Mirtazapine
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
Mirtazapine: Ohdo syndrome and variants
One-Sentence Summary
Mirtazapine is an antidepressant originally used for major depressive disorder and anxiety disorders. The TxGNN model predicts it may be effective for Dysthymic Disorder (persistent depressive disorder), with 1 registered clinical trial (indirect relevance only) and 10 publications currently supporting this direction. Many of the other top-ranked predictions have no supporting evidence at all, so this report focuses on the best-supported prediction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Ohdo syndrome and variants |
| TxGNN Prediction Score | 0.9942 |
| Evidence Level | L5 (observational and open-label data plus a class-level meta-analysis; no mirtazapine-specific Phase 3 RCT. The data compiled for this report assigned L2, but that is not supported by the trial data.) |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Proceed with Guardrails |
Note on the top-ranked predictions: The highest-scoring predictions (Ohdo syndrome and variants, 0.9942; blepharophimosis-intellectual disability syndrome, Ohdo type, 0.9911; benign paroxysmal torticollis of infancy, 0.9911) have no trials or publications and no identifiable mechanistic link. They are Level L5 and should be put on Hold.
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, mirtazapine is a noradrenergic and specific serotonergic antidepressant (alpha-2 antagonism, 5-HT2/5-HT3 blockade, H1 antagonism). Its efficacy in major depressive disorder is established, and mechanistically it may be applicable to dysthymia.
Dysthymic disorder is a chronic, lower-grade form of depression on the same clinical spectrum as major depression. The pharmacology that treats major depression is therefore directly relevant. The literature includes a dedicated mirtazapine-in-dysthymia study, a placebo-controlled meta-analysis of antidepressants in dysthymia, and treatment algorithms for chronic depression.
An important caveat: the meta-analysis covers the antidepressant class rather than mirtazapine specifically. The mirtazapine-specific dysthymia study is a small open-label series of 15 patients.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00080158 | Phase 2/3 | Completed | 120 | Compared three treatments for depressed teenagers who had attempted suicide (TASA). The population and endpoint (suicidality) differ from dysthymia, and mirtazapine is not clearly tested, so relevance is indirect. |
No ANZCTR trials were identified in the data compiled for this report.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 21527126 | 2011 | Meta-analysis | J Clin Psychiatry | Efficacy of antidepressants in dysthymia from placebo-controlled randomised trials (class-level, not mirtazapine-specific) |
| 36999619 | 2023 | Systematic review | Cochrane Database Syst Rev | Antidepressants for depression in people with cancer |
| 10569129 | 1999 | Open-label case series | Depress Anxiety | Mirtazapine 15 to 45 mg in patients with dysthymic disorder |
| 11310816 | 2001 | Review/algorithm | J Clin Psychiatry | Treatment algorithm for chronic depression, including dysthymia |
| 10446741 | 1999 | Review | J Clin Psychiatry | Mirtazapine in indications beyond depression |
| 18833439 | 2008 | Case report | Rev Bras Psiquiatr | Venlafaxine plus mirtazapine for “double depression” (major depression with dysthymia) |
| 9671349 | 1998 | Case report | J Clin Psychiatry | Hypomania with mirtazapine augmentation of sertraline (safety signal) |
| 21057250 | 2010 | Case report | J Clin Psychopharmacol | Delayed-onset mirtazapine-related leukopenia and rechallenge (safety signal) |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 14369G | MIRTANZA ODT | Tablet 15 mg (orally disintegrating) | Not available in the compiled data |
Safety Considerations
Safety label text (warnings and contraindications) was not available. Please refer to the TGA-approved Product Information (PI) for safety information.
Supplementary information from the data compiled for this report:
- Knowledge-graph contraindication signals (not label text): epilepsy, manic bipolar affective disorder, liver disease, impaired renal function, neutropenia, agranulocytosis, hypotension and orthostatic hypotension, serotonin syndrome, drug-induced akathisia, cerebrovascular disease and stroke, myocardial infarction, and obesity-related conditions. These should be verified against the PI.
- Drug interactions: 100 interactions were identified. Those classified as Major among the 20 listed are bupropion, lorcaserin, dolasetron and palonosetron. Moderate interactions include cimetidine, clarithromycin, morphine, dexamethasone, levofloxacin and aprepitant, among others.
- Literature safety signals: reports of leukopenia, hypomania with augmentation, pancreatitis and arthralgia.
- Paediatric use: antidepressants carry suicidality warnings in young people, which is relevant given that the only listed trial involves adolescents.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Dysthymia sits on the same spectrum as mirtazapine’s established indication, and there is dedicated literature, though it is small-scale and mostly open-label or class-level. There is no mirtazapine-specific Phase 3 RCT, so the evidence is moderate rather than confirmatory.
To proceed, the following is needed:
- A randomised, placebo-controlled trial of mirtazapine specifically in dysthymia or persistent depressive disorder
- Mechanism of action data and the ARTG indication text and PI safety information (the compiled data has gaps here)
- A safety monitoring plan covering haematological monitoring (leukopenia and agranulocytosis), hypomania or mania screening, and the major drug interactions
- Clarification of whether this use is already covered by the existing depression indication, since related predictions (melancholia, neurotic depression) are essentially on-label and are not true repurposing opportunities
Other predictions in this dataset:
- Treat as a research question.
- Treat as a research question.
- Melancholia and neurotic depression: effectively on-label. Hold.
- Ohdo syndrome (both entries), benign paroxysmal torticollis of infancy, ligneous conjunctivitis and childhood apraxia of speech: no evidence or mechanistic link. Hold.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.