WhelWomen's Health Evidence Lab
WHEL-C-115 · Exploratory evidence · 3/10

amitriptyline for vulvodynia

A single case series of 20 patients suggests amitriptyline may provide pain relief and quality-of-life improvement in vulvodynia associated with vulvar lichen sclerosus.

Origin · ApprovedPathway · Hypothesis-generation · pre-validationEvidence arm · Direct researchEvidence silent
How to read thisThe summary above and the proposed mechanism are generated by the model from the sources it ingested, and are written as the model’s reasoning rather than established fact. Any figure quoted from MATRIX is a model-derived association score, not a clinical measurement. How far the published record backs this pair is carried by the score’s own rigor dimension and traced to verbatim sources at the foot of the page.

Hypothesized mechanism

Mechanism not yet characterized in the substrate.

This is the model’s proposed mechanism from the sources on file, not a demonstrated causal pathway. How well the published record supports it is reflected in the rigor and plausibility dimensions of the score, and traced to the verbatim sources at the foot of the page.

How the score was reached, for this pair

The composite score is the sum of five dimensions, each scored 0 to 2 by the model from the evidence on file. Below is the sub-score this specific pair received on each, with what that dimension measures. It scored 3 of 10 overall, a exploratory reading, from a direct rated exploratory in strength.

The model’s overall reasoning for this pair is the summary at the top of the page, and the mechanism it proposed is in the section above.

Direct research arm · anchors the headline3.0 / 10 · Exploratory

Scored for women. Evidence generated in women (female population, ~100% female). (band F1, ×1.00).

Corroboration

All claims derive from a single source, a case series of 20 patients. A single primary study scores 0, and there is no independent replication present.

0 / 2

Rigor

The evidence is a case series (claim 1 source explicitly 'a case series of 20 patients'), an uncontrolled observational design with no comparator, placing it at the lowest rigor tier.

0 / 2

Specificity

Both the drug (amitriptyline) and the condition (vulvodynia) are named directly in claims 1-3, satisfying full specificity.

2 / 2

Plausibility

The claims assert pain relief but provide no mechanistic explanation for how amitriptyline acts on vulvodynia. No mechanism is described, so plausibility is only asserted at best.

0 / 2

Consistency

Only a single study is available, so directional consistency cannot be assessed and the default n/a score of 1 applies.

1 / 2
How the scoring rubric works, in general

Independent reading, reported beside the score

One outside model cross-reference is reported alongside the composite score. It is recorded separately and is not combined into the score.

MATRIX cross-reference Top 1%

Every Cure’smachine-learned treatment-probability model, drawn from a biomedical knowledge graph. We read its public dataset release, which covers roughly 1,800 drugs and 22,000 diseases. It provides a model-based estimate of how plausible a drug-disease link is given the structure of biomedical knowledge, reported alongside the substrate’s own evidence.

For this pair. MATRIX places this pair at Top 1%, with a treat-score of 3.88 (higher is better; across the pairs we cover, scores span about 3.1 to 4.5).

Scored over MATRIX’s own entities, confirming the same drug and disease: CHEBI:2666 (drug) and MONDO:0021722 (disease). Validate against the source: Every Cure’s MATRIX dataset ↗.

More on the MATRIX cross-reference and its provenance

Regulatory & development status

Where this candidate sits in the US regulatory landscape: whether the drug is already FDA-approved for vulvodynia (on-label) or approved for something else (off-label), whether the molecule is available as a generic or a single-source brand still under patent, and how far it has been studied as a therapy for this condition. Each fact is drawn from a public US source and reported beside the score; none of it is folded into the score.

This is descriptive context, not regulatory advice. It maps the landscape a 505(b)(2)route would build on (an already-approved active ingredient proposed for a new indication), but it is not a 505(b)(2) viability assessment, and says nothing about whether any particular development path is advisable. “Approved” means FDA-approved (US); approvals elsewhere are out of scope.

