m-RESIST, a Mobile Therapeutic Intervention for Treatment-Resistant Schizophrenia: Feasibility, Acceptability, and Usability Study.

BACKGROUND: In the European Union, around 5 million people are affected by psychotic disorders, and approximately 30%-50% of people with schizophrenia have treatment-resistant schizophrenia (TRS). Mobile health (mHealth) interventions may be effective in preventing relapses, increasing treatment adherence, and managing some of the symptoms of schizophrenia. People with schizophrenia seem willing and able to use smartphones to monitor their symptoms and engage in therapeutic interventions. mHealth studies have been performed with other clinical populations but not in populations with TRS. OBJECTIVE: The purpose of this study was to present the 3-month prospective results of the m-RESIST intervention. This study aims to assess the feasibility, acceptability, and usability of the m-RESIST intervention and the satisfaction among patients with TRS after using this intervention. METHODS: A prospective multicenter feasibility study without a control group was undertaken with patients with TRS. This study was performed at 3 sites: Sant Pau Hospital (Barcelona, Spain), Semmelweis University (Budapest, Hungary), and Sheba Medical Center and Gertner Institute of Epidemiology and Health Policy Research (Ramat-Gan, Israel). The m-RESIST intervention consisted of a smartwatch, a mobile app, a web-based platform, and a tailored therapeutic program. The m-RESIST intervention was delivered to patients with TRS and assisted by mental health care providers (psychiatrists and psychologists). Feasibility, usability, acceptability, and user satisfaction were measured. RESULTS: This study was performed with 39 patients with TRS. The dropout rate was 18% (7/39), the main reasons being as follows: loss to follow-up, clinical worsening, physical discomfort of the smartwatch, and social stigma. Patients' acceptance of m-RESIST ranged from moderate to high. The m-RESIST intervention could provide better control of the illness and appropriate care, together with offering user-friendly and easy-to-use technology. In terms of user experience, patients indicated that m-RESIST enabled easier and quicker communication with clinicians and made them feel more protected and safer. Patients' satisfaction was generally good: 78% (25/32) considered the quality of service as good or excellent, 84% (27/32) reported that they would use it again, and 94% (30/32) reported that they were mostly satisfied. CONCLUSIONS: The m-RESIST project has provided the basis for a new modular program based on novel technology: the m-RESIST intervention. This program was well-accepted by patients in terms of acceptability, usability, and satisfaction. Our results offer an encouraging starting point regarding mHealth technologies for patients with TRS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03064776; https://clinicaltrials.gov/ct2/show/record/NCT03064776. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2017-021346.

A Method to Compare the Delivery of Psychiatric Care for People with Treatment-Resistant Schizophrenia.

INTRODUCTION: Community services are gaining ground when it comes to attention to patients with psychiatric diseases. Regarding patients with treatment-resistant schizophrenia (TRS), the use of information and communication technology (ICT) could help to shift the focus from hospital-centered attention to community services. This study compares the differences in mental health services provided for patients with TRS in Budapest (Hungary), Tel-Aviv (Israel) and Catalonia (Spain) by means of a method for the quick appraisal of gaps among the three places, for a potential implementation of the same ICT tool in these regions. METHODS: An adapted version of the Description and Standardised Evaluation of Services and Directories in Europe for Long Term Care (DESDE-LTC) instrument was made by researchers in Semmelweis University (Budapest, Hungary), Gertner Institute (Tel-Aviv, Israel) and Hospital de la Santa Creu I Sant Pau and Parc Sanitari Sant Joan de Déu (Catalonia, Spain). RESULTS: Two types of outpatient care services were available in the three regions. Only one type of day-care facility was common in the whole study area. Two residential care services, one for acute and the other for non-acute patients were available in every region. Finally, two self-care and volunteer-care facilities were available in the three places. CONCLUSION: Although the availability of services was different in each region, most of the services provided were sufficiently similar to allow the implementation of the same ICT solution in the three places.

Mobile Phone and Wearable Sensor-Based mHealth Approaches for Psychiatric Disorders and Symptoms: Systematic Review.

