SIgns and Symptoms Self-Monitoring and Psychoeducation in bipoLar Patients With a Smart-phonE Application (SIMPLE)

The main aim of this study is to develop and clinically validate a smart-phone application to monitor symptoms and signs in stable bipolar patients, offering also customized embedded psycho-education contents and empower the self-management of their disorder to avoid relapses and hospitalizations. Secondary objectives will be to explore other clinical benefits among the smart-phone application users such as biological rhythms, manic/hypomanic and depressive symptoms, quality of life, suicide attempts, pharmacological treatment changes as well as healthcare resource consumption (outpatient and emergency room consultations) in order to evaluate its cost-efficiency compared to current standard interventions.

The study will include stable bipolar patients (YMRS ≤ 8, HDRS ≤ 6 for at least one month prior to study entry) who have experienced at least one hypomanic, manic or depressive relapse during the 12 months prior to study entry. This will be carried out in three different but complementary phases in order to fully include patients and therapist's preferences. Along the process, confidential information and data handling will be tested to ensure privacy and confidentiality are warranted. In this regard, an anonymized user name and password will be given to the patients who will never have to reveal their real identity to access the application during the study.

• First phase: During the first three months a feasibility study will be conducted evaluating the use, reliability and satisfaction monitoring symptoms (subjective information) using a smart-phone with the SIMPLe 1.0 application installed. The intervention will be consecutively offered to 30 stable adults (>18 years) fulfilling inclusion criteria. The patient will have to read and agree with the terms and sign an informed consent in order to participate. Sociodemographic data and standardized clinical as well as functional assessments will be administered at baseline, at the first, second and third month of the study. The assessments will include present manic symptoms using the Young Mania Rating Scale (YMRS), depressive symptoms using the Hamilton depression Rating Scale (HDRS), biological rhythms using the biological rhythms interview of assessment in neuropsychiatry (BRIAN), quality of life measured by World Health Organization quality of life assessment (WHOQOL-BREF) and treatment adherence using the Medication Adherence Rating Scale (MARS). A smart-phone device with the SIMPLe 1.0 application pre-installed, will be given to the participants for free during the study with the mandatory condition that it has to be their main mobile-phone during the next 3 months. In the case the patient accepts to participate but doesn´t want to switch from his/her current smart-phone, he/she will be offered the possibility to download the SIMPLe 1.0 application from the App Store and a username and password will be given to use it. The SIMPLe 1.0 application will ask the user by customizable automatic reminder notifications to answer daily and weekly questionnaires based on DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) criteria for a manic, hypomanic, mixed or depressive episode. The use frequency will be measured by the daily and weekly questionnaires answered which will be registered online. At the same time they will receive through the application daily customized psychoeducative messages based on the information collected by the application. Feasibility and satisfaction will be assessed with the application usage log data and an electronic survey, while the app reliability to correctly asses the patients mood states will be analyzed comparing the clinical assessments and the information collected by the application.

• Second phase: Individual personal interviews with each SIMPLe 1.0 user will also collect qualitative information about the application and suggestions. Taking into consideration the information collected from participants in the first phase, the application will be adapted and improved with the addition of objective information (signs) monitoring modules using mobile usage parameters and the built-in sensors. Focus groups will be held with participants, psychiatrists and psychologists to better fit their needs and incorporate suggestions.

• Third phase: A randomized controlled trial taking into consideration a significance level of 0.05, power of 0.8 and a minimal detectable difference of 0.5 and an expected drop-out of 15%, will be carried out with two arms of 74 patients each, as follows:

• Intervention group (SIMPLe 2.0 + TAU): The experimental group will use the application SIMPLe 2.0 and simultaneously will receive their usual treatment which includes pharmacological and psychological interventions. A smart-phone device with the SIMPLe 2.0 application pre-installed, will be given to the participants for free during the study with the mandatory condition that it has to be their main mobile-phone during the next 3 months. In the case the patient accept to participate but don´t want to switch from their current smart-phone, they will be offered the possibility to download the SIMPLe 2.0 application from the App Store and a username and password will be given to use it. The patient will be asked by customizable automatic reminder notifications to answer daily and weekly questionnaires based on DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) criteria for a manic, hypomanic or depressive episode. Additionally, the signs will be automatically recorded based on the smart-phone usage measured by the smart-phone screen on time, texts messages sent, telephone calls made and social networking apps activity, in addition to the physical activity monitored by the built-in actimeter. At the same time, they will receive through the application daily psychoeducative customized messages based on the data recollected by the application. Relapse risk will be fixed by means of a logarithm including both subjective and objective data. If the logarithm points at a moderate or high risk, the clinical team will be immediately contacted and the patient will be offered to call emergency services for assistance.

• Treatment as usual group (TAU): The treatment as usual (TAU) only group will be followed-up with their usual treatment including pharmacological and psychological interventions.

An initial evaluation in both groups will be carried out recollecting sociodemographic data and using standardized clinical as well as functional assessments which will be administered again in three follow-up evaluations, at three, six and twelve months. The assessments will include present manic symptoms using the Young Mania Rating Scale (YMRS), depressive symptoms using the Hamilton depression Rating Scale (HDRS), functional impairment using the Functioning assessment short test (FAST), biological rhythms using the biological rhythms interview of assessment in neuropsychiatry (BRIAN), quality of life measured by World Health Organization quality of life assessment (WHOQOL-BREF) and treatment adherence using the Medication Adherence Rating Scale (MARS). During the follow-up the number of relapses, inpatient admissions, outpatient consultations, emergency rooms consultations and suicide attempts will be registered. All participants in both groups must read and agree with the terms and sign an informed consent prior to their inclusion in the study. Psychiatrists and psychologists conducting the evaluations will be blinded to which participant belongs to each group.