BACKGROUND: Despite the proven efficacy of antipsychotics in relapse prevention in schizophrenia and schizoaffective disorder, every third patient experiences a relapse within less than one year. Relapses can worsen psychosocial and treatment related outcomes and lead to substantial economic costs, primarily due to frequent and prolonged hospitalizations. The aim of this project is to evaluate a smartphone- and web-based digital solution for detecting early warning signs of schizophrenia and schizoaffective disorder to reduce relapses and subsequent hospitalizations. METHODS: This randomized controlled trial compares the add-on use of a smartphone-based app for monitoring relapse warning signs in patients with schizophrenia and schizoaffective disorders (ICD-10 F20/F25) used within the routine psychiatric outpatient treatment against treatment as usual (TAU) without any further study-related intervention. Patients in the intervention group use the app for one year, fill in the weekly ten-item Early Warning Signs Questionnaire (EWSQ-10P) and obtain in-app feedback. Clinicians can access the symptom trajectory via a browser-accessible dashboard. If a threshold is exceeded in the inbuilt automatic algorithm, an alert is sent to both, the clinician and patient, enabling timely contact and, as part of a shared decision-making process, an optional adjustment of treatment decision. A total of 110 outpatients are recruited across eight study sites. DISCUSSION: Continuous monitoring of early warning signs is expected to lead to behavioral changes and to decrease the necessity and duration of psychiatric hospital stays, thereby lowering healthcare costs. Additionally, the intervention could reduce symptom severity, alleviate medication adherence, shared decision-making, patient activation or quality of life. Qualitative data is collected to better understand patient needs and preferences regarding app usage and relapses. Insights gained from this study can be integrated into routine psychiatric care, improving the long-term treatment of patients with schizophrenia or schizoaffective disorder. TRIAL REGISTRATION: German Clinical Trials Register (ID: DRKS00034991; registration date: 30.08.2024).

Analysis and interpretation of biomedical data Faculty of Electrical Engineering Prague Czech Republic

Berlin Institute of Health at Charité Universitätsmedizin Berlin BIH Biomedical Innovation Academy BIH Charité Clinician Scientist Program Berlin Germany

Center for first episodes of SMI National Institute of Mental Health Klecany Czech Republic

Department for Psychiatry and Psychotherapy LMU University Hospital Munich Germany

Department for Psychology Medical University Brandenburg Neuruppin Germany

Department of Psychiatry and Neuroscience Charité Universitätsmedizin Berlin Campus Benjamin Franklin Berlin Germany

Department of Psychiatry Psychotherapy and Psychosomatics Faculty of Medicine University of Augsburg Augsburg Germany

Department of Psychology Faculty of Arts Charles University Prague Czech Republic

Department of Psychology LMU Munich Munich Germany

DZPG partner site Berlin Berlin Germany

DZPG partner site Munich Augsburg Munich Germany

Institute of Medical Informatics Charité Universitätsmedizin BerlinFreie Universität Berlin and Humboldt Universität zu Berlin Berlin Germany

Institute of the History Philosophy and Ethics of Medicine Faculty of Medicine Ulm University Ulm Germany

kbo Isar Amper Klinikum Region München München Haar Germany

Max Planck Institute for Psychiatry Munich Germany

Mindpax me Prague Czech Republic

School of Business and Economics Freie Universität Berlin Berlin Germany

Technical University of Munich TUM School of Medicine and Health Department of Psychiatry and Psychotherapy TUM University Hospital Munich Germany

See more in PubMed

Lauriello J (2020) Prevalence and impact of relapse in patients with schizophrenia. J Clin Psychiatry 10.4088/JCP.MS19053BR1C.

