DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for delusional disorder — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDelusional disorder maps to a 3-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
Current lead
No approved-drug candidate for delusional disorder is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
apolipoprotein E (APOE) — APOE is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8AX9 · 1.549 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Only one randomised trial has been conducted for delusional disorder, a 2015 Cochrane review found. That trial compared cognitive behavioural therapy (CBT) to supportive psychotherapy in 17 people, most of whom were already taking medication. A positive effect for CBT was found on the Social Self-Esteem Inventory (mean difference 30.5, confidence interval 7.51 to 53.49), but the evidence was rated very low quality. More people left the supportive psychotherapy group early (6/12 versus 1/6), but the difference was not significant. No randomised trials on medication of any type provided usable data. The review concluded there is insufficient evidence to make evidence-based recommendations for any treatment for delusional disorder.
A 2013 review and case series of six patients treated at a Berlin clinic between 2005 and 2011 reported that delusional disorder has a moderate prognosis when adequately treated, and that noncompliance is often the reason for poor results. Various novel antipsychotics and a combination of medication with psychotherapy produced positive results in those cases. A 2017 case report described a 55-year-old woman whose mental state improved within four months after starting long-acting injectable aripiprazole, after she had rejected oral medication and behavioural disturbances had increased. A 1996 study treated four unselected patients with drug-resistant delusional disorder using eight sessions of cognitive therapy plus monthly booster sessions; all four improved on a global measure of delusional severity and showed a marked reduction in belief conviction, with gains maintained at one-year follow-up. A 2020 case study from the Queensland Fixated Threat Assessment Centre reported that combined pharmacological and psychosocial intervention resulted in stabilisation and improvement in mental state for the case described.
A 2025 review article states that psychotherapy may be the most effective treatment option to date, but it does not provide new trial data. The authors note that both psychodynamic and cognitive-behavioural models appear useful, but offer no controlled evidence. Across all these reports, the total number of patients in controlled or systematic evidence is 17 from a single trial. The remaining evidence consists of case series and single case reports, which cannot establish efficacy. What is still missing is any adequately powered randomised trial for delusional disorder, funding to conduct such trials, and a method to stratify patients by delusional subtype or insight level so that treatment effects, if they exist, can be detected.
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 · 1998 · 183 citations
Efficacy and Safety of Fluvoxamine in Body Dysmorphic Disorder
AbstractBACKGROUND: Body dysmorphic disorder (BDD), a preoccupation with an imagined or slight defect in appearance, has been noted in case reports, retrospective studies, and clinical series to respond to serotonin reuptake inhibitors (SRIs). These data further suggest that the delusional variant of BDD (delusional disorder, somatic type) may also respond to SRIs. However, systematic pharmacologic treatment studies of BDD and its delusional variant are needed. METHOD: Thirty subjects with BDD or its delusional variant (DSM-IV) were prospectively treated in an open-label fashion with fluvoxamine for 16 weeks. Subjects were assessed at regular intervals with the Yale-Brown Obsessive Compulsive Scale Modified for BDD (BDD-YBOCS), the Clinical Global Impressions (CGI) scale, the Hamilton Rating Scale for Depression, the Brown Assessment of Beliefs Scale, and other measures. RESULTS: BDD-YBOCS scores (mean +/- SD) decreased from 31.1 +/- 5.4 at baseline to 16.9 +/- 11.8 at termination (p < .001). Nineteen (63.3%) subjects were rated as responders on the BDD-YBOCS and the CGI (10 [33.3%] were much improved, and 9 [30.0%] were very much improved). Delusional subjects were as likely to respond to fluvoxamine as nondelusional subjects, and delusionality significantly improved. All 5 responders who were delusional at baseline were no longer delusional at study endpoint. The mean dose of fluvoxamine was 238.3 +/- 85.8 mg/day, and mean time to response was 6.1 +/- 3.7 weeks. Fluvoxamine was generally well tolerated. CONCLUSION: These results suggest that fluvoxamine is a safe and effective treatment for BDD, including its delusional disorder variant. Controlled treatment trials are needed to confirm these findings.