BACKGROUND: Mobile Therapeutic Attention for Patients with Treatment-Resistant Schizophrenia (m-RESIST) is an EU Horizon 2020-funded project aimed at designing and validating an innovative therapeutic program for treatment-resistant schizophrenia. The program exploits information from mobile phones and wearable sensors for behavioral tracking to support intervention administration. OBJECTIVE: To systematically review original studies on sensor-based mHealth apps aimed at uncovering associations between sensor data and symptoms of psychiatric disorders in order to support the m-RESIST approach to assess effectiveness of behavioral monitoring in therapy. METHODS: A systematic review of the English-language literature, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was performed through Scopus, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials databases. Studies published between September 1, 2009, and September 30, 2018, were selected. Boolean search operators with an iterative combination of search terms were applied. RESULTS: Studies reporting quantitative information on data collected from mobile use and/or wearable sensors, and where that information was associated with clinical outcomes, were included. A total of 35 studies were identified; most of them investigated bipolar disorders, depression, depression symptoms, stress, and symptoms of stress, while only a few studies addressed persons with schizophrenia. The data from sensors were associated with symptoms of schizophrenia, bipolar disorders, and depression. CONCLUSIONS: Although the data from sensors demonstrated an association with the symptoms of schizophrenia, bipolar disorders, and depression, their usability in clinical settings to support therapeutic intervention is not yet fully assessed and needs to be scrutinized more thoroughly.

Mobile therapeutic attention for treatment-resistant schizophrenia (m-RESIST): a prospective multicentre feasibility study protocol in patients and their caregivers.

INTRODUCTION: Treatment-resistant schizophrenia (TRS) is a severe form of schizophrenia. In the European Union, approximately 40% of people with schizophrenia have TRS. Factors such as the persistence of positive symptoms or higher risk of comorbidities leave clinicians with a complex scenario when treating these patients. Intervention strategies based on mHealth have demonstrated their ability to support and promote self-management-based strategies. Mobile therapeutic attention for treatment-resistant schizophrenia (m-RESIST), an innovative mHealth solution based on novel technology and offering high modular and flexible functioning, has been developed specifically for patients with TRS and their caregivers. As intervention in TRS is a challenge, it is necessary to perform a feasibility study before the cost-effectiveness testing stage. METHODS AND ANALYSIS: This manuscript describes the protocol for a prospective multicentre feasibility study in 45 patients with TRS and their caregivers who will be attended in the public health system of three localities: Hospital Santa Creu Sant Pau (Spain), Semmelweis University (Hungary) and Gertner Institute & Sheba Medical Center (Israel). The primary aim is to investigate the feasibility and acceptability of the m-RESIST solution, configured by three mHealth tools: an app, wearable and a web-based platform. The solution collects data about acceptability, usability and satisfaction, together with preliminary data on perceived quality of life, symptoms and economic variables. The secondary aim is to collect preliminary data on perceived quality of life, symptoms and economic variables. ETHICS AND DISSEMINATION: This study protocol, funded by the Horizon 2020 Programme of the European Union, has the approval of the ethics committees of the participating institutions. Participants will be fully informed of the purpose and procedures of the study, and signed inform consents will be obtained. The results will be published in peer-reviewed journals and presented in scientific conferences to ensure widespread dissemination. TRIAL REGISTRATION NUMBER: NCT03064776; Pre-results.

Measuring Users' Receptivity Toward an Integral Intervention Model Based on mHealth Solutions for Patients With Treatment-Resistant Schizophrenia (m-RESIST): A Qualitative Study.

BACKGROUND: Despite the theoretical potential of mHealth solutions in the treatment of patients with schizophrenia, there remains a lack of technological tools in clinical practice. OBJECTIVE: The aim of this study was to measure the receptivity of patients, informal carers, and clinicians to a European integral intervention model focused on patients with persistent positive symptoms: Mobile Therapeutic Attention for Patients with Treatment-Resistant Schizophrenia (m-RESIST). METHODS: Before defining the system requirements, a qualitative study of the needs of outpatients with treatment-resistant schizophrenia was carried out in Spain, Israel, and Hungary. We analyzed the opinions of patients, informal carers, and clinicians concerning the services originally intended to be part of the solution. A total of 9 focus groups (72 people) and 35 individual interviews were carried out in the 3 countries, using discourse analysis as the framework. RESULTS: A webpage and an online forum were perceived as suitable to get both reliable information on the disease and support. Data transmission by a smart watch (monitoring), Web-based visits, and instant messages (clinical treatment) were valued as ways to improve contact with clinicians. Alerts were appreciated as reminders of daily tasks and appointments. Avoiding stressful situations for outpatients, promoting an active role in the management of the disease, and maintaining human contact with clinicians were the main suggestions provided for improving the effectiveness of the solution. CONCLUSIONS: Positive receptivity toward m-RESIST services is related to its usefulness in meeting user needs, its capacity to empower them, and the possibility of maintaining human contact.