Robinson D, Woerner MG, Alvir JM, Bilder R, Goldman R, Geisler S, Koreen A, Sheitman B, Chakos M, Mayerhoff D, Lieberman JA (1999) Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry 56(3):241–247 PubMed

Brieger P, Marneros A, Jäger M (2017) Schizoaffektive Störungen, akute vorübergehende psychotische Störungen und wahnhafte Störungen. In: Möller H-J, Laux G, Kapfhammer H-P, editors. Psychiatrie, Psychosomatik, Psychotherapie: Band 1: Allgemeine Psychiatrie 1, Band 2: Allgemeine Psychiatrie 2, Band 3: Spezielle Psychiatrie 1, Band 4: Spezielle Psychiatrie 2. Berlin, Heidelberg: Springer Berlin Heidelberg; ISBN:978-3-662-49295-6. pp. 1675–1700

Moncrieff J, Crellin NE, Long MA, Cooper RE, Stockmann T (2020) Definitions of relapse in trials comparing antipsychotic maintenance with discontinuation or reduction for schizophrenia spectrum disorders: A systematic review. Schizophr Res 225:47–54 PubMed

Olivares JM, Sermon J, Hemels M, Schreiner A (2013) Definitions and drivers of relapse in patients with schizophrenia: a systematic literature review. Ann Gen Psychiatry 12(1):32 PubMed PMC

Siafis S, Brandt L, McCutcheon RA, Gutwinski S, Schneider-Thoma J, Bighelli I, Kane JM, Arango C, Kahn RS, Fleischhacker WW, McGorry P, Carpenter WT, Falkai P, Hasan A, Marder SR, Schooler N, Engel RR, Honer WG, Buchanan RW, Davidson M, Weiser M, Priller J, Davis JM, Howes OD, Correll CU, Leucht S (2024) Relapse in clinically stable adult patients with schizophrenia or schizoaffective disorder: evidence-based criteria derived by equipercentile linking and diagnostic test accuracy meta-analysis. Lancet Psychiatry 11(1):36–46 PubMed

Zimmermann J, Wolter A, Krischke NR, Preuß UW, Wobrock T, Falkai P (2011) Response und remission Bei an schizophrenie erkrankten patienten. Nervenarzt 82(11):1440–1448. https://doi.org/10.1007/s00115-010-3202-6 PubMed

Murru A, Verdolini N, Anmella G, Pacchiarotti I, Samalin L, Aedo A, Undurraga J, Goikolea JM, Amann BL, Carvalho AF, Vieta E (2019) A 12-month prospective study on the time to hospitalization and clinical management of a cohort of bipolar type I and schizoaffective bipolar patients. Eur Psychiatry 61:1–8 PubMed

Leucht S, Tardy M, Komossa K, Heres S, Kissling W, Salanti G, Davis JM (2012) Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis. Lancet 379(9831):2063–2071 PubMed

Ceraso A, Lin JJ, Schneider-Thoma J, Siafis S, Tardy M, Komossa K, Heres S, Kissling W, Davis JM, Leucht S (2020) Maintenance treatment with antipsychotic drugs for schizophrenia. Cochrane Database Syst Rev 8(8):CD008016 PubMed

Almond S, Knapp M, Francois C, Toumi M, Brugha T (2004) Relapse in schizophrenia: costs, clinical outcomes and quality of life. Br J Psychiatry 184:346–351 PubMed

Takeuchi H, Siu C, Remington G, Fervaha G, Zipursky RB, Foussias G, Agid O (2019) Does relapse contribute to treatment resistance? Antipsychotic response in first- vs. second-episode schizophrenia. Neuropsychopharmacology 44(6):1036–1042 PubMed

Lin D, Joshi K, Keenan A, Shepherd J, Bailey H, Berry M, Wright J, Meakin S, Benson C, Kim E (2021) Associations between relapses and psychosocial outcomes in patients with schizophrenia in Real-World settings in the united States. Front Psychiatry 12:695672 PubMed PMC

Zukowska Z, Allan S, Eisner E, Ling L, Gumley A (2022) Fear of relapse in schizophrenia: a mixed-methods systematic review. Soc Psychiatry Psychiatr Epidemiol 57(7):1305–1318 PubMed PMC

Gumley A, MacBeth A, Reilly JD, O’Grady M, White RG, McLeod H, Schwannauer M, Power KG (2015) Fear of recurrence: results of a randomized trial of relapse detection in schizophrenia. Br J Clin Psychol 54(1):49–62 PubMed

