Serotonin Supplements and Antidepressants
Important: 5-HTP, L-tryptophan, SAMe and St. John's wort can raise serotonin. Combined with SSRIs, SNRIs, MAOIs, triptans, tramadol or other serotonergic drugs, they can cause serotonin syndrome, which can be life-threatening.[MedlinePlus][PubMed] Do not combine them, and do not stop an antidepressant on your own; talk to your prescriber or pharmacist.
| Supplement | Score | Owner comments | Main caution |
|---|---|---|---|
| Saffron extract (incl. Affron) | 4.0 | 115 | Saffron has been studied alongside antidepressants. Do not add it to, or swap it for, a prescribed antidepressant without your doctor. |
| 5-HTP | 3.5 | 21 | Do not combine with SSRIs, SNRIs, MAOIs, triptans, tramadol or other drugs that raise serotonin without your doctor: the combination can cause serotonin syndrome, which can be life-threatening. |
| L-tryptophan | 3.5 | 6 | Like 5-HTP, it raises serotonin: do not combine it with SSRIs, SNRIs, MAOIs or other serotonin-affecting drugs without your doctor (risk of serotonin syndrome). |
| SAMe | 3.0 | 6 | SAMe may not be safe for people with bipolar disorder and may interact with medicines and other supplements, including antidepressants. |
| St John's wort | 2.8 | 13 | St. John's wort weakens many medicines, including birth control pills, warfarin, digoxin, cyclosporine, some HIV and cancer drugs, some seizure medicines and some antidepressants. |
St. John's wort
NCCIH says St. John's wort weakens many medicines, including birth control pills, warfarin, digoxin, cyclosporine and some HIV and cancer drugs, and can cause serious serotonin-related side effects with antidepressants.[NCCIH] It has the lowest score in our data (2.8).
SAMe
NCCIH says evidence that oral SAMe helps depression is not conclusive, that it may not be safe for people with bipolar disorder, and that it may interact with medicines.[NCCIH]
5-HTP and L-tryptophan
5-HTP is converted into serotonin, and Cochrane reviewers found too few good-quality trials to draw firm conclusions about 5-HTP and tryptophan for depression.[PubMed][PubMed]
Saffron
Saffron is not a serotonin precursor, but meta-analyses have compared it with SSRIs; most trials were small and short.[PubMed][PubMed] It is one of the better-rated ingredients in our data (4.0), and the Affron extract has its own brand page. Do not add it to, or swap it for, a prescribed antidepressant without your doctor.
For the full picture, see our stress and anxiety supplement ratings built from Reddit owner comments. Read which calming supplements need extra caution first. Read our guide on choosing a supplement for stress or anxiety before you buy.