DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for schizophrenia — screening already-approved drugs against its 41-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSchizophrenia maps to a 41-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 schizophrenia 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
Between 1994 and 1997 three new atypical antipsychotics were approved for schizophrenia in the US. In a 2000 study of 21,873 patients in the Veterans Affairs system who had stable three-month prescriptions of any antipsychotic, 25% had their medication switched within one year. Half of those switched patients returned to their original drug, usually within 30 days. Patients on clozapine were least likely to be switched (18%), those on quetiapine most likely (37%). When a switch occurred, 35% went to olanzapine, 14% to quetiapine, and only 1% to clozapine. Quetiapine was the least prescribed of the newer drugs.
A 1998 review notes that methodological problems plague schizophrenia research. A 2000 review states that new generation antipsychotics appear overall more efficacious and better tolerated than older conventional drugs, and may have a broader profile including cognitive effects, possible antiaggressive effects, and potential to reduce comorbid substance abuse. A 2024 review reports that modern treatment still relies on antipsychotics, and that side effects and drug resistance remain significant challenges.
No abstract provides a controlled trial comparing any drug to placebo or to another drug with concrete response rates or survival data. No abstract reports a repurposing attempt. The 2024 review proposes future research directions but does not report new trial results. What is missing is any recent randomised evidence that directly compares these drugs head-to-head for long-term outcomes, any trial that tests a repurposed compound against schizophrenia, and any patient stratification strategy that predicts which drug will work for whom.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
American Journal of Psychiatry · 2002 · 76 citations
From Conventional to Atypical Antipsychotics and Back: Dynamic Processes in the Diffusion of New Medications
AbstractOBJECTIVE: Between 1994 and 1997, the Food and Drug Administration approved three new atypical antipsychotic medications for the treatment of schizophrenia. The authors tracked prescription patterns for these medications, an atypical antipsychotic approved in 1989, and conventional neuroleptics in the Department of Veterans Affairs (VA) to determine how the new drugs have diffused in a national health care system. METHOD: Pharmacy claims data were collected for all patients with a diagnosis of schizophrenia in the VA. Patients who received stable 3-month prescriptions of any antipsychotic medication were followed over fiscal year 2000 to determine how often they were switched to another drug, how much time elapsed before they were switched, the drug to which they were switched, and whether they subsequently switched back to the original drug. RESULTS: Of the 21,873 patients with schizophrenia who had stable 3-month prescriptions of any antipsychotic medication, 5,426 (25%) had their medications switched during the next year. Half of these patients (N=2,708) switched back to their original drug, usually within 30 days. Patients who had stable prescriptions of clozapine were the least likely to be switched (18%), and patients who had stable prescriptions of quetiapine were the most likely to be switched (37%). When medications were switched, 35% of the patients were switched to olanzapine; only 1% were switched to clozapine, and only 14% were switched to quetiapine. CONCLUSIONS: Pharmacotherapy for schizophrenia is a dynamic process. One-quarter of patients with stable antipsychotic drug regimens had their medication changed within 1 year. Quetiapine was the least prescribed of the newer drugs. These results suggest that it is important that all of these medications are included in formularies.
Effect of Aripiprazole on Cognition in the Treatment of Patients with Schizophrenia
AbstractBACKGROUND: The aim of this study was to assess the cognitive effects of aripiprazole in inpatients with schizophrenia. METHODS: This was an investigator-initiated, open label eight-week trial evaluating 56 inpatients with the DSM-IV diagnosis of schizophrenia. Efficacy was assessed weekly using the Positive and Negative Syndrome Scale (PANSS) and tolerability was assessed each week using the Udvalg for Klinske Undersogelser side effect rating scale (UKU). Cognitive function was assessed at baseline, week 4 and week 8. RESULTS: Aripiprazole showed significant improvement in PANSS total score and all subscores between baseline and endpoint visit. The substance was very well tolerated. Patients improved significantly in verbal memory, reaction time and reaction quality/attention from baseline to week eight. Furthermore, mean z-values of individual cognitive domains summarized in a global cognitive index improved significantly from baseline to week eight. DISCUSSION: Our results suggest that aripiprazole provides a valuable treatment option for patients with schizophrenia.
The Journal of Clinical Psychiatry · 2005 · 37 citations
Efficacy of Aripiprazole Against Hostility in Schizophrenia and Schizoaffective Disorder
AbstractOBJECTIVE: The objective was to determine the effects of aripiprazole on hostility. METHOD: A total of 1476 patients diagnosed with DSM-IV schizophrenia or schizoaffective disorder were the subjects in 5 short-term, double-blind studies comparing aripiprazole with placebo; 3 of these studies also included a comparison with haloperidol. The studies were conducted between December 1993 and January 2001. The Positive and Negative Syndrome Scale (PANSS) was the principal outcome measure in these studies. To determine the effect of aripiprazole on hostility, post hoc analyses of the hostility item from the PANSS were conducted for the first 4 weeks of treatment. RESULTS: Aripiprazole was superior to placebo and not significantly different from haloperidol in reducing hostility. CONCLUSION: Aripiprazole is an effective treatment for hostility in patients with schizophrenia or schizoaffective disorder.
