DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for depressive disorder — screening already-approved drugs against its 45-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDepressive disorder maps to a 45-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Structures already discussed alongside depressive disorder in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Human serum albumin — Aripiprazole has a real, experimentally solved structure in complex with this target (PDB 6A7P, 2.28 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet 9scdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6A7P · 2.28 Å · ligand Aripiprazole (9SC). Experimental structure, not a prediction.
What the evidence adds up to
For more than a decade, the stated goal of major depressive disorder treatment has been achieving remission, defined as complete resolution of symptoms and return to previous functioning. A 2009 review notes that measurement-based care and consultation of clinical guidelines may help clinicians improve remission rates, but provides no numerical data on how often remission is actually achieved. A 2021 review states that selecting the best antidepressant for each individual remains largely a matter of informed guesswork, and that many patients do not respond to treatment or experience side effects that cause interruption.
A 2023 bioinformatic analysis of two microarray databases identified 1181 differentially expressed genes in major depressive disorder. The most enriched pathway terms included hematopoietic cell lineage, and 20 hub genes were identified, including KRAS, CD86, RPL9, RPL3, and RPL18. The authors propose these as potential genetic diagnostic markers and therapeutic targets, but no clinical validation or patient data are provided. No blood-based biomarkers for major depressive disorder are currently available.
The REVAMP study, described in a 2025 design report, is a multisite clinical trial evaluating whether adding psychotherapy to a medication algorithm improves outcomes in chronically depressed patients who fail to respond or respond incompletely to an initial antidepressant trial. Patients receive 12 weeks of algorithm-guided monotherapy; those with no response at 8 weeks or less than full response at 12 weeks are randomised 2:2:1 to 16 sessions of Cognitive Behavioral Analysis System of Psychotherapy (CBASP), Supportive Psychotherapy, or medication alone. This is the first prospective randomised controlled trial testing psychotherapy as augmentation for incomplete responders with chronic depression. The report presents only rationale and design; no efficacy results are given. What remains missing is any completed trial showing that gene expression profiling can guide drug selection, any validated blood biomarker for major depressive disorder, and the actual outcome data from the REVAMP trial — including whether adding psychotherapy to medication improves remission rates in this difficult-to-treat population.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Primary Care Companion For CNS Disorders · 2006 · 60 citations · open access
An Open-Label, Rater-Blinded, Augmentation Study of Aripiprazole in Treatment-Resistant Depression
AbstractBACKGROUND: About 30% to 46% of patients with major depressive disorder (MDD) fail to fully respond to initial antidepressants. While treatment-resistant depression commonly refers to nonresponse or partial response to at least 2 adequate trials with antidepressants from different classes, due to variability in terminology, a staging system based on prior treatment response has been suggested. Aripiprazole is a novel atypical antipsychotic with partial agonism at dopamine D(2) and serotonin 5-HT(1A) receptors and antagonism at the 5-HT(2) receptors. The present study evaluated whether augmentation with aripiprazole would be beneficial and tolerable in patients with treatment-resistant MDD who had failed 1 or more trials of antidepressants. METHOD: In an open-label, rater-blinded study conducted from March 2003 through December 2003, 10 patients with DSM-IV MDD without psychotic features who had failed to respond to an adequate trial of at least 1 antidepressant were prescribed aripiprazole (10-30 mg/day) for 6 weeks. The dose of preexisting antidepressants remained unchanged. Treatment response was defined as a 50% or greater reduction in score on the Hamilton Rating Scale for Depression (HAM-D) from baseline to end of treatment. Secondary efficacy measures included scores on the Clinical Global Impressions-Improvement (CGI-I) and -Severity (CGI-S) scales. RESULTS: Eight of 10 patients had failed 2 or more antidepressant trials. The mean daily dose of aripiprazole was 13.21 mg. Intent-to-treat analysis showed that mean ± SD HAM-D scores reduced significantly from baseline (23.0 ± 8.1) to end of treatment (8.1 ± 6.0) (p < .001). There was a significant reduction in CGI-I (p < .05) and a trend toward decrease in CGI-S (p = .06) score. Seventy percent of the subjects were responders and 30% achieved remission. Common adverse effects were akathisia (20%), nausea (20%), and restlessness (20%). CONCLUSIONS: The study indicates the potential utility of aripiprazole as an augmenting agent in treatment-resistant depression, particularly in those who had failed 2 or more antidepressant trials. Adequately powered, randomized controlled trials are necessary to evaluate the role of aripiprazole in treatment-resistant depression.