Approval relationship Off-label

Read from the drug’s FDA label via DailyMed, the US National Library of Medicine’s label repository. A label is only counted when it carries an FDA-approved marketing category (an NDA, ANDA, or biologic BLA); dietary supplements, homeopathics, and OTC-monograph products are not FDA-approved drugs and are excluded.

For this pair. The drug has an FDA-approved label, but for a different indication, so using it for this condition would be off-label.

Generic & patent supply Generic available

Read from the FDA Orange Book (Approved Drug Products with Therapeutic Equivalence Evaluations), using single-ingredient products only so that patents on novel branded combination formulations are never attributed to the base molecule.

For this molecule. A live ANDA lists this active ingredient, so the basic molecule is available as a generic (off-patent in its basic form).

ENDEP · ANDA (generic) · 40MG/ML **Federal Register determination that product was not discontinued or withdrawn for safety or effectiveness reasons** · discn · approved Approved Prior to Jan 1, 1982
AMITRIPTYLINE HYDROCHLORIDE · ANDA (generic) · 10MG/ML · discn · approved Approved Prior to Jan 1, 1982
ELAVIL · NDA (brand) · 10MG/ML · discn · approved Approved Prior to Jan 1, 1982
AMITID · ANDA (generic) · 10MG · discn · approved Approved Prior to Jan 1, 1982
AMITID · ANDA (generic) · 25MG · discn · approved Approved Prior to Jan 1, 1982

Clinical-trial stage, for this condition Phase 3

Read from ClinicalTrials.gov (US National Library of Medicine). A trial only counts when the drug appears as an experimental or active-comparator intervention in an interventional study of this condition; mechanistic, drug-interaction, post-marketing (Phase 4), and comparator-background uses are excluded, so this reflects the drug being tested as a therapy for vulvodynia.

For this pair. Studied in 1 qualifying interventional trial · highest stage reached Phase 3 · status unclear.

NCT02871661 · Phase 3 · unknown
The regulatory and trial sources this status is drawn from

Layers not covered for this pair

Sex-specific pharmacokineticsNone on file

Not covered for this pair. This layer holds documented sex-specific pharmacokinetics for a limited set of drugs, and this compound is not among them yet. A blank here means the drug is not covered by the layer, not that no sex difference exists.

More on the sex-specific pharmacokinetics layer and its sources
Cycle-phase dependenceNone on file

Not covered for this pair. The cycle-phase layer is seeded for the strongest-evidence cases so far (PMDD), and this pair is not among them yet. A blank here means the pair is not covered by the layer, not that the effect was found to be phase-independent.

More on the cycle-phase layer and its sources

Source evidence · what the pipeline ingested

These are the sources the pipeline ingested to detect and score this signal, the published literature the model actually read, each tagged by study type. Where the model combined findings the claim is marked as a synthesis (S), and where the literature disagrees the contradiction is shown (!).

Every source below belongs to this signal’s evidence arm, Direct research. Whel reads each drug-condition pair through four such arms, each held to its own inclusion bar; a signal is surfaced through one of them.

  • 1Amitriptyline for the treatment of vulvodynia in patients with vulvar lichen sclerosus: a case series of 20 patients. PubMed · PMID 39757140
  • 2The results suggest that amitriptyline may offer significant pain relief and improvements in the patients' quality of life, although adverse effects need to be carefully managed. PubMed · PMID 39757140
  • 3amitriptyline may offer significant pain relief and improvements in the patients' quality of life PubMed · PMID 39757140
  • 4The results suggest that amitriptyline may offer significant pain relief and improvements in the patients' quality of life, although adverse effects need to be carefully managed. PubMed · PMID 39757140

These are the verbatim sources the pipeline surfaced and read; they may not be the full published record for a pair, and the score reflects the strength and agreement of the evidence rather than its volume. The strength of these source types is what the rigor dimension of the score reads off. MATRIX, sex-specific pharmacokinetics, and cycle phase are separate layers the pipeline does not ingest, external cross-references reported beside the score, and they link to their own sources in their sections above.

The primary sources and pipelines this evidence is drawn from