SERTRALINE for PMDD
Per Open Targets, sertraline is a clinical-stage (Phase 1/2) serotonin transporter (SLC6A4) inhibitor candidate for PMDD.
Hypothesized mechanism
Sertraline inhibits the serotonin transporter (SLC6A4/SERT), increasing synaptic serotonin availability, which is the proposed basis for its effect in PMDD.
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 5 of 10 overall, a emerging reading, from a pathway rated emerging 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.
Scored for women. Evidence generated in women (female population). (band F1, ×1.00).
Corroboration
Only a single line of evidence is provided: one Open Targets database entry stating sertraline is a serotonin transporter inhibitor clinical candidate for PMDD. No independent mechanistic lines converge.
Rigor
The claim derives from a curated database entry (Open Targets) citing a PHASE_1_2 clinical stage, which is human-relevant but provides no actual study data, models, or outcomes. It is a regulatory/annotation statement rather than experimental evidence.
Specificity
The claim names a precise molecular mechanism: serotonin transporter inhibition acting on solute carrier family 6 member 4 (SLC6A4/SERT). This is a well-defined, specific drug-target action.
Plausibility
Serotonergic modulation via SERT inhibition is a recognized therapeutic rationale for PMDD, and the entry links the target to the named condition. However, no claim explicitly connects the target mechanism to the PMDD phenotype beyond the database annotation.
Consistency
With only one claim there is no opportunity for signals to conflict, but neither is there convergence; the single positive annotation is internally consistent only by default.
Sex-specific pharmacokinetics
Documented differences in how this drug is handled in women, drawn from a primary source, an FDA label or the curated sex-PK literature (Zucker and Prendergast 2020; Soldin and Mattison 2009). It is reported beside the signal and is not part of the composite score; it informs how a result should be interpreted.
Cycle-phase dependence
Why it matters. Some treatments work differently depending on where someone is in the menstrual cycle, and for a cyclical condition like PMDD the timing can be the whole point. A drug that helps in the luteal phase, the roughly two weeks before menstruation, can look weaker than it is when its effect is averaged across the entire cycle.
What tracking the phase adds. Holding the phase as structured data lets a luteal-phase result be read in its phase rather than averaged across the cycle, and records the dosing pattern, taking the drug only in the luteal phase, that a phase-blind record does not capture.
What the literature says. For PMDD this is well established: intermittent luteal-phase SSRI dosing is an accepted first-line regimen (ACOG 2023), and it works within days, which is itself a clue that the drug acts through a faster route here than in depression. The standard outcome instrument for measuring it is the Daily Record of Severity of Problems (DRSP).
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, Pathway insights. 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.
- 1Per Open Targets (retrieved 2026-06-16), SERTRALINE (a Small molecule) is a clinical candidate for PMDD (maximum clinical stage PHASE_1_2); its mechanism of action is Serotonin transporter inhibitor on target solute carrier family 6 member 4. Open Targets · mechanistic ↗
- 2In FDA AEMS (the FDA Adverse Event Reporting System, formerly FAERS; retrieved 2026-06-16), 8157 report(s) of FATIGUE were recorded for SERTRALINE among female patients (of 132336 female reports for SERTRALINE in the analysed sample). This is a raw adverse-event report count, not a disproportionality statistic or evidence of causation, and is subject to reporting bias and confounding. Read two ways: as a safety consideration, and — because it suggests SERTRALINE acts on a system relevant to PMDD — as a mechanistic lead for further investigation, not evidence of benefit. AEMS · adverse-event report ↗
- 3In FDA AEMS (the FDA Adverse Event Reporting System, formerly FAERS; retrieved 2026-06-16), 6487 report(s) of ANXIETY were recorded for SERTRALINE among female patients (of 132336 female reports for SERTRALINE in the analysed sample). This is a raw adverse-event report count, not a disproportionality statistic or evidence of causation, and is subject to reporting bias and confounding. Read two ways: as a safety consideration, and — because it suggests SERTRALINE acts on a system relevant to PMDD — as a mechanistic lead for further investigation, not evidence of benefit. AEMS · adverse-event report ↗
- 4In FDA AEMS (the FDA Adverse Event Reporting System, formerly FAERS; retrieved 2026-06-16), 5654 report(s) of DEPRESSION were recorded for SERTRALINE among female patients (of 132336 female reports for SERTRALINE in the analysed sample). This is a raw adverse-event report count, not a disproportionality statistic or evidence of causation, and is subject to reporting bias and confounding. Read two ways: as a safety consideration, and — because it suggests SERTRALINE acts on a system relevant to PMDD — as a mechanistic lead for further investigation, not evidence of benefit. AEMS · adverse-event report ↗
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 →