Several supplements can interact with psychiatric medication, and St. John's wort is the one with the clearest risk. Others raise concern because they add to serotonin effects, add to drowsiness, may increase bleeding risk, or can change how much medication stays in your body. Some have only limited evidence either way.
Part of our guide: A Guide to Integrative Psychiatry
The safest step is simple: give your prescriber a complete list of everything you take, including gummies, teas and powders, before you add anything new. Please do not stop or change a prescribed medication on your own because of what you read here. If a supplement and a medication are already combined and you feel unwell, call your prescriber. Severe symptoms such as confusion, high fever, or muscle rigidity need emergency care, so call 911.
Why "natural" products can interact with medication
The FDA explains that certain supplements can change the absorption, metabolism or excretion of a medication, and that some combinations can be dangerous. Interactions tend to fall into four groups:
- Too much serotonin effect. Combining products that raise serotonin activity can lead to serotonin syndrome.
- Faster or slower drug clearance. A supplement can change the enzymes that break down a medication, which can leave too little or too much in your system.
- Added sedation. Calming herbs can stack on top of sedating medications or alcohol.
- Added bleeding risk. Some supplements may affect clotting, and some antidepressants carry their own bleeding warning.
One limit is worth stating plainly. The National Center for Complementary and Integrative Health (NCCIH) says that well-designed clinical studies of herb-drug interactions are limited and sometimes inconclusive. A supplement missing from the table below has not been cleared as safe. It may simply not have been studied.
Supplements to discuss with your prescriber
| Supplement | Medications of concern | What sources say |
|---|---|---|
| St. John's wort | Antidepressants and other serotonin drugs, birth control pills, warfarin, benzodiazepines, some seizure medications including carbamazepine | NCCIH warns it can interact in dangerous, sometimes life-threatening ways and weaken many medicines. Documented interactions include benzodiazepines. |
| L-tryptophan | Medicines that affect serotonin | May cause life-threatening serotonin toxicity in combination. The sertraline label lists tryptophan among products that raise serotonin syndrome risk. |
| 5-HTP | SSRIs, MAOIs | The risk is not well measured, and that is a reason for caution. See below. |
| SAMe | Serotonin-raising drugs and supplements, levodopa | NCCIH says it might interact with drugs and supplements that increase serotonin, though evidence for these interactions is very limited. |
| Kava | Benzodiazepines, other sedatives, alcohol | Should not be used together with sedating substances. Linked to rare, sometimes fatal, liver injury. |
| Valerian | Sedatives, alcohol | Should not be taken along with alcohol or sedatives. Evidence for sleep is inconsistent. |
| Ashwagandha | Sedatives, anti-seizure medications, thyroid hormone, immunosuppressants | Might interact with some medications. Rare liver injury cases reported. Not recommended with autoimmune or thyroid disorders, or in pregnancy and breastfeeding. |
| Melatonin | Blood thinners; any regular medication | People on blood thinners or with epilepsy need medical supervision. Anyone on medicine should check first. |
| Ginkgo | Warfarin and other anticoagulants | May increase bleeding risk and may interact with other drugs. |
| Omega-3 fish oil | Drugs that affect platelets or clotting | Generally well tolerated, with some concern about extended bleeding time that NCCIH asks clinicians to discuss. NIH's Office of Dietary Supplements says most research finds no clinically significant bleeding, though labels for omega-3 drugs call for monitoring with anticoagulants. |
| Folate (folic acid) | Carbamazepine, valproate, phenytoin | NIH's Office of Dietary Supplements says these drugs can lower folate levels and folate supplements might lower levels of these drugs, so check first. |
| CBD | Many medications, including sedating ones | NCCIH links CBD with drug interactions, sleepiness and abnormal liver tests. |
St. John's wort deserves its own warning
This herb is often treated like a gentle alternative to an antidepressant. It behaves more like a drug with a long interaction list. It is a potent inducer of liver and intestinal systems that clear many medicines, which is how it can reduce their effect. NCCIH says the combination with certain antidepressants can cause serotonin syndrome, with symptoms ranging from tremor and diarrhea to confusion, muscle stiffness and even death. The sertraline label also lists agitation, fast heartbeat, sweating and high body temperature among possible signs.
NCCIH also notes that a rare side effect is psychosis, and that people with conditions such as bipolar disorder are at risk. Its evidence is real but incomplete: studies suggest it may help mild or moderate depression, while results for severe depression or use beyond 12 weeks are uncertain. NIMH adds that no natural product has FDA approval for treating depression.
