Tranylcypromine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Tranylcypromine: From Depression to Dysthymic Disorder
One-Sentence Summary
Tranylcypromine is an irreversible monoamine oxidase inhibitor (MAOI) originally used for depressive and anxiety disorders. The top-ranked TxGNN predictions (rank 1) are rare conditions with no supporting evidence, whereas the best-supported candidates are depression-related indications. This report focuses on dysthymic disorder (rank 3, the highest-ranked prediction with any supporting literature), which currently has 0 clinical trials and 1 publication (a class-level meta-analysis).
Note on the choice of indication: The two top-ranked predictions (benign paroxysmal torticollis of infancy and Ohdo syndrome) have no clinical trials or literature and no plausible mechanistic link. Dysthymic disorder is therefore used as the primary indication below. Other candidates are summarized in the conclusion.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Unipolar depression, endogenous depression, major depressive disorder, anxiety disorder (from the knowledge graph; US label indication text is not available) |
| Predicted New Indication | Dysthymic disorder |
| TxGNN Prediction Score | 99.63% |
| Evidence Level | L4 |
| US Market Status | Cancelled only (no currently valid licenses) |
| Number of NDAs | 4 (all cancelled; 1 NDA and 3 ANDAs) |
| Recommended Decision | Hold (research question) |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the data compiled for this report. Based on known pharmacology, tranylcypromine irreversibly and non-selectively inhibits monoamine oxidase, which raises serotonin, norepinephrine and dopamine levels. It is also reported to inhibit LSD1 (KDM1A), a histone demethylase, although this is not relevant to the depression indications.
Dysthymia is a chronic, lower-grade depressive disorder that shares monoaminergic pathophysiology with major depressive disorder, for which the drug is already used. This makes the prediction biologically plausible.
However, the only retrieved publication is a 2011 meta-analysis of placebo-controlled trials of antidepressants as a class in dysthymia. It is not specific to tranylcypromine, so the prediction rests on class-level reasoning rather than direct evidence.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 21527126 | 2011 | Meta-analysis of RCTs | J Clin Psychiatry | Examines antidepressant efficacy in dysthymic disorder against placebo and compares response rates with major depressive disorder. Class-level evidence, not specific to tranylcypromine. |
Related supporting literature for depression-spectrum indications (not specific to dysthymia):
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28579071 | 2017 | Review and meta-analysis | Eur Neuropsychopharmacol | Reviews clinical pharmacology and controlled depression studies of tranylcypromine |
| 35837681 | 2023 | Review | CNS Spectrums | Prescriber’s guide to classic MAOIs for treatment-resistant depression |
| 8127928 | 1993 | RCT | Pharmacopsychiatry | Double-blind comparison of moclobemide and tranylcypromine in depression |
| 34369903 | 2021 | Cohort/clinical study | J Clin Psychopharmacol | Tranylcypromine plus mirtazapine in difficult-to-treat depression |
| 3050061 | 1988 | Review | J Psychiatr Res | MAOIs are superior to placebo in some anxiety disorders, particularly agoraphobia and mixed anxiety-depressive states |
US Market Information
All four US authorizations are cancelled, and no approved indication text is available.
| Authorization Number | Product Name | Dosage Form | Status |
|---|---|---|---|
| NDA012342 | PARNATE (Advanz Pharma) | Tablet, film coated | Cancelled |
| ANDA213503 | Tranylcypromine (Solco Healthcare) | Tablet | Cancelled |
| ANDA206856 | Tranylcypromine (Novitium Pharma) | Tablet | Cancelled |
| ANDA040640 | Tranylcypromine sulfate (Strides Pharma) | Tablet, film coated | Cancelled |
Safety Considerations
- Contraindications (knowledge graph, not label text): The knowledge graph lists many contraindicated conditions, including hypertension, orthostatic hypotension, cardiovascular and heart conduction disease, coronary artery disease, pheochromocytoma and paraganglioma, hyperthyroidism, epilepsy, kidney and liver disease, diabetes, bipolar disorder and substance abuse/dependence.
- Drug Interactions: 100 interactions were identified. Major interactions include isometheptene, bupropion, morphine, lorcaserin, diethylpropion, dolasetron, palonosetron and phentermine. Moderate interactions include epinephrine, chlorpropamide, glimepiride, repaglinide, dronabinol and insulin aspart.
- Other safety signals in the literature: Hypertensive crisis with dietary tyramine (a 1964 fatality report with cheese), serotonin syndrome risk with many antidepressants, and withdrawal/discontinuation phenomena and abuse/dependence potential (2013 systematic review).
Please also refer to the package insert, as label warnings were not available for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: The predicted new indication (dysthymic disorder) is supported only by class-level antidepressant evidence, with no tranylcypromine-specific studies or registered trials, so it is a research question rather than a candidate for development. The US licenses are all cancelled, and the MAOI safety burden is substantial (hypertensive crisis, extensive interactions).
Status of other candidates:
- Agoraphobia (rank 4, L4): Research question. Evidence includes a 2010 case report of tranylcypromine in treatment-resistant agoraphobia with panic and older MAOI reviews. It is close to the original anxiety indication.
- Melancholia (rank 5, L3), neurotic depression (rank 6, L3) and neurotic disorder (rank 8, L3): Research questions that mostly reflect the existing depression and anxiety indications rather than a distinct repurposing.
- Benign paroxysmal torticollis of infancy, Ohdo syndrome and variants, Ohdo-type blepharophimosis syndrome, ligneous conjunctivitis and Keppen-Lubinsky syndrome (L5): Hold. These are model predictions only, with no evidence and no plausible mechanistic link. An epigenetic (LSD1) rationale for the Ohdo syndromes is speculative, and an irreversible MAOI is a poor fit for infants and developmental disorders.
To proceed, the following is needed:
- Tranylcypromine-specific controlled data in dysthymia or other target indications
- Mechanism-of-action data and FDA package insert warnings and contraindications
- A risk-management plan covering dietary tyramine, drug interactions and hypertensive crisis
- Clarification of current US market and regulatory status, since all licenses are cancelled
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.