If you take an SSRI antidepressant like sertraline, citalopram or fluoxetine, most supplements are fine alongside it. But two are a genuine hard stop, and a few more deserve a conversation with your GP first. The reason comes down to one thing: SSRIs raise serotonin, and anything else that also raises serotonin can push it too high.
The two hard stops
5-HTP is the clearest one. It is a direct building block of serotonin, so taken with an SSRI it stacks serotonin on serotonin. This is not a "be careful" situation; it is a do-not-combine one, because the result can be serotonin syndrome, a real and occasionally dangerous reaction. The same applies across antidepressant types, including the SNRIs.
St John's Wort is the second. It raises serotonin in its own right, so the same stacking risk applies, and on top of that it speeds up the liver enzymes that clear many other medicines, which makes it doubly unsuitable. Both 5-HTP and St John's Wort sit firmly on the avoid list with an SSRI.
The ones to clear with your GP first
A few supplements taken for mood or stress sit in a more cautious middle. Saffron, SAM-e and ashwagandha all have some serotonergic or mood activity, and while they are not automatic exclusions the way the first two are, they are worth raising with whoever prescribes your antidepressant before you start. The point is not that they are dangerous, but that the interaction is real enough to want a clinician's eye on it.
What is genuinely fine
Plenty of common supplements have no serotonin involvement and sit comfortably alongside an SSRI. Omega-3, vitamin D and magnesium are the obvious examples, all reasonable to take for their own reasons without touching how your antidepressant works.
If you are weighing up a supplement for low mood or anxiety specifically while on an SSRI, that is exactly the situation to check rather than guess. The free checker assesses your exact combination and shows you which tier each pair falls into and why.