Karve S, Markowitz M, Fu D-J, Lindenmayer J-P, Wang C-C, Candrilli SD, Alphs L (2014) Assessing medication adherence and healthcare utilization and cost patterns among hospital-discharged patients with schizoaffective disorder. Appl Health Econ Health Policy 12(3):335–346 PubMed PMC

Pennington M, McCrone P (2017) The cost of relapse in schizophrenia. PharmacoEconomics 35(9):921–936 PubMed

Ascher-Svanum H, Zhu B, Faries DE, Salkever D, Slade EP, Peng X, Conley RR (2010) The cost of relapse and the predictors of relapse in the treatment of schizophrenia. BMC Psychiatry 10:2 PubMed PMC

Weiden PJ, Olfson M (1995) Cost of relapse in schizophrenia. Schizophr Bull 21(3):419–429 PubMed

Kovács G, Almási T, Millier A, Toumi M, Horváth M, Kóczián K, Götze Á, Kaló Z, Zemplényi AT (2018) Direct healthcare cost of schizophrenia - European overview. Eur Psychiatry 48:79–92 PubMed

Jørgensen P (1998) Early signs of psychotic relapse in schizophrenia. Br J Psychiatry 172:327–330 PubMed

van Meijel B, van der Gaag M, Kahn RS, Grypdonck MHF (2004) Recognition of early warning signs in patients with schizophrenia: a review of the literature. Int J Ment Health Nurs 13(2):107–116 PubMed

Gleeson JF, McGuckian TB, Fernandez DK, Fraser MI, Pepe A, Taskis R, Alvarez-Jimenez M, Farhall JF, Gumley A (2024) Systematic review of early warning signs of relapse and behavioural antecedents of symptom worsening in people living with schizophrenia spectrum disorders. Clin Psychol Rev 107:102357 PubMed

Španiel F, Bakstein E, Anyz J, Hlinka J, Sieger T, Hrdlicka J, Görnerová N, Höschl C (2018) Relapse in schizophrenia: definitively not a bolt from the blue. Neurosci Lett 669:68–74 PubMed

Addington J (2003) The prodromal stage of psychotic illness: observation, detection or intervention? J Psychiatry Neurosci 28(2):93–97 PubMed PMC

Pietzcker A, Wolfgang G, Wolfgang K, Michael L, Peter M, Franz M-S, Joachim T (1993) Intermittent versus maintenance neuroleptic long-term treatment in Schizophrenia—2-year results of a German multicenter study. J Psychiatr Res 27(4):321–339. https://doi.org/10.1016/0022-3956(93)90059-B

Španiel F, Vohlídka P, Hrdlicka J, Kozený J, Novák T, Motlová L, Cermák J, Bednarík J, Novák D, Höschl C (2008) ITAREPS: information technology aided relapse prevention programme in schizophrenia. Schizophr Res 98(1–3):312–317 PubMed

Komatsu H, Sekine Y, Okamura N, Kanahara N, Okita K, Matsubara S, Hirata T, Komiyama T, Watanabe H, Minabe Y, Iyo M (2013) Effectiveness of information technology aided relapse prevention programme in schizophrenia excluding the effect of user adherence: a randomized controlled trial. Schizophr Res 150(1):240–244 PubMed

Hamann J, Cohen R, Leucht S, Busch R, Kissling W (2007) Shared decision making and long-term outcome in schizophrenia treatment. J Clin Psychiatry 68(7):992–997 PubMed

Stovell D, Morrison AP, Panayiotou M, Hutton P (2016) Shared treatment decision-making and empowerment-related outcomes in psychosis: systematic review and meta-analysis. Br J Psychiatry 209(1):23–28 PubMed

Anýž J, Bakštein E, Dally A, Kolenič M, Hlinka J, Hartmannová T, Urbanová K, Correll CU, Novák D, Španiel F (2021) Validity of the Aktibipo Self-rating questionnaire for the digital Self-assessment of mood and relapse detection in patients with bipolar disorder: instrument validation study. JMIR Ment Health 8(8):e26348 PubMed PMC

Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG (2009) Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inf 42(2):377–381

Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O’Neal L, McLeod L, Delacqua G, Delacqua F, Kirby J, Duda SN (2019) The REDCap consortium: Building an international community of software platform partners. J Biomed Inf 95:103208

Hendrikoff L, Kambeitz-Ilankovic L, Pryss R, Senner F, Falkai P, Pogarell O, Hasan A, Peters H (2019) Prospective acceptance of distinct mobile mental health features in psychiatric patients and mental health professionals. J Psychiatr Res 109:126–132 PubMed

Soellner R, Huber S, Reder M (2014) The concept of eHealth literacy and its measurement: German translation of the eHEALS. J Media Psychology: Theor Methods Appl 26(1). https://doi.org/10.1027/1864-1105/a000104

Kriston L, Scholl I, Hölzel L, Simon D, Loh A, Härter M (2010) The 9-item shared decision making questionnaire (SDM-Q-9). Development and psychometric properties in a primary care sample. Patient Educ Couns 80(1):94–99 PubMed

Juergen S, Nübling R (2002) ZUF-8. Fragebogen zur Messung der Patientenzufriedenheit. In: Diagnostische Verfahren in der Psychotherapie; ISBN:978-3-8017-1289-1. pp. 392–396

Zill JM, Dwinger S, Kriston L, Rohenkohl A, Härter M, Dirmaier J (2013) Psychometric evaluation of the German version of the patient activation measure (PAM13). BMC Public Health 13:1027 PubMed PMC

Arnet I, Sahm LJ, Gregório J, Tuula A, Krüger M, Wurmbach VS, Hoti K, Schulz M, Eickhoff C (2024) Development and validation of the 15-STARS - A novel self-report pharmacy-based questionnaire to screen for medication non-adherence. Res Social Adm Pharm 20(3):308–320 PubMed

Østergaard SD, Lemming OM, Mors O, Correll CU, Bech P (2016) PANSS-6: a brief rating scale for the measurement of severity in schizophrenia. Acta Psychiatr Scand 133(6):436–444 PubMed

Haro JM, Kamath SA, Ochoa S, Novick D, Rele K, Fargas A, Rodríguez MJ, Rele R, Orta J, Kharbeng A, Araya S, Gervin M, Alonso J, Mavreas V, Lavrentzou E, Liontos N, Gregor K, Jones PB (2003) The clinical global Impression-Schizophrenia scale: a simple instrument to measure the diversity of symptoms present in schizophrenia. Acta Psychiatr Scand Suppl 107(416):16–23

Morosini PL, Magliano L, Brambilla L, Ugolini S, Pioli R (2000) Development, reliability and acceptability of a new version of the DSM-IV social and occupational functioning assessment scale (SOFAS) to assess routine social functioning. Acta Psychiatr Scand 101(4):323–329 PubMed

Brähler E, Mühlan H, Albani C, Schmidt S (2007) Teststatistische Prüfung und normierung der Deutschen versionen des EUROHIS-QOL Lebensqualität-index und des WHO-5 Wohlbefindens-index. [Testing and standardization of the German version of the EUROHIS-QOL and WHO-5 quality-of life-indices]. Diagnostica 53(2):83–96. https://doi.org/10.1026/0012-1924.53.2.83

Ustün TB, Chatterji S, Kostanjsek N, Rehm J, Kennedy C, Epping-Jordan J, Saxena S, von Korff M (2010) Pull C. Developing the world health organization disability assessment schedule 2.0. Bull World Health Organ 88(11):815–823 PubMed PMC

Lingjaerde O, Ahlfors UG, Bech P, Dencker SJ, Elgen K (1987) The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand Suppl 334:1–100 PubMed

Voß E, Salize HJ (2016) Health care utilization and cost-effectiveness analyses in prevention studies in the mental health care field. Mental Health Prev 4(1):19–23. https://doi.org/10.1016/j.mhp.2016.01.004

