Mianserin

證據等級: L5

預測適應症: 10 個

Mianserin: From Antidepressant Use to Melancholia (Depressive Subtype)

One-Sentence Summary

Mianserin is a tetracyclic antidepressant; the drug’s original registered indication and detailed mechanism of action are not captured in the source data (data gap), but literature within this evidence pack confirms it as an established α2-adrenergic antagonist antidepressant. Among the TxGNN model’s top-10 predictions, most (including the single highest-scoring candidate, benign paroxysmal torticollis of infancy, and four rare genetic syndromes) are flagged by the evidence pack itself as likely knowledge-graph noise with no supporting evidence. The strongest-supported candidate is Melancholia, a depressive subtype, backed by direct mianserin randomised controlled trials (L2 evidence) — though this represents confirmation of mianserin’s known antidepressant activity rather than a genuinely novel repurposing signal.

Quick Overview

Item	Content
Original Indication	Not recorded in source data (data gap); literature in this evidence pack identifies mianserin as a tetracyclic antidepressant for depression
Predicted New Indication	Melancholia (depressive subtype)
TxGNN Prediction Score	99.17%
Evidence Level	L2
Australia Market Status	Not marketed
Number of ARTG Entries	0
Recommended Decision	Proceed with Guardrails

Important caveat on ranking: TxGNN’s single highest-scoring prediction (benign paroxysmal torticollis of infancy, 99.49%) and four rare genetic-syndrome predictions (Ohdo syndrome and variants, blepharophimosis–intellectual disability syndrome, Keppen-Lubinsky syndrome, ligneous conjunctivitis) all returned zero clinical trials and zero literature. The evidence pack’s own rationale explicitly labels these as having “no plausible mechanistic link” and likely reflecting knowledge-graph noise rather than a real pharmacological hypothesis. This report therefore leads with the best-evidenced candidate (melancholia) rather than the raw top-ranked score.

Why is This Prediction Reasonable?

Detailed mechanism-of-action data for mianserin was not available from the primary drug record (data gap DG002). However, literature captured in this evidence pack consistently describes mianserin as a tetracyclic antidepressant that acts as a presynaptic α2-adrenergic receptor antagonist, increasing central noradrenaline and serotonin release — the same mechanistic class discussed for its close analogue, mirtazapine.

The original indication field for this drug is also empty in the source data. Based on the literature retrieved (e.g. PMID 6346303, “Efficacy and side effects of mianserin, a tetracyclic antidepressant”; PMID 7048075, a mianserin pharmacology monograph), mianserin’s established clinical use is as an antidepressant. Melancholia is a recognised subtype of depressive illness, so a prediction linking mianserin to melancholia sits squarely within its known pharmacological class rather than representing a mechanistically distant “new” indication.

This has a direct implication for interpretation: unlike a true repurposing case (e.g. an oncology drug predicted for a cardiovascular indication), this candidate is best understood as confirmatory evidence of an existing therapeutic domain, not discovery of a novel use. The genuinely novel high-score predictions in this dataset (rare paediatric and genetic syndromes) carry no mechanistic or evidentiary support at all.

Clinical Trial Evidence

Currently no related clinical trials registered for melancholia (or for any of the other nine predicted indications in this dataset — all clinical trial and ICTRP searches returned zero results).

Literature Evidence

PMID	Year	Type	Journal	Key Findings
8773291	1995	RCT	Pharmacopsychiatry	Controlled study of 51 depressive inpatients; mianserin vs amitriptyline showed no significant difference in HAMD outcome, similar tolerability
2864794	1985	RCT	Acta Psychiatr Scand Suppl	Double-blind multicentre trial in 61 depressive patients; mianserin vs nomifensine, no significant differences at baseline or outcome
11294041	2001	RCT	L’Encéphale	Multicentre double-blind trial in geriatric patients (≥60y) with major depression; paroxetine vs mianserin, comparable efficacy and safety
6371875	1984	RCT	Psychopathology	Double-blind, non-crossover trial in 125 general-practice depression patients; trazodone vs mianserin, higher withdrawal rate on mianserin
8249653	1993	RCT	Acta Psychiatr Scand	Double-blind, placebo-controlled crossover study of mianserin in chronic pain with and without depression
27289172	2016	Meta-analysis	Lancet	Network meta-analysis comparing antidepressants (including mianserin’s class) for major depressive disorder in children/adolescents
7048075	1982	Review	Mod Probl Pharmacopsychiatry	Mianserin pharmacology and clinical monograph
6346303	1983	Review	Postgrad Med J	Efficacy and side-effect profile of mianserin as a tetracyclic antidepressant
40616802	2025	Review	Prilozi	Discusses α2-autoreceptor/heteroreceptor antagonists (mianserin, trazodone, mirtazapine) in combination antidepressant therapy
3068469	1988	Review	Medicina (Firenze)	General review of mianserin

Australia Market Information

Mianserin is not currently registered on the ARTG (Australian Register of Therapeutic Goods) — 0 entries found. No product, dosage form, or approved-indication information is available for the Australian market.

Safety Considerations

Please refer to the TGA-approved Product Information (PI) for safety information. No TFDA/TGA warnings, contraindications, or drug interaction data were retrievable for this drug in the current evidence pack (flagged as a Blocking data gap, DG001) — this must be resolved before any S1 safety review can proceed.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Direct mianserin RCT evidence (L2) supports antidepressant efficacy in melancholia-type depression, but this reflects the drug’s known pharmacological class rather than a novel repurposing opportunity, and the drug has no current Australian market presence or safety documentation.

To proceed, the following is needed:

Resolve DG001 (Blocking): obtain TFDA/TGA product information for warnings, contraindications, and interactions
Resolve DG002: confirm mechanism of action and original approved indication via DrugBank/regulatory source
Clarify regulatory strategy given 0 ARTG entries — no existing Australian registration to build on
Independently verify whether “melancholia” offers distinct clinical/regulatory value over mianserin’s already-established antidepressant use, given the overlap noted above
Given the top TxGNN-scored candidates (rare paediatric/genetic syndromes) show no mechanistic or evidentiary support, deprioritise or discard these from further development pending stronger signal
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.