DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for major depressive disorder — screening already-approved drugs against its 46-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMajor depressive disorder maps to a 46-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
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Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Structures already discussed alongside major 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
A 2021 review notes that many patients with major depressive disorder do not respond to antidepressant treatment or experience side effects that cause treatment to be interrupted, and that selecting the best antidepressant for each individual remains largely a matter of informed guesswork. The review suggests that analysing gene expression levels might play a key role in treatment, but does not report any concrete results from such an approach. A 2023 bioinformatic study identified 1181 differentially expressed genes from two microarray databases, with enrichment in mRNA splicing, neutrophil degranulation, and immune-related processes. Twenty hub genes were identified, including KRAS, CD86, RPL9, RPL3, and RPL18, but the study offers no clinical data on whether these genes can serve as diagnostic markers or therapeutic targets in patients.
The REVAMP study, described in a 2025 design paper, is a multisite clinical trial evaluating whether adding psychotherapy to a medication algorithm improves outcomes in chronically depressed patients who failed to respond or responded incompletely to an initial antidepressant trial. The study randomises partial or non-responders in a 2:2:1 ratio to either Cognitive Behavioral Analysis System of Psychotherapy (CBASP) plus medication, Supportive Psychotherapy (SP) plus medication, or medication alone. No results are reported in this design paper; the study is still in progress. A 1980 selective overview of behaviour therapy, cognitive-behaviour therapy, and cognitive therapy for depression reviews single-case studies, comparative projects with volunteers, and clinical trials with outpatients, but provides no numerical outcomes or comparative efficacy data.
A 2004 abstract on acupuncture treatment in Europe states that the mechanism of depressive disorder involves biological processes and signalling pathways related to inflammation and lipid metabolism, and that key biomarkers identified by proteomics are important for revealing the biological basis of the disorder. No patient data, response rates, or survival figures are given. Across all these abstracts, no trial reports a definitive improvement in remission rates, no biomarker has been validated in a clinical setting, and no drug is mentioned by name. What is still missing are completed randomised trials that report outcomes for psychotherapy augmentation, validated blood-based biomarkers for diagnosis or treatment selection, and any prospective data linking the identified gene expression changes to patient response.
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 Journal of Clinical Psychiatry · 2005 · 103 citations
Aripiprazole Augmentation of Antidepressants for the Treatment of Partially Responding and Nonresponding Patients With Major Depressive Disorder
AbstractOBJECTIVE: To determine the efficacy and tolerability of aripiprazole, a dopamine D2 and 5-HT1A receptor partial agonist, as augmentation of antidepressant treatment of partially responding and nonresponding patients with major depressive disorder. METHOD: Fifteen patients with major depressive disorder (diagnosed with a site-generated form described in the text) and an incomplete response or no response to > or = 8 weeks of antidepressant (selective serotonin reuptake inhibitor, venlafaxine, or bupropion) monotherapy were treated with aripiprazole augmentation in an 8-week, open-label study. Data were gathered from July 2003 to March 2004. RESULTS: The mean duration of antidepressant monotherapy at baseline was 43.1 weeks. At baseline, mean Clinical Global Impressions-Severity of Illness scale and Hamilton Rating Scale for Depression (HAM-D) scores were 4.3 and 18.9, respectively. After initiation of aripiprazole augmentation, 6 of 15 patients achieved remission (HAM-D score < or = 7) at week 1, and 9 of 15 patients remitted by week 2. All 8 completers achieved remission by study endpoint. Akathisia in 2 patients who withdrew prematurely prompted a reduction in the starting dose of aripiprazole from 10 mg/day to 2.5 mg/day, resulting in a 50% reduction in attrition due to akathisia (2/7 withdrew due to akathisia with the 10-mg starting dose, 1/8 withdrew due to akathisia with the 2.5-mg starting dose). Discontinuation rates after 4 weeks of treatment were lower for the 2.5-mg starting dose (1/8 patients) than for the 10-mg starting dose (3/7 patients). Overall discontinuation rates at endpoint were lower for the 2.5-mg dose (3/8 patients) than the 10-mg dose (4/7 patients). Response to aripiprazole augmentation did not appear to be related to the antidepressant used at study initiation. CONCLUSION: Aripiprazole is an effective augmentation strategy for improving therapeutic response in patients with treatment-resistant major depressive disorder when administered in combination with standard antidepressant therapy. Based on this clinical signal, a double-blind, placebo-controlled trial is warranted.
American Journal of Psychiatry · 1980 · 43 citations
The efficacy of cognitive and behavior therapies for depression
AbstractThis selective overview looks at the effectiveness of behavior therapy, cognitive-behavior therapy, and cognitive therapy for depressive disorders. The outcome of single-case studies, comparative treatment projects with volunteers, and clinical trials with outpatients are used to evaluate the current state of the art and to suggest future research directions.
Journal of Clinical Psychopharmacology · 2011 · 27 citations
Adjunctive Low-Dose Aripiprazole With Standard-Dose Sertraline in Treating Fresh Major Depressive Disorder
AbstractOBJECTIVES: Second-generation (atypical) antipsychotics have been accepted as an adjunctive medication in patients with treatment-resistant depression. This clinical trial evaluated the efficacy and safety of low-dose aripiprazole combined with regular-dose sertraline for acute major depressive episode in non-treatment-resistant depression outpatients. METHODS: The study patients were 18- to 65-year-old outpatients fulfilling the criteria of major depressive disorder in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The patients were randomly assigned to 2 groups: one with sertraline 50 mg/d plus aripiprazole 2.5 mg/d and the other with sertraline 50 mg/d plus placebo. After baseline assessment, the subjects were followed up at weeks 1, 2, 4, 6, and 10. The primary efficacy was the score change of the 17-item Hamilton Rating Scale for Depression (HAM-D17), and secondary efficacies were the score of Short Form 36 Health Survey, Clinical Global Impressions-Severity, and Clinical Global Impressions-Improvement. This study also monitored patients for movement disorder using Simpson-Angus Scale and Barnes Akathisia Rating Scale. RESULTS: Twenty-one patients were assigned to the aripiprazole group and 20 to the placebo group. Because of high dropout rate, only data of the first 4 weeks were analyzed. The aripiprazole group exhibited significantly better efficacy than the placebo group in mean total score changes of HAM-D17 from the baseline to weeks 1, 2, and 4. The item "work and social activities" of HAM-D17 showed significant improvement at week 2, and the item "somatic symptoms (GI)" showed significant improvement at week 1. The aripiprazole group exhibited significant improvement in "social role function" section of Short Form 36 Health Survey at week 4. The mean total score of Clinical Global Impressions-Severity showed marginally significant improvement in the aripiprazole group. In Clinical Global Impressions-Improvement, patients in the aripiprazole group had scores of less than 2 (much improved) at weeks 2 and 4, and the scores of the placebo group were greater than 2.4 (indicating a minimal improvement). No patients had akathisia during the trial period. CONCLUSIONS: The primitive data showed that adjunctive low-dose aripiprazole could augment the efficacy of regular-dose sertraline in fresh major depressive disorder. A large-scale study is needed to confirm this finding.
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.
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.
Current State of Acupuncture Treatment in Europe( 鍼灸とリハビリテーション)(第41回 日本リハビリテーション学術集会)
AbstractThe mechanism of depressive disorder mainly involves biological processes and signaling pathways related to inflammation and lipid metabolism. The key biomarkers identified by proteomics and the signaling pathways involved are highly important for revealing the biological basis of depressive disorder and guiding its clinical diagnosis and treatment.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