Böge K, Karadza A, Fuchs LM, Ehlen F, Ta TMT, Thomas N, Bajbouj M, Hahn E (2020) Mindfulness-Based interventions for In-Patients with schizophrenia spectrum Disorders-A qualitative approach. Front Psychiatry 11:600 PubMed PMC

Schulze T, Hahn E, Hahne I, Bergmann N, Fuchs LM, Mähler F, Zierhut MM, Ta TMT, Pijnenborg GHM, Böge K (2021) Yoga-Based group intervention for In-patients with schizophrenia spectrum Disorders-A qualitative approach. Front Psychiatry 12:715670 PubMed PMC

Töbelmann L, Hahne I, Schulze T, Bergmann N, Fuchs L, Zierhut M, Hahn E, Böge K (2023) Mechanisms of action and processes of yoga-based group intervention for inpatients with schizophrenia spectrum disorders-A longitudinal qualitative study. Front Psychiatry 14:1086468 PubMed PMC

Hennink M, Kaiser BN (2022) Sample sizes for saturation in qualitative research: A systematic review of empirical tests. Soc Sci Med 292:114523 PubMed

Hughes RA, Heron J, Sterne JAC, Tilling K (2019) Accounting for missing data in statistical analyses: multiple imputation is not always the answer. Int J Epidemiol 48(4):1294–1304 PubMed PMC

Sullivan TR, White IR, Salter AB, Ryan P, Lee KJ (2018) Should multiple imputation be the method of choice for handling missing data in randomized trials? Stat Methods Med Res 27(9):2610–2626 PubMed

Lewin S, Glenton C, Oxman AD (2009) Use of qualitative methods alongside randomised controlled trials of complex healthcare interventions: methodological study. BMJ 339:b3496 PubMed PMC

Moore GF, Audrey S, Barker M, Bond L, Bonell C, Hardeman W, Moore L, O’Cathain A, Tinati T, Wight D, Baird J (2015) Process evaluation of complex interventions: medical research Council guidance. BMJ 350:h1258 PubMed PMC

Hepburn A, Bolden GB The Conversation Analytic Approach to Transcription. The handbook of conversation analysis 2012:57–76

Kuckartz U, Rädiker S (2022) Qualitative inhaltsanalyse. Methoden, praxis, computerunterstützung, 5th edn. Beltz Juventa

Torous J, Smith KA, Hardy A, Vinnikova A, Blease C, Milligan L, Hidalgo-Mazzei D, Lambe S, Marzano L, Uhlhaas PJ, Ostinelli EG, Anmella G, Zangani C, Aronica R, Dwyer B, Cipriani A (2024) Digital health interventions for schizophrenia: setting standards for mental health. Schizophr Res 267:392–395 PubMed

Lim MH, Penn DL (2018) Using digital technology in the treatment of schizophrenia. Schizophr Bull 44(5):937–938 PubMed PMC

Firth J, Torous J (2015) Smartphone apps for schizophrenia: A systematic review. JMIR Mhealth Uhealth 3(4):e102 PubMed PMC

Furukawa TA, Bighelli I (2022) Digital aids for relapse prevention in schizophrenia. Lancet Psychiatry 9(6):424–425 PubMed

Arnautovska U, Trott M, Vitangcol KJ, Milton A, Brown E, Warren N, Leucht S, Firth J, Siskind D, Morales-Pillado C, Fernández-Castilla B, Sánchez-Gutiérrez T, González-Fraile E, Barbeito S, Calvo A (2023) Efficacy of technology-based interventions in psychosis: a systematic review and network meta-analysis. Psychol Med ;53(13):6304–6315

Morales-Pillado C, Fernández-Castilla B, Sánchez-Gutiérrez T, González-Fraile E, Barbeito S, Calvo A. Efficacy of technology-based interventions in psychosis: a systematic review and network meta-analysis. Psychol Med 2023;53(13):6304–6315