Safety, tolerability and pharmacokinetics of open label sarcosine added on to anti-psychotic treatment in schizophrenia - preliminary study.

BACKGROUND: Hypofunction of NMDA receptor-mediated neurotransmission might play a critical role in schizophrenia. Sarcosine, N- methylglycine and inhibitor of the glycine transporter-1 (Gly-T1), has been suggested as a novel treatment for schizophrenia. METHODS: Open label sarcosine was added to 22 stabilized patients: 5 patients received 2 gm/d, and 17 received 4gm/d. Pharmacokinetics samples, clinical and cognitive parameters using PANSS, CGI and MCCB were collected for all patients. RESULTS: Significant improvement was observed after one week of treatment on PANSS sub-scale of 'positive symptoms' (Z= -2.68; P=0.007) and 'general psychopathology' (Z= -3.02; P=0.003), an improvement in PANSS total score and CGI-S showed a trend (Z= -2.72; P=0.06; Z=-2.69; P=0.08). Speed of processing (MCCB subscale) improved significantly (Z=-2.13; P=0.03). Sarcosine exhibited linear kinetics, with a Tmax and t½ of ~1½- 2½ hr and ~1hr, respectively. LIMITATIONS: This was a short period, open label pilot study with small sample size per dosage group. CONCLUSIONS: Sarcosine is a safe compound and might be efficacious in the treatment of schizophrenia.

Everyday functioning of male adolescents who later died by suicide: Results of a pilot case-control study using mixed-method analysis.

OBJECTIVE: Previous research has shown a link between difficulties in everyday functioning and suicidality in adolescence. The majority of research in this field focuses on suicidal ideation and attempts, rather than on completed suicide. The main goal of this study is to better characterize everyday functioning among young men who later completed suicide. Based on previous literature, we hypothesized that the functioning of adolescents who died by suicide would be poor, compared to controls. METHODS: The current study is a record-driven study, which examined summaries of screening interviews performed by the Israeli Defense Forces (IDF) of 20 male adolescents who later completed suicide, compared with 20 matched living controls. The current study is a pilot stage of a larger project. The study used unique data, collected as part of the IDF pre-induction process, in the months or years before the tragic outcome. The data were extracted by two psychologists, blinded to the participants׳ suicide or non-suicide outcome, using mixed-method technique, combining qualitative and quantitative analysis. RESULTS: The main findings indicated that, in comparison with controls, male adolescents who later died by suicide were described as having more interpersonal difficulties, were more likely to be involved in violent behavior, had more difficulties in dealing with problems in everyday functioning and had an avoidant conflict resolution style. CONCLUSIONS: Functional difficulties are apparent in a wide range of behavioral domains in adolescents who later complete suicide. These findings indicate a need for interventions that might assist young persons, and it is possible that such assistance might reduce the likelihood of suicide. However, because suicide is a rare outcome and these behavioral traits are common in adolescence, the presence of such traits might not be useful in identifying people at risk of suicide.

A randomized controlled trial of allopurinol vs. placebo added on to antipsychotics in patients with schizophrenia or schizoaffective disorder.

Adenosine agonists produce behavioral effects similar to dopamine antagonists, hence increasing adenosine levels might improve symptoms of schizophrenia. This hypothesis is supported by three single-site studies indicating that allopurinol, which increases adenosine levels, improved symptoms in patients with schizophrenia. We performed a multi-center, 8-week RCT of allopurinol vs. placebo added to anti-psychotic medications in 248 patients with schizophrenia or schizoaffective disorder. Both groups showed improvement in the PANSS (effect size 1.13) and in clinical and cognitive measures. No difference was observed between groups in primary (t=0.01, p=0.992) or secondary outcome measures. These findings do not support allopurinol as a treatment for schizophrenia.