DeCure's autonomous Psychiatry AI scientist is researching a drug-repurposing hypothesis for psychosis — screening already-approved drugs against its 26-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePsychosis maps to a 26-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 psychosis in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of the cytochrome P4503A4-bromoergocryptine complex — Bromocriptine has a real, experimentally solved structure in complex with this target (PDB 3UA1, 2.15 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 08ydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3UA1 · 2.15 Å · ligand Bromocriptine (08Y). Experimental structure, not a prediction.
What the evidence adds up to
A 2013 systematic review and meta-analysis of 11 trials (1246 participants) found moderate-quality evidence that cognitive behavioural therapy reduced transition to psychosis at 12 months (risk ratio 0.54, 95% CI 0.34 to 0.86; risk difference −0.07, 95% CI −0.14 to −0.01). Very low-quality evidence for omega-3 fatty acids and low to very low-quality evidence for integrated psychotherapy also suggested reductions in transition at 12 months. The authors concluded that evidence for any specific intervention is not conclusive.
A 1994 pilot study of cognitive behaviour therapy for drug-resistant psychosis (diagnosis of schizophrenia or schizo-affective psychosis with unremitting positive symptoms) delivered an average of 16 sessions over six months. The treatment group showed significant reductions in delusional conviction, general symptomatology, and depression scores compared with controls. The authors described the results as promising but noted the need for longer therapy and targeting of social change.
A 2010 randomised double-blind placebo-controlled trial in Hong Kong assigned 178 patients with remitted first episode psychosis (at least one year of prior antipsychotic treatment) to maintenance quetiapine (400 mg/day) or placebo for 12 months. The Kaplan-Meier estimate of relapse risk at 12 months was 41% (95% CI 29% to 53%) for quetiapine and 79% (95% CI 68% to 90%) for placebo (P<0.001). Discontinuation due to adverse or serious adverse events was 18% (16/89) in the quetiapine group versus 8% (7/89) in the placebo group (relative risk 2.29, 95% CI 0.99 to 5.28; P=0.07).
A 2013 study of 90 individuals with non-affective psychosis found that most reported willingness to participate in a psychological therapy trial but preferred not to be randomly allocated. Reasons for preferences were diverse and not associated with socio-demographic or clinical variables. What remains missing are larger, longer trials with adequate statistical power, particularly for psychological interventions; clearer patient stratification to identify who benefits from which treatment; and funding to move beyond pilot studies and small meta-analyses.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
BMJ · 2013 · 435 citations · open access
Early interventions to prevent psychosis: systematic review and meta-analysis
AbstractOBJECTIVE: To determine whether any psychological, pharmacological, or nutritional interventions can prevent or delay transition to psychotic disorders for people at high risk. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Embase, Medline, PreMedline, PsycINFO, and CENTRAL were searched to November 2011 without restriction to publication status. REVIEW METHODS: Randomised trials comparing any psychological, pharmacological, nutritional, or combined intervention with usual services or another treatment. Studies of participants with a formal diagnosis of schizophrenia or bipolar disorder were excluded. Studies were assessed for bias, and relevant limitations were considered in summarising the results. RESULTS: 11 trials including 1246 participants and eight comparisons were included. Median sample size of included trials was 81 (range 51-288). Meta-analyses were performed for transition to psychosis, symptoms of psychosis, depression, and mania; quality of life; weight; and discontinuation of treatment. Evidence of moderate quality showed an effect for cognitive behavioural therapy on reducing transition to psychosis at 12 months (risk ratio 0.54 (95% confidence interval 0.34 to 0.86); risk difference -0.07 (-0.14 to -0.01). Very low quality evidence for omega-3 fatty acids and low to very low quality evidence for integrated psychotherapy also indicated that these interventions were associated with reductions in transition to psychosis at 12 months. CONCLUSIONS: Although evidence of benefits for any specific intervention is not conclusive, these findings suggest that it might be possible to delay or prevent transition to psychosis. Further research should be undertaken to establish conclusively the potential for benefit of psychological interventions in the treatment of people at high risk of psychosis.