Sutton RT, Pincock D, Baumgart DC, Sadowski DC, Fedorak RN, Kroeker KI (2020) An overview of clinical decision support systems: benefits, risks, and strategies for success. NPJ Digit Med 3:17 PubMed PMC

Steinwachs DM, Roter DL, Skinner EA, Lehman AF, Fahey M, Cullen B, Everett AS, Gallucci G (2011) A web-based program to empower patients who have schizophrenia to discuss quality of care with mental health providers. Psychiatric Serv 62(11):1296–1302

Yu H, Sun Y-J, Qin M-N, Ren J-X, Yu K, Song J, Zhou Y-Q, Liu L (2023) Perception of risk of relapse among patients with first episode and recurrent schizophrenia: a descriptive phenomenological study. BMC Psychiatry 23(1):582 PubMed PMC

Ybarra ML, Rodriguez KM, Fehmie DA, Mojtabai R, Cullen B (2022) Acceptability of texting 4 relapse prevention, text Messaging-Based relapse prevention program for people with schizophrenia and schizoaffective disorder. J Nerv Ment Dis 210(2):123–128 PubMed PMC

Thomas N, Bless JJ, Alderson-Day B, Bell IH, Cella M, Craig T, Delespaul P, Hugdahl K, Laloyaux J, Larøi F, Lincoln TM, Schlier B, Urwyler P, van den Berg D, Jardri R (2019) Potential applications of digital technology in assessment, treatment, and Self-help for hallucinations. Schizophr Bull 45(45 Suppl 1):S32–S42 PubMed PMC

Ybarra ML, Rodriguez K, Madison H, Mojtabai R, Cullen BA (2019) Developing texting for relapse prevention: A scalable mHealth program for people with schizophrenia and schizoaffective disorder. J Nerv Ment Dis 207(10):854–862 PubMed PMC

Španiel F, Novák T, Bankovska Motlova L, Capkova J, Slovakova A, Trancik P, Matejka M, Höschl C (2015) Psychiatrist’s adherence: a new factor in relapse prevention of schizophrenia. A randomized controlled study on relapse control through telemedicine system. J Psychiatr Ment Health Nurs 22(10):811–820 PubMed

Španiel F, Hrdlička J, Novák T, Kožený J, Höschl C, Mohr P, Motlová LB (2012) Effectiveness of the information technology-aided program of relapse prevention in schizophrenia (ITAREPS): a randomized, controlled, double-blind study. J Psychiatr Pract 18(4):269–280 PubMed

Gumley A, Bradstreet S, Ainsworth J, Allan S, Alvarez-Jimenez M, Beattie L, Bell I, Birchwood M, Briggs A, Bucci S, Castagnini E, Clark A, Cotton SM, Engel L, French P, Lederman R, Lewis S, Machin M, MacLennan G, Matrunola C, McLeod H, McMeekin N, Mihalopoulos C, Morton E, Norrie J, Reilly F, Schwannauer M, Singh SP, Smith L, Sundram S, Thomson D, Thompson A, Whitehill H, Wilson-Kay A, Williams C, Yung A, Farhall J, Gleeson J (2020) Early signs monitoring to prevent relapse in psychosis and promote Well-Being, engagement, and recovery: protocol for a feasibility cluster randomized controlled trial Harnessing mobile phone technology blended with peer support. JMIR Res Protoc 9(1):e15058 PubMed PMC

Gumley A, Bradstreet S, Ainsworth J, Allan S, Alvarez-Jimenez M, Aucott L, Birchwood M, Briggs A, Bucci S, Cotton SM, Engel L, French P, Lederman R, Lewis S, Machin M, MacLennan G, McLeod H, McMeekin N, Mihalopoulos C, Morton E, Norrie J, Schwannauer M, Singh SP, Sundram S, Thompson A, Williams C, Yung AR, Farhall J, Gleeson J (2022) The EMPOWER blended digital intervention for relapse prevention in schizophrenia: a feasibility cluster randomised controlled trial in Scotland and Australia. Lancet Psychiatry 9(6):477–486 PubMed