Haloperidol

證據等級: L5

預測適應症: 10 個

Haloperidol: From Psychotic Disorders to Manic Episodes in Bipolar Affective Disorder

One-Sentence Summary

Haloperidol is a first-generation (typical) antipsychotic, pharmacologically established as a potent D2 dopamine receptor antagonist used for schizophrenia and acute psychosis. Among the 10 TxGNN-predicted candidates in this evidence pack, only one — Manic Bipolar Affective Disorder — is backed by substantive evidence, with 9 clinical trials and 20 publications currently on file; the other 9 higher-scoring candidates (e.g., congenital glycosylation disorders, retinal dystrophy, myopia subtypes) have zero supporting trials/literature and are flagged in the evidence pack itself as algorithmic noise with no plausible mechanistic link.

Note on candidate selection: This report focuses on the mania indication (TxGNN rank 10) rather than the top-scoring rank 1 candidate, because rank 1–9 show no mechanistic rationale and no corroborating evidence (0 trials / 0 literature each), while rank 10 is the only candidate meeting a real evidence bar.

Quick Overview

Item	Content
Original Indication	Schizophrenia and other psychotic disorders (general pharmacological consensus; no TFDA-approved label text currently on file — data gap)
Predicted New Indication	Manic Bipolar Affective Disorder
TxGNN Prediction Score	99.83%
Evidence Level	L1
US Market Status	Not Marketed
Number of NDAs	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

The formal original_moa field is currently a data gap (DG002, High severity). Based on known pharmacology, however, Haloperidol is a butyrophenone-class typical antipsychotic and a potent dopamine D2 receptor antagonist. Its efficacy in psychotic disorders comes from blocking mesolimbic dopamine transmission.

The repurposing rationale supplied with this candidate explains the mechanistic link directly: by blocking D2 receptors in the limbic system, Haloperidol reduces the excessive arousal, grandiosity, and psychomotor agitation characteristic of manic episodes. This is not a novel repurposing hypothesis in the scientific sense — Haloperidol has long been used clinically as an antimanic agent and appears repeatedly as the active comparator in pivotal atypical-antipsychotic trials (risperidone, olanzapine, aripiprazole) for bipolar mania. The open question for this evidence pack is therefore one of local market availability (Taiwan/reference jurisdiction shows “Not Marketed,” 0 licenses) rather than scientific plausibility.

By contrast, the 9 other TxGNN-ranked candidates (congenital disorders of glycosylation, retinal dystrophy, hydranencephaly, myopia subtypes, Charcot-Marie-Tooth disease, polymicrogyria, glycine encephalopathy) are all genetic/structural developmental disorders with no dopaminergic pathophysiology, zero clinical trials, and zero literature — consistent with the evidence pack’s own annotation of these as prediction noise.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00253149	Phase 3	Completed	158	Risperidone vs. placebo vs. haloperidol as add-on to mood stabilizers for manic episodes in bipolar disorder
NCT00097266	Phase 3	Completed	615	Aripiprazole monotherapy vs. placebo in acute mania (bipolar I); haloperidol’s role as comparator not confirmed from available summary
NCT00253162	Phase 3	Completed	439	Flexible-dose risperidone vs. placebo or haloperidol in manic episodes of bipolar I disorder, including 12-week maintenance comparison
NCT00126009	Phase 2	Completed	120	Valproate+amisulpride vs. valproate+haloperidol in bipolar I manic episode, efficacy and safety comparison
NCT00129220	Phase 3	Completed	224	Olanzapine vs. placebo and haloperidol (active comparator) in manic/mixed bipolar I episode
NCT00767715	Phase 4	Terminated	11	Olanzapine vs. conventional antipsychotics (incl. haloperidol) for acute mania in Sweden; terminated due to low enrollment
NCT06049953	N/A	Recruiting	200	Observational study of antenatal antipsychotic exposure and infant development; haloperidol not the primary focus
NCT03541031	N/A	Unknown	120	Micronutrient/fish-oil adjunct trial for bipolar disorder; no direct haloperidol comparison
NCT04327843	Phase 3	Completed	22	Long-acting injectable antipsychotic + adherence program for chronic psychotic disorders in Tanzania; haloperidol likely local standard-of-care comparator

Literature Evidence

PMID	Year	Type	Journal	Key Findings
34642461	2022	Network Meta-Analysis	Molecular Psychiatry	Systematic review/NMA of double-blind RCTs comparing efficacy, acceptability, tolerability and safety of pharmacological treatments (including haloperidol) for acute bipolar mania
22134043	2012	RCT	Journal of Affective Disorders	Randomized, double-blind, placebo- and haloperidol-controlled study of olanzapine in Japanese patients with bipolar I manic/mixed episode
27151529	2016	Systematic Review/Meta-Analysis	Human Psychopharmacology	Short-term pharmacological interventions (incl. haloperidol) for acute agitation associated with psychotic and bipolar disorder
369472	1979	Controlled Trial	Archives of General Psychiatry	Double-blind five-week controlled trial of lithium carbonate plus haloperidol vs. placebo plus haloperidol in excited schizo-affective patients
18344731	2008	Systematic Review	Journal of Clinical Psychopharmacology	Comparison of antipsychotic-induced extrapyramidal side effects (incl. haloperidol) in bipolar disorder vs. schizophrenia
15147609	2004	Systematic Review/Economic Evaluation	Health Technology Assessment	Clinical and cost-effectiveness of newer drugs (vs. haloperidol as reference) for mania associated with bipolar disorder
36789916	2023	Review	BMJ Mental Health	Comparison of antipsychotic dose equivalents (incl. haloperidol) for acute bipolar mania and schizophrenia
33460070	2020	Review	Acta Psychiatrica Scandinavica	Evidence-based treatment options for bipolar mania, including choice of antipsychotic (haloperidol among options)
22070611	2012	Review	CNS Neuroscience & Therapeutics	Refractoriness in bipolar disorder; add-on haloperidol among strategies for partial responders to lithium/valproate/carbamazepine
19454110	2007	Review	BMJ Clinical Evidence	General overview of bipolar disorder treatment landscape

US Market Information

No approved licenses or NDAs are currently on file for Haloperidol in the reference jurisdiction (total_licenses = 0, market status: Not Marketed). Market entry/registration status should be confirmed with the local regulatory authority before proceeding.

Safety Considerations

Please refer to the package insert for safety information.

(Key warnings, contraindications, and drug-interaction data are currently not on file — see DG001, a Blocking-severity data gap preventing formal S1 safety review.)

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: The mania indication is supported by Evidence Level L1 (multiple completed Phase 3 RCTs, plus a 2022 network meta-analysis, with haloperidol repeatedly used as the active comparator), and the mechanism is well established rather than speculative. However, this is a market-availability question rather than a novel-science question — the drug currently shows 0 NDAs/Not Marketed status — and the local safety dossier (TFDA warnings/contraindications, DG001) is a Blocking gap that must be resolved before any S1 safety review can proceed. The other 9 TxGNN-ranked candidates should remain on Hold — they have no clinical, literature, or mechanistic support and are best treated as prediction noise, not as active leads.

To proceed, the following is needed:

TFDA package insert (warnings/contraindications) — DG001, currently blocking
Formal DrugBank-sourced mechanism-of-action documentation — DG002
Completed DDI profile (current query status: not found)
Confirmation of local market/registration pathway given current “Not Marketed” status
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.