American Journal of Psychiatry · 2003 · 407 citations
Comparative Efficacy and Safety of Atypical and Conventional Antipsychotic Drugs in First-Episode Psychosis: A Randomized, Double-Blind Trial of Olanzapine Versus Haloperidol
AbstractOBJECTIVE: Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder. This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large, controlled clinical trial. METHOD: Patients with first-episode psychosis (N=263) were randomly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks. Domains measured included psychopathology, psychosocial variables, neurocognitive functioning, and brain morphology and metabolism. This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase. RESULTS: Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity, which did not differ significantly in last-observation-carried-forward analyses. However, in a mixed-model analysis, olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Asberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating. Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain, compared with the haloperidol-treated patients. Overall, significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study (67% versus 54%). CONCLUSIONS: As expected on the basis of previous studies, both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis. However, olanzapine had several relative advantages in therapeutic response. Although the nature of adverse events differed between the two agents, retention in the study was greater with olanzapine. Retention in treatment is important in this patient population, given their risk of relapse. Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia.
British Journal of Medical Psychology · 1994 · 193 citations
Cognitive behavioural therapy for drug‐resistant psychosis
AbstractA small controlled trial of cognitive behaviour therapy for drug-resistant psychosis is reported. The study was designed as a pilot study for a future larger and longer randomized controlled trial. The therapy was offered to patients with a diagnosis of schizophrenia or schizo-affective psychosis who presented unremitting positive symptoms. An average of 16 sessions were delivered over a six-month period. The results of this pilot study are promising. Rates of engagement in therapy were high. The treatment group also improved significantly on a number of key symptom measures when compared with the controls. These were reductions in delusional conviction, general symptomatology and depression scores. Future studies should offer therapy over a longer period, targeting social as well as symptom change, and considering factors which will enhance maintenance of improvement.
Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial
AbstractOBJECTIVE: To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment. DESIGN: 12 month randomised, double blind, placebo controlled trial. SETTING: Early psychosis outpatient clinics in Hong Kong. PARTICIPANTS: 178 patients with first episode psychosis who had received at least one year of antipsychotic drug treatment between September 2003 and July 2006 and had no positive symptoms of psychosis. INTERVENTIONS: Patients received either maintenance treatment with quetiapine (400 mg/day) or placebo and were followed up for the next 12 months or until a relapse occurred. MAIN OUTCOME MEASURE: Relapse assessed monthly and defined as re-emergence of psychotic symptoms (delusions, conceptual disorganisation, hallucinations, suspiciousness, and unusual thought content) according to predefined thresholds. RESULTS: 178 patients were randomised (89 to quetiapine and 89 to placebo). The Kaplan-Meier estimate of the risk of relapse at 12 months was 41% (95% confidence interval 29% to 53%) for the quetiapine group and 79% (68% to 90%) for the placebo group (P<0.001). Although quetiapine was generally well tolerated, the rate of discontinuation due to adverse or serious adverse events was greater in the quetiapine group (18%; 16/89) than in the placebo group (8%; 7/89) (relative risk 2.29, 95% confidence interval 0.99 to 5.28; chi(2)=3.20, df=1; P=0.07). CONCLUSION: In a group of asymptomatic patients with first episode psychosis and at least one year of previous antipsychotic drug treatment, maintenance treatment with quetiapine compared with placebo resulted in a substantially lower rate of relapse during the following year. Trial registration Clinical trials NCT00334035.
Preferences for psychological therapy in psychosis: trial participation, mode of treatment, and willingness to be randomised
AbstractBACKGROUND: Psychological therapies for psychosis are well evidenced; however, service user preferences for psychological treatment and trial participation have been little researched. AIMS: To investigate preferences for psychological treatments for psychosis and trial participation decisions within a sample of people with experience of psychosis. METHOD: Hypothetical preferences were assessed in 90 individuals diagnosed with non-affective psychosis: (a) willingness/unwillingness to participate in a psychological therapy trial; (b) willingness/unwillingness to be randomised to treatment condition; (c) preference for mode of therapy; (d) reasons for preferences; (e) socio-demographic and clinical characteristics associated with preferences. RESULTS: Most participants reported willingness to participate in a therapy trial and preferred not to be randomly allocated. Reasons for preferences were diverse, and preferences were not associated with socio-demographic or clinical variables. CONCLUSIONS: The need for treatment choice in services for psychosis and further research in this area has been highlighted.
