Risperidone
| 證據等級: L5 | 預測適應症: 6 個 |
目錄
Risperidone: From Schizophrenia to Major Affective Disorder
One-Sentence Summary
Risperidone is a well-established atypical antipsychotic. This evidence pack’s TxGNN model generated six repurposing candidates, but the top three (ultra-rare pediatric genetic syndromes such as familial horizontal gaze palsy) have zero supporting clinical trials or literature and are treated here as low-confidence model artifacts. The strongest evidence-backed candidate is Major Affective Disorder (treatment-resistant depression / bipolar disorder), supported by 38 clinical trials (multiple completed Phase 3 RCTs) and 20 publications, including systematic reviews and meta-analyses.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Schizophrenia (well-established international indication; not present in this evidence pack’s license data) |
| Predicted New Indication | Major Affective Disorder (treatment-resistant depression / bipolar disorder) |
| TxGNN Prediction Score | 99.11% |
| Evidence Level | L1 |
| US Market Status | Not Marketed (per evidence pack) |
| Number of NDAs | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in this evidence pack (flagged as a High-severity data gap, DG002). Based on established pharmacology, risperidone is a second-generation (atypical) antipsychotic with combined dopamine D2 and serotonin 5-HT2A receptor antagonism. Its efficacy in schizophrenia and bipolar mania is well documented internationally.
Schizophrenia and major affective disorder (particularly bipolar disorder and treatment-resistant depression) share overlapping neurobiology, including dopaminergic and serotonergic dysregulation, and both conditions are already managed within the same class of second-generation antipsychotics. Risperidone’s dual receptor antagonism is mechanistically consistent with mood-stabilizing and antidepressant-augmenting effects, which is reflected in its extensive off-label and later on-label use as an adjunct in treatment-resistant depression and as monotherapy/maintenance therapy in bipolar I disorder.
This repurposing direction is further supported by the fact that risperidone augmentation of SSRIs in treatment-resistant depression, and risperidone long-acting injectable (LAI) for bipolar I disorder relapse prevention, have already been evaluated in multiple completed Phase 3 randomized controlled trials — indicating the TxGNN prediction reflects a clinically active and evidence-mature area rather than a purely speculative signal.
Note on lower-ranked candidates: Ranks 1–3 (familial horizontal gaze palsy with progressive scoliosis, Asperger syndrome susceptibility, amelocerebrohypohidrotic syndrome) had no clinical trial or literature evidence in this pack and are not discussed further. Phelan-McDermid syndrome (rank 4, L4, case reports/preclinical only) and trichotillomania (rank 5, case reports/case series only, evidence level pending) are secondary candidates worth monitoring but are not the focus of this report given weaker evidence maturity.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00095134 | Phase 3 | Completed | 630 | Risperidone vs placebo as adjunctive therapy in MDD with sub-optimal response to antidepressants |
| NCT00044681 | Phase 3 | Completed | 258 | Risperidone augmentation of SSRI monotherapy in treatment-resistant depression, incl. maintenance effect |
| NCT00391222 | Phase 3 | Completed | 585 | Risperidone long-acting injectable vs placebo for prevention of mood episodes in Bipolar I disorder |
| NCT00057681 | Phase 3 | Completed | 379 | TEAM study: lithium vs valproate vs risperidone in pediatric mania/bipolar disorder |
| NCT00221403 | Phase 3 | Completed | 46 | Placebo-controlled trial of valproate and risperidone in young children with bipolar disorder |
| NCT00176202 | Phase 3 | Completed | 65 | Risperidone vs divalproex sodium with MRI assessment in pediatric bipolar disorder |
| NCT00277654 | Phase 3 | Completed | 111 | Risperidone monotherapy in bipolar disorder with comorbid anxiety/panic disorder |
| NCT00167479 | Phase 4 | Completed | 60 | Risperidone monotherapy in ambulatory bipolar disorder with anxiety |
| NCT01888107 | Phase 3 | Completed | 347 | Maintenance of clinical response with risperidone LAI in schizophrenia/schizoaffective disorder |
| NCT00107939 | Phase 3 | Completed | 453 | Adjunctive therapy trial in manic episodes of Bipolar I disorder (risperidone among background antipsychotics) |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 17975181 | 2007 | RCT | Annals of Internal Medicine | Randomized trial of risperidone for treatment-refractory major depressive disorder |
| 34986373 | 2022 | Systematic Review / Network Meta-analysis | Journal of Affective Disorders | Compares augmentation agents (incl. risperidone) for treatment-resistant depression |
| 35861202 | 2023 | Systematic Review / Meta-analysis | J Psychopharmacology | Augmentation/combination treatments for early-stage treatment-resistant depression |
| 21154393 | 2010 | Cochrane Systematic Review | Cochrane Database Syst Rev | Second-generation antipsychotics for MDD and dysthymia |
| 35510505 | 2023 | Meta-analysis | Psychological Medicine | Efficacy and safety/tolerability of antipsychotics in adult MDD |
| 24919175 | 2014 | Meta-analysis | Braz J Med Biol Res | Efficacy/tolerability of antidepressant augmentation with atypical antipsychotics in MDD |
| 23554581 | 2013 | Meta-analysis | PLoS Medicine | Adjunctive atypical antipsychotic treatment for MDD: depression, QoL, safety outcomes |
| 34238049 | 2021 | Review | J Psychopharmacology | SGAs + antidepressants vs esketamine vs lithium for combination MDD treatment |
| 25295435 | 2014 | Population-based study | J Clin Psychiatry | Nationwide effectiveness of SGA (incl. risperidone) augmentation for MDD |
| 21189367 | 2011 | Review | Annals of Pharmacotherapy | Risperidone as augmentation treatment for major depressive disorder |
US Market Information
No license/authorization records are available in this evidence pack (total_licenses: 0, market status “Not Marketed”). Risperidone is a globally marketed drug under multiple brand names (e.g., Risperdal) for schizophrenia and bipolar disorder, but no NDA-level data was provided for this jurisdiction.
Safety Considerations
Please refer to the package insert for safety information. This evidence pack’s own safety fields (key warnings, contraindications, drug-drug interactions) contain no data, and a Blocking-severity data gap (DG001: TFDA label warnings/contraindications) has been flagged — this must be resolved before any S1 safety review can proceed.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Major Affective Disorder is supported by L1-level evidence (multiple completed Phase 3 RCTs plus systematic reviews/meta-analyses), and risperidone’s mood-related pharmacology is well characterized internationally. However, this specific evidence pack lacks TFDA-sourced safety labeling (Blocking gap) and MOA documentation (High-severity gap), so a full safety review cannot yet be completed.
To proceed, the following is needed:
- Resolve DG001: obtain TFDA package insert (warnings, contraindications) to complete S1 safety screening
- Resolve DG002: retrieve DrugBank MOA data to formalize the mechanistic rationale
- Obtain drug-drug interaction data (current DDI query returned no results)
- Confirm regulatory/market status and any existing NDA/license records for this jurisdiction
- If pursuing rank 4–5 candidates (Phelan-McDermid syndrome, trichotillomania) in parallel, note these remain at case-report/preclinical evidence level (L4 or lower) and require further clinical validation before advancing
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.