Sertraline
| Evidence Level: L5 | Predicted Indications: 8 |
Table of Contents
Sertraline: From Anxiety Disorders to Agoraphobia
One-Sentence Summary
Sertraline is an SSRI antidepressant, originally used for anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, social phobia and related conditions. The TxGNN model predicts it may be effective for Agoraphobia, supported by 2 clinical trials (only one of them relevant) and 19 publications, including several randomized trials and network meta-analyses in panic disorder with or without agoraphobia.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Anxiety disorder, neurotic disorder, dysthymic disorder, post-traumatic stress disorder, social phobia, phobic disorder, obsessive-compulsive disorder (from the knowledge graph; no approved-indication text is available from US licenses) |
| Predicted New Indication | Agoraphobia |
| TxGNN Prediction Score | 99.54% |
| Evidence Level | L1 (based on the literature; see note below) |
| US Market Status | Cancelled only (all 8 listed licenses are cancelled) |
| Number of NDAs | 8 (all ANDA generic applications, all cancelled) |
| Recommended Decision | Proceed with Guardrails |
Note on the evidence level: The only registered sertraline trial in this set (NCT00182533) is in social phobia, is Phase 4 and was terminated. The L1 level rests on the published randomized trials and network meta-analyses in panic disorder with or without agoraphobia, not on a completed Phase 3 trial in agoraphobia itself.
Note on the other predictions: Seven other predicted indications were also evaluated: paranoid, histrionic, schizoid, schizotypal, dependent and narcissistic personality disorders, and benign paroxysmal torticollis of infancy. They share very high scores, but the evidence is only L4–L5 (indirect or absent), so they are not the focus of this report. Agoraphobia is the only one with strong supporting evidence.
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, sertraline is a selective serotonin reuptake inhibitor (SSRI). SSRIs are thought to reduce anxiety and panic by modulating serotonergic signalling in fear circuitry (amygdala, prefrontal cortex and brainstem pathways).
Sertraline’s original indications already cover several anxiety-spectrum conditions, including social phobia, phobic disorder and anxiety disorder. Agoraphobia usually occurs together with panic disorder and belongs to the same family of conditions. This prediction is therefore a close extension of existing use, not a distant repurposing.
The published evidence supports this link. It includes a double-blind multicenter trial of sertraline in panic disorder, comparator trials against imipramine and alprazolam, and recent network meta-analyses of drug treatment for panic disorder with or without agoraphobia. The high TxGNN score is consistent with this, though the score on its own is a graph-based prediction and not clinical proof.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00182533 | Phase 4 | Terminated | 170 | Sertraline in generalized social phobia with comorbid conditions. Related to agoraphobia through the anxiety-disorder spectrum, but it does not target agoraphobia directly. No results were provided. |
| NCT05930912 | N/A | Unknown | 1 | Psychiatric orders in psychoanalytic treatment of autism spectrum disorder. Not relevant to sertraline in agoraphobia. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 35045991 | 2022 | Systematic review and network meta-analysis | BMJ | Compares drug classes and individual SSRIs for remission rates and adverse events in panic disorder with or without agoraphobia |
| 38014714 | 2023 | Network meta-analysis | Cochrane Database Syst Rev | Pharmacological treatments for panic disorder in adults |
| 9734541 | 1998 | RCT | Am J Psychiatry | Double-blind multicenter trial of sertraline’s efficacy and safety in panic disorder |
| 14971862 | 2003 | RCT | Ann Clin Psychiatry | Imipramine vs. sertraline in panic disorder, 24-week completers |
| 16505130 | 2006 | RCT | Am J Geriatr Psychiatry | CBT and sertraline vs. waitlist control for anxiety disorders in older adults |
| 16053461 | 2005 | Comparative trial | Bosn J Basic Med Sci | 12-week placebo-controlled comparison of sertraline and alprazolam in panic disorder with and without agoraphobia |
| 11206597 | 2000 | Post-hoc analysis of RCT | J Clin Psychiatry | Sertraline response in panic disorder patients at risk of poor outcome, including those with agoraphobia |
| 9819070 | 1998 | Clinical trial | Arch Gen Psychiatry | Flexible-dose multicenter trial of sertraline in panic disorder |
| 11110016 | 2000 | Review | Int Clin Psychopharmacol | SSRIs, including sertraline, were superior to placebo in panic disorder and agoraphobia |
| 37676054 | 2023 | Systematic review | Expert Rev Neurother | Pharmacological management of panic disorder in older patients |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA214790 | Sertraline Hydrochloride (Camber Pharmaceuticals) | Tablet | Cancelled |
| ANDA077206 | Sertraline Hydrochloride (PD-Rx Pharmaceuticals) | Tablet, film coated | Cancelled |
| ANDA076465 | Sertraline (Bryant Ranch Prepack) | Tablet, film coated | Cancelled |
| ANDA077670 | Sertraline (A-S Medication Solutions) | Tablet, film coated | Cancelled |
| ANDA219714 | Sertraline Hydrochloride (ANI Pharmaceuticals) | Capsule | Cancelled |
All 8 licenses compiled for this report are cancelled, and no approved-indication text was available. The remaining three are ANDA077397 (Exelan, film-coated tablet), ANDA202825 (Bryant Ranch Prepack, film-coated tablet) and ANDA078861 (Rising Pharma, concentrate solution). The “Cancelled” status reflects these specific records only and should be verified against current FDA listings before drawing conclusions about availability.
Safety Considerations
- Contraindication-related conditions (from the knowledge graph, not label text): epilepsy, bipolar disorder, major affective disorder, liver disease, gallbladder disease, blood coagulation disease, neuroleptic malignant syndrome, inappropriate ADH syndrome (including nephrogenic syndrome of inappropriate antidiuresis), and serotonin syndrome.
- Drug Interactions: 100 interactions were found in total. Examples classified as Major include bupropion, lorcaserin, diethylpropion, dolasetron, eliglustat, palonosetron and phentermine. Examples classified as Moderate include acetylsalicylic acid, morphine, clarithromycin, famotidine, loperamide, glimepiride and chlorpropamide.
Package insert warnings and contraindications were not available for this report. Please refer to the current package insert for complete safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Randomized trials and network meta-analyses support SSRIs, including sertraline, in panic disorder with or without agoraphobia, and agoraphobia is a close neighbour of sertraline’s existing anxiety-spectrum indications. The caveats are that no registered trial targets agoraphobia directly, and that the one registered sertraline trial in the set (social phobia) was terminated.
To proceed, the following is needed:
- FDA package insert warnings and contraindications, which are required for safety screening
- Detailed mechanism of action data from DrugBank
- Confirmation of current US marketing status, since all compiled licenses are cancelled
- Agoraphobia-specific efficacy data, or confirmation that evidence from panic disorder with agoraphobia is acceptable
- A monitoring plan for the major drug interactions and the knowledge-graph contraindication conditions listed above
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.