AbstractA 35-year-old man, without any prior history or family history of psychosis, developed psychotic symptoms after starting with low-dose bromocriptine therapy for a macroprolactinoma. Seven days after the initiation of treatment with this medication, the patient suddenly plunged to his death in our hospital without any obvious signs. This case suggests a bromocriptine-induced very serious psychosis in which the patient killed himself without a family history and personal history of psychosis. Therefore, as for all patients with bromocriptine, their mood should be cared after, in case they might commit a suicide. We advise caution in the use of bromocriptine even in patients without a preexisting psychiatric history, and we also recommend that such changes in mental status should be monitored when bromocriptine is prescribed.
Mental Health Clinician · 2021 · 3 citations · open access
Loxapine in patient with clozapine-resistant psychosis
AbstractClozapine is recognized as the drug of choice for treatment-refractory schizophrenia, but use may be limited because of strict monitoring requirements and adverse effects including severe neutropenia, seizures, and myocarditis. Loxapine is a first-generation antipsychotic with similarities to clozapine in both structure and receptor binding. This case describes a 57-year-old male with a history of severe paranoid schizophrenia despite treatment with clozapine and other psychotropic agents, who experienced clinical improvement after a cross titration from clozapine to loxapine. Loxapine may be a reasonable alternative in patients with treatment-refractory schizophrenia who do not tolerate or respond to clozapine.
Journal of the Endocrine Society · 2024 · 2 citations · open access
7173 Cabergoline Induced Psychosis in a Patient with no Previous History of Psychiatric Disorder
AbstractAbstract Disclosure: B. Aryal: None. K. Kim: None. A. Shafi: None. M. Ganesh: None. Introduction: Cabergoline is a dopamine agonist (DA) used to treat prolactinomas. It is well established that DAs may cause psychotic symptoms. However, very few cases report cabergoline-associated psychosis in patients without personal or family history of psychiatric disorders. We report a rare case of cabergoline-induced psychosis in a patient with a prolactinoma without any underlying psychiatric disorder, which was managed with the addition of olanzapine. Case: A 41 year old male with no history of psychiatric disorder was started on cabergoline 0.5mg twice a week for a newly diagnosed prolactinoma. 4 weeks later, he presented to the emergency room for aggressive behavior and confusion for the past 2 weeks. He endorsed visual and auditory hallucinations. Cabergoline was discontinued. During hospitalization, he attempted suicide and required 1:1 observation. He was started on olanzapine per the inpatient psychiatry team. Surgical resection of the prolactinoma was considered given his acute psychosis associated with cabergoline. However, complete resection of the tumor was deemed impossible given encasement of the internal carotid arteries. After discussion with the patient, he underwent re-challenge with cabergoline 0.25mg weekly while on olanzapine under 1:1 observation in the ICU. He was monitored for 2 weeks and eventually discharged home on cabergoline 0.25mg twice a week and olanzapine with improvement in prolactin levels to 4973.7 ng/mL after 4 weeks. He continued to remain free of psychotic symptoms upon follow up as an outpatient. Discussion: Psychosis is a rare side effect of DA mediated via D2/D3 receptors in the mesocortical and mesolimbic pathways. Several cases report psychosis associated with cabergoline in patients with a history of psychiatric disorders. However only one case reports de novo psychosis. Our patient developed severe psychosis while on low-dose cabergoline for 4 weeks. This rare case of de novo cabergoline-associated psychosis re-emphasizes that psychosis may occur regardless of previous history of psychiatric disorder and independent of the dose or duration of cabergoline. Treatment of a prolactinoma in the setting of cabergoline-associated psychosis requires a multidisciplinary approach. Alternative treatment of surgical resection was considered for our patient. However surgical resection was not plausible given difficult surgical anatomy. Therefore he was monitored closely to re-initiate cabergoline while on olanzapine. Several cases report successful use of clozapine, aripiprazole, and quetiapine for patients with psychiatric symptoms while on cabergoline. Patients who are on cabergoline should be closely monitored for any psychotic symptoms. Further studies are warranted to identify patients at risk of developing psychosis while on cabergoline to tailor an individualized approach to therapy and monitoring. Presentation: 6/2/2024
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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