The PEDAL Intervention - Reducing Affective Lability in Bipolar Disorder

Bipolar disorder (BD) is a severe mental illness with significant costs for the affected individuals, their families, and society. Although a substantial proportion of individuals with BD respond relatively well to currently available treatment, sub-syndromal affective symptoms and affective lability (AL) are common and have a clear negative impact on functioning and quality of life. Targeting AL is an important new opportunity for intervention with high clinical potential through its links to severe outcomes, both independently and as a mediator of other risk factors. There is also a need for interventions that can easily be implemented in regular clinical practice. As such, we have a clear ambition of achieving efficacy and cost-efficiency, i.e., that the PEDAL intervention can be implemented in standard clinical settings without requiring substantial additional resources or structural changes. If successful, we believe that the PEDAL trial will contribute to increasing the quality and availability of treatment for patients with BD. Since group psychoeducation (GPP) is already implemented across many health regions in Norway and worldwide, there is potential for the PEDAL intervention to have both nationwide and international reach and impact if the current trial is successful.

PEDAL (PsychoEducation with Digital elements and focus on Affective Lability) is a group intervention for individuals with BD with educational and therapeutic elements. Its main purpose is to facilitate a learning and developmental process for the patient, in order to enable better self-management of the disorder. PEDAL builds on the well-established GPP program for BD, which has been found to be effective in reducing relapses and hospitalisations. GPP is likely to have further untapped potential in targeting additional burdensome aspects of BD and augmenting the didactic elements. In PEDAL, we reinforce traditional GPP through digital tools and several components targeting affective lability. In a randomised controlled trial, we will investigate whether the PEDAL intervention is superior to traditional GPP in reducing affective lability in BD. Five catchment-area-based clinical sites in and close to Oslo will participate, covering a total population of approximately 740.000. We aim to recruit 120 patients with BD to the trial.

AL is defined as rapid, excessive, and unpredictable shifts in affective states, is common in individuals with BD and adds to the illness burden. It is, however, not targeted successfully in current pharmacological or non-pharmacological treatments. Although a substantial proportion of individuals with BD respond relatively well to currently available treatment, sub-syndromal affective symptoms and AL have a clear negative impact on functioning and quality of life. Targeting AL is an important new opportunity for intervention with high clinical potential through its links to severe outcomes, both independently and as a mediator between e.g. early traumatic experiences and clinical expressions of BD.

New digital tools are promising for enhancing treatments and empowering individuals with mental disorders including BD. Such tools are increasingly used to expand mental health services' availability, flexibility, and personalization. These tools often require limited resources and enable the provision of quality health care irrespective of geographical location. Digital interventions currently in use in the mental health field include online and app-based cognitive behavioural therapy interventions, training of coping skills, and self-help programs with or without therapist guidance. The functional possibilities of digital tools align well with the objectives of psychoeducation, and such tools are increasingly used to enhance its availability and improve the personalization of delivery. So far, studies of digital interventions have not shown the anticipated effects in reducing affective episodes or hospitalisations in BD, or the effects, if present, have not been maintained at follow-up. One possible explanation could be that these interventions do not encompass interactive group sessions. Although they are still based on the principles of psychoeducation, they have omitted the group format, which is highly significant. Consequently, combining the well-established group format with digital tools directed at self-monitoring and self-management, such as an app-based mood diary and skills training sessions, may be a novel and more effective way of increasing empowerment, awareness, and engagement with the intervention.

Traditional GPP consists of modules, where predefined topics are addressed in group sessions and in paper-based written material for the participants to read and prepare for the relevant session. The most frequently used version of GPP in Norway comprises 10-12 weekly group sessions that are relatively independent of each other. The sessions cover topics such as the characteristics of BD, theories about etiology, managing depression and mania, psychopharmacological treatment and lifestyle advice to enhance illness stabilization. Each session has an introductory lecture on the topic held by the therapist, small-group discussions based on the participants' experiences in this area, and plenary discussions led by the therapist. The written material is provided in a booklet. It contains the educational parts, a toolkit with a mood diary, an overview of potential "warning signs" for relapse and an emergency plan. The toolkit is used to engage the participants in self-management of their disorder. Traditional GPP is generic in that it addresses the "standard bipolar patient", i.e. provides limited optional material targeting the specific needs of the individual participants. Furthermore, while the existing program improves several clinical outcomes in BD, it does not specifically target AL and does not appear to affect suicidality - the most severe clinical outcome possibly mediated by AL. Consequently, there is a need to incorporate additional elements to reduce suicide risk. Targeting AL through, e.g., improving affect regulation skills has the potential to do so.

The content of the PEDAL intervention:

The intervention will include the original sessions of GPP while enhancing the program with the following elements:

1. A new group session specifically addressing AL: Characteristics, and theories about etiology, as well as an introduction to relevant coping skills such as mindfulness, affect regulation strategies and distress tolerance.
2. A practical skills training group session, where mindfulness, affect regulation and distress tolerance strategies are demonstrated by a therapist.
3. An online platform with the following content:

• All written course material for participants, including self-management tools (overview of coping strategies, emergency plan, etc.).
• Three video tutorials for further skills training; mindfulness, affect regulation, and distress tolerance techniques.
• All written course material, including an intervention manual for the PEDAL therapists.
• A brief online "Clinician's booklet" for other clinicians involved in treating the patients attending the intervention.

1. App-based mood diary ("MyPEDAL").

Aims and hypotheses: The short-term and main aim of the current study is to test whether the PEDAL intervention is more efficient in reducing AL compared to traditional GPP, which is considered TAU in the current trial. We hypothesize that enhancing the traditional GPP for BD with new elements, as planned in the PEDAL intervention, will reduce AL in individuals with BD. It is also an aim to ensure that the PEDAL intervention is well received by patients and clinicians.

The PEDAL trial is a randomised controlled trial, where patients with BD will receive either TAU or the PEDAL intervention. To test whether the PEDAL intervention is more efficient than TAU in reducing AL, we will compare the two groups on pre- and post-intervention assessments of AL (primary outcome). We will also test for group differences on other relevant outcomes with important implications for individuals affected by BD such as affective symptoms, suicidal ideation, perceived stress, and quality of life. To investigate to which degree the PEDAL intervention is well received by patients and clinicians, we will conduct structured post-study evaluations of both arms.

All the clinical units participating in the PEDAL trial normally run traditional GPP 2-3 times a year with 12-16 patients in each group. Patients are referred to GPP from other units within the secondary psychiatric services and, in some cases, from general practitioners or contract psychiatrists and psychologists. All five study sites will run one TAU arm and one PEDAL arm in parallel, and patients will be randomized to TAU or PEDAL. Thus, approximately 60 participants will receive TAU, and 60 will receive PEDAL in the trial.

Inclusion and exclusion criteria: Routine criteria for participation in GPP in adult psychiatric units are as follows and will form the basis for which patients are considered candidates for the PEDAL trial: age between 18 and 65 years, a BD diagnosis, a clinical state that is considered adequate for group participation (i.e. the patient is not in a severe depressive or manic state or has severe ongoing substance abuse) and has adequate understanding of Scandinavian language. In addition, the following inclusion criteria will apply for the current trial: Ability to give informed consent and a valid DSM-5 or ICD-10 diagnosis of bipolar I, II or NOS disorder. Exclusion criteria are: Previous participation in GPP, pregnancy in a stage preventing completion of the intervention, and not owning a smartphone or computer, and/or objecting to the use a mood diary app.