5-HTP: thin evidence, good reason for caution
5-HTP is a building block of serotonin, so combining it with an antidepressant raises an obvious question, and good data are lacking. A published case report describes serotonin syndrome in a man taking sertraline, 5-HTP and many other products, who also said he had adjusted his sertraline himself. Its authors say 5-HTP should not be used with SSRIs or MAOIs and that combining it with sertraline is not recommended. A separate narrative review argued that adding 5-HTP to this type of antidepressant can be safe, but it also says that all previous 5-HTP trials were small, and four of its authors have financial or advisory ties to a company developing a 5-HTP drug.
Federal sources add less than you might hope. The NCCIH pages checked for this article give no 5-HTP interaction warning. Its sleep page says 5-HTP has been under close watch for its safety because of a contamination outbreak tied to L-tryptophan, and that testing found no similar contaminants, which is a separate question from interactions. The sertraline label does not name 5-HTP, but it warns that other serotonin-raising products, including tryptophan, increase the risk of serotonin syndrome. The label for phenelzine, an MAOI, tells patients not to take L-tryptophan.
A fair reading: the size of the risk is not well measured, and that is different from being shown safe. Do not combine 5-HTP with an antidepressant, especially an MAOI, unless your prescriber has reviewed it.
Medications that need extra care
SSRIs and SNRIs
Serotonin-related interactions are the main concern here. The sertraline label warns about serotonin syndrome with St. John's wort and tryptophan, among others. It also warns that aspirin, NSAIDs, warfarin and other anticoagulants may increase bleeding risk. The sources checked here do not settle whether fish oil or ginkgo adds meaningfully to that risk with an antidepressant, so it is worth raising, especially before surgery or if you take a blood thinner. The FDA notes that warfarin, ginkgo, aspirin and vitamin E together may increase the chance of internal bleeding or stroke.
Benzodiazepines and sleep medications
Kava and valerian are the two to raise first, since both carry cautions about sedatives. Drowsiness can affect driving and falls risk, particularly with alcohol in the mix.
Lithium
The lithium label explains that diuretics and NSAIDs can raise lithium levels, while xanthine preparations can lower them. Salt matters too. The label says it is essential to keep a normal diet, including salt, and its Medication Guide warns that changing the amount of salt in your diet could change the amount of lithium in your blood. Dehydration from prolonged sweating, diarrhea or a fever raises the risk of lithium toxicity, so call your prescriber if those happen. Ask before using anything sold as a "water pill" or debloating product, before changing your salt intake, or before taking over-the-counter pain relievers such as ibuprofen. A boxed warning on the label says toxicity can occur at doses close to therapeutic concentrations, so small changes can matter.
Birth control, if you also take St. John's wort
This one is easy to overlook because it is not a psychiatric medication. Birth control pills are on NCCIH's list of medicines St. John's wort can weaken.
How to reduce your risk
- Keep one written list. The FDA advises bringing a list of all supplements and medications to appointments. Include brand, amount, how often, and when you started.
- Read combination products closely. Sleep and mood blends often contain several herbs, and one product can include more than one item from the table above.
- Add one thing at a time. If something changes, you will have a better idea of what caused it.
- Remember that labels can be wrong. The FDA does not approve dietary supplements before they are marketed. In testing described by NCCIH, most melatonin supplements did not match their labels, and some contained serotonin. The guide to choosing safe supplements covers quality checks.
- Update your list after any change. Pregnancy, breastfeeding, surgery, a new diagnosis or a new prescription are all good moments to check again.
A pharmacist can be a useful second check, since pharmacies can look across all your prescriptions. For a broader comparison of these two categories, see Supplements vs Medication: What’s the Difference?.
Getting help with your list
If you take psychiatric medication and want to use supplements, the useful conversation covers what each product is meant to do, whether there is decent evidence for it, and what could go wrong with what you already take. Nutrition and supplement support at Mind Body Seven and medication management are good places to start that conversation.
FAQs
Is it safe to take magnesium or vitamin D with an antidepressant?
NIH's fact sheets name other drugs as examples: for magnesium, some antibiotics, osteoporosis drugs, diuretics and acid reducers; for vitamin D, orlistat, statins, steroids and thiazide diuretics. Antidepressants are not among those examples, but the lists are not complete, so this is not a clearance. Add them to your list and ask your prescriber or pharmacist.
What should I do if I have been taking St. John's wort with my antidepressant?
Call your prescriber soon and tell them exactly what you have been taking. Do not change the medication on your own. If you have severe symptoms such as confusion or muscle stiffness, call 911.
Do I need to tell my therapist about supplements?
NCCIH advises telling all your health care providers about complementary approaches you use. Your prescriber needs the details most, though it is helpful if your whole care team has the same list.
Are teas and gummies safer than capsules?
Not necessarily. The form does not remove the interaction risk, and the amount in a tea or gummy can be harder to judge. Include them on your list like any other supplement.