Current Medical Research and Opinion · 2015 · 15 citations
A review of aripiprazole long-acting injection
AbstractOBJECTIVES: To review the published literature on aripiprazole once monthly, a second generation antipsychotic (SGA) recently developed as a long-acting injection (LAI), in the form of a suspension of lyophilized aripiprazole reconstituted with an aqueous diluent, for intramuscular administration. METHODS: An electronic database search was conducted using the key words; relevant articles were then hand searched and websites (FDA, EMA, Otsuka, Lundbeck, NIH) reviewed. RESULTS: Efficacy has been demonstrated in preventing relapse in a 52 week study versus placebo, and non-inferiority to oral aripiprazole in a 38 week study, as well as in the treatment of hospitalized adult patients with acutely relapsed schizophrenia. Aripiprazole LAI appears cost-effective versus other SGA-LAIs, with improved health-related quality of life and functioning in a head-to-head study with paliperidone LAI. A 6 month (pre and post), mirror-image switch study demonstrated a reduction in hospitalization and associated costs compared with previous antipsychotic treatment. Safety and tolerability are comparable to oral aripiprazole with no new safety signals. CONCLUSIONS: Experience with oral aripiprazole and the current availability of the long-acting formulation suggest a potential benefit in a variety of clinical scenarios and therefore consideration as a treatment option in the treatment of schizophrenia.
Schizophrenia: a review of current research and thinking
AbstractSchizophrenia is the major mental illness of our time and causes serious disturbances for those with the condition as well as using up significant proportions of scarce health resources. This paper reviews the recent literature on advances in classification, aetiology, epidemiology and treatments. Methodological problems encountered in researching this condition are discussed. Advances in treatments offered for this condition have improved outcomes but whether the patient receives these treatments may depend on what local services are prepared to offer.
Neuropsychiatric Disease and Treatment · 2011 · 10 citations · open access
Comparative study of treatment continuation using second-generation antipsychotics in patients with schizophrenia or schizoaffective disorder
AbstractBACKGROUND: Effectiveness of a drug is a key concept dependent on efficacy, safety, and tolerability. Time to discontinuation of treatment is also representative of effectiveness. We investigated differences in treatment discontinuation among newly started second-generation antipsychotics in the clinical setting. METHODS: Using a retrospective cohort study design, we screened all outpatients (n = 7936) who visited the Shioiri Mental Clinic between July 1, 2008 and June 30, 2010. We identified a cohort of patients (n = 703) diagnosed with schizophrenia or schizoaffective disorder and calculated the time to discontinuation of each second-generation antipsychotic. RESULTS: Of the 703 patients, 149 were newly treated with aripiprazole, 67 with blonanserin, 95 with olanzapine, 36 with quetiapine, 74 with perospirone, and 120 with risperidone. The time to discontinuation for all causes was significantly longer for aripiprazole than for blonanserin, olanzapine, and risperidone. In addition, aripiprazole tended to be continued for longer than quetiapine and perospirone, but these differences were not significant. CONCLUSION: Aripiprazole may be considered the best available option for long-term treatment of patients with schizophrenia or schizoaffective disorder.
Comprehensive disease management for schizophrenia
AbstractThis is a period of rapid development in the pharmacotherapy of schizophrenia. New generation antipsychotic medications appear overall to be more efficacious and better tolerated than the older, conventional antipsychotics. Moreover, these atypical antipsychotics appear to have a broader profile of efficacy which likely includes cognitive effects, possibly antiaggressive effects and the potential to reduce comorbid substance abuse in schizophrenia. Future research efforts are aimed at clarifying the relative profile and potentially broader efficacy of each of these drugs. Future clinical and administrative efforts should focus on availability and access to new treatments, the promulgation of "best practices" and the articulation and implementation of comprehensive care for persons with schizophrenia.
International Journal of Reproductive Research · 2024 · 0 citations · open access
The Past and Present of Schizophrenia
AbstractSchizophrenia is a severe mental disorder and one of the most challenging psychiatric diseases to treat clinically. Modern medical treatment for schizophrenia primarily relies on antipsychotic medications, but issues such as side effects and drug resistance remain significant challenges in treatment. This review systematically examines the etiology, clinical symptoms, treatment methods, and rehabilitation strategies for schizophrenia, explores the advantages and shortcomings of current treatment options, and, based on the latest research findings, proposes future directions for research and clinical 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.
