Paroxetine
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Paroxetine: From Anxiety and Depressive Disorders to Ohdo Syndrome and Variants
One-Sentence Summary
Paroxetine is a selective serotonin reuptake inhibitor (SSRI) originally used for anxiety disorders, depression, post-traumatic stress disorder, social phobia and obsessive-compulsive disorder. The TxGNN model predicts it may be effective for Ohdo syndrome and variants, but there are currently 0 clinical trials and 0 publications supporting this direction. The prediction rests on the model score alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Anxiety disorder, major depressive disorder, post-traumatic stress disorder, social phobia, obsessive-compulsive disorder (from the knowledge graph; no label text available) |
| Predicted New Indication | Ohdo syndrome and variants |
| TxGNN Prediction Score | 99.11% |
| Evidence Level | L5 |
| US Market Status | Cancelled only (no currently valid licenses) |
| Number of NDAs | 10 (2 NDAs and 8 ANDAs, all cancelled) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, paroxetine is an SSRI that blocks serotonin reuptake and has also been reported to inhibit GRK2. Its efficacy in depression and anxiety-spectrum disorders is established, but no mechanistic pathway linking it to Ohdo syndrome could be identified from the data compiled for this report.
Ohdo syndrome variants (for example Say-Barber-Biesecker-Young-Simpson syndrome, linked to KAT6B variants, and the Maat-Kievit-Brunner type) are rare neurodevelopmental disorders. They involve intellectual disability, blepharophimosis and hypotonia, and the underlying problem is a chromatin-regulation defect. Nothing in the available data suggests that paroxetine acts on this defect.
The high score most likely reflects proximity in the knowledge network, such as shared neurodevelopmental or psychiatric-symptom associations, rather than disease-modifying biology. At most, any benefit would be symptomatic, such as treating comorbid anxiety or depression, and would not change the underlying syndrome.
Safety Considerations
Label-based warnings and contraindications were not available in the data compiled for this report. Please refer to the package insert for these.
- Knowledge-graph contraindication associations (not label text): epilepsy, bipolar disorder, major affective disorder, liver disease, gallbladder disease, blood coagulation disease, neuroleptic malignant syndrome, inappropriate ADH syndrome, nephrogenic syndrome of inappropriate antidiuresis, serotonin syndrome, drug-induced akathisia, and pathologic fracture (an obsolete term).
- Drug interactions: 100 interactions were identified. Examples of those rated Major:
- Bupropion
- Lorcaserin
- Diethylpropion
- Dolasetron
- Eliglustat
- Palonosetron
- Phentermine
Moderate interactions include:
- Morphine
- Acetylsalicylic acid (aspirin)
- Cimetidine
- Clarithromycin
- Chlorpropamide
- Glimepiride
- Repaglinide
Of these, aspirin may increase bleeding risk, and several others are serotonergic or affect CYP2D6 metabolism.
Conclusion and Next Steps
Decision: Hold
Rationale: The recommendation rests only on a computational prediction score. There are no clinical trials or publications, and no plausible mechanistic link to Ohdo syndrome. The evidence level is L5. In addition, all US licenses for paroxetine are currently cancelled.
To proceed, the following is needed:
- Mechanism of action data for paroxetine and a testable biological hypothesis connecting it to KAT6B or chromatin-regulation pathways
- Preclinical evidence in relevant disease models
- Package insert warnings and contraindications, which are a blocking gap for safety screening
- Confirmation of the current US regulatory and market status, and of the route and dosage-form requirements for the proposed use
- A clear definition of the intended benefit (for example, treating comorbid anxiety or depression versus modifying the disease)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.