Risperidone
| 證據等級: L5 | 預測適應症: 6 個 |
目錄
Risperidone: From Psychotic Disorders to Major Affective Disorder
One-Sentence Summary
Risperidone is a widely known atypical antipsychotic (D2/5-HT2A antagonist) generally used for schizophrenia and bipolar disorder — no Taiwan/NZ regulatory indication text is on file for this drug in this evidence pack. Among 6 TxGNN-predicted indications, Major Affective Disorder (depression/bipolar spectrum) is by far the strongest candidate, supported by 37 clinical trials (including multiple completed Phase 3 RCTs directly testing risperidone) and 20 publications, several of which are systematic reviews/meta-analyses of risperidone augmentation in depression and bipolar disorder. The remaining 5 predicted indications range from weakly indirect (Asperger susceptibility, Phelan-McDermid syndrome, trichotillomania) to mechanistically implausible (gaze palsy with scoliosis, amelocerebrohypohidrotic syndrome) and are not pursued as the headline finding.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available on file (see note below) |
| Predicted New Indication | Major Affective Disorder |
| TxGNN Prediction Score | 99.11% |
| Evidence Level | L1 |
| New Zealand Market Status | ✗ Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Note on Original Indication: No Taiwan/NZ license or indication text exists in the regulatory data provided (market_status: 未上市, 0 licenses, original_indications: []). The original-indication context above (schizophrenia/bipolar disorder) reflects general public drug knowledge, not data extracted from this evidence pack, and should be confirmed against a formal source before use in any regulatory submission.
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in this evidence pack (original_moa: [Data Gap]). Based on generally known pharmacology, risperidone is a potent dopamine D2 and serotonin 5-HT2A receptor antagonist ("atypical antipsychotic"), a receptor profile long associated with mood-stabilizing and antidepressant-augmenting effects in addition to its antipsychotic action.
Major affective disorder (encompassing bipolar disorder and treatment-resistant major depressive disorder, MDD) sits directly adjacent to risperidone's core pharmacological class. Risperidone is already an established treatment for bipolar mania in several jurisdictions, and its use as an adjunct to SSRIs/SNRIs in treatment-resistant depression is supported by multiple completed Phase 3 randomized controlled trials in this evidence pack (e.g., NCT00095134, NCT00044681) plus several systematic reviews and meta-analyses of second-generation antipsychotic augmentation in MDD. This is a mechanistically direct and clinically well-precedented link, not merely a computational artifact.
For context, the top-ranked TxGNN prediction overall ("gaze palsy, familial horizontal, with progressive scoliosis," score 99.76%) is explicitly flagged in this evidence pack's own rationale as having "no known mechanistic or clinical link" to risperidone's receptor pharmacology — a rare ROBO3-mutation brainstem axon-guidance disorder — and returned zero trials and zero literature. "Amelocerebrohypohidrotic syndrome" (rank 3) is similarly a rare ectodermal dysplasia with no plausible pharmacological connection and no evidence. "Asperger syndrome, susceptibility to" (rank 2) and "Phelan-McDermid syndrome" (rank 4) have indirect support only — risperidone is used off-label for irritability/behavioral symptoms in autism-spectrum populations broadly, but no disease-specific trials or strong literature exist for either entity in this pack. "Trichotillomania" (rank 5) has 10 case-report/case-series-level publications (L3) showing SSRI-augmentation benefit but no RCTs. None of these four match the strength of evidence behind Major Affective Disorder, so this report focuses on that indication.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00095134 | Phase 3 | Completed | 630 | Adjunctive risperidone vs. placebo in MDD with sub-optimal response to standard antidepressant therapy |
| NCT00044681 | Phase 3 | Completed | 258 | Risperidone augmentation of SSRI monotherapy in young and older adults with unipolar treatment-resistant depression, including long-term maintenance effect |
| NCT00391222 | Phase 3 | Completed | 585 | Risperidone long-acting injectable monotherapy vs. placebo for prevention of mood episodes in bipolar I disorder |
