support, phone support with non-clinical staff, or no support at all. S-iCBT is effective in treating sub-threshold and mild depression. Moreover, S-iCBT has been demonstrated to be less harmful than a waitlist condition, indicating that self-guided programs are safer than no treatment. This is an important point considering that many patients are currently untreated, and a this unmet need could potentially be addressed by a cost-efficient and low-barrier service, such as self-guidet iCBT.

Patients suffering from more severe depression or comorbid disorders may need more clinician contact and support. This is especially true of those at risk of dropping out of treatment. In these cases, blended care iCBT (B-iCBT) can be employed. This type of iCBT consists of a mix of video/face-to-face consultations with a clinician and online exercises in a digital program. This format was tested in a randomized study on the clinical effectiveness of B-iCBT and was compared to face-to-face CBT for depression. In this study, it was found that although the blended condition only received half the consultations as the face-to-face condition, attrition rates and effects of treatment were similar in the two conditions. In a large-scale EU study, e-Compared, the effectiveness of B-iCBT was comparable to or better than face-to-face treatment. These two studies indicate effectiveness of B-CBT, in a patient population with moderate to severe symptom levels compared to treatment as usual in primary and secondary care.

The heterogeneous nature of depression

Symptoms of depression include rumination, guilt and shame, sleep problems, depressed mood, anhedonia, concentration difficulties, low energy/fatigue, agitation/inhibition, weight changes and suicidal ideations.

Per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) there are 256 different combinations of symptoms that will lead to a diagnosis of depression, some of which are opposites (sleeping too much or too little or gaining or losing weight). Unipolar depression can be further divided into subtypes such as melancholic, seasonal, anxious, psychotic or atypical and they have varying characteristics such as onset, severity and recurrence. The same person can also experience different types of depression across a lifespan. Based on this heterogeneous nature, personalized treatment for depression is warranted. The problem is that iCBT for depression as it has been offered until now, is a very inflexible treatment that is often delivered as a "one-size-fits-all" approach to therapy. One approach to overcome this problem with iCBT is to engage in a care model, which adapts to the patient's needs regarding treatment intensity (self-guided, guided, or blended care) and to personalize the content based on each person's manifestation of depression.

Drop-out rates and predictors of adherence

Drop-out rates in iCBT vary widely in different conditions. A meta-analysis from 2012 found that in a completely self-guided setting, the drop-out rate was 74%. With administrative support, the drop-out rate decreased to 38%, and with non-clinical staff supporting treatment, it decreased to 28%. In a meta-analysis from Karyotaki et al., 2015, predictors for drop-out in guided iCBT were found to be male gender, lower educational level, and younger age. Furthermore, patients reported that drop-out could be caused by interference from external parameters that exist apart from the treatment itself, e.g., relationship problems and work scheduling issues, or from internal factors such as dissatisfaction with treatment allocation, time constrains, lack of treatment effect, not understanding how the programs work, or technical issues. Interestingly, some patients dropout because their condition improves. Higher rates of drop-out have also been found in people low in neuroticism and high in openness to experience. Conversely, extroversion and patients' ability to acquire new skills has been associated with completion. Importantly, it has been found that patients are more likely to stay committed to treatment if the treatment is experienced as meaningful for them and fosters motivation.

Dose dependent effect

Earlier evidence from traditional psychotherapy suggests that 11-13 sessions are needed for participants to have received adequate treatment and attain an effect on mental health problems. In the newer literature discussing iCBT and the effectiveness of CBT in general, an adequate dose is used to describe the saturation where participants have received enough treatment for it to work and last. The dose is often designated as 75% of the planned treatment or eight sessions.

Motivation for treatment

When learning new skills, such as when children start learning mathematics or languages, it is generally assumed that starting with small steps is the best approach. Children start learning at a simple level and move up in complexity by staying in the zone of proximal development. The zone of proximal development was defined by Vygotsky as the next step for learning new skills, with the help from adults or, more relevant for psychotherapy, more capable peers. This stepwise rise in complexity grants you experiences of success, which, in turn, fosters intrinsic motivation. Today this method has been augmented and is better known as scaffolding. Psychotherapy, especially CBT, can be compared to learning new skills as a clinician enables patients to understand and change dysfunctional learned and innate behavior through the patients' process of change and identification. Therefore, if depression treatment is scaled based on the level the participant is currently able to understand and profit from, it could provide more experiences of success and enable more autonomy, relatedness and experience of competency.

To increase adherence and effect of the treatment, the treatment has been developed to be meaningful for the individual patient, to target heterogenuity of depression and designed to be self-guidet, guidet and blended depending on the individual need of participants.