Tranylcypromine
| Evidence Level: L5 | Predicted Indications: 7 |
Table of Contents
Tranylcypromine: Benign paroxysmal torticollis of infancy
One-Sentence Summary
Tranylcypromine is a monoamine oxidase inhibitor (MAOI) originally used to treat depression (unipolar, endogenous and major depressive disorder) and anxiety disorders. The TxGNN model’s top-ranked prediction is benign paroxysmal torticollis of infancy, but it has 0 clinical trials and 0 publications, so it rests on computation alone. The better-supported directions are depression-related and anxiety-related conditions (melancholia, neurotic depression, agoraphobia, dysthymic disorder), which are mostly on-label or near-label uses.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Benign paroxysmal torticollis of infancy |
| TxGNN Prediction Score | 0.9967 |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs: 2 of 2) |
| Number of DINs | 2 (marketed: 2) |
| Recommended Decision | Hold |
For comparison, the other top-10 predictions:
| Rank | Predicted Indication | Score | Evidence Level | Recommendation |
|---|---|---|---|---|
| 1 | Benign paroxysmal torticollis of infancy | 0.9967 | L5 | Hold |
| 2 | Ohdo syndrome and variants | 0.9966 | L5 | Hold |
| 4 | Agoraphobia | 0.9962 | L4 | Research Question |
| 7 | Blepharophimosis – intellectual disability syndrome, Ohdo type | 0.9950 | L5 | Hold |
| 8 | Neurotic disorder | 0.9950 | L5 | Research Question |
| 9 | Ligneous conjunctivitis | 0.9943 | L5 | Hold |
| 10 | Keppen-Lubinsky syndrome | 0.9938 | L5 | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known information, tranylcypromine is an irreversible, non-selective MAOI. Raising monoamine neurotransmitter levels is its established route to antidepressant and anxiolytic effects, and its efficacy in depression is well documented.
Top-ranked prediction (benign paroxysmal torticollis of infancy): This is a childhood disorder related to the migraine spectrum and often linked to channelopathy genes. No plausible connection to MAO inhibition is established in the data. MAOIs also carry significant safety concerns in infants. The high score is a purely computational result.
Rare developmental syndromes (Ohdo syndrome and variants, Ohdo-type blepharophimosis, Keppen-Lubinsky syndrome, ligneous conjunctivitis): There is no trial or literature support. A speculative epigenetic link exists for the Ohdo syndromes because tranylcypromine also inhibits LSD1 (KDM1A), a histone demethylase, and these syndromes involve chromatin regulation (e.g., KAT6B). No evidence shows clinical benefit. Ligneous conjunctivitis (plasminogen deficiency) and Keppen-Lubinsky syndrome (KCNJ6-related) have no evident mechanistic link.
Mood and anxiety predictions: Dysthymia, melancholia, neurotic depression and neurotic disorder are closely related to the labelled depression indications. Agoraphobia is related to the labelled anxiety indication, and MAOIs have a long history in panic disorder and agoraphobia. Much of this is on-label or near-label use rather than true repurposing, and the supporting evidence is class-level or historical.
Clinical Trial Evidence
Currently no related clinical trials registered for the top-ranked prediction (benign paroxysmal torticollis of infancy), and none for any of the other nine predictions.
Literature Evidence
Currently no related literature available for the top-ranked prediction (benign paroxysmal torticollis of infancy).
