Fluvoxamine
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
- Fluvoxamine
- Fluvoxamine: From Social Phobia and Obsessive-Compulsive Disorder to Schizotypal Personality Disorder
Fluvoxamine: From Social Phobia and Obsessive-Compulsive Disorder to Schizotypal Personality Disorder
One-Sentence Summary
Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) originally used for social phobia and obsessive-compulsive disorder (OCD). The TxGNN model's top-ranked prediction is schizotypal personality disorder, but there are no clinical trials and only 5 publications (all case reports or small open-label studies), none of which tests fluvoxamine for this condition. The best-supported predictions further down the list are anxiety disorder and agoraphobia, which largely overlap with the drug's existing indications.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Social phobia, phobic disorder, obsessive-compulsive disorder (from the knowledge graph; the Singapore licence records contain no indication text) |
| Predicted New Indication | Schizotypal personality disorder |
| TxGNN Prediction Score | 99.997% |
| Evidence Level | L5 (model prediction only; the data compiled for this report graded it L4) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available. Based on known information, fluvoxamine is an SSRI that increases serotonin signalling. Its efficacy in OCD and social phobia is established, and mechanistically it may be applicable to conditions that share anxiety or obsessive features.
For schizotypal personality disorder specifically, the link is weak. The retrieved literature concerns antipsychotic augmentation in fluvoxamine-refractory OCD, in which comorbid schizotypal disorder was associated with response, plus case reports of comorbidity and drug interactions. Any connection comes indirectly through OCD-spectrum overlap and serotonergic modulation. The very high TxGNN score is not supported by clinical data.
Other top-ranked predictions have a very different evidence profile:
- Schizoid, paranoid, histrionic, dependent and narcissistic personality disorders: no trials, and the few papers retrieved are comorbidity studies or unrelated reviews. These are prediction-only signals.
- Benign paroxysmal torticollis of infancy: no trials, no literature, and no plausible mechanism. The score is likely spurious.
- Anxiety disorder (rank 5) and agoraphobia (rank 6): supported by Phase 3 trials, placebo-controlled RCTs and meta-analyses. Both are close extensions of the already-approved social phobia and OCD indications, so they are not novel repurposing signals.
- Endogenous depression (rank 10): supported by class-level antidepressant meta-analyses and one Phase 2 trial of unknown status.
Clinical Trial Evidence
No clinical trials are registered for schizotypal personality disorder, the top prediction. Currently no related clinical trials registered.
For reference, trials linked to the next best-supported predictions are shown below.
Anxiety disorder (rank 5), most relevant trials
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01933919 | Phase 3 | Completed | 38 | Fluvoxamine (SME3110) vs placebo in pediatric/adolescent OCD, using the JCY-BOCS scale over 10 weeks |
| NCT00000389 | Phase 3 | Completed | Not reported | RUPP study of fluvoxamine for childhood anxiety disorders (generalized anxiety, social phobia, separation anxiety) |
| NCT00074815 | Phase 3 | Completed | 124 | Cognitive behavioural therapy added to SRI treatment in pediatric OCD partial responders |
| NCT02022709 | Phase 4 | Completed | 78 | Exposure and response prevention vs SSRIs vs combination in OCD |
| NCT00352768 | Phase 4 | Terminated | 20 | Post-marketing placebo-controlled study of fluvoxamine in pediatric OCD; small and ended early |
| NCT04539951 | Phase 2 | Recruiting | 1600 | Pragmatic trial of switching and augmentation strategies after unsatisfactory initial OCD treatment |
| NCT02194075 | Phase 4 | Completed | 60 | Methylphenidate controlled-release augmentation in OCD patients receiving fluvoxamine |
| NCT00012584 | NA | Completed | 120 | Stimulant with or without fluvoxamine in youth with comorbid ADHD and anxiety |
Endogenous depression (rank 10)
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04160377 | Phase 2 | Unknown | 150 | Fluvoxamine for melancholia, with MRI, cytokine and microbiome assessments; no results available |
Literature Evidence
Schizotypal personality disorder (top prediction)
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 1970224 | 1990 | Case series | Am J Psychiatry | 9 of 17 fluvoxamine-refractory OCD patients responded to added neuroleptics; comorbid tic or schizotypal disorder predicted response |
| 11063782 | 2000 | Open-label trial | Psychiatry Res | Olanzapine augmentation in fluvoxamine-refractory OCD, assessing whether schizotypal comorbidity predicted response |
| 14999178 | 2004 | Case report | CNS Spectrums | Compulsive hoarding with ADHD and schizotypal disorder treated with fluvoxamine, amphetamine salts, risperidone and behavioural therapy |