The Journal of Clinical Psychiatry · 2009 · 27 citations
Treating Depression to Full Remission
AbstractFor more than a decade, the goal of major depressive disorder treatment has been achieving and sustaining remission, which involves complete resolution of depressive symptoms and a return to previous levels of mental and physical functioning. By implementing measurement-based care, clinicians may better assess patient response to treatment. Several depression rating scales are available for use in clinical practice. Consulting clinical guidelines and findings of clinical trials that include remission as a primary outcome measure may also help clinicians to improve remission rates among their patients.
REVAMP - Research Evaluating the Value of Augmenting Medication with Psychotherapy: Rationale and Design
AbstractUNLABELLED: This report presents the rationale, design, and baseline sample characteristics for the REVAMP study. This project is a multisite clinical trial designed to evaluate the efficacy of augmenting state-of-the-art pharmacotherapy with psychotherapy in chronically depressed patients who fail to respond or respond incompletely to an initial trial of antidepressant medication. BACKGROUND: Chronic forms of major depression disorder (cMDD) are longitudinally continuous forms of major depressive disorder (MDD), and may account for a significant portion of the societal burden of disease associated with M D D. Antidepressant medications and depression-focused psychotherapies have been shown to be effective for cMDD, though the majority fail to achieve remission following an acute course of treatment. There is a pressing need to evaluate whether the outcomes obtained from a well implemented medication algorithm combined with depression-focused psychotherapy can significantly enhance outcomes for cMDD. RATIONALE: Although there is evidence for the effectiveness of depression-focused psychotherapy for the treatment of cMDD, this is the first prospective, randomized, controlled trial investigating psychotherapy as an augmentation strategy for patients with cMDD incompletely responsive to a trial of antidepressant medication. SPECIFIC AIMS: The REVAMP study has three specific aims: first, to compare the efficacy of adding psychotherapy to a medication change versus changing medication alone in chronic depressives with partial response or nonresponse to an initial trial of antidepressant medication; second, to test efficacy of the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) as an augmentation strategy by comparing it to Supportive Psychotherapy (SP); and third, to test a hypothesized mechanism of therapeutic action of CBASP by examining whether patients receiving CBASP exhibit significantly greater improvements in social problem solving than patients receiving adjunctive SP or continued medication alone. As a subsidiary aim, the study also compares the effects of the three randomized treatments on psychosocial outcomes. DESIGN: The study involves two 12-week phases. During Phase 1, patients with cMDD receive antidepressant monotherapy selected according to an algorithm that takes into account their prior treatment history. Their pattern of response is evaluated, those with no response at 8 weeks or less than a full response at 12 weeks advance to Phase 2. At the beginning of Phase 2, patients who did not respond to the initial antidepressant monotherapy during Phase 1 are switched to the next medication in the pharmacotherapy algorithm and randomly assigned in a 2:2:1 ratio to one of three treatment cells: 16 sessions of either CBASP (40% of randomizations) or SP (40%) added to pharmacotherapy, or medication alone (20%) with no added psychotherapy. Similarly, patients achieving a partial response during Phase 1 have their initial medication augmented with a second antidepressant agent during Phase 2 and are randomly assigned to either CBASP, SP, or medication alone. Patients who achieve remission during Phase 1 are not randomized to Phase 2, but rather are monitored monthly for an additional 12 weeks. COMMENT: Recent sequential treatment studies have provided state-of-the-art knowledge about the need for multiple steps in order to achieve remission. The current study, therefore, provides an important next step in understanding the role of depression-focused psychotherapy in a treatment algorithm so essential in the management of difficult-to-treat depression such as chronic forms of major depression.