Cochrane Database of Systematic Reviews · 2015 · 51 citations · open access
Treatments for delusional disorder
AbstractBACKGROUND: Delusional disorder is commonly considered to be difficult to treat. Antipsychotic medications are frequently used and there is growing interest in a potential role for psychological therapies such as cognitive behavioural therapy (CBT) in the treatment of delusional disorder. OBJECTIVES: To evaluate the effectiveness of medication (antipsychotic medication, antidepressants, mood stabilisers) and psychotherapy, in comparison with placebo in delusional disorder. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Trials Register (28 February 2012). SELECTION CRITERIA: Relevant randomised controlled trials (RCTs) investigating treatments in delusional disorder. DATA COLLECTION AND ANALYSIS: All review authors extracted data independently for the one eligible trial. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis with a fixed-effect model. Where possible, we calculated illustrative comparative risks for primary outcomes. For continuous data, we calculated mean differences (MD), again with a fixed-effect model. We assessed the risk of bias of the included study and used the GRADE approach to rate the quality of the evidence. MAIN RESULTS: Only one randomised trial met our inclusion criteria, despite our initial search yielding 141 citations. This was a small study, with 17 people completing a trial comparing CBT to an attention placebo (supportive psychotherapy) for people with delusional disorder. Most participants were already taking medication and this was continued during the trial. We were not able to include any randomised trials on medications of any type due to poor data reporting, which left us with no usable data for these trials. For the included study, usable data were limited, risk of bias varied and the numbers involved were small, making interpretation of data difficult. In particular there were no data on outcomes such as global state and behaviour, nor any information on possible adverse effects.A positive effect for CBT was found for social self esteem using the Social Self-Esteem Inventory (1 RCT, n = 17, MD 30.5, CI 7.51 to 53.49, very low quality evidence), however this is only a measure of self worth in social situations and may thus not be well correlated to social function. More people left the study early if they were in the supportive psychotherapy group with 6/12 leaving early compared to 1/6 from the CBT group, but the difference was not significant (1 RCT, n = 17, RR 0.17, CI 0.02 to 1.18, moderate quality evidence). For mental state outcomes the results were skewed making interpretation difficult, especially given the small sample. AUTHORS' CONCLUSIONS: Despite international recognition of this disorder in psychiatric classification systems such as ICD-10 and DSM-5, there is a paucity of high quality randomised trials on delusional disorder. There is currently insufficient evidence to make evidence-based recommendations for treatments of any type for people with delusional disorder. The limited evidence that we found is not generalisable to the population of people with delusional disorder. Until further evidence is found, it seems reasonable to offer treatments which have efficacy in other psychotic disorders. Further research is needed in this area and could be enhanced in two ways: firstly, by conducting randomised trials specifically for people with delusional disorder and, secondly, by high quality reporting of results for people with delusional disorder who are often recruited into larger studies for people with a variety of psychoses.
Journal of Clinical Psychopharmacology · 2013 · 22 citations
Comparative Efficacy and Acceptability of Existing Pharmacotherapies for Delusional Disorder
AbstractUNLABELLED: Delusional disorder is an uncommon, yet not rare, psychotic disorder. Because of the distinct lack of high-evidence-level research conducted in this area, no definitive clinical guidelines are available on its treatment. The aim of this article was to summarize the current literature on the pharmacological treatment of delusional disorder in the form of a review, as well as to analyze a series of 6 cases treated at the Department of Psychiatry at "Charité-University Medicine Berlin, Campus Benjamin Franklin" between 2005 and 2011; in each case paying special attention to the relative efficacy and acceptability of the antipsychotics used. REVIEW: A MEDLINE search was conducted to capture all articles on the treatment of delusional disorder published since 2004. After viewing titles and abstracts, these articles were then assessed for relevance. CASE SERIES: The files of 6 cases of delusional disorder treated at the previously mentioned clinic were analyzed and information regarding the type of medication, dose, and duration of treatment as well as adverse effects was extracted and summarized. In line with previous studies, it was found that delusional disorder has a moderate prognosis when adequately treated and that noncompliance is often the reason for poor treatment results. Various novel antipsychotics as well as a combination of medication treatment and psychotherapy produced positive results. Generally, adverse effects were easily managed by a reduction in dose or a switch to another antipsychotic, and it was often necessary to try out a number of antipsychotics before arriving at a satisfactory solution.
