Duloxetine

證據等級: L5

預測適應症: 10 個

Note on candidate selection: predicted_indications is sorted by raw TxGNN score, not by evidence quality. Rank 1 ("benign paroxysmal torticollis of infancy") and ranks 4–10 all carry L5 / Hold, zero trials, zero literature, and the pack's own rationale explicitly flags them as likely knowledge-graph noise. The only candidate with real clinical and literature support is rank 3 — Obsessive-Compulsive Disorder (L2 / S2 / Proceed with Guardrails). As a repurposing evaluation, that is the candidate worth reporting on; the report below is built on it, with the low-evidence candidates summarized briefly at the end for completeness.

Duloxetine: From Depression/Anxiety Disorders to Obsessive-Compulsive Disorder

One-Sentence Summary

Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) originally used for mood and anxiety disorders (per literature evidence; no formal Norway license record exists, as the drug is currently not marketed there). The TxGNN model predicts it may also be effective for Obsessive-Compulsive Disorder (OCD), with 5 clinical trials (1 directly on-topic, Phase 4, completed) and 20 publications — including a double-blind RCT — currently supporting this direction.

Quick Overview

Item	Content
Original Indication	Not available from an official license record (drug not marketed in Norway, 0 licenses). Literature (PMID 31749717) describes duloxetine as approved elsewhere for major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain
Predicted New Indication	Obsessive-Compulsive Disorder
TxGNN Prediction Score	99.84%
Evidence Level	L2
Norway Market Status	✗ Not Marketed
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in structured form (DrugBank MOA field: Data Gap). Based on known pharmacology, duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) whose efficacy in mood and anxiety disorders is well established; mechanistically this dual-reuptake action may extend to OCD.

The current first-line pharmacotherapy for OCD is SSRIs (serotonin-pathway only). Duloxetine's SNRI mechanism adds enhanced noradrenergic transmission on top of the serotonergic effect, which provides a theoretical basis for use as an augmentation or alternative option in patients who do not respond adequately to standard serotonin reuptake inhibitors (SRIs).

This extension is not purely theoretical: a double-blind controlled trial (PMID 27811556) demonstrated an augmentation benefit, a completed Phase 4 trial (NCT00464698) was specifically designed to test duloxetine in OCD, and multiple open-label studies, case series, and reviews reinforce the signal. Taken together, the mechanistic extension has moderate-to-high plausibility, but it remains an off-label extension — it is not an original approved indication, and no large Phase 3 monotherapy RCT exists yet.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00464698	Phase 4	Completed	20	Directly designed to assess duloxetine efficacy in OCD; small sample, no placebo arm reported in summary
NCT01404871	N/A	Completed	26	Predicts differential medication response in OCD (clomipramine, escitalopram, or duloxetine); relevant population but not a pure efficacy trial
NCT02476136	N/A	Unknown	8,800	Large IPD meta-analysis of antidepressant efficacy across anxiety disorders by baseline severity; may include OCD subgroup but not OCD-specific
NCT01944657	N/A	Withdrawn	0	TMS vs. medication monotherapy for major depression — withdrawn, no enrollment; low relevance to OCD (database keyword overlap only)
NCT05930912	N/A	Unknown	1	Psychoanalytic treatment case study in autism spectrum disorder; N=1, low relevance (keyword overlap only)

Literature Evidence

PMID	Year	Type	Journal	Key Findings
27811556	2016	RCT	J Clin Psychopharmacol	Double-blind controlled trial evaluating duloxetine augmentation in treatment-resistant OCD
25637377	2015	Open-label	Int J Neuropsychopharmacol	Open-label study of duloxetine monotherapy for DSM-IV OCD
18208931	2008	Case series	J Psychopharmacol	Case series switching from SSRIs to duloxetine in resistant OCD, building on the SNRI rationale seen with venlafaxine
21779536	2011	Review	Innov Clin Neurosci	Reviews SNRIs as pharmacological alternatives for OCD when SSRIs/clomipramine are inadequate
16669725	2006	Critical Review	J Clin Psychiatry	Critical review of SNRIs (venlafaxine, clomipramine) in OCD as an alternative to first-line SSRIs
24766145	2014	Review	Expert Opin Pharmacother	Updated review of serotonergic antidepressants, including SNRIs, in OCD pathophysiology and treatment
31749717	2019	Review	Front Psychiatry	Systematic review of duloxetine use beyond MDD/GAD, covering psychiatric indications including OCD
19483491	2009	Case report	Clin Neuropharmacol	High-dose duloxetine in treatment-resistant OCD with sustained full remission
17632660	2007	Case report	Prim Care Companion J Clin Psychiatry	Case of OCD responding to duloxetine treatment
39735048	2024	Case report	Cureus	Supratherapeutic duloxetine combined with CBT in severe treatment-resistant OCD with comorbid depression

Norway Market Information

Duloxetine currently holds no marketing authorization in Norway (0 licenses on record; market status: Not Marketed). No product/dosage-form/indication data is available to tabulate.

Safety Considerations

Please refer to the package insert for safety information. Structured safety data (key warnings, contraindications, drug-drug interactions) is not currently available in this evidence pack — this is flagged as a Blocking data gap (DG001: TFDA/package-insert warnings and contraindications) that must be resolved before this candidate can enter the S1 safety review stage.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Duloxetine's SNRI mechanism, supported by a double-blind RCT (PMID 27811556) and a completed Phase 4 trial (NCT00464698) specifically designed around OCD, gives this candidate moderate-to-high plausibility as an augmentation/alternative option for SRI-refractory OCD patients. However, it lacks large Phase 3 monotherapy RCTs, is not a formally approved indication anywhere reviewed, and the drug is not currently marketed in Norway.

To proceed, the following is needed:

TFDA/Norway package-insert warnings and contraindications (Blocking data gap, DG001) — required before any S1 safety evaluation
Formal mechanism-of-action documentation from DrugBank (High-priority data gap, DG002)
Drug-drug interaction data (current DDI query status: not_found)
A larger, controlled monotherapy trial in a primary (non-augmentation) OCD population
Regulatory pathway/market-access assessment, since duloxetine is not currently marketed in Norway

Appendix: Other Predicted Indications (Not Recommended for Further Action)

The remaining 9 predicted indications for duloxetine all scored L5 (model prediction only) with zero clinical trials and zero literature, and are recommended Hold:

Agoraphobia (rank 2, L4/S1, "Research Question") — indirect evidence only, via panic disorder/GAD literature; no agoraphobia-specific study
Benign paroxysmal torticollis of infancy, paranoid/schizotypal/histrionic/schizoid personality disorders, Ohdo syndrome and variants, ligneous conjunctivitis, blepharophimosis–intellectual disability syndrome (Ohdo type) — all L5/Hold, with the evidence pack's own rationale describing these as mechanistically implausible or likely knowledge-graph noise (e.g., Ohdo syndrome and ligneous conjunctivitis have no biological connection to monoamine reuptake inhibition).

These are not recommended for pharmacist reporting or further evaluation at this time.

Disclaimer

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