St. John's Wort Drug Interactions With Antidepressants

Risk of Serotonin Syndrome With St. John's Wort and Antidepressants

St. John's wort and antidepressants

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St. John's wort is a dietary supplement people often take as a natural treatment for depression. The herb has similar actions as antidepressants, which means taking the supplement can interact with, or add to, the effect of certain medications prescribed to treat depression.

How Does St. John's Wort Work?

If you plan to take St. John's wort, there are a few things you should know about how it can interact with your other medications as well as its potential side effects.

St. John's wort is an herbal supplement marketed as a natural remedy for depression, anxiety, and other mood disorders. Proponents of St. John's wort believe the herb can increase the amount of serotonin in the brain. Serotonin is a neurotransmitter (a chemical signal in the brain) that may be deficient in some people with depression.

Potential Interactions

St. John's wort can interact with antidepressant medications. As a result, your doctor will likely advise you to avoid the combination. If you're considering adding St. John's wort to your treatment plan, it's important to discuss why you are considering taking both medications with your doctor. Instead, your doctor may suggest adjusting your dose or trying a new medication rather than taking St. John's wort and a prescription antidepressant together.

Some people try taking St. John's wort as a way of reducing or minimizing their need for prescription medication. It's important to realize, however, that St. John's wort is an active medication and should be approached the same way you would a pharmaceutical prescribed to you.

St. John's wort has the potential to interact with several different classes of antidepressant drugs, including:

There are specific medications in each class, including well-known drugs like Prozac (fluoxetine), Cymbalta (duloxetine), and Zoloft (sertraline). In addition to being prescribed as a treatment for depression, many of these medications can be used to treat anxiety and other mental health conditions such as bipolar disorder.

Selective Serotonin Reuptake Inhibitors

Common SSRIs include:

Selective Norepinephrine Reuptake Inhibitors

Common SNRIs include:

Tricyclic Antidepressants

Common TCAs include:

  • Anafranil (clomipramine)
  • Ascendin (amoxapine)
  • Elavil (amitriptyline)
  • Norpramin (desipramine)
  • Pamelor (nortriptyline)
  • Sinequan (doxepin)
  • Surmontil (trimipramine)
  • Tofranil (imipramine)
  • Vivactil (protriptyline)

Monoamine Oxidase Inhibitors

Common MAOIs include:

  • Nardil (phenelzine)
  • Parnate (tranylcypromine)

Risk of Serotonin Syndrome

Increasing serotonin may help improve symptoms of depression, but levels that are too high can cause a potentially serious condition known as serotonin syndrome. If you are using a prescription antidepressant or a nutritional supplement for depression, it's important to know the symptoms of serotonin syndrome, such as:

  • Agitation, confusion
  • Diarrhea
  • Dilated pupils
  • Coma
  • Fever
  • Headache
  • High blood pressure
  • Involuntary twitching, tremors, overactive reflexes
  • Loss of consciousness
  • Muscle stiffness
  • Rapid or irregular heartbeat
  • Seizures
  • Sudden mood changes
  • Sweating or shivering

Elevated serotonin levels can result if you are taking:

  • A high dose of a single antidepressant
  • Two or more antidepressants or an antidepressant plus St. John's wort
  • St. John's wort or an antidepressant plus another medication that interacts with and raises serotonin levels (including common medications found in cold and cough preparations)

Serotonin syndrome is a serious condition that can be fatal without treatment. Contact your healthcare provider right away if you are experiencing symptoms of serotonin syndrome while taking medications or supplements used to treat depression.


The first step in treating serotonin syndrome is stopping all medications and nutritional supplements (including St. John's wort). Due to the risk of a condition known as SSRI discontinuation syndrome, you should not stop taking these medications suddenly or without first consulting your doctor.

While SSRI discontinuation syndrome can be uncomfortable, serotonin syndrome can be quite serious if not life-threatening, and it requires immediate medical treatment.

Treatment for serotonin syndrome may include the administration of serotonin antagonists such as methysergide and cyproheptadine. Benzodiazepines, such as Ativan (lorazepam) or Valium (diazepam), may also be given in order to reduce symptoms such as muscle rigidity.


In order to prevent serotonin syndrome, closely follow your doctor's prescription for taking your medications. In addition, make sure each of your healthcare providers is aware of the medications or supplements you take, including herbal remedies like St. John's wort and over-the-counter medications, such as those used for sleep or cold and cough medicine.

If you want or need to transition from one antidepressant to another, or from a prescription antidepressant to herbal supplements, only do so after talking with your doctor.

Your serotonin levels could remain elevated for a period of time after you stop taking your medication. You may need to allow a "washout period" before starting another medication, herb, or supplement which may have similar effects on serotonin.

Other Drugs Linked to Serotonin Syndrome

If you are taking St. John's wort or an antidepressant, it's important to be aware of other drugs that may also lead to serotonin syndrome, including:

  • 5-HTP (5-hydroxytryptamine or 5-HT) 
  • Buspar (buspirone)
  • Chlorpheniramine
  • Dextromethorphan (found in many cough and cold remedies)
  • Dopamine agonists including levodopa, amantadine, and bromocriptine
  • Illegal drugs such as cocaine, LSD, ecstasy (MDMA), and amphetamines
  • Lithium
  • Pain medications including codeine, fentanyl, meperidine, and tramadol
  • Panax ginseng
  • Selegiline
  • Triptans (migraine medications)

The interaction of St. John's wort with some antidepressant medications is just one example of how nutritional supplements, though marketed as natural, plant-based, and even organic, can cause side effects or interact with other medications as prescription drugs can.

Before taking any herbal or nutritional supplement, discuss it with your doctor to ensure you are educated and empowered to make the right decisions for your health.

A Word From Verywell

If you are looking for non-medication methods to help manage your depression or anxiety, there are many options. Psychotherapy can be very helpful either alone, or when combined with an herbal supplement like St. John's wort or an antidepressant.

Short-term options such as interpersonal therapy for depression can also be effective for some people. Other therapies, such as cognitive behavioral therapy, behavioral therapy, and rational emotive behavior therapy, can also be used to help people cope with depression with or without medication.

You may also want to explore self-help strategies including self-help books, depression support groups, and online support communities.

4 Sources
Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. National Center for Complementary and Integrative Health. St. John’s Wort and Depression: In Depth.

  2. Cleveland Clinic. Serotonin Syndrome.

  3. Iqbal MM, Basil MJ, Kaplan J, Iqbal MT. Overview of serotonin syndrome. Ann Clin Psychiatry. 2012;24(4):310-8.

  4. Apaydin EA, Maher AR, Shanman R, et al. A systematic review of St. John’s wort for major depressive disorder. Systematic Reviews. 2016;5(1). doi:10.1186/s13643-016-0325-2

Additional Reading

By Nancy Schimelpfening
Nancy Schimelpfening, MS is the administrator for the non-profit depression support group Depression Sanctuary. Nancy has a lifetime of experience with depression, experiencing firsthand how devastating this illness can be.