Journal of Psychiatric Practice · 2019 · 8 citations
Aripiprazole and Delusional Disorder
AbstractDelusional disorder is a relatively rare psychotic illness characterized by delusions with contents that are theoretically possible but highly unlikely, and an absence of the disorganized thought and negative symptoms characteristic of schizophrenia. The illness is rarely studied systematically and most guidance with regard to the treatment derives from case reports and small case series. Antipsychotic medications are the mainstay of treatment, but it is not clear whether any particular agent is more effective than others. We report the case of a patient with delusional disorder who had failed to respond to risperidone but improved markedly with aripiprazole. Aripiprazole may show promise as a treatment for delusional disorder, possibly as a result of its effects on both dopaminergic and serotonergic receptors.
Cognitive Therapy in the Treatment of Drug-Resistant Delusional Disorder
AbstractFour unselected patients with drug-resistant delusional disorder were individually treated with eight sessions of cognitive therapy plus a booster session every month up to 1 year. All patients improved on a global measure of delusional severity (the GSDS), and showed a marked reduction in belief conviction. Related psychopathology as measured on the Comprehensive Psychopathological Rating Scale (CPRS) also markedly improved and all the gains were maintained at 1-year follow-up. Improved compliance with medication was achieved with half of the patients, and contributed to the improvement gained.
Treating the untreatable? The biopsychosocial treatment of delusional disorder: a case study
AbstractOBJECTIVE: Delusional disorder (DD) is well recognised, but its treatment is controversial. This article presents a case study that highlights the therapeutic benefits associated with assertive biopsychosocial treatment of DD. METHOD: The literature on pharmacological and psychological treatments for DD is briefly reviewed, and a case example from the Queensland Fixated Threat Assessment Centre is given to illustrate a comprehensive biopsychosocial treatment framework. RESULTS: Combined pharmacological and psychosocial intervention resulted in stabilisation and improvement in mental state for the case described. CONCLUSIONS: There is an emergent evidence base for an assertive biopsychosocial approach to treating DD. The case study demonstrates that a range of therapeutic goals is achievable.
American Journal of Psychotherapy · 2025 · 1 citations
Psychotherapy for Delusional Disorder: Theoretical Models and Therapeutic Techniques
AbstractDelusional disorder is a challenging mental health condition given its resistance to conventional treatment with antipsychotic medications. Although patients with delusional disorder often retain good functioning outside of their delusional theme, they often become functionally impaired as delusional ideas become more central in their lives. Psychotherapy represents an important treatment modality for these patients, in that it may be the most effective treatment option to date. Theorists from both the psychodynamic and cognitive-behavioral schools have offered frameworks for understanding and treating delusions and delusional disorder, and both models appear to be useful in working with this difficult-to-treat condition. In this Psychotherapy Tools article, the authors briefly review delusional disorder, assess current research data on its psychodynamic and cognitive-behavioral treatment, and offer practical suggestions for integrating these models from a unified biopsychosocial perspective.
AbstractIntroduction Functioning of patients with delusional disorder may be impaired, particularly if the delusional thinking is chronic rather than episodic. They refuse to characterize their beliefs as false and view opposing views with surprise, if not hostility and disdain, dismissing or ignoring them, and continuing their struggle to find resolution or restitution for the wrongs they have endured or the illnesses from which they suffer. They typically reject and often resent the suggestion that they are mentally compromised. They are a difficult group to engage clinically, often refusing to meet with a clinician about their delusions and/or to take medication. The first-line treatment of delusional disorder is antipsychotic medication rather than other clinical interventions. Patients with the disorder often reject psychiatric treatment, it is particularly important that medication be prescribed in the context of a therapeutic relationship that includes support, education, encouragement of healthier pursuits, and discouragement of damaging, delusion-inspired actions. Methods We describe a case of a 55-year-old woman with a delusional disorder that was diagnosed 4 years before. The supervision of the right take of the treatment was not possible and the intensity of behavioral disturbances increased. Then we started the treatment with long-acting injectable aripiprazole. Results Within the 4 months following the start of treatment, her mental state improved by attenuation of psychotic symptoms. Conclusions Long-acting aripiprazole could be an effective tool for treatment of psychotic symptoms in patients with no insight and difficulties to check the proper treatment take. Disclosure of interest The authors have not supplied their declaration of competing interest.
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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