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Can I take 5-HTP with SSRIs like Zoloft or Lexapro?

Not without your prescriber's OK. 5-HTP is turned into serotonin, and SSRIs keep serotonin active. That the two add up is documented in drug-level studies: people on fluoxetine (Prozac) had a bigger hormone response to a dose of 5-HTP. We found no published case of serotonin syndrome from the pair, but SSRI labels warn about tryptophan, which 5-HTP is made from. Ask your prescriber or pharmacist first.

How well documented: Documented in drug-level studies. Studies in people measured the effect directly: the medicine’s blood levels or its effect, or a test result.

Last reviewed

How we grade evidenceEditorial policy

What's known

  • Drug-level study. Doctors gave a single dose of 5-HTP to people with depression or OCD and measured cortisol and prolactin, hormones that serotonin releases. The rise was significantly bigger in people taking fluoxetine (Prozac) than in people on older antidepressants or no medicine. In other words, the SSRI made 5-HTP's serotonin effect stronger. (Meltzer 1997)
  • On the labels, by family. The sertraline (Zoloft) and escitalopram (Lexapro) labels say serotonin syndrome, a potentially life-threatening reaction, is more likely when an SSRI is combined with other serotonin products, and they name tryptophan and St John's wort. 5-HTP itself isn't named, but it is the step between tryptophan and serotonin. (Zoloft label; Lexapro label; Das 2004)
  • Case reports. We found no published case of serotonin syndrome from 5-HTP with an SSRI. With another kind of antidepressant, an MAOI, one person developed mania after adding a 5-HTP supplement. (Pardo 2012)
  • Supervised trials. Psychiatrists have tested the pair on purpose: in a 12-week trial, 60 people with OCD took fluoxetine with 5-HTP or with a placebo. The published summary gives no safety results, and a monitored trial is not the same as combining them on your own. (Yousefzadeh 2020)
  • Hidden sources. Griffonia seed extracts are rich in 5-HTP (6 to 20% of the seed's weight), so a griffonia product counts as 5-HTP. (Cunningham 2021)

What to do

  • Talk to your prescriber or pharmacist before you take 5-HTP or griffonia with any antidepressant, and mention triptans, tramadol or other serotonin drugs you use.
  • Know the warning signs the labels list: agitation, confusion or hallucinations, a fast heartbeat, sweating, flushing, a high temperature, shaking, stiff or twitching muscles, poor coordination, seizures, nausea, vomiting or diarrhea. Contact your health care provider or go to an emergency room if they appear. (Zoloft label)
  • Don't stop or change a prescribed medicine on your own. The Zoloft label tells prescribers to lower the dose gradually rather than stop it suddenly.

Sources

  1. US National Library of Medicine. Zoloft (sertraline) tablets and oral solution: prescribing information. DailyMed, revised August 2023. DailyMed
  2. US National Library of Medicine. Lexapro (escitalopram) tablets and oral solution: prescribing information. DailyMed, revised October 2023. DailyMed
  3. Meltzer H, et al. Fluoxetine, but not tricyclic antidepressants, potentiates the 5-hydroxytryptophan-mediated increase in plasma cortisol and prolactin secretion in subjects with major depression or with obsessive compulsive disorder. Neuropsychopharmacology. 1997. PubMed 9194044 · doi:10.1016/S0893-133X(96)00280-1
  4. Das YT, et al. Safety of 5-hydroxy-L-tryptophan. Toxicol Lett. 2004. PubMed 15068828 · doi:10.1016/j.toxlet.2003.12.070
  5. Pardo JV. Mania following addition of hydroxytryptophan to monoamine oxidase inhibitor. Gen Hosp Psychiatry. 2012. PubMed 21963353 · doi:10.1016/j.genhosppsych.2011.08.014
  6. Yousefzadeh F, et al. 5-Hydroxytryptophan as adjuvant therapy in treatment of moderate to severe obsessive-compulsive disorder: a double-blind randomized trial with placebo control. Int Clin Psychopharmacol. 2020. PubMed 32541380 · doi:10.1097/YIC.0000000000000321
  7. Cunningham AB, et al. From forest to pharmacy: Should we be depressed about a sustainable Griffonia simplicifolia (Fabaceae) seed supply chain? J Ethnopharmacol. 2021. PubMed 33991640 · doi:10.1016/j.jep.2021.114202