| NCT00277654 | Phase 3 | Completed | 111 | Risperidone monotherapy vs. placebo in ambulatory bipolar disorder with comorbid panic disorder/generalized anxiety disorder |
| NCT00167479 | Phase 4 | Completed | 60 | Risperidone monotherapy efficacy/tolerability in bipolar disorder with moderately severe anxiety |
| NCT00107939 | Phase 3 | Completed | 453 | Adjunctive therapy trial in bipolar mania where risperidone was one of five background atypical antipsychotics studied |
| NCT00057681 | Phase 3 | Completed | 379 | TEAM study: lithium vs. valproate vs. risperidone in children/adolescents with bipolar disorder or mania symptoms |
| NCT00571688 | Phase 4 | Completed | 50 | Risperidone Consta (LAI) vs. treatment-as-usual for reducing relapse/rehospitalization in bipolar disorder |
| NCT01282632 | Phase 1/2 | Completed | 42 | Pilot trial of risperidone vs. olanzapine as add-on to a failed SSRI in treatment-resistant depression |
| NCT00203723 | Phase 4 | Terminated | 45 | Combined ECT + risperidone vs. ECT alone for treatment-resistant depression |
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 |
| 25295435 | 2014 | Population-based study | Journal of Clinical Psychiatry | Nationwide effectiveness study of aripiprazole/olanzapine/quetiapine/risperidone augmentation for MDD |
| 21154393 | 2010 | Cochrane systematic review | Cochrane Database of Systematic Reviews | Second-generation antipsychotics (incl. risperidone) for major depressive disorder and dysthymia |
| 34986373 | 2022 | Systematic review + network meta-analysis | Journal of Affective Disorders | Compares efficacy/discontinuation of augmentation agents, including risperidone, in treatment-resistant depression |
| 35861202 | 2023 | Systematic review + meta-analysis | Journal of Psychopharmacology | Augmentation/combination treatments for early-stage treatment-resistant depression |
| 35510505 | 2023 | Systematic review + meta-analysis | Psychological Medicine | Efficacy and safety/tolerability of antipsychotics (monotherapy and adjunctive) in adult MDD |
| 24919175 | 2014 | Meta-analysis | Brazilian Journal of Medical and Biological Research | Efficacy/tolerability of antidepressant augmentation with atypical antipsychotics (17 trials, 3807 patients) in MDD |
| 23554581 | 2013 | Meta-analysis | PLoS Medicine | Adjunctive atypical antipsychotic treatment for MDD: depression, quality-of-life, and safety outcomes |
| 21189367 | 2011 | Review | The Annals of Pharmacotherapy | Efficacy and safety review of risperidone augmentation specifically for MDD |
| 20486830 | 2010 | Review | Expert Opinion on Pharmacotherapy | Risperidone long-acting injection as monotherapy and adjunctive therapy in maintenance treatment of bipolar I disorder |
New Zealand Market Information
Risperidone is currently not marketed in New Zealand under this evidence pack's regulatory data source, with 0 authorizations on file. No product license records are available to summarize.
Safety Considerations
Please refer to the package insert for safety information. (Key warnings, contraindications, and drug-interaction data are all marked as data gaps in this evidence pack; the TFDA package insert warnings/contraindications item is flagged as a Blocking data gap — DG001 — that must be resolved before a formal safety assessment (S1) can proceed.)
Conclusion and Next Steps
Decision: Hold
Rationale: Efficacy evidence for risperidone in major affective disorder is strong (L1 — multiple completed Phase 3 RCTs plus several systematic reviews/meta-analyses), but the Blocking data gap on TFDA package insert warnings/contraindications (DG001) means a formal safety evaluation cannot yet be completed, and the drug has no current NZ market presence in this dataset.
To proceed, the following is needed:
- TFDA/regulatory package insert warnings and contraindications (Blocking gap, DG001)
- Confirmed original indication and MOA data from DrugBank or an authoritative label (DG002)
- Formal DDI dataset (current query returned
not_found) - Clarification of NZ market and licensing status, since no product is currently on file
- Disease-specific evaluation of the four indirect/low-evidence predictions (Asperger susceptibility, Phelan-McDermid syndrome, trichotillomania) if pursued as secondary candidates
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.