Major Depressive Disorder (MDD) is a leading cause of disability and there is a paucity of tools to personalize and manage treatments. A cluster-randomized, patient-and-rater-blinded, clinician-partially-blinded study was conducted to assess the effectiveness and safety of the Aifred Clinical Decision Support System (CDSS) facilitating algorithm-guided care and predicting medication remission probabilities using clinical data. Clinicians were randomized to the Active (CDSS access) or Active-Control group (questionnaires and guidelines access). Primary outcome was remission (<11 points on the Montgomery Asberg Depression Rating Scale (MADRS) at study exit). Of 74 eligible patients, 61 (42 Active, 19 Active-Control) completed at least two MADRS (analysis set). Remission was higher in the Active group (n = 12/42 (28.6%)) compared to Active-Control (0/19 (0%)) (p = 0.01, Fisher exact test). No adverse events were linked to the CDSS. This is the first effective and safe longitudinal use of an artificial intelligence-powered CDSS to improve MDD outcomes.

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DB, KW, MR, GG, KP, JM, RF, CA, SI, CP, AA, and SQ were employees and/or shareholders of Aifred Health Inc. and supported this research in the context of their work for Aifred Health. JFK, SP are members of Aifred Health's scientific advisory board. SP has received honoraria from Aifred Health. DB, SG, EEMM, and SR receive a salary award from the Fonds de recherche du Quebec Sante (FRQS). EEMM is a Canada Research Chair (Tier 1) in Statistical Methods for Precision Medicine. BWD has received research support from Boehringer Ingelheim, Compass Pathways, Intra-Cellular Therapies, NIMH, Otsuka, Usona Institute, and has served as a consultant for Biohaven, Cerebral Therapeutics, Myriad Neuroscience, and Otsuka. SR receives grant funding from Mitacs (for a graduate student), is on a steering committee for Abbvie, and owns shares of Aifred Health. SK reports grants from the Labatt Family Innovation Fund in Brain Health (Department of Psychiatry, University of Toronto), the Max Bell Foundation, the Canadian Centre on Substance Use and Addiction, the Centre for Addiction and Mental Health Discovery Fund, the Ontario Ministry of Health and Long-Term Care (MOHLTC), the Canadian Institutes of Health Research (CIHR), and the International OCF Foundation (IOCDF). SK received honorarium for consultation from EmpowerPharm. JFK has been provided options in Aifred Health. HCM has received honoraria, sponsorship, or grants for his participation as a consultant, advisory committee member, and/or as a speaker at educational events for AbbVie, HLS Therapeutics Inc., Janssen, Lundbeck, Otsuka, Newron, Sunovion and Teva. He has received grants and/or research support from the MGH Hospital Foundation, SyneuRX and Aifred Health. SJ, TF, and YB recieved honoraria from Aifred Health for working on this paper. All other authors report no relevant conflicts.

NCT04655924

Funding was provided by Aifred Health; MEDTEQ FSISSS; Bell Lets Talk and Brain Canada; Investissement Quebec; the Quebec Ministry of Economy and Innovation; the Mindstrong Foundation at the Jewish General Hospital; and the McGill Industry and Partnership grant. The study was co-designed and supervised by HM and Aifred Health. No other funder had a role in the development or reporting of this research.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was conducted in accordance with all relevant ethical regulations including the Declaration of Helsinki and the Tri-Council Policy Statement. The research ethics board of the Douglas Research Center gave ethical approval for this work and it was subsequently approved by central and local ethics review boards for each site. The study was conducted in accordance with Good Clinical Practice. Written informed consent was obtained from all study participants.

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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Data requests will be considered by the study sponsor for non-commercial applications, on the condition that this publication is referenced in publications using the dataset. Requests for data access should be directed to david.benrimoh@mcgill.ca and will be responded to within 30 days. Data requested will be transferred in a de-identified format using patient ID numbers.