International Clinical Psychopharmacology · 2014 · 6 citations
Psychomotor symptoms and treatment outcomes of ziprasidone monotherapy in patients with major depressive disorder
AbstractThe aim of this study was to evaluate efficacy of ziprasidone monotherapy for major depressive disorder (MDD) with and without psychomotor symptoms. In accordance with the sequential parallel comparison design, 106 MDD patients (age 44.0±10.7 years; female, 43.4%) were recruited and a post-hoc analysis was carried out on 12-week double-blind treatment with either ziprasidone (40-160 mg/day) or placebo, divided into two phases of 6 weeks each to the assigned treatment sequences, drug/drug, placebo/placebo, and placebo/drug. Psychomotor symptoms were evaluated on the basis of the Mini-International Neuropsychiatric Interview at baseline. Efficacy assessments, on the basis of the 17-item Hamilton Depression Rating Scale (HDRS-17) and the Quick Inventory of Depressive Symptomatology Scale, Self-Rated (QIDS-SR), were performed every week throughout the trial. In phase I, ziprasidone monotherapy produced significant improvement in patients with psychomotor symptoms compared with placebo on the basis of HDRS-17 (F=5.95, P=0.017) and QIDS-SR (F=5.26, P=0.025) scores, whereas no significant changes were found in HDRS-17 (F=2.32, P=0.15) and QIDS-SR (F=3.70, P=0.074) scores in patients without psychomotor symptoms. In phase II, ziprasidone monotherapy produced no significant differences compared with placebo. In the pooled analysis, ziprasidone monotherapy showed significance according to QIDS-SR (Z=2.00, P=0.046) and a trend toward statistical significance according to the HDRS-17 (Z=1.66, P=0.10) in patients with psychomotor symptoms. Ziprasidone monotherapy may produce significant improvement compared with placebo in MDD patients with psychomotor symptoms.
Brain Behavior & Immunity - Health · 2021 · 4 citations · open access
Can (immune and other) gene expression help us to treat depression?
AbstractIt is becoming clearer that it might be a combination of different biological processes such as genetic, environmental, and psychological factors, together with immune system, stress response, brain neuroplasticity and the regulation of neurotransmitters, that leads to the development of major depressive disorder (MDD). A growing number of studies have tried to investigate the underlying mechanisms of MDD by analysing the expression levels of genes (mRNA) involved in such biological processes. In this review, I have highlighted a possible key role that gene expression might play in the treatment of MDD. This is critical because many patients do not respond to antidepressant treatment or can experience side effects, causing treatment to be interrupted. Unfortunately, selecting the best antidepressant for each individual is still largely a matter of making an informed guess.
Psychiatry and Clinical Psychopharmacology · 2023 · 3 citations · open access
Identification and Analyses of Crucial Genes Associated with Pathogenesis of Major Depressive Disorder
AbstractBackground: Major depressive disorder is a debilitating mental condition that causes severe disability leading to a high fatality rate. No valid blood-based biomarkers for major depressive disorder are currently available. The purpose of this research is to investigate gene biomarkers and pathways that may be linked to major depressive disorder pathogenesis. Methods: Two microarray databases were retrieved from Gene Expression Omnibus for screening of candidate differentially expressed genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed followed by protein-protein interaction network of differentially expressed genes. Results: About 1181 differentially expressed genes were identified from the microarray databases. Gene Ontology analyses indicated that these differentially expressed genes were significantly enriched in mRNA splicing via spliceosome, neutrophil degranulation, peptide antigen assembly with MHC class II protein complex, and immunoglobulin production-mediated immune response. The most enriched Kyoto Encyclopedia of Genes and Genomes pathway terms of the 10 significant were Hematopoietic cell lineage. About 20 genes were identified as hub genes after pathway analyses, mostly involved in colorectal cancer and the composition of ribosomes and protein processing, including KRAS, CD86, RPL9, RPL3, and RPL18. Conclusion: New candidate genes have been identified using bioinformatic approaches that suggest their involvement in the pathogenesis of major depressive disorder and serve as potential genetic diagnostic markers as well as new therapeutic targets.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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