Selected publications for the better-supported predictions are shown below.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28579071 | 2017 | Review / Meta-analysis | Eur Neuropsychopharmacol | Tranylcypromine-specific review with meta-analysis of controlled studies in depression (neurotic depression) |
| 8127928 | 1993 | RCT (double-blind) | Pharmacopsychiatry | Moclobemide vs tranylcypromine in depression (79 patients on tranylcypromine) (neurotic depression) |
| 21527126 | 2011 | Meta-analysis | J Clin Psychiatry | Placebo-controlled RCTs of antidepressants in dysthymia; class-level evidence, not tranylcypromine-specific (dysthymic disorder) |
| 35837681 | 2023 | Review | CNS Spectrums | Prescriber’s guide to classic MAOIs (including tranylcypromine) for treatment-resistant depression (melancholia, neurotic depression) |
| 7612154 | 1995 | Review / Meta-analysis | Neuropsychopharmacology | Meta-analyses of controlled MAOI trials; comparable efficacy for phenelzine, isocarboxazid and tranylcypromine (melancholia) |
| 8453432 | 1993 | Clinical study (double-blind) | Br J Psychiatry | 80 inpatients with major depression randomised to tranylcypromine, amitriptyline or both; all improved with no difference between groups (neurotic disorder) |
| 3050061 | 1988 | Review | J Psychiatr Res | MAOIs superior to placebo in some anxiety disorders, particularly agoraphobia; no convincing evidence in pure anxiety states (agoraphobia) |
| 20703987 | 2010 | Case report | Psychiatr Prax | Tranylcypromine as part of combined therapy in treatment-resistant agoraphobia with panic disorder and depression (agoraphobia) |
| 34369903 | 2021 | Cohort / Case series | J Clin Psychopharmacol | Tranylcypromine plus mirtazapine in difficult-to-treat depression (melancholia, neurotic depression) |
| 23359339 | 2013 | Systematic review | Pharmacopsychiatry | Withdrawal and discontinuation phenomena after abrupt tranylcypromine termination; notes risk of abuse and dependence |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 01919598 | PARNATE | Not specified | Not specified |
| 02542188 | M-TRANYLCYPROMINE | Not specified | Not specified |
Both are valid single-ingredient authorisations.
Safety Considerations
- Contraindications suggested by the knowledge graph (not label text): hypertension and other hypertensive disorders; cardiovascular, coronary artery and heart conduction disease; sudden cardiac arrest; orthostatic hypotension and other hypotensive disorders; postural orthostatic tachycardia syndrome; multiple system atrophy; epilepsy; kidney disease; liver disease; gallbladder disease; diabetes mellitus and diabetic ketoacidosis; bipolar disorder and major affective disorder; substance abuse/dependence; phaeochromocytoma and paraganglioma; hyperthyroidism and Graves disease; and several cancers (duodenum, small intestine, heart, adrenal gland).
- Drug Interactions: 100 interactions were identified. Major-level examples include isometheptene, bupropion, morphine, lorcaserin, diethylpropion, dolasetron, palonosetron and phentermine. Moderate examples include epinephrine, chlorpropamide, glimepiride, repaglinide and insulin aspart (blood-glucose-lowering agents), plus dronabinol and several bowel-preparation products. Minor examples include hyoscyamine, atropine and dicyclomine.
- Literature-based safety signals: A 1964 case report describes a fatal hypertensive event with tranylcypromine and cheese (tyramine risk). A 2013 systematic review describes withdrawal or discontinuation phenomena and a relevant risk of abuse and dependence. MAOIs also carry serotonin syndrome risk when combined with many antidepressants.
- Paediatric use: MAOIs carry significant safety concerns in infants, which is directly relevant to the top-ranked prediction.
Package insert warnings and contraindications were not available for this report. Please refer to the Health Canada package insert for authoritative safety information.
Conclusion and Next Steps
Decision: Hold (for the top-ranked prediction, benign paroxysmal torticollis of infancy)
Rationale:
- The top prediction has a very high model score (0.9967) but no trials, no literature and no plausible mechanistic link, and MAOIs raise infant safety concerns. The same applies to the rare developmental syndromes in the list.
- Melancholia and neurotic depression are rated Proceed with Guardrails and are largely on-label or near-label uses. They rest on reviews, meta-analyses and older or observational studies rather than a clearly identified Phase 3 RCT. Dysthymic disorder, agoraphobia and neurotic disorder are Research Questions.
To proceed, the following is needed:
- Health Canada package insert warnings, contraindications and approved indication text. This is a blocking gap for safety screening.
- Mechanism of action data (a DrugBank query).
- For mood and anxiety indications: tranylcypromine-specific controlled trials, and a guardrail plan covering the dietary tyramine restriction, screening for serotonergic and sympathomimetic co-medications, and blood pressure monitoring for hypertensive crisis.
- For the rare disease predictions: preclinical or mechanistic evidence (for the Ohdo syndromes, LSD1/epigenetic data) before any clinical consideration.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.