Melatonin may enhance SSRI side effects
Some SSRIs (especially fluvoxamine) inhibit CYP1A2, which metabolizes melatonin. This can increase melatonin blood levels, causing excessive sedation.
Use lower melatonin doses (0.3-0.5mg) with SSRIs. Monitor for oversedation.
Start with lower melatonin doses
Melatonin may enhance SSRI side effects. Use lower melatonin doses (0.3-0.5mg) with SSRIs. Monitor for oversedation.
Start with lower melatonin doses
This interaction is rated “Caution” by Formulate. Some SSRIs (especially fluvoxamine) inhibit CYP1A2, which metabolizes melatonin. This can increase melatonin blood levels, causing excessive sedation.
Studies from our registry that mention melatonin or ssri. Each links to the primary source and the other Formulate pages citing it.
Mentions ssri · 2024
St. John's Wort — StatPearls
Primary literature · Monograph
Identifies SSRIs (sertraline, paroxetine, fluoxetine, citalopram) as high-concern co-administration targets due to serotonin syndrome risk. Typical SJW doses implicated: 600-900 mg/day standardized extract. Typical SSRI doses in case reports: 20-75 mg/day.
Mentions ssri · 2015
Rhodiola rosea versus sertraline for major depressive disorder: a randomized placebo-controlled trial
Mao JJ, Xie SX, Zee J, et al. · Phytomedicine
12-week three-arm RCT (n=57) found rhodiola produced smaller antidepressant effect than sertraline but with significantly fewer adverse events, supporting it as an option for milder depression.
Mentions melatonin · 2013
Meta-analysis: melatonin for the treatment of primary sleep disorders
Ferracioli-Oda E, Qawasmi A, Bloch MH · PLOS ONE
Meta-analysis of 19 RCTs (n=1,683) found melatonin reduced sleep-onset latency by ~7 minutes, increased total sleep time by ~8 minutes, and improved overall sleep quality — small but consistent effect across populations.
Mentions melatonin · 2012
The effect of magnesium supplementation on primary insomnia in elderly: a double-blind placebo-controlled clinical trial
Abbasi B, Kimiagar M, Sadeghniiat K, et al. · Journal of Research in Medical Sciences
8-week RCT in elderly with insomnia: 500mg/day magnesium significantly improved subjective insomnia score, sleep efficiency, sleep onset latency, and serum melatonin concentration.
Mentions melatonin · 2007
Efficacy of prolonged release melatonin in insomnia patients aged 55–80 years: quality of sleep and next-day alertness outcomes
Wade AG, Ford I, Crawford G, et al. · Current Medical Research and Opinion
3-week RCT in older insomnia patients (n=354) found prolonged-release melatonin 2mg improved sleep quality and morning alertness, supporting lower doses (1–3mg) over the often-oversold 5–10mg.
Other interactions to know
Combining St John's wort with any SSRI risks serotonin syndrome — a potentially fatal hyperserotonergic state.
Risk of serotonin syndrome
SAM-e with SSRIs: Serotonin syndrome risk
Melatonin may affect blood clotting
Both cause sedation - enhanced drowsiness
Rhodiola may have mild MAOI effects
Ashwagandha may enhance SSRI effects
Complementary sleep support
Check your full stack in the free interaction checker.
The free checker lets you add any combination of supplements and medications at once. The free web app goes further — every stack change surfaces interaction alerts automatically.
Medical disclaimer. This page is for educational purposes only and does not replace advice from a qualified healthcare provider.
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