Melatonin and Sertraline
Supplement–drug interaction evidence from the TruthStack database.
| Severity | HIGH |
|---|---|
| Evidence Tier | Moderate |
| Interaction Type | SEROTONERGIC RISK |
| Mechanism | PHARMACODYNAMIC |
| Last Reviewed | 2026-02-24 |
Summary
Melatonin is metabolized by CYP1A2 and has serotonergic properties. SSRIs may inhibit CYP1A2, increasing melatonin levels. Additive serotonergic effects theoretically possible. FAERS: 2,390 reports. Generally lower risk than other serotonergic combinations but monitor for excessive sedation.
CYP Enzyme Pathway Overlap
Melatonin and Sertraline share activity on the following CYP enzymes:
| Enzyme | Melatonin | Sertraline |
|---|---|---|
| CYP2C19 | SUBSTRATE (WEAK) | SUBSTRATE (MODERATE) |
Shared Pharmacodynamic Endpoints
Both compounds influence the same physiological endpoints in the same direction:
| Endpoint | Direction | Melatonin | Sertraline |
|---|---|---|---|
| SEROTONIN | INCREASE | WEAK | STRONG |
Cumulative effect on shared endpoints may exceed individual compound profiles. This is relevant to discussion with a prescribing clinician.
API Reference
GET https://api.truthstack.co/v1/check?c1=melatonin&c2=sertraline
Open, unauthenticated. Returns JSON. Developer documentation
Sources
Primary: 25503107
Related Interactions
What this page is and is not. TruthStack is an informational reference database that describes published pharmacological findings. It does not provide medical advice, diagnosis, or treatment recommendations. The information on this page reflects flags in our database and should not replace consultation with a qualified healthcare provider. Always discuss supplement-drug combinations with your prescriber or pharmacist.