Duloxetine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Duloxetine: Benign paroxysmal torticollis of infancy
One-Sentence Summary
Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI), originally used for major depressive disorder, anxiety disorders, fibromyalgia, myofascial pain and female stress incontinence. The TxGNN model’s top-ranked prediction is benign paroxysmal torticollis of infancy, but this has no supporting evidence. The best-supported prediction is obsessive-compulsive disorder (OCD), backed by 3 registered clinical trials and 19 publications, mostly small studies, case reports and reviews.
This report covers OCD as the lead evidence-supported candidate. The other nine predictions have little or no supporting evidence (see the note below the Quick Overview).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Benign paroxysmal torticollis of infancy |
| TxGNN Prediction Score | 0.9985 |
| Evidence Level | L5 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Proceed with Guardrails (research use only) |
Note on the other predictions:
- The top-ranked prediction, benign paroxysmal torticollis of infancy (score 0.9985), has no clinical trials or literature (L5, Hold). It is a rare infantile disorder with no plausible link to duloxetine, and duloxetine is not appropriate for routine use in infants.
- Agoraphobia (0.9984, L3) has only open-label and case-level evidence in panic disorder, not agoraphobia itself. It is a research question.
- Schizotypal, paranoid, schizoid and histrionic personality disorders, Ohdo syndrome and variants, ligneous conjunctivitis, and Ohdo-type blepharophimosis-intellectual disability syndrome all have no trials or literature (L5, Hold). Their scores come from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence.
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available in the data compiled for this report. Based on known pharmacology, duloxetine inhibits the reuptake of both serotonin and norepinephrine. Serotonergic reuptake inhibition is the core mechanism of drug treatment for OCD, and duloxetine has potent serotonin reuptake inhibition in addition to its noradrenergic effect.
Duloxetine is already used for depression and anxiety disorders, which frequently co-occur with OCD and share serotonergic treatment targets. Small studies, including a double-blind controlled augmentation trial in resistant OCD and open-label studies, suggest benefit.
Reviews note that SNRIs are less well established than SSRIs for OCD. The evidence base is small, with only a Phase 4 trial of 20 participants and no Phase 3 RCT. Larger controlled trials are needed before use can be recommended.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00464698 | Phase 4 | Completed | 20 | Directly tests duloxetine efficacy in OCD. The small sample limits conclusions. No results summary is available in the data compiled. |
| NCT01404871 | N/A | Completed | 26 | Studies predictors of medication response in OCD. Participants are randomised to clomipramine or escitalopram, and those who have previously tried these may take duloxetine instead. Not a direct efficacy test. |
| NCT02476136 | N/A | Unknown | 8,800 | Individual patient data meta-analysis of initial severity and antidepressant efficacy in anxiety disorders. Not specific to duloxetine in OCD. |
No ANZCTR trial identifiers were found in the data compiled for this report.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27811556 | 2016 | RCT (double-blind) | J Clin Psychopharmacol | Evaluates duloxetine augmentation in resistant OCD. |
| 25637377 | 2015 | Open-label study | Int J Neuropsychopharmacol | Investigates duloxetine efficacy for DSM-IV OCD. |
| 31749717 | 2019 | Systematic review | Front Psychiatry | Reviews duloxetine in psychiatric disorders beyond major depression and generalised anxiety disorder. |
| 16669725 | 2006 | Review | J Clin Psychiatry | Critical review of the antiobsessional properties of SNRIs (venlafaxine, clomipramine) as an alternative to SSRIs. |
| 24766145 | 2014 | Review | Expert Opin Pharmacother | Reviews double-blind studies of serotonergic antidepressants in OCD. |
| 28477500 | 2017 | Meta-analysis | J Affect Disord | OCD shows a reduced placebo and antidepressant response compared with other anxiety disorders. |
| 18208931 | 2008 | Case series | J Psychopharmacol | Switching from serotonin reuptake inhibitors to duloxetine in resistant OCD. |
| 39735048 | 2024 | Case report | Cureus | Supratherapeutic duloxetine plus cognitive-behavioural therapy in severe treatment-resistant OCD with comorbid depression. |
| 19483491 | 2009 | Case report | Clin Neuropharmacol | High-dose duloxetine in treatment-resistant OCD with sustained full remission. |
| 22567604 | 2012 | Case report | Innov Clin Neurosci | Suprathreshold duloxetine in treatment-resistant depression, anorexia nervosa and OCD. |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 14712H | APO-Duloxetine | Capsule 60 mg (as hydrochloride) | Not available in the data compiled for this report |
Safety Considerations
Warnings and contraindications from the product label were not available in the data compiled for this report. Please refer to the TGA-approved Product Information (PI) for these.
Conditions linked to duloxetine contraindications or cautions (from a knowledge graph, not label text):
- Cardiovascular: hypertension, orthostatic hypotension, postural orthostatic tachycardia syndrome, multiple system atrophy
- Neurological and psychiatric: epilepsy, bipolar disorder, major affective disorder, substance abuse/dependence, neuroleptic malignant syndrome, serotonin syndrome
- Hepatic: liver disease, cirrhosis, fatty liver disease, hepatitis, gallbladder disease
- Other: hyperglycaemia, blood coagulation disease, angle-closure glaucoma, inappropriate ADH syndrome (including nephrogenic form)
Drug interactions: The interaction screen returned 100 entries. The examples below are from the first 20 reviewed.
- Major: bupropion, lorcaserin, diethylpropion, dolasetron, dexfenfluramine
- Moderate: epinephrine, morphine, acetylsalicylic acid (aspirin), cimetidine, picosulfuric acid, polyethylene glycol with electrolytes, difenoxin, diphenoxylate, dronabinol
- Minor: famotidine, ranitidine, rabeprazole, dexlansoprazole, aluminium hydroxide, calcium carbonate
The remaining 80 entries were not reviewed here. Review the full interaction list before any clinical use.
Conclusion and Next Steps
Decision: Proceed with Guardrails (research use only)
Rationale: OCD is the only prediction with direct duloxetine studies, including one small double-blind augmentation RCT, open-label studies and a completed Phase 4 trial (N=20). The evidence is small and has no Phase 3 confirmation, and SNRIs are considered less established than SSRIs in OCD, so this supports further research rather than clinical adoption. The other nine predictions should be on Hold or treated as research questions only (agoraphobia).
To proceed, the following is needed:
- Larger, adequately powered controlled trials of duloxetine in OCD, with a comparison against first-line SSRIs
- Mechanism of action data for duloxetine
- The approved indications and the label warnings and contraindications from the TGA Product Information
- A review of the full drug interaction list, especially for serotonergic combinations
- A safety monitoring plan, including for comorbid bipolar disorder, hepatic disease and cardiovascular risk
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.