| 16146185 | 2005 | Case report | Seishin Shinkeigaku Zasshi | OCD symptoms improved with fluvoxamine after neuroleptics were stopped in a patient with schizotypal-type personality |
| 8473723 | 1993 | Case report | Int Clin Psychopharmacol | Seizures with combined levomepromazine and fluvoxamine; a safety signal, not efficacy |
Agoraphobia / panic disorder (rank 6), selected
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 8927663 | 1996 | RCT | Psychopharmacol Bull | Double-blind comparison of fluvoxamine, imipramine and placebo in panic disorder with or without agoraphobia (n=54) |
| 7726307 | 1995 | RCT | Am J Psychiatry | Fluvoxamine vs placebo vs psychological panic management, combined with exposure in vivo |
| 38014714 | 2023 | Network meta-analysis | Cochrane Database Syst Rev | Pharmacological treatments for panic disorder in adults |
| 11110016 | 2000 | Review | Int Clin Psychopharmacol | SSRIs including fluvoxamine were superior to placebo in panic disorder and agoraphobia |
Anxiety disorder (rank 5), selected
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27318812 | 2016 | Network meta-analysis | Lancet Psychiatry | Comparison of drug and psychological treatments for adult OCD |
| 32039743 | 2020 | Network meta-analysis | Acta Neuropsychiatr | Pharmacological treatments for social anxiety disorder |
| 29995828 | 2018 | Meta-analysis | Medicine | Efficacy and tolerability of fluvoxamine in adult social anxiety disorder |
| 40143130 | 2025 | Overview of reviews | Pharmaceuticals | Efficacy of fluvoxamine in anxiety disorders and OCD |
Endogenous depression (rank 10), selected
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29477251 | 2018 | Network meta-analysis | Lancet | Comparative efficacy of 21 antidepressants in adult major depression |
| 18562407 | 2009 | Meta-analysis | J Psychopharmacol | Efficacy, tolerability and side effects of fluvoxamine in major depression |
| 6215443 | 1982 | Randomised double-blind | J Affect Disord | Fluvoxamine vs chlorimipramine in endogenous depression (n=30); no significant difference |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN09491P | FAVERIN TABLET 100 mg (WHITE) | Film-coated tablet | Not stated in the available records |
| SIN09489P | FAVERIN TABLET 50 mg (WHITE) | Film-coated tablet | Not stated in the available records |
| SIN13559P | APO-FLUVOXAMINE 100MG TABLET | Film-coated tablet | Not stated in the available records |
All three licences are valid single-ingredient oral products.
Safety Considerations
- Knowledge-graph contraindication signals (from the TxGNN graph, not label text): epilepsy, bipolar disorder, major affective disorder, liver disease, gallbladder disease, blood coagulation disease, neuroleptic malignant syndrome, inappropriate ADH syndrome (including the nephrogenic form), and serotonin syndrome.
- Drug interactions: 100 interactions were identified. Major-level examples include alosetron, bupropion, diethylpropion and dolasetron. Moderate-level examples include rabeprazole, aspirin, clarithromycin, morphine, pioglitazone, aprepitant, chlorpropamide and several corticosteroids (hydrocortisone, dexamethasone, betamethasone, budesonide, triamcinolone).
- Literature signals: seizures with combined levomepromazine and fluvoxamine (case report); CYP-mediated interactions, including a methadone toxicity case; and pediatric suicidality, sexual dysfunction and gastrointestinal adverse effects, which are class effects of antidepressants.
Please refer to the package insert for official warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction, schizotypal personality disorder, rests on a very high model score but has no trials and only indirect case-level literature. The same applies to the other personality disorders and to benign paroxysmal torticollis of infancy. Anxiety disorder and agoraphobia carry a "Proceed with Guardrails" rating (L1) and are well supported, but they largely overlap with fluvoxamine's existing indications and are not new repurposing opportunities. Endogenous depression remains a research question pending results from the Phase 2 melancholia trial.
To proceed, the following is needed:
- Mechanism of action data (currently unavailable)
- Package insert warnings and contraindications from the Health Sciences Authority (HSA), which are required before any safety screening
- Approved indication text for the Singapore licences, to confirm which indications are already covered
- For schizotypal and other personality disorders: controlled studies, or a clear mechanistic rationale, before any further evaluation
- For anxiety disorder subtypes and agoraphobia: confirmation that current guidelines support use, and a plan to manage CYP-mediated interactions, initial anxiety exacerbation and pediatric suicidality monitoring
- For endogenous depression: results from NCT04160377 and review of its status
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.